A mongolian medicine composition, its preparation method and application in preparing medicine for preventing gastric ulcer caused by non-steroidal anti-inflammatory drugs

Abstract

The application provides a Mongolian medicine composition, a preparation method thereof and application thereof in preparing a medicine for preventing gastric ulcer caused by non-steroidal anti-inflammatory drugs, and belongs to the technical field of medicine compositions.The Mongolian medicine composition provided by the application is composed of sodium chloride, gallic acid, piperine and 6-gingerenol in a specific ratio, the accurate ratio of the active ingredients overcomes the defects of difficult quality control of traditional Mongolian medicine, and realizes the standardization of the effective ingredients;the Mongolian medicine composition has a significant preventive effect on indomethacin-induced gastric ulcer, can reduce the ulcer index and reduce the gastric mucosa damage, the raw material ingredients are natural medicine effective ingredients, the safety is relatively high, based on the compatibility principle of Mongolian medicine, the components are synergistically compatible, and the efficacy of the prepared Mongolian medicine composition is improved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical composition technology, and in particular to a Mongolian medicine composition, its preparation method, and its application in the preparation of a drug for preventing gastric ulcers caused by nonsteroidal anti-inflammatory drugs. Background Technology

[0002] Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used first-line anti-inflammatory, analgesic, and antipyretic drugs in clinical practice. With their definite efficacy and rapid onset of action, they are commonly used in the clinical treatment of rheumatoid arthritis, osteoarthritis, postoperative pain, infectious fever, and various aseptic inflammations, covering multiple core diagnostic and treatment areas such as orthopedics, internal medicine, and emergency medicine, demonstrating extremely high clinical application value. Indomethacin, as a classic representative of this class of drugs, has significantly better anti-inflammatory and analgesic efficacy than ordinary NSAIDs, showing outstanding intervention effects on moderate to severe inflammation and intractable pain, and is a commonly used drug in the clinical management of refractory inflammation and pain.

[0003] However, NSAIDs pose significant safety risks, with gastrointestinal damage being the most common and serious adverse reaction, severely limiting their long-term and safe clinical application. These drugs exert their effects by inhibiting cyclooxygenase activity and blocking the synthesis of inflammatory mediators. Simultaneously, they inhibit the production of protective prostaglandins in the gastric mucosa, damaging the gastric mucosal barrier structure and reducing mucosal blood flow and self-repair capabilities. Long-term use or high-dose use can easily lead to gastric mucosal congestion, erosion, and edema, gradually inducing chronic gastritis and gastric ulcers. In severe cases, it can cause fatal complications such as gastric bleeding and perforation, not only reducing patient adherence and affecting the continued effectiveness of treatment but also significantly increasing the risk of clinical complications and the medical burden.

[0004] Currently, there are no highly effective and safe protective measures against NSAID-induced gastric mucosal damage in clinical practice. Traditional Mongolian medicine is often used to treat gastrointestinal diseases such as indigestion and gastric mucosal damage. It is mild in nature, has few side effects, and possesses unique diagnostic and therapeutic advantages and development potential. However, traditional Mongolian medicine currently suffers from problems such as unclear active ingredients, imperfect quality control systems, and the inability to standardize dosage, hindering modern research and development and precise clinical application. Therefore, exploring the medicinal value of Mongolian medicine, investigating its protective mechanism against NSAID-induced gastric mucosal damage, and developing novel reduced-toxicity gastric protection regimens are of significant research importance for addressing the side effects of NSAID use and promoting the modernization of Mongolian medicine. Summary of the Invention

[0005] The purpose of this invention is to provide a Mongolian medicine composition and its preparation method, as well as its application in the preparation of a drug for preventing gastric ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The Mongolian medicine composition provided by this invention achieves precise quantification of active ingredients by accurately determining the quantitative ratio of each component, and can be used to prepare a drug for preventing gastric ulcers caused by NSAIDs (especially indomethacin).

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a Mongolian medicine composition prepared from the following raw materials: sodium chloride, gallic acid, piperine, and 6-shogaol.

[0007] Preferably, the Mongolian medicine composition is prepared from the following raw materials in parts by mass: 6-9 parts sodium chloride, 12-17 parts gallic acid, 5-9 parts piperine, and 0.15-0.25 parts 6-shogaol.

[0008] Preferably, the Mongolian medicine composition is prepared from the following raw materials in parts by weight: 7.28 parts sodium chloride, 14.62 parts gallic acid, 7.03 parts piperine, and 0.20 parts 6-shogaol.

[0009] Preferably, the dosage form of the Mongolian medicine composition is at least one of powder, tablet, capsule and granule.

[0010] The present invention also provides a method for preparing the Mongolian medicine composition described in the above technical solution. When the dosage form of the Mongolian medicine composition is a powder, the method for preparing the Mongolian medicine composition includes the following steps: pulverizing, sieving and mixing sodium chloride, gallic acid, piperine and 6-shogaol in sequence to obtain the Mongolian medicine composition powder.

[0011] The present invention also provides a method for preparing the Mongolian medicine composition described in the above technical solution. When the dosage form of the Mongolian medicine composition is a tablet, the method for preparing the Mongolian medicine composition includes the following steps: mixing sodium chloride, gallic acid, piperine and 6-shogaol with excipients, and then granulating and compressing them in sequence to obtain the Mongolian medicine composition tablet.

[0012] The present invention also provides the application of the Mongolian medicine composition described above in the preparation of a drug for preventing gastric ulcers caused by nonsteroidal anti-inflammatory drugs.

[0013] Preferably, the nonsteroidal anti-inflammatory drug is indomethacin.

[0014] The present invention has the following beneficial effects: (1) Precise quantification: Determining the precise ratio of each active ingredient overcomes the shortcomings of traditional Mongolian medicine quality control difficulties and realizes the standardization of effective ingredients; (2) Clear efficacy: Animal experiments have confirmed that the Mongolian medicine composition of the present invention has a significant preventive effect on indomethacin-induced gastric ulcers, can reduce the ulcer index and reduce gastric mucosal damage. (3) The formula has synergistic properties: Based on the compatibility principle of Mongolian medicine, the components are synergistically combined to improve the efficacy of the prepared Mongolian medicine composition; (4) Good safety: The Mongolian medicine composition of the present invention consists of natural drug active ingredients and has high safety. Attached Figure Description

[0015] Figure 1 The graph shows the gastric ulcer index detection results of Control, IND, CMP-L, CMP-M, CMP-H, MD-4 and KFXY in this invention; Figure 2 The images show the gastric tissue pathological examination results of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 2 The first column shows the HE staining results of rat gastric tissue pathology in each group. Figure 2 The second column shows actual images of gastric ulcer damage in rats from each group; Figure 3 This is a bar chart showing the serum PGE2 levels (pg / mL) of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 4 This is a bar chart showing the gastric PGE2 (pg / mL) levels of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 5 This is a bar chart showing the gastric VEGF (pg / mL) levels of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 6 This is a bar chart showing the gastric PP (ng / mL) levels of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 7 This is a bar chart showing the gastric SOD (ng / mL) levels of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 8 This is a bar chart showing the gastric LPO (nmol / g) levels of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 9 is a bar chart of the gastric COX-1 (ng / g) indicators of Control, IND, CMP-L, CMP-M, CMP-H, MD-4 and KFXY in the present invention; Figure 10 is a bar chart of the gastric COX-2 (ng / g) indicators of Control, IND, CMP-L, CMP-M, CMP-H, MD-4 and KFXY in the present invention. DETAILED DESCRIPTION

[0016] The present invention provides a Mongolian medicinal composition, which is prepared from the following raw materials: sodium chloride, gallic acid, piperine and 6-shogaol.

[0017] In the present invention, unless otherwise specified, all the raw materials used are conventional commercially available products in the art.

[0018] In the present invention, in parts by mass, the Mongolian medicinal composition preferably is prepared from the following raw materials: 6 to 9 parts of sodium chloride, 12 to 17 parts of gallic acid, 5 to 9 parts of piperine, and 0.15 to 0.25 parts of 6-shogaol, more preferably is prepared from the following raw materials: 7.28 parts of sodium chloride, 14.62 parts of gallic acid, 7.03 parts of piperine, and 0.20 parts of 6-shogaol. By controlling the proportion of each raw material, the present invention not only retains the synergistic relationship of the equal-proportion compatibility of the original Mongolian medicinal Guangming Siwei Tang powder, but also realizes the precise quantification of active ingredients. In the present invention, the dosage form of the Mongolian medicinal composition is preferably at least one of powder, tablet, capsule and granule.

[0019] The Mongolian medicinal composition provided by the present invention is composed of sodium chloride, gallic acid, piperine and 6-shogaol in a specific proportion. Through the precise proportioning of each active ingredient, the defect of difficult quality control of traditional Mongolian medicine is overcome, and the standardization of effective ingredients is realized; the Mongolian medicinal composition has a significant preventive effect on indomethacin-induced gastric ulcer, can reduce the ulcer index and alleviate gastric mucosal damage, the used raw material components are active ingredients of natural medicines with high safety, and based on the compatibility principle of Mongolian medicine, the components are synergistically compatible to improve the medicinal efficacy of the prepared Mongolian medicinal composition.

[0020] The present invention further provides a preparation method of the Mongolian medicinal composition described in the above technical solutions. When the dosage form of the Mongolian medicinal composition is a powder, the preparation method of the Mongolian medicinal composition preferably comprises the following steps: sequentially pulverizing, sieving and mixing sodium chloride, gallic acid, piperine and 6-shogaol respectively, to obtain the Mongolian medicinal composition powder.

[0021] This invention does not impose any particular limitation on the pulverization method; any technical solution well-known in the art can be used. In this invention, the sieving is preferably performed through a 100-mesh sieve. In this invention, the mixing method is preferably an equal-incremental mixing method.

[0022] The present invention also provides a method for preparing the Mongolian medicine composition described in the above technical solution. When the dosage form of the Mongolian medicine composition is a tablet, the method for preparing the Mongolian medicine composition preferably includes the following steps: mixing sodium chloride, gallic acid, piperine and 6-shogaol with excipients, and then granulating and compressing them in sequence to obtain the Mongolian medicine composition tablet.

[0023] In this invention, the excipients include at least one of starch and microcrystalline cellulose. This invention does not impose any particular limitation on the granulation and tableting methods; any Mongolian medicine composition tablet can be prepared using techniques well-known in the art.

[0024] The present invention also provides the application of the Mongolian medicine composition described above in the preparation of a drug for preventing gastric ulcers caused by nonsteroidal anti-inflammatory drugs.

[0025] In this invention, the nonsteroidal anti-inflammatory drug is preferably indomethacin.

[0026] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0027] Unless otherwise specified, all experiments were repeated three times, and the results are expressed as averages.

[0028] Example 1 A Mongolian medicine composition, by mass parts, is prepared from the following raw materials: 7.28 parts sodium chloride, 14.62 parts gallic acid, 7.03 parts piperine, and 0.20 parts 6-shogaol.

[0029] The dosage form of the Mongolian medicine composition is a powder, and the preparation method of the Mongolian medicine composition includes the following steps: Take 7.28g of sodium chloride, 14.62g of gallic acid, 7.03g of piperine, and 0.20g of 6-shogaol, pulverize them separately, pass them through a 100-mesh sieve, and mix them evenly using the equal-increment method to obtain the Mongolian medicine composition powder.

[0030] The following study investigates the preventive effect of the Mongolian medicine composition prepared according to the embodiments of the present invention on indomethacin-induced gastric ulcers in rats.

[0031] 1. Experimental Materials Experimental animals: SPF-grade male SD rats, weighing 180–220g. Test drug: The Mongolian medicine composition prepared in Example 1 of this invention Positive control drug: Kangfuxin Liquid Modeling drug: Indomethacin 2. Animal grouping and administration SD rats were randomly divided into the following groups (n=8 rats per group): Control (i.e., blank control group): Administered an equal volume of physiological saline; IND: Indomethacin-induced gastric ulcer model group; CMP-L: Low-dose group of the Mongolian medicine composition prepared in Example 1 of this invention, 15 mH / kg; CMP-M: The dosage group of the Mongolian medicine composition prepared in Example 1 of this invention, 30 mH / kg; CMP-H: High-dose group of the Mongolian medicine composition prepared in Example 1 of this invention, 60 mH / kg; MD-4: Original formula of Guangming Siwei Tang San (Guangming Salt, Terminalia chebula, dried ginger, and Piper longum in a weight ratio of 1:1:1:1), 40mg / kg; KFXY: Positive control group (Kangfuxin liquid), 40mh / kg.

[0032] # indicates comparison with the control group (blank); * indicates comparison with the IND model group. P < 0.0001, P < 0.01, P < 0.05; ns indicates no statistically significant difference. Statistical analysis was performed using one-way ANOVA combined with Bonferroni-Dunn and Dunnett multiple comparison tests. Each group was administered the drug by gavage for 21 consecutive days. Four hours after the last administration, except for the blank control group, the other groups were given indomethacin 40 mg / kg by gavage to induce gastric ulcers.

[0033] 3. Gastric ulcer index measurement Four hours after indomethacin induction, rats were sacrificed, their stomachs were removed, cut open along the greater curvature, rinsed with physiological saline, and placed under a dissecting microscope to observe gastric mucosal damage. The ulcer index (UI) and ulcer inhibition rate were calculated according to the Guth criteria.

[0034] The results of the detection of gastric ulcer indexes Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY obtained in this invention are shown in the figure below. Figure 1 As shown.

[0035] Test results and Figure 1The results show that, compared with the IND model group, all dosage groups of the Mongolian medicine composition prepared in Example 1 of this invention can significantly reduce the gastric ulcer index induced by indomethacin (P<0.05 or P<0.01), and this reduction is dose-dependent, suggesting that the composition of this invention has a good preventive effect on gastric ulcers caused by NSAIDs.

[0036] 4. Histopathological observation of gastric tissue Gastric tissues from rats in each group were collected, fixed in 10% neutral formaldehyde, embedded in paraffin, stained with hematoxylin and eosin (HE), and observed under a light microscope for histopathological changes in the gastric mucosa.

[0037] The pathological examination results of gastric tissue containing Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY obtained in this invention are shown in the figure below. Figure 2 As shown, Figure 2 The first column shows the HE staining results of rat gastric tissue pathology in each group. Figure 2 The second column shows actual images of gastric ulcer damage in rats from each group.

[0038] Test results and Figure 2 The results showed that the gastric mucosa of rats in the IND model group showed obvious pathological changes such as epithelial cell shedding, gland destruction, and inflammatory cell infiltration; the gastric mucosa damage of each dose group of the Mongolian medicine composition prepared in Example 1 of this invention was significantly reduced, the mucosal structure was relatively intact, and the inflammatory cell infiltration was reduced.

[0039] 5. Detection of inflammatory factors in gastric tissue Gastric tissue homogenate was collected, and the levels of inflammatory factors TNF-α, IL-1β, and IL-6 were detected by ELISA.

[0040] The results showed that, compared with the IND model group, the levels of TNF-α, IL-1β, and IL-6 in the gastric tissue of each dose group of the Mongolian medicine composition prepared in Example 1 of the present invention were significantly reduced (P<0.05 or P<0.01), indicating that the composition of the present invention can exert a protective effect on the gastric mucosa by inhibiting the inflammatory response.

[0041] Figure 3 This is a bar chart showing the serum PGE2 levels (pg / mL) of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figure 3 It can be seen that the serum PGE2 levels in each dose group of the Mongolian medicine composition in Example 1 significantly increased (P<0.05), which is consistent with the trend of PGE2 changes in gastric tissue. Figure 4 This suggests that the Mongolian medicine composition in this invention may exert a gastric mucosal protective effect through a combination of systemic anti-inflammatory and COX activation mechanisms.

[0042] 6. Detection of antioxidant indicators in gastric tissue Gastric tissue homogenate was collected, and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected by biochemical methods.

[0043] The results showed that, compared with the model group, the SOD and GSH-Px activities in the gastric tissue of each dose group of the Mongolian medicine composition prepared in Example 1 of the present invention were significantly increased, and the MDA content was significantly decreased (P<0.05 or P<0.01), indicating that the composition of the present invention can prevent the occurrence of gastric ulcers by enhancing antioxidant capacity and reducing oxidative stress damage.

[0044] Figures 4-10 This is a bar chart showing the gastric PGE2 (pg / mL), gastric VEGF (pg / mL), gastric PP (ng / mL), gastric SOD (ng / mL), gastric LPO (nmol / g), gastric COX-1 (ng / g), and gastric COX-2 (ng / g) indices of Control, IND, CMP-L, CMP-M, CMP-H, MD-4, and KFXY in this invention. Figures 4-10 It was found that, compared with the IND model group, the levels of PGE2, COX-1, and SOD in the gastric tissue of each dose group of the Mongolian medicine composition of the present invention were significantly increased, while the levels of LPO and COX-2 were significantly decreased (P<0.05 or P<0.01), and this was in a certain dose-dependent manner; serum PGE2 showed no significant change. This indicates that the Mongolian medicine composition of the present invention can exert a protective effect on the gastric mucosa by locally upregulating gastric mucosal protective factors (PGE2 / COX-1), enhancing antioxidant capacity (SOD), and inhibiting lipid peroxidation (LPO) and inflammation-related COX-2 expression.

[0045] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A Mongolian medicine composition, characterized in that, It is prepared from the following raw materials: sodium chloride, gallic acid, piperine and 6-shogaol.

2. The Mongolian medicine composition according to claim 1, characterized in that, The Mongolian medicine composition, by mass, is prepared from the following raw materials: 6-9 parts sodium chloride, 12-17 parts gallic acid, 5-9 parts piperine, and 0.15-0.25 parts 6-shogaol.

3. The Mongolian medicine composition according to claim 1, characterized in that, The Mongolian medicine composition, by weight, is prepared from the following raw materials: 7.28 parts sodium chloride, 14.62 parts gallic acid, 7.03 parts piperine, and 0.20 parts 6-shogaol.

4. The Mongolian medicine composition according to any one of claims 1 to 3, characterized in that, The dosage form of the Mongolian medicine composition is at least one of powder, tablet, capsule and granule.

5. A method for preparing the Mongolian medicine composition according to any one of claims 1 to 4, characterized in that, When the dosage form of the Mongolian medicine composition is a powder, the preparation method of the Mongolian medicine composition includes the following steps: pulverizing, sieving and mixing sodium chloride, gallic acid, piperine and 6-shogaol in sequence to obtain the Mongolian medicine composition powder.

6. A method for preparing the Mongolian medicine composition according to any one of claims 1 to 4, characterized in that, When the dosage form of the Mongolian medicine composition is a tablet, the preparation method of the Mongolian medicine composition includes the following steps: mixing sodium chloride, gallic acid, piperine and 6-shogaol with excipients, and then granulating and compressing them sequentially to obtain the Mongolian medicine composition tablet.

7. The use of the Mongolian medicine composition according to any one of claims 1 to 4 in the preparation of a medicament for preventing gastric ulcers caused by nonsteroidal anti-inflammatory drugs.

8. The application according to claim 7, characterized in that, The nonsteroidal anti-inflammatory drug mentioned is indomethacin.

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