Pharmaceutical composition for improving acute alcoholic gastric mucosal injury and application thereof

Abstract

The present application relates to the technical field of medicine, in particular to a kind of drug composition for improving acute alcoholic gastric mucosal injury and application.The present application discloses the new medical use of ganoherbae decoction for the first time, and the composition can increase the activity of key enzyme in the stomach and liver tissue of acute alcoholic gastric mucosal injury mice, reduce the content of pro-inflammatory factor TNF-α in gastric tissue, increase the production of anti-inflammatory factor IL-10 in gastric tissue, reduce the inflammatory damage of ethanol to gastric mucosa, increase the level of protective factor EGF, SS and PGE-2 in serum, enhance the defense mechanism of gastric mucosa, and improve the repair ability of gastric mucosa.The discovery will have a significant impact on the research and treatment of acute alcoholic gastric mucosal injury disease, and has clinical practical value.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to a pharmaceutical composition and its application for improving acute alcoholic gastric mucosal injury. Background Technology

[0002] Acute alcoholic gastric mucosal injury (AGI) refers to damage to the gastric mucosa caused by excessive alcohol consumption within a short period. In severe cases, it can lead to gastrointestinal perforation and is a significant cause of gastric bleeding. Epidemiological surveys show that the incidence of AGI is increasing year by year. Drinking alcohol is a common habit; however, excessive drinking or consuming large amounts of alcohol in a short period are key factors causing gastric mucosal damage, seriously affecting people's health. Currently, clinical treatments for AGI mainly include drugs that reduce gastric acid secretion, such as H2 receptor antagonists and proton pump inhibitors; gastric mucosal protectants, such as sucralfate and misoprostol; and gastric mucosal repair agents, such as teprenone. While these can provide short-term symptom relief, they are expensive and have significant side effects. Therefore, the multi-target and multi-pathway advantages of traditional Chinese medicine (TCM) treatment represent an effective strategy for intervening in AGI.

[0003] Existing technologies also disclose various pharmaceutical compositions with anti-gastric mucosal damage properties. For example, Chinese Patent Publication No. CN103736054B discloses a pharmaceutical composition for protecting the gastric mucosa and its preparation method, which is composed of ginsenoside diol, Codonopsis pilosula, Atractylodes lancea, Magnolia officinalis, Citrus aurantium, Amomum villosum, Amomum cardamomum, Zingiber officinale, Glycyrrhiza uralensis, and Poria cocos. Chinese Patent Publication No. CN107744577B discloses a pharmaceutical composition for treating gastric mucosal damage, composed of American cockroach extract, Citrus reticulata peel, Acorus tatarinowii, Rheum palmatum, Poria cocos, Polygonatum odoratum, Atractylodes macrocephala, and Amomum villosum. However, these compositions contain many ingredients and are complex, making it difficult to control product quality.

[0004] Lingzhi-Ginseng-Pueraria Formula is a compound preparation with Lingzhi, ginseng, and kudzu root as its core ingredients. All three are important medicinal and edible resources, commonly found in health products or formulas containing ingredients with liver-protecting, immune-regulating, and metabolic-improving effects. However, there are no reports of using this formula to improve acute alcoholic gastric mucosal injury. Summary of the Invention

[0005] In response to the shortcomings of existing technologies, this invention has conducted in-depth research on the efficacy of the Ganoderma lucidum and Ginseng formula, and found that the formula has a significant therapeutic effect on acute alcoholic gastric mucosal injury, and has fewer medicinal ingredients, which facilitates product quality control.

[0006] One of the objectives of this invention is to provide a pharmaceutical composition comprising the following raw materials: 3-10 parts by weight of Ganoderma lucidum, 6-15 parts by weight of Pueraria lobata, 6-15 parts by weight of ginseng, 12-20 parts by weight of Poria cocos, and 110-440 mg / kg of oligo-walnut peptides.

[0007] Among them, Ganoderma lucidum is sweet in taste and neutral in nature. It enters the liver, heart, spleen, lung, and kidney meridians, nourishing the liver qi and is the primary herb for nourishing the liver, mainly used to soothe the liver and resolve alcohol intoxication. Kudzu root is sweet and pungent in taste and cool in nature. It enters the lung and stomach meridians. It disperses from the surface to relieve alcohol intoxication, guides other herbs to replenish qi and clear the mind, and generates fluids to quench thirst and relieve symptoms such as dry mouth after drinking. These two herbs together serve as the principal herbs.

[0008] Ginseng is sweet and slightly bitter in taste, and slightly warm in nature. It enters the spleen and lung meridians. It nourishes the five internal organs, especially strengthening the qi of the middle jiao (middle burner), enhancing its dampness-removing function, and preventing the tonifying effect from generating heat. Poria is sweet and bland in taste, and neutral in nature. It enters the heart, lung, spleen, and kidney meridians. It strengthens the spleen and promotes diuresis and eliminates dampness, guiding the elimination of alcoholic toxins from the lower jiao, restraining excessive tonification, and ensuring that tonification is balanced with elimination, without causing stagnation. The two herbs combined strengthen the spleen and remove dampness, assist in the smooth flow of qi in the middle jiao, and disperse the effects of alcohol, acting as assistant herbs.

[0009] Walnut peptides are extracted from walnut kernels and can warm and nourish the liver and kidneys, replenish blood, and moisten the intestines. They have a sweet taste and enter the lung, kidney, and large intestine meridians. They can nourish and protect the liver and kidneys, moisten the intestines to help eliminate alcohol toxins from the lower abdomen, expelling toxins without harming the body's vital energy. They also assist Poria cocos in eliminating alcohol toxicity through urination and defecation, and harmonize other herbs, serving as an adjuvant.

[0010] In some specific embodiments, the amount of Ganoderma lucidum in the pharmaceutical composition of the present invention may be 3-10 parts by weight, or 3-10 parts by weight, or 5-10 parts by weight, or 3-6 parts by weight, or 6-9 parts by weight, or 6 parts by weight; and,

[0011] The amount of kudzu root can be 6–15 parts by weight, or 6–12 parts by weight, or 6–9 parts by weight, or 9–15 parts by weight, or 9–12 parts by weight, or 9 parts by weight; and / or

[0012] The amount of ginseng can be 6–15 parts by weight, or 6–12 parts by weight, or 6–9 parts by weight, or 9–15 parts by weight, or 9–12 parts by weight, or 9 parts by weight; and / or

[0013] The amount of Poria cocos can be 12-20 parts by weight, or 15-20 parts by weight, or 15-18 parts by weight, or 12-18 parts by weight, or 12-15 parts by weight, or 15 parts by weight; and / or

[0014] The amount of oligowalnut peptides can be 110–440 mg / kg, or 110–380 mg / kg, or 110–350 mg / kg, or 150–300 mg / kg, or 200–250 mg / kg, or 220 mg / kg.

[0015] In some specific embodiments, the Ganoderma lucidum is one or a combination of Ganoderma lucidum powder, Ganoderma lucidum extract; and / or,

[0016] The kudzu root is one or a combination of kudzu root powder, kudzu root extract; and / or,

[0017] The ginseng mentioned is one or a combination of ginseng powder, ginseng extract; and / or,

[0018] The Poria cocos mentioned is one or a combination of Poria cocos powder, Poria cocos extract, or Poria cocos.

[0019] A second objective of this invention is to provide the use of the above-mentioned pharmaceutical composition in the preparation of a drug for preventing, alleviating or improving acute alcoholic gastric mucosal injury.

[0020] Furthermore, the following applications are also within the scope of protection of this invention:

[0021] The pharmaceutical composition, as the active ingredient, can be used in combination in the preparation of the drug, or it can be used in combination with other components with anti-inflammatory activity; the active ingredient composition is: 3-10 parts by weight of Ganoderma lucidum, 6-15 parts by weight of Pueraria lobata, 6-15 parts by weight of ginseng, 12-20 parts by weight of Poria cocos, and 110-440 mg / kg of oligowalnut peptides.

[0022] The drug does not contain any other active ingredients with anti-inflammatory activity besides the drug composition; the active components are: 3-10 parts by weight of Ganoderma lucidum, 6-15 parts by weight of Pueraria lobata, 6-15 parts by weight of ginseng, 12-20 parts by weight of Poria cocos, and 110-440 mg / kg of oligowalnut peptides.

[0023] A third objective of this invention is to provide a pharmaceutical formulation in which the above-mentioned pharmaceutical composition is formulated into a pharmaceutically acceptable dosage form using pharmaceutically acceptable excipients.

[0024] Furthermore, the dosage form of the pharmaceutical preparation is an oral dosage form or an injectable dosage form, and it can also adopt a controlled-release or sustained-release dosage form known in the modern pharmaceutical industry. Preferably, the drug is a gastrointestinal dosage form.

[0025] Gastrointestinal administration dosage forms refer to drug preparations that enter the gastrointestinal tract after oral administration, exerting local effects or systemic effects through absorption, such as powders, tablets, granules, capsules, solutions, emulsions, and suspensions.

[0026] Further, the amount of the active ingredient is 0.001-90 wt% relative to the total weight of the drug; or, 0.02-50 wt%; or 0.1-20%; or 0.005-5%.

[0027] In some specific embodiments, the amount of the active ingredient can be selected as 0.01%, 0.05%, 0.1%, 0.5%, 2%, 5%, 10%, 30%, 40%, 50%, or 80% of the total weight of the drug;

[0028] Those skilled in the art will fully understand that the pharmaceutically acceptable carrier is generally recognized for this purpose and as an inactive ingredient in the pharmaceutical preparation.

[0029] The auxiliary agents include solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesion agents, binding agents, penetration enhancers, pH adjusters, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, encapsulating agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, and release inhibitors.

[0030] The diluent can be one or more of mannitol, sucrose, lactose, sorbitol, xylitol, polyethylene glycol, propylene glycol, vegetable oil, and mineral oil; the disintegrant can be one or more of croscarmellose sodium, colloidal silica, and citric acid; the binder can be one or more of starch paste, ethanol, water, and povidone alcohol solution; the preservative can be one or more of ethylparaben, propylparaben, sorbic acid, potassium sorbate, calcium propionate, sodium dehydroacetate, sodium diacetate, and sodium lactate; and the antioxidant can be ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate, butylated hydroxytoluene, glycine, inositol, and other antioxidants. The flavoring agent may be one or more of the following: citric acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite; the flavoring agent may be one or more of the following: aspartame, sucrose, xylitol, steviol glycosides, cyclamate, sorbitol, cocoa, pure vanilla, vanillin, ethyl vanillin, chocolate, malt, and mint; the suspending agent may be one or more of the following: xanthan gum, polyvinylpyrrolidone, sodium alginate, aluminum stearate, and hydrogenated vegetable oil; the emulsifier may be one or more of the following: alkyl sulfate, soap, dodecylbenzene sulfonate, lactate, sulfosuccinate, monoglyceride sulfonate, phosphate ester, siloxane, and taurine.

[0031] Pharmaceutical compositions may be prepared according to methods known in the art. For this purpose, if desired, the active ingredient may be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to form a suitable administration or dosage form for human use.

[0032] In addition, colorants, preservatives, flavorings, tasters, sweeteners or other materials may be added to pharmaceutical preparations if necessary.

[0033] The dosage of the pharmaceutical composition of the present invention depends on many factors, such as the sex, age, weight, and individual response of the patient or animal, the route of administration, and the frequency of administration. The dosage can be administered as a single dose or in several doses, such as two, three, or four doses. The dosage level must be selected based on the specific route of administration, the severity of the condition being treated, and the patient's condition and medical history. However, it is the practice in the art to start with a dosage below the level required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

[0034] However, it should be recognized that the total daily dosage of the pharmaceutical compositions of the present invention must be determined by the attending physician within the bounds of reliable medical judgment. For any given patient, the specific therapeutically effective dosage level must be determined based on a variety of factors, including the disorder being treated and its severity; the specific composition used; the patient's age, weight, general health condition, sex, and diet; the timing, route of administration, and excretion rate; the duration of treatment; any drugs used in combination or concurrently; and similar factors known in the medical field. For example, it is practiced in the art to start with a dose below the level required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved.

[0035] Generally speaking, the dosage of the pharmaceutical composition of the present invention for mammals, especially humans, calculated based on the active ingredient, can be between 1 and 1000 mg / kg body weight / day, for example between 1 and 500 mg / kg body weight / day, for example between 50 and 500 mg / kg body weight / day, or 100 and 500 mg / kg, or 150 and 500 mg / kg, or 200 and 500 mg / kg, or 250 and 500 mg / kg.

[0036] Compared with existing technologies, this invention discloses for the first time a novel medicinal use of the Ganoderma lucidum and Ginseng formula. Experimental and clinical verification has shown that this formula can increase the activity of key enzymes in the gastric and liver tissues of mice with acute alcoholic gastric mucosal injury, reduce the content of the pro-inflammatory factor TNF-α in gastric tissue, increase the production of the anti-inflammatory factor IL-10 in gastric tissue, alleviate the inflammatory damage of ethanol to the gastric mucosa, increase the levels of protective factors EGF, SS, and PGE-2 in serum, enhance the defense mechanism of the gastric mucosa, and improve the repair capacity of the gastric mucosa. This discovery will have a significant impact on the research and treatment of acute alcoholic gastric mucosal injury and has clinical practical value. Attached Figure Description

[0037] Figure 1 This is a diagram showing the HE staining results of mouse gastric tissue according to the present invention;

[0038] Figure 2 This is an image of AB-PAS staining of mouse gastric tissue according to the present invention;

[0039] Figure 3 The effect of this invention on the activity of key enzymes in mouse gastric tissue; 3A represents the expression level of ADH in gastric tissue; 3B represents the expression level of ALDH in gastric tissue; *P<0.05;

[0040] Figure 4 The effect of this invention on gastric tissue protective factors in mouse gastric tissue; 4A represents the expression level of PGE2 in gastric tissue; 4B represents the expression level of EGF in gastric tissue; 4C represents the expression level of SS in gastric tissue; *P<0.05;

[0041] Figure 5 The effect of this invention on inflammation-related proteins in mouse gastric tissue; 5A represents the expression level of TNF-α; 5B represents the expression level of IL-10; *P<0.05. Detailed Implementation

[0042] To enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be described in detail below with reference to specific embodiments. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise specified, the test materials used in the following embodiments were purchased from conventional biochemical reagent stores. Unless otherwise stated, percentages and parts are by weight. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar with the art. Furthermore, any methods and materials similar to or equivalent to those described herein can be applied to the present invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0043] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0044] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the following embodiments are only used to explain the present invention and are not intended to limit the present invention.

[0045] Example 1

[0046] 6 parts Ganoderma lucidum, 9 parts Pueraria lobata, 9 parts Ginseng, 15 parts Poria cocos, and 220 mg / kg of oligo-walnut peptides.

[0047] Example 2

[0048] 3 parts Ganoderma lucidum, 15 parts Pueraria lobata, 12 parts Ginseng, 20 parts Poria cocos, and 110 mg / kg of oligo-walnut peptides.

[0049] Example 3

[0050] 10 parts Ganoderma lucidum, 6 parts Pueraria lobata, 9 parts Ginseng, 12 parts Poria cocos, and 300 mg / kg of oligo-walnut peptides.

[0051] Example 4

[0052] 9 parts Ganoderma lucidum, 15 parts Pueraria lobata, 9 parts Ginseng, 18 parts Poria cocos, and 440 mg / kg of oligo-walnut peptides.

[0053] Example 5

[0054] 5 parts Ganoderma lucidum, 12 parts Pueraria lobata, 12 parts Ginseng, 15 parts Poria cocos, and 150 mg / kg of oligo-walnut peptides.

[0055] The synergistic protective effect of the drug composition on acute alcoholic gastric mucosal injury in mice was investigated.

[0056] Experimental animals: 15 male C57BL / 6J mice, weighing 18-22g, provided by Beijing Spaford Biotechnology Co., Ltd.

[0057] Drug sources: Ginseng, Ganoderma lucidum, Poria cocos, and Pueraria lobata were purchased from Yunnan Yixintang Pharmacy and identified by the School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine; walnut peptide was from Shaanxi Panier Biotechnology Co., Ltd.; enzyme-linked immunosorbent assay (ELISA) kits for tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), prostaglandin E2 (PGE2), epidermal growth factor (EGF), and somatostatin (SS) were from Jiangsu Enzyme Biotechnology Co., Ltd.; alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) kits were from Beijing Solarbio Science & Technology Co., Ltd.

[0058] Experimental Methods: C57BL / 6J mice were randomly divided into three groups of five mice each: a control group (C), a model group (M), and a Lingzhi Shenge Decoction group (M+LSD). After acclimatization for 3 days (day), the mice were fasted but allowed free access to water for 24 hours. The model group (M) and the Lingzhi Shenge Decoction group (M+LSD) were administered 56% ethanol by gavage at a dose of 10 mL / kg, while the control group (C) received an equal volume of physiological saline. Intervention was performed every other day, once daily for a total of 4 times. Simultaneously, the drug intervention experiment began on day 1. The Lingzhi Shenge Decoction group was administered the drug composition of Example 1 at a dose of 6.24 g / kg daily, while the model group and the control group received an equal volume of physiological saline for a total of 7 days.

[0059] Experimental data are expressed as mean ± standard deviation. SPSS 29.0 software was used for analysis of variance to compare multiple groups, and the LSD method was used for pairwise comparisons between groups. GraphPad Prism 10.4.1 software was used for plotting, and P < 0.05 was considered statistically significant.

[0060] (1) Observe the effects of drug administration on mouse histopathology.

[0061] HE staining microscopic observation of histopathological changes: After the drug intervention experiment, gastric tissue was taken, fixed with 4% paraformaldehyde for later use, and then dehydrated in a gradient manner. The tissue was then embedded in paraffin, sectioned (about 4 μm thick), dewaxed, stained with hematoxylin-eosin (HE), and placed under a microscope to observe the pathological changes of the tissue.

[0062] like Figure 1 As shown, in the control group, the gastric mucosal epithelial structure of mice was intact, the glands were neatly arranged, and the mucosal layer structure was clear and intact, with no obvious edema or inflammatory cell infiltration. Compared with the control group, the normal structure of the gastric mucosa in the model group mice disappeared, the epithelial cells were disordered or partially sloughed off, inflammatory cells infiltrated, and the mucosal layer was edematous. After administration, the gastric mucosal tissue structure of mice in the Lingzhi Shenge formula group was intact, the glandular cells were relatively neatly arranged, and there was no obvious edema in the mucosal layer, which was closer to the structure of normal gastric tissue. This suggests that the Lingzhi Shenge formula can effectively alleviate gastric mucosal damage.

[0063] Microscopic observation of pathological changes in mouse gastric tissue using AB-PAS staining: Alcian blue-periodic acid-Schiff and Alcian blue stain (AB-PAS) combines with colorless fuchsin in Schiff's reagent to form a purplish-red dye deposit, which appears in the corresponding areas. Paraffin sections of gastric tissue were stained with AB-PAS, mounted, and observed and imaged using a digital slide scanner to observe specific lesions.

[0064] like Figure 2 As shown, the gastric mucosa of mice in the blank control group had normal morphology, with cells arranged regularly and tightly, and intact cell and nucleus polarity. No obvious blue staining foci were observed, indicating the absence of glands secreting mucus. Compared with the blank control group, the gastric mucosa of mice in the model group was severely damaged, with disordered cell arrangement, abundant inflammatory cell infiltration, obvious vacuolar degeneration of cells, and mucus lakes of varying sizes forming in the glandular lumens. The glands showed deep blue staining, indicating the formation of intestinal metaplastic glands secreting acidic mucus. Compared with the model group, the abnormal cell morphology of the gastric mucosa in mice in the Lingzhi-Shenge formula group was improved, with reduced inflammatory infiltration areas, vacuolar degeneration, mucus lakes, and tissue atypia, suggesting that the Lingzhi-Shenge formula can improve the gastric mucosal defense barrier.

[0065] (2) Observe the effects of drug administration on the activity of key enzymes ADH and ALDH in mouse gastric tissue.

[0066] After homogenizing and centrifuging mouse gastric tissue, the supernatant was collected and samples were prepared according to the instructions of the test kit. The activity of alcohol dehydrogenase (ADH) was detected by enzyme-coupled rate method, and the activity of aldehyde dehydrogenase (ALDH) was detected by colorimetric method combined with aldehyde dehydrogenase catalytic reaction.

[0067] Figure 3 As can be seen, the activities of key enzymes ADH and ALDH in the gastric tissue of model group mice were significantly lower than those in blank control group. After administration, the activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in Lingzhi Shenge formula group were significantly increased. It can be seen that administration can effectively increase the expression of ADH and ALDH in mice, regulate the alcohol metabolism enzyme system, and thus improve its damage.

[0068] (3) Observe the effect of drug administration on gastric tissue protective factors in mice

[0069] Enzyme-linked immunosorbent assay (ELISA) was used to determine the protective factors PGE2, EGF, and SS in gastric tissue. Specifically:

[0070] 1) Sample processing: Approximately 20 mg of gastric tissue sample was rinsed with physiological saline to remove any blood and impurities. Then, 9 times its weight of physiological saline was added, and the tissue was homogenized into a homogenate using a tissue homogenizer. The homogenate was then centrifuged at 4°C for 15 minutes, and the supernatant was collected and kept on ice.

[0071] 2) Immunoassay: Quantitative analysis of PGE2, EGF, and SS in gastric tissue was performed using an ELISA kit. The kit was incubated at room temperature for 30 minutes to achieve equilibration. Standard curve wells, blank control wells, and sample detection wells were prepared according to the instructions. 50 μL of the corresponding standard was added to each standard well; 45 μL of diluent and 5 μL of sample were added to each sample well. Then, 100 μL of the corresponding antibody was added to each sample well and standard well, except for the blank wells. The plate was incubated in a sealed incubator at 37°C for 1 hour to ensure sufficient antibody binding reaction.

[0072] 3) Washing and color development: After incubation, perform 5 washes to remove unbound antibodies and other non-specific conjugates. Then, add chromogenic substrates A and B to each well and incubate in a sealed incubator at 37°C for 15 minutes in the dark to allow for color development. After color development is complete, quickly add stop solution to stop the reaction.

[0073] 4) Content determination: The absorbance value of each well is read at a wavelength of 450 nm using a microplate reader. This value reflects the concentration of each detection index, and the content of the target protein in the sample can be quantitatively analyzed by combining it with a standard curve.

[0074] In acute gastric mucosal injury, SS levels show a trend of "initially increasing and then decreasing." In the early stage, SS secretion increases as a protective response to inhibit gastric acid, while in the later stage, SS secretion decreases, exacerbating gastric acid erosion and mucosal ischemia, and delaying healing. EGF, on the other hand, can counteract the destructive effect of pepsin on the gastric mucosa and inhibit excessive gastric acid secretion, thereby providing protection for the gastric mucosa and maintaining its structural and functional integrity. PGE2 is an inhibitor of monocyte pro-inflammatory factor expression, which can alleviate oxidative stress and exert anti-inflammatory and antipyretic effects. At the same time, PGE2 can protect the gastric mucosa through mechanisms such as inhibiting gastric acid secretion, regulating gastric wall mucus secretion, and improving gastric mucosal blood circulation.

[0075] like Figure 4 As shown, the levels of EGF, SS, and PGE-2 in the gastric tissue of mice in the model group were significantly lower than those in the blank group. After administration, the levels of EGF, SS, and PGE-2 in the gastric tissue of mice in the Ganoderma lucidum and Ginseng formula group were significantly increased. This suggests that the Ganoderma lucidum and Ginseng formula of the present invention can exert a protective effect by increasing the levels of protective factors.

[0076] (4) Observe the effect of drug administration on inflammatory factors in the gastric tissue of mice.

[0077] Mouse serum was collected and enzyme-linked immunosorbent assay (ELISA) was used to detect serum inflammatory factors IL-10 and TNF-α. The specific method was as follows: 40 μL of sample diluent, 10 μL of sample, and 100 μL of enzyme-labeled reagent were added to each sample well; 50 μL of each standard solution and 100 μL of enzyme-labeled reagent were added to each standard well; 40 μL of sample diluent was added to each blank well; the plates were sealed with sealing film and incubated at 37°C in the dark for 1 hour; the plates were washed rapidly 5 times with a multi-pipette, and the plates were blistered after each wash; then 50 μL of chromogenic reagent A and 50 μL of chromogenic reagent B were added, and the plates were incubated at a constant temperature in the dark for 15 minutes; the optical density (OD value) of each well was measured sequentially at a wavelength of 450 nm using an ELISA reader, and the concentrations were calculated according to the standard curve (see [reference missing]). Figure 5 ).

[0078] like Figure 5 The results showed that, compared with the model group, the levels of TNF-α in the gastric tissue of mice in the blank group and the Ganoderma lucidum and Ginseng formula group were significantly reduced, while the levels of IL-10 were significantly increased. TNF-α is a pro-inflammatory factor that assesses the degree of inflammation. It can induce the release of platelet-activating factor, thereby accelerating the generation of harmful substances such as oxygen free radicals and leukotrienes, causing hypoxia and ischemia of the intestinal mucosa and aggravating gastric mucosal damage. The anti-inflammatory factor IL-10 can inhibit the chemotactic function of macrophages and neutrophils and reduce the activity of pro-inflammatory factors. This indicates that the Ganoderma lucidum and Ginseng formula of the present invention has good anti-inflammatory activity against acute alcoholic gastric mucosal injury in mice.

[0079] Finally, it should be noted that the above description is only a preferred embodiment of the present invention. Those skilled in the art, under the guidance of the present invention, can make various similar representations without departing from the spirit and claims of the present invention, and such modifications all fall within the protection scope of the present invention.

Claims

1. The use of the pharmaceutical composition in the preparation of a medicament for improving acute alcoholic gastric mucosal injury, characterized in that, The pharmaceutical composition consists of the following raw materials: 6 parts by weight of Ganoderma lucidum, 9 parts by weight of Pueraria lobata, 9 parts by weight of ginseng, 15 parts by weight of Poria cocos, and 220 mg / kg of oligo-walnut peptide.

2. The application according to claim 1, characterized in that, The Ganoderma lucidum is one or a combination of Ganoderma lucidum powder, Ganoderma lucidum extract; and / or The kudzu root is one or a combination of kudzu root powder, kudzu root extract; and / or The ginseng mentioned is one or a combination of ginseng powder, ginseng extract; and / or The Poria cocos mentioned is one or a combination of Poria cocos powder, Poria cocos extract.

3. The application according to claim 1, characterized in that, The pharmaceutical composition, as an active ingredient, is used in combination with other components having anti-inflammatory activity in the preparation of a drug. The active ingredients of the pharmaceutical composition are: Ganoderma lucidum, kudzu root, ginseng, Poria cocos, and oligowalnut peptides.

4. The application according to claim 1, characterized in that, The drug does not contain any other active ingredients with anti-inflammatory activity besides the drug composition, wherein the active components of the drug composition are: Ganoderma lucidum, kudzu root, ginseng, Poria cocos, and oligowalnut peptides.

5. The application according to claim 1, characterized in that, The drug uses a pharmaceutical composition as its active ingredient and is formulated into a pharmaceutically acceptable dosage form with pharmaceutically acceptable excipients. The active components of the pharmaceutical composition are: Ganoderma lucidum, kudzu root, ginseng, Poria cocos, and oligowalnut peptides.

6. The application according to claim 5, characterized in that, The drug is available in oral, controlled-release, or sustained-release formulations.

7. The application according to claim 6, characterized in that, The excipients include one or more of solvents, disintegrants, flavoring agents, preservatives, colorants, binders, lubricants, and diluents.

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