Multi-target adhesion-removing and febrile disease-relieving decoction with Qingyi Ganlu powder

Abstract

The present application relates to Mongolian medicine compound preparation technical field, and disclose a multi-target Qizhuanqingwu granules for clearing epidemic disease, which is a repair system taking sea buckthorn flavonoids and white grape polysaccharide as the core, can quickly rebuild the physical barrier of respiratory tract, block the key channel of repeated invasion of sticky toxin, improve the imbalance of Xieyi-blood by matching the harmonizing effect of Tibetan wood and agarwood, and then cooperate with matrine and other sticky components to efficiently remove pathogenic microorganisms, so that the three form a whole chain intervention of killing sticky toxin, repairing mucosa, regulating qi and strengthening primordial qi, break the closed loop pathology which cannot be solved by the prior art, make the mucosa repair rate reach more than 92%, the recurrence rate of sticky toxin reduce to less than 8%, and significantly improve the content of immunoglobulin, improve the problem of deficiency of primordial qi and low immunity of patients, and finally achieve the treatment goal of attacking evil without damaging normal, repairing without stagnating evil, and regulating and preventing recurrence, solve the closed loop pathology intervention problem which cannot be realized by simple stacking of medicinal materials in the prior art.

Description

Technical Field

[0001] This invention relates to the field of Mongolian medicine compound preparation technology, and in particular to Qingyi Ganlu San granules for multi-target removal of phlegm and clearing heat. Background Technology

[0002] In Mongolian medicine theory, "sticky toxins" are the core pathogenic factors of epidemics (corresponding to viruses, bacteria, and other pathogenic microorganisms in modern medicine). "Hei-blood imbalance" manifests as disordered Qi and blood circulation, corresponding to immune disorders and organ dysfunction during the recovery period of an epidemic. Clinically, patients with epidemics such as influenza and COVID-19 often experience residual respiratory mucosal damage and repeated invasion of sticky toxins after acute treatment. Clinical data shows that 62% of patients have persistent mucosal damage, and 38% experience secondary retention of sticky toxins, forming a vicious cycle of "mucosal damage → sticky toxin retention → Hei-blood imbalance → repair obstacles." This not only leads to recurring symptoms such as cough, sore throat, and hoarseness but also causes deficiency of vital energy, persistently low immunity, and an increased risk of secondary infection.

[0003] Currently, the main Mongolian medicine regimens used clinically for treating influenza virus infection (specifically, the "Killing Mucus and Clearing Heat" compound) are classic Mongolian medicine compound formulas, such as the one disclosed in publication number CN111773258A. This disclosure provides the application of Kochia scoparia and / or its aqueous and / or alcoholic extracts in the preparation of antiviral drug compositions or pharmaceutical formulations. It also provides a drug composition prepared from the following raw materials in parts by weight: 45-55 parts of *Polygonum cuspidatum*, 25-35 parts of *Inula japonica*, and 15-25 parts of *Kchia scoparia*. The drug composition disclosed herein exhibits excellent anti-H1N1 and / or anti-H3N2 influenza virus effects and has no toxic side effects.

[0004] The aforementioned and existing related technologies often have the following shortcomings: Because the existing Mongolian medicine formulas for killing phlegm and clearing heat only focus on the pathogenic factors of killing phlegm and clearing heat, they do not include respiratory mucosal repair and the regulation of He Yi and blood and Qi in the synergistic intervention targets. Moreover, in clinical practice, patients with infectious diseases such as influenza and COVID-19 often experience persistent respiratory mucosal damage and repeated invasion of phlegm and toxins after the epidemic, resulting in a vicious cycle of mucosal damage → retention of phlegm and toxins → He Yi-blood imbalance → repair obstacles. Patients not only face repeated symptoms such as cough and sore throat, but also secondary damage such as deficiency of vital energy and persistently low immunity. Existing technologies cannot solve this closed-loop pathological problem by simply adding mucosal repair herbs and Qi-regulating herbs. Summary of the Invention

[0005] The technical problem to be solved by this invention is that the existing technology does not include respiratory mucosal repair and the regulation of blood and gas as synergistic intervention targets, which often leads to the protracted and unhealed respiratory mucosal damage and repeated invasion of mucosal toxins after the epidemic. To address this, we propose a multi-target anti-mucosal and anti-epidemic Ganlu San granule.

[0006] To achieve the above objectives, this application adopts the following technical solution: Multi-target anti-adhesion and anti-inflammatory granules for clearing heat and regulating the body, the raw materials of which are composed of the following components in parts by weight: 2-3 parts of Artemisia annua extract, 4-5 parts of fennel, 2-3 parts of pearl stalk, 5-7 parts of Sophora flavescens, 8-10 parts of Terminalia chebula, 2-4 parts of Melia toosendan, 5-7 parts of Gardenia jasminoides, 2-4 parts of Artemisia annua, 8-10 parts of Adenophora stricta, 8-10 parts of Gentiana macrophylla, 2-4 parts of Lithospermum erythrorhizon, 2-4 parts of Rubia cordifolia, 5-7 parts of Hippophae rhamnoides, 4-5 parts of Glycyrrhiza uralensis, 2-4 parts of Fritillaria cirrhosa, 2-4 parts of Eriobotrya japonica leaf, 8-10 parts of white grape, 2-4 parts of Aucklandia lappa, and 8-10 parts of Aquilaria sinensis.

[0007] Preferably, the weight ratio of the mucosal repair component to the anti-adhesion component in this composition is 1:2.8-3.3; The mucosal repair component is a combination of sea buckthorn, white grape, and Tibetan costus root. The anti-sticky component is a combination of Artemisia annua extract, fennel, Terminalia chebula, Melia toosendan, and Gardenia jasminoides; This specific ratio is used to kill mucin while simultaneously achieving early physical barrier repair of the respiratory mucosa through the flavonoids and organic acids in sea buckthorn and white grapes.

[0008] Preferably, the preparation process of the multi-target anti-adhesion and anti-inflammatory Qingyi Ganlu San granules includes the following steps: Step 1: Identify fennel, costus root, and agarwood as volatile components and use supercritical CO2 extraction. Set the extraction pressure to 20 MPa, extraction temperature to 35℃, extraction time to 2 h, and CO2 flow rate to 2 L / min. Collect extract A. Step 2: Classify sea buckthorn and white grape as heat-sensitive components, add 5 times the amount of purified water, and extract using ultrasound at 30-40℃ and 200W for 30 minutes, and collect extract B; Step 3: Classify Artemisia annua extract, Terminalia chebula, Melia toosendan, and Gardenia jasminoides as the core cold-natured components, add 8 times the amount of purified water, and extract at 55-65℃ for 2 hours. Collect the extract C. Step 4: Pearl stem, Sophora flavescens, Artemisia annua, Adenophora stricta, Gentiana scabra, Lithospermum erythrorhizon, Rubia cordifolia, Fritillaria cirrhosa, Eriobotrya japonica leaf, and Glycyrrhiza uralensis are classified as conventional components. Add 10 times the amount of purified water and extract at 70℃ for 1.5 hours. Add 8 times the amount of purified water to the residue and extract again for 1 hour. Combine and collect extract D. Step 5: Combine the extracts AD, concentrate under reduced pressure at 60℃ and -0.08MPa to a clear extract with a relative density of 1.15-1.25, add ethanol to a concentration of 60%, let stand for 24 hours, filter through a 0.45μm filter membrane, and recover the ethanol until there is no alcohol odor to obtain the purified extract. Step 6: Mix the purified extract and dextrin at a weight ratio of 1:1.5, add 0.5% of the weight of the purified extract of steviol glycosides to make a soft mass, granulate through a 14-mesh sieve, dry with hot air circulation at 50℃ for 4 hours, turning it over once every hour during the process, and then granulate through a 12-mesh sieve to control the moisture content of the particles to 5%-7%.

[0009] Preferably, in step 1, supercritical CO2 extraction also involves adding 5-10% anhydrous ethanol by weight of the raw materials as an entrainer to improve the dissolution rate of volatile components.

[0010] Preferably, in step 2, the ultrasonic extraction process is stirred once every 5-10 minutes at a stirring speed of 40-60 r / min.

[0011] Preferably, in step 5, the preparation of the purified extract also includes removing proteins and tannins, and increasing the mass percentage of total flavonoids and total alkaloids in the granules.

[0012] Preferably, in step 6, the dextrin is... - The amount of cyclodextrin and steviol glycoside added is 0.5% of the weight of the clear extract, and the stirring time is 10-15 min when preparing the soft material.

[0013] Preferably, the raw material components are as follows by weight: 2 parts Artemisia annua extract, 4.5 parts fennel, 2 parts pearl stalk, 6 parts Sophora flavescens, 9 parts Terminalia chebula, 3 parts Melia toosendan, 6 parts Gardenia jasminoides, 3 parts Artemisia annua, 9 parts Adenophora stricta, 9 parts Gentiana macrophylla, 3 parts Lithospermum erythrorhizon, 3 parts Rubia cordifolia, 6 parts Hippophae rhamnoides, 4.5 parts Glycyrrhiza uralensis, 3 parts Fritillaria cirrhosa, 3 parts Eriobotrya japonica, 9 parts white grape, 3 parts Aucklandia lappa, and 9 parts Aquilaria sinensis. At this point, the weight ratio of the mucosal repair component to the anti-adhesion component is 1:3.0.

[0014] Preferably, the granules contain ≥0.1wt% matrine, ≥0.2wt% glycyrrhizic acid, and ≥0.3wt% sea buckthorn flavonoids, as determined by HPLC, and the fingerprint spectrum has a similarity of ≥0.95 with the standard control spectrum.

[0015] Preferred application of multi-target anti-viscosity and anti-inflammatory Qingyi Ganlu San granules in the preparation of drugs for treating cough, fever, sore throat and respiratory mucosal damage caused by viral influenza, acute bronchitis and pneumonia.

[0016] The technical effects and advantages of this invention are as follows: This invention utilizes a repair system centered on sea buckthorn flavonoids and white grape polysaccharides to rapidly rebuild the respiratory tract's physical barrier, blocking key pathways for repeated invasion of mucotoxins. Combined with the harmonizing effects of Tibetan costus root and agarwood to improve blood-mucosal imbalance, and further synergistically with anti-mucosin components such as matrine to efficiently eliminate pathogenic microorganisms, these three elements form a complete chain of intervention encompassing mucosal elimination and detoxification, mucosal repair, qi regulation, and vital energy strengthening. This completely breaks through the closed-loop pathology that existing technologies cannot address, achieving a mucosal repair rate of over 92% and reducing the recurrence rate of mucotoxins to below 8%. Simultaneously, it significantly increases immunoglobulin levels, improving patients' vital energy deficiency and weakened immunity. The segmented extraction process is specifically adapted to the characteristics of volatile, heat-sensitive, and conventional active ingredients, avoiding... This method avoids the inactivation of components or imbalance of medicinal properties caused by traditional processes. Compared with existing technologies that simply combine and repair medicinal materials, it improves the retention rate of core components by more than 40%, ensuring that the repair, anti-adhesion, and harmonizing effects work synergistically rather than antagonistically. In addition, the dual guarantee of core quality control indicators and fingerprint spectrum by HPLC method, especially by strictly limiting the content of geniposide, effectively controls the cold and cooling properties of the whole formula, avoiding damage to the spleen and stomach function by cold components, so as to ensure stable and uniform product quality. The granule dosage form is suitable for different medication scenarios in the acute and recovery phases, greatly improving patient compliance. Ultimately, it achieves the treatment goal of attacking the pathogen without harming the body's resistance, repairing without stagnating the pathogen, and harmonizing to prevent recurrence. It solves the problem of closed-loop pathological intervention that existing technologies cannot achieve through simple combination of medicinal materials. Attached Figure Description

[0017] The disclosure of this invention is illustrated with reference to the accompanying drawings. It should be understood that the drawings are for illustrative purposes only and are not intended to limit the scope of protection of this invention. In the drawings, the same reference numerals are used to refer to the same parts: Figure 1 This is a bar chart showing the mucosal repair rate of each group in Example 5; Figure 2 This is a bar chart showing the recurrence rate of myxotropic virus in each group in Example 5; Figure 3 This is a bar chart showing the IgG content of each group in Example 5; Figure 4 The above are superimposed comparative chromatograms of 10 batches of samples in Example 7; abbreviations and annotations: Time (min) is the chromatographic elution time (unit: minutes); Absorbance (mAU) is the absorbance (unit: milliabsorbance units, reflecting the concentration of the corresponding chemical component); Batch-01 to Batch-10 are the test samples of batches 01 to 10 respectively, of which Batch-01 to Batch-03 are the laboratory-prepared samples of Examples 1 to 3, and Batch-04 to Batch-10 are the pilot-scale production samples; Reference is the standard reference fingerprint chromatogram of Qingyi Ganlu San granules established in this invention; Figure 5This is a batch similarity analysis chart from Example 7; abbreviations and annotations: Similarity refers to the degree of matching between the fingerprint spectrum of the test sample and the fingerprint spectrum of the standard control; Threshold (0.95) is the similarity pass threshold (0.95), which is the minimum pass line for fingerprint spectrum similarity set by this invention; Batch-01 to Batch-10 have the same meaning. Figure 4 ; Figure 6 This is the characteristic peak identification diagram in Example 7; abbreviation notes: Time (min) and Absorbance (mAU) have the same meaning as in Example 7. Figure 4 P1 to P14 are 14 common characteristic peaks in the standard reference fingerprint spectrum, which are the chromatographic peaks of the characteristic chemical components of Qingyi Ganlu San granules of the present invention; In the legend, the indicator component (Target) is the core efficacy component with a clearly defined lower limit of content in the quality control system of the present invention, the control component (Control) is the limiting component with a clearly defined upper limit of content in the quality control system of the present invention, and the other components (Minor) are the common characteristic components of the remaining auxiliary effects in the whole formula. Detailed Implementation

[0018] It is readily understood that, based on the technical solution of this invention, those skilled in the art can propose various interchangeable structural methods and implementations without altering the essential spirit of the invention. Therefore, the following detailed embodiments and accompanying drawings are merely illustrative examples of the technical solution of this invention and should not be considered as the entirety of the invention or as limitations or restrictions on the technical solution of this invention.

[0019] This invention provides a technical solution: a multi-target anti-adhesion and anti-inflammatory granule, comprising the following components by weight: 2-3 parts of Artemisia annua extract, 4-5 parts of fennel, 2-3 parts of pearl stalk, 5-7 parts of Sophora flavescens, 8-10 parts of Terminalia chebula, 2-4 parts of Melia toosendan, 5-7 parts of Gardenia jasminoides, 2-4 parts of Artemisia annua, 8-10 parts of Adenophora stricta, 8-10 parts of Gentiana macrophylla, 2-4 parts of Lithospermum erythrorhizon, 2-4 parts of Rubia cordifolia, 5-7 parts of Hippophae rhamnoides, 4-5 parts of Glycyrrhiza uralensis, 2-4 parts of Fritillaria cirrhosa, 2-4 parts of Eriobotrya japonica, 8-10 parts of white grape, 2-4 parts of Aucklandia lappa, and 8-10 parts of Aquilaria sinensis.

[0020] Each medicinal material complies with the provisions of the Chinese Pharmacopoeia or relevant standards for Mongolian medicine. Their sources, main known components, medicinal properties, and functions in the compositions of this invention are summarized below, precisely addressing the synergistic intervention needs of closed-loop pathologies: Ironwood Ointment is an ointment made from the dried aerial parts of the plant Ironwood (Artemisia argyi) of the Asteraceae family through extraction and concentration. It has a bitter and pungent taste, is cold in nature, and enters the lung and liver meridians. It mainly contains sesquiterpene lactones and flavonoids. In this formula, it is the principal ingredient, which is specifically responsible for killing "sticky" toxins, detoxifying, clearing heat and relieving pain. It directly targets the core of the epidemic disease, inhibiting the retention and reproduction of pathogenic microorganisms, and is the core of the entire formula for attacking the pathogen.

[0021] Anise, the dried whole herb of the poppy family plant fennel, is bitter and cold in nature. It enters the lung and liver meridians and mainly contains alkaloids such as protopine and berberine. As an assistant herb, it assists the principal herb in strengthening the power to kill phlegm and clear heat, enhancing the inhibitory effect on epidemic fever and inflammation, and relieving sore throat caused by phlegm.

[0022] Pearl stem, the dried stem and branch of the pearl bush plant in the Rosaceae family, has a pungent and bitter taste, is neutral in nature, and enters the liver and lung meridians. It mainly contains flavonoids and tannins. As an auxiliary medicine, it has the effects of clearing away epidemic heat and regulating vital energy. While assisting in clearing away epidemics, it initially improves the body's deficiency of vital energy and lays the foundation for subsequent repair.

[0023] Sophora flavescens is the dried root of the legume Sophora flavescens. It is bitter and cold in nature, and enters the heart, liver, stomach, large intestine and bladder meridians. It mainly contains alkaloids such as matrine and oxymatrine. As an adjuvant medicine, it is used to clear heat and relieve cough and asthma. It is effective for lung heat cough caused by mucus and reduces respiratory inflammation.

[0024] Terminalia chebula, Melia toosendan, and Gardenia jasminoides form the core of the Sanzi San formula. As the assistant herbs, Terminalia chebula is bitter, sour, and astringent in taste, neutral in nature, and enters the lung and large intestine meridians. It contains tannins, which clear heat from the blood and fight heat while protecting the spleen and stomach and preventing the cold properties of the medicine from damaging the middle jiao. Sichuan pepper has a bitter taste and cold nature. It enters the liver and small intestine meridians and contains components such as azadirachtin. It can soothe the liver and clear heat, promote qi circulation and relieve pain, and alleviate the qi disorder caused by the imbalance of He Yi. Gardenia has a bitter taste and cold nature. It enters the heart and lung meridians and contains components such as geniposide and chlorogenic acid. It clears blood heat, soothes the throat, helps to clear blood heat stagnation, and reduces mucosal inflammation and exudation.

[0025] The three work together to enhance the effects of clearing heat from the blood and regulating Qi, and assist the principal drug in breaking down the pathological basis of the retention of viscous toxins.

[0026] Artemisia annua, Adenophora stricta, Gentiana scabra, Lithospermum erythrorhizon, and Rubia cordifolia are used as the first group of adjuvant herbs: Artemisia annua is bitter and pungent in taste, cold in nature, enters the liver and gallbladder meridians, contains artemisinin-like components, clears away latent heat, and prevents residual epidemic heat; Adenophora stricta has a sweet and slightly bitter taste, and is slightly cold in nature. It enters the lung and stomach meridians. It contains coumarins and polysaccharide components, which nourish yin and clear the lungs, benefit the stomach and promote the production of body fluids, and repair the dry mucous membranes caused by lung yin deficiency. White gentian has a bitter taste and cold nature. It enters the lung and liver meridians and contains gentianin and other components. It clears heat and dampness, detoxifies and soothes the throat, and reduces congestion and edema of the respiratory mucosa. Lithospermum has a sweet and salty taste, is cold in nature, and enters the heart and liver meridians. It contains components such as shikonin, which can cool the blood and detoxify, promote blood circulation and unblock the meridians, promote local blood circulation in the mucous membranes, and help repair damage. Madder has a bitter taste and cold nature. It enters the liver meridian and contains components such as alizarin. It can promote blood circulation, regulate menstruation, cool the blood and stop bleeding, improve the stagnation of microvessels in the mucous membrane, and accelerate the repair of damaged tissues.

[0027] This group of medicinal materials focuses on the reduction and repair of respiratory mucosal inflammation, providing a foundation for breaking the closed loop.

[0028] Sea buckthorn, the dried, ripe fruit of the sea buckthorn plant (Elaeagnaceae family), has a sour and astringent taste, is warm in nature, and enters the spleen, stomach, lung, and heart meridians. It contains sea buckthorn flavonoids, vitamin C, polysaccharides, and other components. As the core of the second group of adjuvant medicines, it is specifically used to repair the respiratory mucosa, promote the regeneration of damaged mucosal epithelial cells, form a protective barrier, and block the channels for the re-invasion of mucosal toxins. It is a key repair medicine for breaking the closed loop.

[0029] White grapes are the dried, ripe fruit of the grape plant (Vitis vinifera). They are sweet and sour in taste, neutral in nature, and enter the spleen, lung, and kidney meridians. They contain glucose, polysaccharides, amino acids, and other components. As the core of the second group of adjuvant medicines, they nourish the lung and kidney qi, enhance the body's self-repair ability and immunity, resolve the qi deficiency caused by the imbalance of He Yi and blood, provide energy and immune support for mucosal repair, and form a synergistic repair and strengthening effect with sea buckthorn.

[0030] Fritillaria cirrhosa and Eriobotrya japonica are used as adjuvants in the third group: Fritillaria cirrhosa is sweet and bitter in taste, slightly cold in nature, and enters the lung and heart meridians. It contains alkaloids and steroidal components, which moisten the lungs, resolve phlegm, disperse nodules and reduce swelling, and relieve irritating cough caused by mucosal damage; Eriobotrya japonica is bitter in taste, slightly cold in nature, and enters the lung and stomach meridians. It contains triterpenoid acid components, which clear the lungs, stop cough, relieve nausea and vomiting, reduce cough and throat discomfort symptoms, and create a stable local environment for mucosal repair.

[0031] Tibetan costus root, the dried root of the Tibetan costus plant (Asteraceae family), is pungent and bitter in taste, warm in nature, and enters the spleen, stomach, and large intestine meridians. It contains volatile oils, costus lactones, and other components. As the core of the fourth group of adjuvant medicines, it is specifically used to harmonize the Qi-blood mechanism, improve Qi disorder, relieve breathing difficulties and chest tightness caused by Qi imbalance, and at the same time promote the circulation of Qi and blood, amplify the repair and strengthening effects of sea buckthorn and white grape, and break the connection between "Qi-blood imbalance → repair obstacles".

[0032] Agarwood is the resinous wood of the Aquilaria sinensis plant, belonging to the Thymelaeaceae family. It has a pungent and bitter taste, is slightly warm in nature, and enters the spleen, stomach, and kidney meridians. It contains volatile oils and chromones. As the fourth auxiliary medicine, it warms and unblocks the Qi, dispels cold and relieves pain. It not only enhances the effect of Tibetan agarwood in harmonizing He Yi-blood, but also neutralizes the cold properties of the whole prescription, avoiding the suppression of spleen and stomach function during the mucosal repair period, and ensuring nutrient absorption and efficacy.

[0033] Licorice is the dried root and rhizome of the legume plant Glycyrrhiza uralensis. It is sweet in taste and neutral in nature, and enters the heart, lung, spleen, and stomach meridians. It contains glycyrrhizic acid, glycyrrhizin, and other components. As an adjuvant, it harmonizes the cold and hot properties of the whole formula, alleviates the irritation of cold herbs such as Artemisia capillaris and Gardenia, and enhances the detoxification effect. It guides the other herbs directly to the respiratory tract and blood, achieving the synergistic goal of "attacking pathogens without harming the body's vital energy and repairing without hindering the elimination of pathogens".

[0034] To facilitate a precise understanding of the nature of the diseases addressed by this invention by those skilled in the art, the modern medical connotations of the core Mongolian medical terms "Xier" and "Heyi" in the context of this invention are explained here.

[0035] To facilitate a precise understanding of the nature of the disease targeted by this invention by those skilled in the art, the modern medical connotations of the core Mongolian medical terms "Xierri" and "Heyi" in the context of this invention are explained here, clarifying their correspondence with the pathological mechanisms of the recovery period of an epidemic, and providing theoretical support for the understanding of subsequent technical solutions.

[0036] In Mongolian medicine theory, "Heyi" is one of the three basic substances in the human body (Heyi, Xila, and Badagan). It has the characteristics of being light, dynamic, cool, and fine. It is in charge of the circulation of Qi in the human body, mental activities, and regulation of organ functions, and is widely involved in physiological processes such as metabolism and immunity.

[0037] In the context of the recovery period from an epidemic, which is the focus of this invention, "Heyi" imbalance mainly corresponds to three major pathological states in modern medicine: Qi stagnation, immune dysfunction, and neuroendocrine dysregulation. Firstly, the disorder of Qi manifests as spasm of the smooth muscle of the respiratory tract, chest tightness, and difficulty breathing, which is related to the abnormal local nerve reflexes caused by the damage of the respiratory mucosa by mucosal toxins. Secondly, immune dysfunction manifests as low lymphocyte count and insufficient secretion of immunoglobulins (IgG, IgA), leading to a decreased ability of the body to clear residual toxins and making it prone to recurring symptoms. Third, the imbalance of the nervous and endocrine systems manifests as deficiency of vital energy, fatigue, and lethargy, which is closely related to the dysfunction of the hypothalamic-pituitary-adrenal axis caused by the consumption of vital energy during the epidemic and the long-term stimulation of inflammatory factors.

[0038] The harmonizing effects of medicinal materials such as Tibetan costus root and agarwood in this invention are essentially achieved by regulating the body's Qi, repairing immune function, and balancing the neuroendocrine system, thereby breaking down the pathological link between Hei-blood imbalance and repair obstacles.

[0039] In Mongolian medicine, "Xiera" (also known as Xila) has characteristics such as heat, sharpness, dryness, and yellowness. It is mainly responsible for the body's temperature regulation and metabolism. Its imbalance often leads to heat syndromes. Depending on the location of the lesion, it can be divided into blood Xiera, lung Xiera, etc.

[0040] In the context of this invention, it mainly corresponds to pathological mechanisms in modern medicine such as over-activation of inflammatory response, blood heat stagnation, and enhanced oxidative stress. Firstly, excessive activation of the inflammatory response is manifested in the presence of TNF-α in bronchoalveolar lavage fluid. Elevated levels of inflammatory factors such as IL-6 lead to congestion, edema, and increased exudation of the respiratory mucosa, exacerbating symptoms such as sore throat and cough. Secondly, blood heat and stagnation manifest as local microvascular stasis and poor blood circulation in the respiratory tract, which hinders the supply of nutrients and the repair process of damaged mucous membranes. This is directly related to the blood-cooling and meridian-clearing targets of herbs such as madder and purple gromwell. Third, enhanced oxidative stress manifests as a decrease in the body's ability to scavenge free radicals, further aggravating mucosal cell damage and prolonging the repair cycle.

[0041] The core of the efficacy of the medicinal materials such as Sanzi San, Gardenia, and Gentiana macrophylla in clearing heat and clearing blood heat is to create a good local microenvironment for mucosal repair by inhibiting excessive inflammatory response, improving local blood circulation, and reducing oxidative stress damage.

[0042] It should be clarified that "Heyi-blood imbalance" and "blood 'hira' fighting fever" in this invention are not isolated Mongolian medicine syndromes, but rather complex pathological states that synergistically worsen with respiratory mucosal damage and retention of mucosal toxins. The above-mentioned terminology provides a modern medical basis for understanding the synergistic design logic of "killing mucosal toxins and clearing heat-mucosal repair-harmonizing Heyi-heri-strengthening vital energy" in this invention.

[0043] Through long-term clinical practice and experimental screening, it has been found that for the above-mentioned combination to be transformed into a stable and significant clinical effect, it not only depends on the fixed combination of medicinal materials, but more importantly, the specific weight ratio between several groups of synergistic medicinal materials must be met. According to one embodiment of the present invention, a preferred Mongolian medicine composition is provided, comprising, by weight: 2 parts of Artemisia annua extract, 4.5 parts of fennel, 2 parts of pearl stalk, 6 parts of Sophora flavescens, 9 parts of Terminalia chebula, 3 parts of Melia toosendan, 6 parts of Gardenia jasminoides, 3 parts of Artemisia annua, 9 parts of Adenophora stricta, 9 parts of Gentiana macrophylla, 3 parts of Lithospermum erythrorhizon, 3 parts of Rubia cordifolia, 6 parts of Hippophae rhamnoides, 4.5 parts of Glycyrrhiza uralensis, 3 parts of Fritillaria cirrhosa, 3 parts of Eriobotrya japonica leaf, 9 parts of white grape, 3 parts of Aucklandia lappa, and 9 parts of Aquilaria sinensis.

[0044] The formula was verified by orthogonal experiments. The synergistic index of sea buckthorn-white grape-Tibetan costus reached 1.32, and the synergistic effect of mucosal repair and He Yi-blood harmonization was optimal, which can maximize the breaking of closed-loop pathology.

[0045] In the composition, the total weight ratio of the mucosal repair and tonifying herbs (sea buckthorn, white grape, and Tibetan costus root) to the total weight ratio of the anti-adhesion and detoxifying herbs (Imperata cylindrica extract, fennel, and Sanzi powder) is 1:2.8-3.3. Within this ratio range, the core efficacy of anti-adhesion and detoxifying can be guaranteed, while the repair and tonifying effects can be fully synergistic, avoiding the inability to break the closed loop due to excessive single efficacy.

[0046] The composition is prepared in granule form using a differentiated extraction process, which maximizes the retention of the core active ingredients of each medicinal material. It dissolves quickly, takes effect rapidly, and is suitable for home and outpatient use during the recovery period of an epidemic, thereby improving patient compliance.

[0047] According to an embodiment of the present invention, a multi-target anti-adhesion and anti-inflammatory granule for clearing heat and regulating the body is provided, comprising the following steps: Step 1: First, prepare Artemisia annua extract: Take 20kg of Artemisia annua medicinal material, add 200L of purified water, and decoct twice. Each decoction temperature is 100-110℃ and the decoction time is 1 hour. Combine the two decoctions. Vacuum concentrate the combined decoction at 75-80℃ until it becomes a thick paste with a relative density of 1.25-1.30 (measured at 60℃). Weigh it about 2kg to obtain Artemisia annua extract. Then take all the prescribed medicinal materials (including the self-made Artemisia annua extract mentioned above), remove impurities and moldy parts, wash and dry them, and divide them into four groups according to their composition characteristics: The first group of volatile components (fennel, costus root, and agarwood) was pulverized into a fine powder of 100 mesh to ensure that the volatile oil components could be fully collected during subsequent extraction, thus avoiding the loss of the core components of the blended Hei-Blood. The second group of heat-sensitive ingredients (sea buckthorn and white grape) is pulverized into 80-mesh fine powder to prevent the subsequent high-temperature extraction from damaging heat-sensitive repair and strengthening components such as polysaccharides and flavonoids. The third group of cold-natured core ingredients (Artemisia annua extract, Terminalia chebula, Melia toosendan, Gardenia jasminoides) involves pulverizing Terminalia chebula, Melia toosendan, and Gardenia jasminoides into a 120-mesh fine powder; Artemisia annua extract is a separate component, weighed directly for use, and does not participate in the pulverization process; this facilitates precise control of the dissolution rate of cold-natured ingredients and balances efficacy and irritation. The fourth group of conventional ingredients (pearl stem, sophora flavescens, artemisia annua, adenophora stricta, gentiana macrophylla, gromwell root, madder root, fritillaria cirrhosa, loquat leaf, licorice) are pulverized into 100-mesh fine powder and processed using conventional water extraction technology to fully extract the lung-clearing, cough-relieving, and repair-aiding components.

[0048] This step, through group pretreatment, enables precise control of components with different characteristics, providing a prerequisite for subsequent synergistic extraction and efficacy balance, and avoiding component loss or antagonism caused by existing uniform pretreatment.

[0049] Step 2: Extraction of cold-natured core components: Put the fine powder of this group and the prepared and weighed Artemisia annua extract into the extraction tank, add 8 times the amount of purified water, and extract at 60℃ for 2 hours. Stir continuously during the extraction process, stirring once every 30 minutes at a speed of 50 r / min. After the extraction is completed, filter with a 100-mesh filter cloth and collect the extract for later use. These temperature and time parameters can reduce the dissolution rate of geniposide in gardenia by 30%, weaken its overall cold nature, while retaining more than 91% of sesquiterpene lactones in Artemisia annua extract, ensuring that the anti-adhesive efficacy is not affected.

[0050] Extraction of volatile components: The fine powder was fed into a supercritical CO2 extraction device, and the extraction pressure was set to 20 MPa, the extraction temperature to 35℃, the extraction time to 2 h, and the CO2 flow rate to 2 L / min. The extract (volatile oil) was collected, sealed, and stored in a low-temperature environment at 4℃. This process can fully preserve the volatile oil components in Tibetan incense and agarwood, avoid the hydrolysis and loss of components caused by high-temperature extraction, and ensure the efficacy of He Yi-Xue.

[0051] Extraction of heat-sensitive components: The fine powder of this group was put into an ultrasonic extraction device, 5 times the amount of purified water was added, and the temperature was controlled at 30℃, the ultrasonic power at 200W and the extraction time at 30min. After extraction, the mixture was filtered and the extract was collected for later use. Ultrasonic extraction can rapidly dissolve sea buckthorn flavonoids and white grape polysaccharides at low temperatures, with a retention rate of over 90%, enhancing the synergistic effect of mucosal repair and vital energy replenishment.

[0052] Extraction of conventional components: The fine powder of this group is put into an extraction tank, 10 times the amount of purified water is added, and the temperature is controlled at 70℃ for 1.5 hours. After one extraction, 8 times the amount of purified water is added to the residue, and the extraction is carried out again at 70℃ for 1 hour. The two extracts are combined, filtered and set aside. Secondary water extraction can fully extract components such as matrine and glycyrrhizic acid, enhancing their effects in assisting in clearing heat and harmonizing the properties of other medicines.

[0053] This step utilizes a differentiated extraction process to achieve the goals of controllable coldness, retention of volatile oils, integrity of heat-sensitive components, and full dissolution of conventional components. The components of each extract are complementary, laying the foundation for subsequent synergistic effects.

[0054] Step 3: Combine the four extracts from Step 2 and import them into a vacuum concentration tank. Control the temperature at 60℃ and the vacuum at -0.08MPa, and continue to concentrate until a clear extract with a relative density of 1.20 (measured at 60℃) is obtained. Low-temperature concentration can prevent the deterioration of the active ingredients. Slowly add anhydrous ethanol to the clear extract while stirring until the alcohol content of the system reaches 60%. Let it stand for 24 hours to precipitate impurities such as proteins and tannins. Filter the solution through a 0.45 μm filter membrane and take the supernatant. The supernatant is introduced into a vacuum recovery tank, and ethanol is recovered at 60°C until there is no alcohol odor, resulting in a purified extract. At this point, the concentration of active ingredients is more than 3 times higher than that of the crude extract, and the impurity content is reduced to below 5%, thus avoiding the impact of impurities on subsequent granulation and efficacy.

[0055] Step 4: Take the purified extract from Step 3, add dextrin at a weight ratio of 1:1.5, and then add 0.5% of stevioside by weight of the extract to adjust the taste. Stir thoroughly to make a soft material that can be formed into a ball by hand and crumbles easily when touched. The soft material is fed into a gyratory granulator and granulated using a 14-mesh sieve to obtain wet granules. Place the wet granules into a hot air circulating drying oven, control the temperature at 50℃ and the air speed at 2m / s, and dry for 4 hours. During this period, turn the granules over once every 1 hour to ensure uniform drying and control the moisture content of the granules at 5%-7%. After drying, the particles are granulated using a 12-mesh sieve to remove coarse particles and fine powder, resulting in brownish-gray granules, which are the Qingyi Ganlu Powder granules of this invention.

[0056] This step ensures rapid granulation (complete dissolution within 3 minutes) and good flowability by precisely controlling granulation parameters, while avoiding moisture absorption and deterioration, thus meeting the needs of modern clinical oral administration.

[0057] Step 5: Establish a multi-index content control system using high-performance liquid chromatography (HPLC): The content of matrine in Sophora flavescens was determined to be ≥0.10wt%, the content of glycyrrhizic acid in Glycyrrhiza uralensis was ≥0.20wt%, the content of flavonoids in Hippophae rhamnoides was ≥0.30wt%, and the content of geniposide in Gardenia jasminoides was ≤0.15wt% (to control for coldness). Simultaneously, a full-spectrum fingerprint was constructed, with 20 characteristic peaks set, requiring the fingerprint similarity of each batch of particles to be ≥0.95; The particle size, moisture content, and content variation of the sampled granules all met the requirements of the Granules section of the Chinese Pharmacopoeia.

[0058] This step addresses the issue of significant differences in efficacy between existing batches of compound medicines through multi-dimensional quality control, ensuring that each batch of granules consistently achieves a closed-loop pathological intervention effect.

[0059] Step 6: Pack the qualified granules into 3g and 5g bags, using aluminum-plastic composite bags, and seal them to prevent moisture and light. Each bag is labeled with the dosage and administration information (oral administration, 3-5g each time, 1-3 times a day, dissolved in boiling water; 3 times a day during the acute phase of the disease, 1-2 times a day during the recovery phase, adjust as directed by a physician), contraindications, expiration date, etc. Store in a cool, dry place (temperature ≤25℃, relative humidity ≤60%), avoid direct sunlight. Shelf life is up to 24 months. Once opened, it should be used within 1 month.

[0060] Example 1 This embodiment aims to verify the repair effect of the composition of the present invention on respiratory mucosal damage during the recovery period of an epidemic, using a mouse model of influenza virus infection in the recovery period.

[0061] Eighty SPF-grade male ICR mice, weighing 180-220g, were used as experimental animals and housed in a barrier environment with a temperature of 22±2℃ and a relative humidity of 50±10% for one week of acclimatization.

[0062] The test drug is the Qingyi Ganlu Powder Granules of the present invention, prepared according to the above-mentioned preferred ratio and preparation method, and prepared into a suspension with 0.5% sodium carboxymethyl cellulose (CMC-Na) solution before use; The positive control drug was Kangfuxin Liquid (a commonly used mucosal repair drug in clinical practice), which was prepared into a suspension using the same method. The influenza virus strain was H1N1 subtype (A / PR / 8 / 34), purchased from the China Center for Type Culture Collection.

[0063] A flu infection model was established by nasally instilling H1N1 virus solution into 70 mice, while the remaining 10 mice served as a blank control group and were instilled with an equal volume of physiological saline.

[0064] On day 7 post-infection, the mice were confirmed to have entered the recovery period, with their body temperature returning to normal and respiratory symptoms lessening but mucosal damage remaining. The model mice were randomly divided into 7 groups of 10 mice each: Model control group (gavage with equal volume of 0.5% CMC-Na solution), positive control group (gavage with Kangfuxin liquid suspension, dose 5 mL / kg), low-dose group of the present invention (gavage with granule suspension, dose 1.0 g crude drug / kg), medium-dose group (2.0 g crude drug / kg), high-dose group (4.0 g crude drug / kg), sea buckthorn single-drug group (sea buckthorn extract only, dose 0.6 g crude drug / kg), sea buckthorn + white grape group (sea buckthorn 0.6 g + white grape 0.9 g crude drug / kg).

[0065] Each group was administered the drug once daily by gavage, with a dosage of 0.1 mL / 10 g body weight, for 14 consecutive days.

[0066] Twenty-four hours after the last administration, all mice were sacrificed, and tracheal and bronchial tissues were quickly dissected, fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and the mucosal morphology was observed under an optical microscope. The mucosal repair rate (intact mucosal length / total mucosal length × 100%) was calculated. Simultaneously, the inflammatory factor TNF-α in bronchoalveolar lavage fluid was detected. The levels of IL-6 were used to evaluate the resolution of inflammation. The experimental results are shown in Table 1 below.

[0067]

[0068] Table 1 Comparison of respiratory mucosal repair and inflammatory factor levels in mice of different groups The results in Table 1 show that the mucosal repair rate of mice in the model control group was extremely low, and the level of inflammatory factors was significantly increased, indicating that the mucosal injury model was successfully established.

[0069] All dosage groups of this invention can significantly improve the mucosal repair rate and reduce the level of inflammatory factors, and the effect is better than the positive control group, the sea buckthorn single drug group and the sea buckthorn + white grape group. The mucosal repair rate in the medium and high dose groups reached over 92%, and the level of inflammatory factors was close to that in the blank control group. This confirms that the composition of the present invention can effectively repair the respiratory mucosa and reduce residual inflammation through the synergistic effect of multiple medicinal materials. Moreover, the synergistic effect far exceeds that of simple medicinal material superposition, providing core support for breaking the closed loop.

[0070] Example 2 This embodiment aims to verify the regulatory effect of the composition of the present invention on Her-blood imbalance and vital energy deficiency. A rat model in the recovery period of influenza was used, and immune function and blood-related indicators were used as evaluation criteria.

[0071] Fifty SPF-grade male SD rats, weighing 170-220g, were used as experimental animals and were kept under the same conditions as in Example 1.

[0072] The test drug and positive control drug are the same as in Example 1; The testing reagents include rat immunoglobulin IgG and IgA kits, and routine blood test kits (red blood cells RBC and hemoglobin HGB).

[0073] An influenza model was established by nasally instilling H1N1 virus solution into 40 rats, with the remaining 10 rats serving as a blank control group.

[0074] On the 7th day after infection, the model rats were randomly divided into 4 groups of 10 rats each: model control group (gavaged with an equal volume of 0.5% CMC-Na solution), positive control group (gavaged with Kangfuxin liquid, 5 mL / kg), medium dose group of the present invention (2.0 g crude drug / kg), and high dose group of the present invention (4.0 g crude drug / kg).

[0075] Each group received the medication once daily via gavage for 21 consecutive days (covering the entire recovery period of the disease). Twenty-four hours after the last administration, blood was drawn via the abdominal aorta to measure serum IgG and IgA levels (to evaluate immune function), and RBC and HGB levels were measured in a complete blood count (to evaluate blood status). Simultaneously, the spleen and thymus were dissected, and the organ coefficient (organ weight / body weight × 100%, to evaluate the function of immune organs) was calculated. The experimental results are shown in Table 2 below.

[0076]

[0077] Table 2 Comparison of immune function and blood status of rats in each group The immunoglobulin content, RBC, HGB and immune organ coefficient of the rats in the model control group were significantly lower than those in the blank control group, indicating that the Heri-blood dysregulation and vital energy deficiency model was successfully established.

[0078] The high-dose group of this invention can significantly increase immunoglobulin content, improve blood and qi indicators, and restore immune organ function, with effects far exceeding those of the positive control group. The medium-dose group's indicators are close to those of the blank control group, confirming that the composition of this invention can effectively harmonize Hey-blood imbalance, nourish vital energy, enhance the body's immunity, break the link between Hey-blood imbalance and repair barriers, and provide the body's support for mucosal repair and recurrence prevention.

[0079] Example 3 This embodiment aims to verify the overall intervention effect of the composition of the present invention on the closed-loop pathology of mucosal damage → mucotoxin retention → Heric-blood imbalance → repair obstruction, with symptom recurrence rate and mucotoxin residue as the core evaluation indicators.

[0080] One hundred SPF-grade male ICR mice, weighing 180-220g, were used as experimental animals and were kept under the same conditions as in Example 1.

[0081] The test drug was the same as in Example 1; the control drug was the Mongolian medicine Shazhan Qingwen Compound with publication number CN111773258A, which was composed of 45-55 parts of Saponaria, 25-35 parts of Inula japonica and 15-25 parts of Kochia scoparia by weight. Before use, it was prepared into a suspension with 0.5% sodium carboxymethyl cellulose, and the dosage was 2.0g of raw drug / kg.

[0082] An influenza model was established by nasally instilling H1N1 virus solution into 90 mice, with the remaining 10 mice serving as a blank control group.

[0083] On the 7th day after infection, the model mice were randomly divided into 3 groups of 30 mice each: control drug group (Mongolian medicine Sha Nian Qing Wen compound administered by gavage, the dosage of the control drug was determined according to the effective dose in publication number CN111773258A converted to the equivalent dose in mice (body surface area method), which was 2.0 g crude drug / kg), medium dose group of the present invention (2.0 g crude drug / kg), and high dose group of the present invention (4.0 g crude drug / kg).

[0084] Each group was given the medication once daily by gavage for 14 consecutive days. After discontinuation of the medication, the group was observed for another 14 days (to monitor for recurrence).

[0085] Record the time when cough and sore throat (scratching the throat) symptoms disappeared in mice during the drug administration period; On the 14th day after drug withdrawal, the residual amount of H1N1 virus in the respiratory tract of mice was detected (H1N1 virus nucleic acid content was detected by real-time fluorescence quantitative PCR), and the symptom recurrence rate was calculated (number of recurrence cases / total number of cases × 100%). The experimental results are shown in Table 3 below.

[0086]

[0087] Table 3 Comparison of closed-loop pathological improvement and recurrence rate in mice of different groups The control group had a longer symptom disappearance time, higher viral residual levels, and a relapse rate of 36.7%, indicating that it could only clear part of the mucoid virus and could not break the closed-loop pathology. In this invention, the symptom disappearance time in the medium and high dose groups was significantly shortened, the viral residue was extremely low, and the recurrence rate was reduced to below 8.3%. The high dose group even had no viral residue. This proves that the composition of this invention can break the closed-loop pathology as a whole, achieve the synergistic effect of killing the virus, clearing away the pathogen, repairing the mucosa, and harmonizing and consolidating the body, and completely solve the problems of recurring symptoms and retention of the virus.

[0088] Example 4 This experiment aims to evaluate the safety of long-term administration of the composition of the present invention and to provide a basis for long-term use during the clinical recovery period. A long-term toxicity test was conducted on rats.

[0089] Eighty SPF-grade SD rats were used as experimental animals, half male and half female, weighing 80-100g, and were kept under the same conditions as in Example 1.

[0090] The test drug was Qingyi Ganlu San granules of the present invention, which were prepared into low, medium and high dose suspensions (1.0g, 2.0g and 4.0g crude drug / kg).

[0091] Rats were randomly divided into four groups according to body weight and sex, with 20 rats in each group (half male and half female): blank control group (gavaged with an equal volume of 0.5% CMC-Na solution), low-dose group, medium-dose group, and high-dose group.

[0092] Administer the medication once daily by gavage for 4 consecutive weeks, and continue to observe for 2 weeks after discontinuation (recovery period observation).

[0093] Detection indicators: During the drug administration period, the general condition of rats (activity, fur, food intake, excretion) was observed daily, and they were weighed twice a week; After the medication is administered and the recovery period is over, blood samples are taken to test complete blood count and liver and kidney function indicators. Major organs (heart, liver, spleen, lungs, and kidneys) are dissected for pathological examination.

[0094] Experimental results: During the administration and recovery period, the rats in each drug administration group were in good general condition, with no animal deaths, and there were no significant differences in weight gain and food intake compared with the blank control group. Blood routine tests and liver and kidney function indicators were all within the normal range, and there was no statistically significant difference compared with the blank control group. The pathological sections of major organs showed no drug-related specific damage, and the observation during the recovery period showed no delayed toxicity, confirming that the composition of the present invention has good safety for long-term use, with no obvious toxic side effects, and is suitable for the long-term conditioning needs during the recovery period of epidemic diseases.

[0095] Example 5 like Figure 1-3As shown, this study clarifies the effects of different weight ratios of mucosal repair components and anti-adhesion components on respiratory mucosal damage repair, mucotoxin clearance, and immune function, and verifies the synergistic effect of the weight ratio of mucosal repair components to anti-adhesion components in the range of 1:2.8-3.3.

[0096] Materials: 240 SPF-grade male ICR mice were randomly divided into blank control group, model control group, experimental groups 1-3, and control groups 1-3, with 30 mice in each group.

[0097] Except for the blank control group, the other groups established a respiratory mucosal injury model by nasal instillation of H1N1 virus solution. Each group was given a corresponding proportion of granule preparation at a dose of 2.0g crude drug / kg for 14 consecutive days. The mucosal repair rate, mucoviral recurrence rate, and immunoglobulin (IgG, IgA) content were detected.

[0098] Experimental group 1: ratio 1:3.0 (optimal ratio), mucosal repair component (6 parts sea buckthorn + 9 parts white grape + 3 parts Tibetan costus root), anti-adhesion component (2 parts Artemisia annua extract + 4.5 parts fennel + 9 parts Terminalia chebula + 3 parts Sichuan pepper + 6 parts gardenia). Experimental group 2: ratio 1:2.8 (lower limit of ratio range), mucosal repair component (5 parts sea buckthorn + 8 parts white grape + 2 parts Tibetan costus root), anti-adhesion component (2 parts Artemisia annua extract + 4 parts fennel + 8 parts Terminalia chebula + 2 parts Sichuan pepper + 5 parts gardenia). Experimental group 3: ratio 1:3.3 (upper limit of ratio range), mucosal repair component (7 parts sea buckthorn + 10 parts white grape + 4 parts Tibetan costus root), anti-adhesion component (3 parts Artemisia annua extract + 5 parts fennel + 10 parts Terminalia chebula + 4 parts Sichuan pepper + 7 parts gardenia). Control group 1: ratio 1:2.0 (below the range), mucosal repair components are the same as experimental group 2, anti-adhesion components (1 part Artemisia annua extract + 3 parts fennel + 6 parts Terminalia chebula + 2 parts Melia toosendan + 4 parts Gardenia jasminoides). Control group 2: ratio 1:4.0 (higher than the range), mucosal repair components are the same as experimental group 2, anti-adhesion components (3 parts of Artemisia annua extract + 6 parts of fennel + 12 parts of Terminalia chebula + 4 parts of Melia toosendan + 8 parts of Gardenia jasminoides). Control group 3: ratio 1:2.5 (intermediate deviation value), the mucosal repair component is the same as that of experimental group 2, and the anti-adhesion component is (2 parts of Artemisia annua extract + 4 parts of fennel + 7 parts of Terminalia chebula + 3 parts of Melia toosendan + 6 parts of Gardenia jasminoides).

[0099] Experimental results:

[0100] Conclusion: The mucosal repair rate and immunoglobulin content of experimental groups 1-3 (ratio 1:2.8-3.3) were significantly higher than those of the control groups, and the recurrence rate of mucosal toxins was significantly lower than that of the control groups. Among them, experimental group 1 (1:3.0) had the best synergistic effect, which confirms that this ratio range can achieve a closed-loop intervention of killing mucosal toxins, repairing mucosa and enhancing immunity, and has clear scientific validity and non-obviousness.

[0101] Example 6 To compare the effects of the differentiated extraction process of this invention on the retention rate of effective components with the traditional one-pot cooking process, and to verify the technological advancement of the differentiated extraction process.

[0102] Materials: Two groups of samples were prepared. The experimental group used the group extraction process in step 2 above (supercritical CO2 extraction of volatile components + low-temperature ultrasonic extraction of thermosensitive components + warm immersion extraction of core cold components + secondary water extraction of conventional components). The control group used a traditional boiling water extraction process (all raw materials were mixed and pulverized, then boiled in 10 times the amount of purified water at 90°C for 2 hours, and the residue was boiled again in 8 times the amount of water for 1 hour, and the extracts were combined), with the remaining granulation and purification conditions being the same.

[0103] Simultaneously, the retention rates of sea buckthorn flavonoids, Tibetan costus root volatile oil, and Artemisia annua sesquiterpene lactones were determined using HPLC. The reason for selecting to determine the retention rates of sea buckthorn flavonoids, Tibetan costus root volatile oil, and Artemisia annua sesquiterpene lactones is that these three components correspond to the three core functions of the granules of this invention: mucosal repair, harmonization and prevention of recurrence, and detoxification and anti-adhesion. They also represent three key categories of substances: heat-sensitive, volatile, and conventional active ingredients. Their retention rates directly determine the scientific nature of the process design and the reliability of the efficacy, and are the core basis for verifying the advantages of the cluster extraction process technology.

[0104] Experimental results:

[0105] Conclusion: The experimental group extraction process significantly improved the retention rate of heat-sensitive and volatile active ingredients compared with the traditional process in the control group. The retention rate of Tibetan costus root volatile oil increased by more than 100%, and the retention rate of sea buckthorn flavonoids increased by more than 50%, which can fully guarantee the efficacy of mucosal repair and immune regulation. The retention rate of sesquiterpene lactone, the core anti-adhesion component, was also slightly improved. This confirms that the group extraction process can accurately adapt to the characteristics of each component, solve the pain points of component loss and efficacy reduction in the traditional process, and has clear technological progress.

[0106] Example 7 like Figure 1-6As shown, based on the verification of the synergistic effect of the specific ratio of mucosal repair components and anti-adhesion components, and the comparison of the effectiveness of the differentiated extraction process with the traditional process, in order to compare the quality consistency of different batches of products prepared according to this invention, and the technological advancement of the HPLC multi-index quantitative + full-spectrum fingerprint quality control system established by this invention compared with the traditional single-index quality control, and to verify the stability and controllability of product quality, the following experiments were conducted: 1. Experimental Objective A standardized multi-index content determination method and fingerprint spectrum evaluation method for the granules of this invention were established. The quality differences of products prepared by different batches and different processes were compared to verify the reliability of the quality control system of this invention.

[0107] 2. Experimental Materials Test samples: Particles prepared in Examples 1-3 of this invention, and batches 4-10 of particles produced in pilot-scale production (using the same formulation, differentiated extraction process, concentration and purification process and granulation process parameters as in Example 1). Reference standards: matrine reference standard (purity ≥98%), glycyrrhizic acid ammonium reference standard (purity ≥98%), total flavonoids from sea buckthorn reference standard (purity ≥95%), geniposide reference standard (purity ≥98%); Reagents: Methanol (chromatographic grade), phosphoric acid (analytical grade), purified water (ultrapure water) Instruments: High performance liquid chromatograph (with UV detector), electronic analytical balance (accuracy 0.0001g), ultrasonic cleaner, 0.45μm organic filter membrane.

[0108] 3. Chromatographic conditions The determination was performed using high-performance liquid chromatography (HPLC), under the following conditions: Chromatographic column: C18 column (4.6 mm × 250 mm, 5 μm); Mobile phase: methanol-0.1% phosphoric acid aqueous solution, gradient elution program (0-10 min: methanol 10%→30%; 10-30 min: methanol 30%→50%; 30-45 min: methanol 50%→70%; 45-60 min: methanol 70%→10%). Flow rate: 1.0 mL / min; Column temperature: 30℃; Detection wavelength: 254nm (also applicable to the determination of matrine, glycyrrhizic acid, sea buckthorn flavonoids and geniposide); Injection volume: 10 μL.

[0109] 4. Measurement Method Accurately weigh approximately 0.5 g of the powder and place it in a stoppered conical flask. Accurately add 25 mL of 70% ethanol, seal tightly, weigh, and extract ultrasonically for 30 min. Cool to room temperature and weigh again. Make up the lost weight with 70% ethanol, shake well, and filter through a 0.45 μm organic filter membrane. Collect the filtrate to obtain the test solution. Prepare reference solutions of matrine, glycyrrhizic acid ammonium, total flavonoids from sea buckthorn, and geniposide using the same method. Inject and determine the contents of matrine, glycyrrhizic acid, sea buckthorn flavonoids, and geniposide using the external standard method.

[0110] Ten batches of the test samples of this invention were taken, processed according to the above-mentioned test sample solution preparation method, and chromatograms were recorded for 60 minutes. The similarity between each batch of samples and the fingerprint chromatogram of the standard reference was calculated.

[0111]

[0112] Figure 4 The HPLC fingerprint chromatograms of 10 batches of test samples are superimposed for comparison. The horizontal axis represents chromatographic elution time, and the vertical axis represents absorbance (the value is positively correlated with the component concentration). Different color curves correspond to different batches of test samples, and the black dashed line represents the standard control fingerprint chromatogram. It can be seen that the elution time, peak number, peak shape, and peak height of the 10 batches of test samples with different preparation scales are highly consistent with the standard control fingerprint chromatogram, with no significant differences. This directly proves that the preparation process of this invention is stable and controllable, and the chemical composition and content of different batches of products are highly consistent, ensuring the stability and uniformity of the product's efficacy from a material basis level.

[0113] The quantitative analysis results of similarity metrics between the fingerprint chromatograms of 10 batches of test samples and the standard control fingerprint chromatograms are as follows: Figure 5 As shown, the horizontal axis represents the similarity value (the closer to 1, the higher the matching degree with the standard spectrum). The red dashed line represents the 0.95 pass threshold set by this invention. Different color bars correspond to the similarity results of different batches of samples. The fingerprint spectrum similarity of all 10 batches of test samples is higher than the 0.95 pass threshold. The lowest value is 0.973 for Batch-10 and the highest value is 0.996 for Batch-05. This quantitatively verifies that all batches of samples meet the quality control requirement of this invention, "the similarity between the fingerprint spectrum and the standard control fingerprint spectrum is ≥0.95", and the quality consistency between batches is excellent. The characteristic peak identification diagram of the standard comparison fingerprint spectrum of Qingyi Ganlu San granules established in this invention is shown in the figure below. Figure 6 As shown, the horizontal axis represents elution time, the vertical axis represents absorbance, and P1~P14 are the 14 common characteristic peaks identified through screening, which can comprehensively characterize the overall chemical composition of the compound. The specific assignment and explanation of each characteristic peak are as follows: P1: Matrine (indicator component), derived from the principal ingredient Sophora flavescens, is the core anti-adhesive and detoxifying component of this invention, and the quality standard requires its content to be ≥0.10wt%; P3: Geniposide (controlled ingredient), derived from the herb Gardenia jasminoides, is a limiting ingredient in this invention used to control the overall cold and cooling properties of the formula. The quality standard requires its content to be ≤0.15 wt%. P6: Glycyrrhizic acid (indicator component), derived from the medicinal herb licorice, is the core component of this invention for harmonizing the overall medicinal properties and enhancing detoxification efficacy. The quality standard requires its content to be ≥0.20wt%. P9: Sea buckthorn flavonoids (indicator component), derived from sea buckthorn as an adjuvant, are the core mucosal repair efficacy component of this invention, and the quality standard requires its content to be ≥0.30wt%; P2, P4, P5, P7, P8, P10, P11, P12, P13, and P14 are characteristic peaks shared by the rest of the formula. They correspond to the hallmark chemical components of herbs such as Terminalia chebula, Melia toosendan, Foeniculum vulgare, Aucklandia lappa, Aquilaria sinensis, Gentiana macrophylla, Rubia cordifolia, and Lithospermum erythrorhizon. Together, they constitute the characteristic identifiers of the formula's fingerprint spectrum, used to comprehensively monitor the consistency of the overall chemical composition of the compound and avoid product quality differences caused by fluctuations in herbs and processes. This invention clarifies the core quality control characteristic peaks of the fingerprint spectrum, distinguishes core efficacy indicator components, medicinal property limiting control components, and auxiliary characteristic components, and establishes a fingerprint spectrum standard that can comprehensively and accurately monitor the overall quality of the compound. This solves the deficiency of traditional Mongolian medicine compound formulas that rely on only a single indicator for quality control and cannot guarantee the consistency of overall efficacy.

[0114] 5. Experimental Conclusions In the 10 batches of Qingyi Ganlu San granules in this embodiment, the content of matrine was ≥0.10wt%, the content of glycyrrhizic acid was ≥0.20wt%, the content of sea buckthorn flavonoids was ≥0.30wt%, and the content of geniposide was ≤0.15wt%. Moreover, the similarity between the fingerprint spectrum and the standard control spectrum was ≥0.95, which fully met the quality control requirements.

[0115] Compared with the traditional one-pot cooking process, the content of the core active ingredients in the product of this invention is increased by 30%-75%, the batch-to-batch component fluctuation range is ≤10%, and the fingerprint spectrum similarity is increased by more than 15%, proving that the cluster extraction process and quality control system of this invention can significantly improve the stability and uniformity of product quality.

[0116] 6. Clinical Cases Case 1 Female, 84 years old, hospitalized for 11 days, with a history of allergies to penicillin, leukomycin, Qingkailing, and saffron.

[0117] Diagnosis: Respiratory tract infection, novel coronavirus infection, emphysema, electrolyte imbalance, type 2 diabetes.

[0118] Admission history: Four days prior, the patient began experiencing headache, sore throat, cough with yellow phlegm, nausea, loss of appetite, fever (highest temperature 38.5℃), and body aches. The patient self-medicated with painkillers. Two days later, the body aches subsided and the fever disappeared, but other symptoms worsened, including fatigue. The patient visited the hospital outpatient clinic and was diagnosed with respiratory infection and novel coronavirus infection, and was hospitalized.

[0119] The patient presented with high fever, loss of appetite, and nausea, but without vomiting or diarrhea.

[0120] Medication: Qingyi Ganlu Powder Granules of this invention, 5g, twice a day, orally; The condition improved after taking the medication.

[0121] Case 2 Male, 13 years old, hospitalized for 5 days, with no history of allergies.

[0122] Diagnosis: Pneumonia, hypoxemia.

[0123] Admission Status: Two days prior, the patient developed a fever (highest temperature 39.3℃) due to a sudden change in weather, accompanied by a dry cough (no phlegm), headache, body aches, and fatigue. Upon examination at the hospital outpatient clinic, a chest CT scan revealed infectious lesions in the upper and middle lobes of the right lung. The patient was diagnosed with pneumonia and hospitalized for treatment.

[0124] During the illness, there was no shortness of breath, no coughing up blood, no chest pain, loss of appetite, poor sleep, and normal bowel movements.

[0125] Medication: 5g of Qingyi Ganlu Powder Granules of this invention, taken orally twice a day, morning and evening; The condition improved after taking the medication.

[0126] Case 3 Male, 45 years old, hospitalized for 23 days, with no history of allergies.

[0127] Diagnosis: pneumonia, novel coronavirus infection, post-cerebral hemorrhage dialysis, epilepsy, lower extremity deep vein thrombosis, heart failure, electrolyte imbalance, type II respiratory failure.

[0128] Admission status: The patient was bedridden due to paralysis and had been hospitalized multiple times for intravenous treatment due to worsening cough and phlegm.

[0129] Three days ago, the patient developed a cough with worsening phlegm, coughing up large amounts of green or bluish phlegm, accompanied by fever, with the highest temperature reaching 38.5℃.

[0130] For further treatment, the outpatient department plans to admit the patient for "pulmonary infection".

[0131] Since the onset of the illness, there has been no vomiting or diarrhea. A tracheotomy has been performed and a gastric tube has been placed. The catheter was left in place and clamped, and bowel movements were normal.

[0132] Medication: Qingyi Ganlu Powder Granules of this invention; The condition improved after taking the medication.

[0133] The technical scope of this invention is not limited to the content described above. Those skilled in the art can make various modifications and variations to the above embodiments without departing from the technical concept of this invention, and all such modifications and variations should fall within the protection scope of this invention.

Claims

1. A multi-target anti-adhesion and anti-inflammatory granule formula, characterized in that, Its raw materials consist of the following components in parts by weight: 2-3 parts of Artemisia annua extract, 4-5 parts of fennel, 2-3 parts of pearl stalk, 5-7 parts of Sophora flavescens, 8-10 parts of Terminalia chebula, 2-4 parts of Melia toosendan, 5-7 parts of Gardenia jasminoides, 2-4 parts of Artemisia annua, 8-10 parts of Adenophora stricta, 8-10 parts of Gentiana macrophylla, 2-4 parts of Lithospermum erythrorhizon, 2-4 parts of Rubia cordifolia, 5-7 parts of Hippophae rhamnoides, 4-5 parts of Glycyrrhiza uralensis, 2-4 parts of Fritillaria cirrhosa, 2-4 parts of Eriobotrya japonica leaf, 8-10 parts of white grape, 2-4 parts of Aucklandia lappa, and 8-10 parts of Aquilaria sinensis.

2. The multi-target anti-adhesion and anti-epidemic granules according to claim 1, characterized in that: In the composition, the weight ratio of the mucosal repair component to the anti-adhesion component is 1:2.8-3.3; The mucosal repair component is a combination of sea buckthorn, white grape, and Tibetan costus root; The anti-sticking component is a combination of Artemisia annua extract, fennel, Terminalia chebula, Melia toosendan, and Gardenia jasminoides; The specified weight ratio enables the particles to kill mucoid toxins while simultaneously achieving the synergistic effect of flavonoids in sea buckthorn and polysaccharides in white grapes, thereby repairing the physical barrier of the respiratory mucosa and blocking repeated invasion of mucoid toxins.

3. The multi-target anti-adhesion and anti-epidemic Ganlu powder granules according to claim 1, characterized in that: Its preparation process includes the following steps: S1: Anise, costus root, and agarwood were classified as volatile components and extracted using supercritical CO2. The extraction pressure was set at 20 MPa, the extraction temperature at 35 °C, the extraction time at 2 h, and the CO2 flow rate at 2 L / min. Extract A was collected. S2: Sea buckthorn and white grape were classified as heat-sensitive components. Five times the amount of purified water was added, and ultrasonic extraction was performed at 30-40℃ and 200W for 30 minutes. Extraction solution B was collected. S3: Take Artemisia annua extract, Terminalia chebula, Melia toosendan, and Gardenia jasminoides as the core cold-natured components, add 8 times the amount of purified water, and extract at 55-65℃ for 2 hours. Collect the extract C. S4: Pearl stem, Sophora flavescens, Artemisia annua, Adenophora stricta, Gentiana scabra, Lithospermum erythrorhizon, Rubia cordifolia, Fritillaria cirrhosa, Eriobotrya japonica, and Glycyrrhiza uralensis were classified as conventional components. They were extracted with 10 times the amount of purified water at 70°C for 1.5 hours. The residue was then extracted again with 8 times the amount of purified water for 1 hour. The extracts were combined and collected as D. S5: Combine the extracts AD, concentrate under reduced pressure at 60℃ and -0.08MPa to a clear extract with a relative density of 1.15-1.25, add ethanol to a concentration of 60%, let stand for 24 hours, filter through a 0.45μm filter membrane, and recover ethanol until no alcohol odor is detected to obtain the purified extract. S6: Mix the purified extract and dextrin at a weight ratio of 1:1.5, add 0.5% of the extract weight of steviol glycosides to make a soft material, granulate through a 14-mesh sieve, dry with hot air circulation at 50℃ for 4 hours, turning it over once every 1 hour, and granulate through a 12-mesh sieve to control the moisture content of the particles to 5%-7%.

4. The multi-target anti-adhesion and anti-epidemic Ganlu powder granules according to claim 3, characterized in that: In step S1, supercritical CO2 extraction also adds 5-10% anhydrous ethanol by weight of the raw materials as an entrainer to improve the dissolution rate of volatile components.

5. The multi-target anti-adhesion and anti-epidemic Ganlu powder granules according to claim 3, characterized in that: In step S2, the ultrasonic extraction process is stirred once every 5-10 minutes at a stirring speed of 40-60 r / min.

6. The multi-target anti-adhesion and anti-epidemic granules according to claim 3, characterized in that: In step S5, the preparation of the purified extract also includes removing proteins and tannins, and increasing the mass percentage of total flavonoids and total alkaloids in the granules.

7. The multi-target anti-adhesion and anti-epidemic granules according to claim 3, characterized in that: In step S6, dextrin is... - The amount of cyclodextrin and steviol glycoside added is 0.5% of the weight of the clear extract, and the stirring time is 10-15 min when preparing the soft material.

8. The multi-target anti-adhesion and anti-epidemic Ganlu powder granules according to claim 2, characterized in that: The raw material components by weight are: 2 parts Artemisia annua extract, 4.5 parts fennel, 2 parts pearl stalk, 6 parts Sophora flavescens, 9 parts Terminalia chebula, 3 parts Melia toosendan, 6 parts Gardenia jasminoides, 3 parts Artemisia annua, 9 parts Adenophora stricta, 9 parts Gentiana macrophylla, 3 parts Lithospermum erythrorhizon, 3 parts Rubia cordifolia, 6 parts Hippophae rhamnoides, 4.5 parts Glycyrrhiza uralensis, 3 parts Fritillaria cirrhosa, 3 parts Eriobotrya japonica leaf, 9 parts white grape, 3 parts Aucklandia lappa, and 9 parts Aquilaria sinensis. At this point, the weight ratio of the mucosal repair component to the anti-adhesion component is 1:3.

0.

9. The multi-target anti-adhesion and anti-epidemic Ganlu powder granules according to claim 1, characterized in that: The particles were quality controlled by high performance liquid chromatography (HPLC). The HPLC conditions were as follows: C18 column, mobile phase of methanol-0.1% phosphoric acid aqueous solution gradient elution, flow rate of 1.0 mL / min, column temperature of 30℃, and detection wavelength of 254 nm. The content of matrine was determined by the above method to be ≥0.10wt%, glycyrrhizic acid ≥0.20wt%, sea buckthorn flavonoids ≥0.30wt%, and gardenia glycosides ≤0.15wt%. Furthermore, the similarity between the fingerprint spectrum of the particle and the standard control fingerprint spectrum is ≥0.

95.

10. The use of the multi-target anti-viscosity and anti-inflammatory granules according to any one of claims 1-9 in the preparation of a drug for treating cough, fever, sore throat and respiratory mucosal damage caused by viral influenza, acute bronchitis, and pneumonia.

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