Application of Panax notoginseng polysaccharides in the preparation of drugs for the prevention or treatment of alcoholic gastric ulcers

Abstract

This application discloses the use of Panax notoginseng polysaccharide in the preparation of drugs for the prevention or treatment of alcoholic gastric ulcers. The research in this application shows that Panax notoginseng polysaccharide can reduce the area of ​​gastric ulcers, alleviate mucosal edema and congestion; the drug reduces the levels of GAS, IL-6, IL-10, and TNF-α and MPO activity in gastric tissue, and can be used in drugs and health products for the prevention or treatment of alcoholic gastric ulcers.

Description

Technical Field

[0001] This application pertains to the fields of gastric disease treatment and plant extracts. Specifically, this application provides the use of Panax notoginseng polysaccharide in the preparation of drugs for the prevention or treatment of alcoholic gastric ulcers. Background Technology

[0002] Alcoholic gastric ulcers are a common type of peptic ulcer caused by excessive alcohol consumption, resulting in damage to the gastric mucosa and ulcer formation. The main mechanism of alcoholic gastric ulcers is that alcohol directly damages the gastric mucosal epithelial cells, disrupting the mucosal barrier, increasing gastric acid secretion and the release of gastrointestinal inflammatory factors, leading to mucosal ischemia, hypoxia, necrosis, and bleeding. The main symptoms of alcoholic gastric ulcers are burning pain in the stomach, which worsens on an empty stomach or after drinking alcohol, and may be accompanied by nausea, vomiting, and melena (black stools). Diagnosis of alcoholic gastric ulcers mainly relies on gastroscopy, which reveals gastric mucosal erosion, bleeding, or superficial ulcers. Treatment primarily includes abstinence from alcohol, inhibition of gastric acid secretion, protection of the mucosa, promotion of healing, and prevention of complications.

[0003] Panax notoginseng, a herbaceous plant belonging to the Araliaceae family, is widely used in clinical practice. It possesses the effects of promoting blood circulation, removing blood stasis, reducing swelling, and relieving pain, effectively alleviating symptoms of blood stasis. Modern research has found that Panax notoginseng contains effective components such as saponins, volatile oils, flavonoids, and polysaccharides. The total polysaccharide content in Panax notoginseng is approximately 9.45%, exhibiting diverse biological activities. Studies have shown that Panax notoginseng polysaccharides play an important role in promoting skin health, delaying skin aging, and maintaining the balance of skin's immune-derived tolerance. These effects suggest a potential protective effect against gastric ulcers. Through systematic research on the protective effect and molecular mechanism of Panax notoginseng polysaccharides against alcoholic gastric ulcers in mice, it was found that Panax notoginseng polysaccharides have a protective effect against gastric ulcers, reducing congestion and lesions. The drugs and methods of this invention have advantages such as high safety, few side effects, and ease of preparation and use. Summary of the Invention

[0004] On the one hand, this application provides the use of Panax notoginseng polysaccharide in the preparation of drugs for the prevention or treatment of alcoholic gastric ulcers.

[0005] The Panax notoginseng polysaccharide of this application can be prepared using methods known in the art, including but not limited to water extraction and alcohol precipitation.

[0006] Preferably, the Panax notoginseng sample is added to 6-8 times its mass of pure water and boiled for 0.5-3 hours; cooled, centrifuged, and the supernatant is collected; the precipitate is added again to 6-8 times its mass of pure water and boiled for 0.5-3 hours; cooled, centrifuged, and the supernatant is collected; the supernatants collected twice are mixed and concentrated to 1 / 4-1 / 2 volume; 0.7-1.3 times the volume of the supernatant is added to 95% ethanol for alcohol precipitation; after alcohol precipitation, the supernatant is rotary evaporated to recover the ethanol and collect the Panax notoginseng polysaccharides.

[0007] More preferably, after washing the Panax notoginseng sample, add it to 6-7 times its weight of pure water and boil for 1-2 hours; cool, centrifuge, and collect the supernatant; add the precipitate back to 6-7 times its weight of pure water and boil for 1-2 hours; cool, centrifuge, and collect the supernatant; mix the supernatants collected twice and concentrate to 1 / 3-1 / 2 volume; add 0.9-1.1 times the volume of the supernatant to 95% ethanol for alcohol precipitation; after alcohol precipitation, rotary evaporate the supernatant to recover the ethanol and collect the Panax notoginseng polysaccharides.

[0008] Specifically, accurately weigh 8g of Panax notoginseng sample and dissolve it in 50mL of pure water; vortex for 3min to wash away impurities, then centrifuge at 3000rpm / min for 10min; collect the residue, then add 50mL of pure water and boil for 1.5h; allow to stand and cool, centrifuge at the same speed, collect the supernatant, and repeat the above steps; mix the supernatants collected twice, concentrate to 35mL at 90℃; add 100mL of 95% ethanol for alcohol precipitation, allow to stand overnight at room temperature, and then treat the supernatant by rotary evaporation to recover the ethanol and collect the precipitate. Those skilled in the art can adjust the specific amounts of raw materials and reagents according to the proportions.

[0009] Furthermore, the drug is in the form of an injection or oral dosage form.

[0010] Furthermore, the drug is in the form of tablets or aqueous injections.

[0011] Furthermore, the drug contains pharmaceutically acceptable excipients.

[0012] Furthermore, the drug reduces the area of ​​gastric ulcers and alleviates mucosal edema and congestion.

[0013] Furthermore, the drug reduces the content of GAS and the activity of MPO in gastric tissue.

[0014] Furthermore, the drug reduces the levels of IL-6, IL-10, and TNF-α in gastric tissue.

[0015] Furthermore, the minimum dose unit of the drug contains 200-800 mg of Panax notoginseng polysaccharide.

[0016] Furthermore, Panax notoginseng polysaccharide is the only active ingredient in the drug.

[0017] Furthermore, the medication also contains other drugs for treating gastric ulcers, including but not limited to magnesium aluminum carbonate, colloidal bismuth pectin, and omeprazole.

[0018] On the other hand, this application provides the application of Panax notoginseng polysaccharide in the preparation of health products that have an auxiliary protective effect against gastric mucosal damage.

[0019] Furthermore, the health product in question is an oral health product.

[0020] The smallest unit of dosage for a pharmaceutical composition refers to a tablet, a capsule, a sachet of granules, or an injection, etc.

[0021] The pharmaceutical composition described in this invention can be any clinically acceptable dosage form, including various dosage forms for oral and parenteral administration. For oral administration, it can be tablets, capsules, soft capsules, oral solutions, syrups, granules, pellets, orally disintegrating tablets, sustained-release tablets, sustained-release capsules, controlled-release tablets, and controlled-release capsules; for parenteral administration, it can be an injection, lyophilized powder for injection, sterile powder for injection, or an infusion.

[0022] The pharmaceutically acceptable excipients may be selected from pharmaceutical excipients suitable for oral formulations, including but not limited to fillers, binders, lubricants, disintegrants, capsule shells, coating agents, surfactants, adsorbents, etc.

[0023] The pharmaceutically acceptable excipients may be selected from pharmaceutical excipients suitable for injection, including but not limited to solvents, antioxidants, cosolvents, adsorbents, osmotic pressure regulators, and pH regulators.

[0024] The dosage forms of the present invention can be produced using any method conventionally used in pharmaceutical formulation technology, without particular limitation. For example, the tablets of the present invention can be granulated, dried, and sieved using suitable methods known in the art, with the main active ingredient and excipients, binders, etc., added to the resulting mixture, followed by mixing and forming tablets. Granulation can be carried out by any suitable method known in the art, such as wet granulation, dry granulation, or heat granulation. Suitable non-limiting examples include granulation using a high-speed stirring granulator, a flow granulator dryer, an extrusion granulator, or a roller press. Furthermore, methods such as drying and sieving can be carried out as needed for granulation. The mixture of the main active ingredient, excipients, binders, lubricants, etc., can also be directly formed into tablets. If film coating is required, any film coating device known in the art can be used, and suitable examples of film coating matrices include sugar coating bases, hydrophilic film coating bases, enteric film coating bases, and sustained-release film coating bases. Attached Figure Description

[0025] Figure 1 Effects of Panax notoginseng polysaccharide on the morphology of gastric tissue in mice with gastric ulcers (scale bar = 1 mm).

[0026] Figure 2Effect of Panax notoginseng polysaccharides on ulcer area in an alcohol-induced mouse gastric ulcer model. Experimental data are expressed as mean ± standard error (mean ± SEM) (n = 8). ### indicates P < 0.001 compared with the sham group. ** indicates P < 0.01 compared with the model group; *** indicates P < 0.001 compared with the model group.

[0027] Figure 3 Effects of Panax notoginseng polysaccharide on the pathological morphology of an alcohol-induced mouse gastric ulcer model (scale bar = 200 μm).

[0028] Figure 4 Effects of Panax notoginseng polysaccharides on GAS content and MPO activity in an alcohol-induced mouse gastric ulcer model. Experimental data are expressed as mean ± standard error (mean ± SEM) (n = 6). ### indicates P < 0.001 compared with the sham group. ** indicates P < 0.01 compared with the model group; *** indicates P < 0.001 compared with the model group.

[0029] Figure 5 Effects of Panax notoginseng polysaccharides on the levels of IL-6, IL-10, and TNF-α in an alcohol-induced mouse gastric ulcer model. Experimental data are expressed as mean ± standard error (mean ± SEM) (n = 6). ### indicates P < 0.001 compared to the sham group. * indicates P < 0.05 compared to the model group; ** indicates P < 0.01 compared to the model group; *** indicates P < 0.001 compared to the model group. Detailed Implementation

[0030] Example 1: Preparation of Panax notoginseng polysaccharides

[0031] Accurately weigh 8g of Panax notoginseng sample and dissolve it in 50mL of pure water. Vortex for 3min to wash away impurities, then centrifuge at 3000rpm / min for 10min. Collect the residue, then add 50mL of pure water and boil to extract for 1.5h. Allow to cool and stand, then centrifuge at the same speed, collect the supernatant, and repeat the above steps. Mix the supernatants collected in the two steps and concentrate to 35mL at 90℃. Add 100mL of 95% ethanol to the supernatant for alcohol precipitation, let stand overnight at room temperature, and then treat the supernatant by rotary evaporation to recover the ethanol and collect the precipitate.

[0032] Example 2: Establishment of a mouse model of alcoholic gastric ulcer

[0033] Balb / c mice aged 6-8 weeks (Beijing Vital River Pharmaceutical Co., Ltd., Beijing, China) were used. Animals were acclimatized for one week with free access to food and water. Seventy-two mice were randomly divided into six groups: a blank control group, a model group, a low-dose Panax notoginseng polysaccharide group (100 mg / kg), a medium-dose Panax notoginseng polysaccharide group (200 mg / kg), a high-dose Panax notoginseng polysaccharide group (400 mg / kg), and a positive control group (ranitidine 50 mg / kg). All treatments were administered via gavage once daily for 10 days at a dose of 0.1 mL / 10 g. The blank control group and the model group received an equal volume of physiological saline. One hour after gavage on the tenth day, mice were administered 0.1 mL / 10 g of anhydrous ethanol to induce the model.

[0034] Example 3: The protective effect of Panax notoginseng polysaccharides against alcoholic gastric ulcers in mice.

[0035] Effects of Panax notoginseng polysaccharide on gastric tissue morphology in mice with gastric ulcers

[0036] After dissecting the mouse cadaver, the stomach was removed, cut open along the greater curvature, and images were captured using a digital camera and stored in a computer. ImageJ was used for image processing and analysis to calculate the ulcer area. Figure 1 As shown, in the blank control group, the gastric mucosa of mice exhibited orderly arrangement of folds, a light pink color, and no ulceration, congestion, erosion, or edema in the entire gastric tissue. In the model group, lesions were concentrated in the gastric mucosa and its edges, manifesting as ulcerative erosion, fibrosis, mucosal edema, congestion, and cryptitis, accompanied by significant hemorrhage. In the high-dose group of Panax notoginseng polysaccharide, the area of ​​gastric ulcers was significantly reduced, and mucosal edema and congestion were significantly alleviated, although hemorrhage still occurred. This indicates that the recovery of gastric tissue morphology in the high-dose group of Panax notoginseng polysaccharide was significantly better than that in the model group, and the high-dose group was more effective than the low-dose group. These results suggest that Panax notoginseng polysaccharide has a certain protective effect against anhydrous ethanol-induced gastric ulcers in mice.

[0037] Effect of Panax notoginseng polysaccharide on ulcer area in an alcohol-induced mouse model of gastric ulcer

[0038] The gastric ulcer area of ​​each group of mice is statistically analyzed as follows: Figure 2 As shown, compared with the model control group, the ulcer area of ​​different doses of Panax notoginseng polysaccharide decreased significantly, and the decrease was most pronounced in the 200 mg / kg and 400 mg / kg groups (P < 0.001), indicating that its effect was better than that of the positive control drug. This suggests that Panax notoginseng polysaccharide has a certain protective effect against alcoholic ulcers in mice.

[0039] Effects of Panax notoginseng polysaccharide on pathological morphology of alcohol-induced gastric ulcer model in mice

[0040] Anesthesia was administered after the drug administration, and gastric tissue was harvested and fixed in 4% formaldehyde. Morphological examination was performed under a light microscope using hematoxylin-eosin staining. Figure 3As shown, in the blank control group: the tissue structure was basically normal, the glands were neatly arranged, the gastric tissue structure was intact, and there were no edema, congestion, or cell shedding in the gastric mucosa epithelium. In the model group: the normal glandular structure of the mucosa layer disappeared, the glandular structure was disordered, gastric mucosal congestion was more severe, accompanied by a large number of mucosal epithelial cell erosions and shedding, and inflammatory cell infiltration. In the 100mg / kg group of Panax notoginseng polysaccharide: gastric mucosal epithelial cell shedding was still present, but gastric mucosal congestion and glandular structure disorder were reduced, and inflammatory cell infiltration decreased. In the 200mg / kg group of Panax notoginseng polysaccharide: a small amount of gastric mucosal epithelial cell shedding was present, but gastric mucosal congestion and glandular structure disorder were reduced, and inflammatory cell infiltration decreased. In the 400mg / kg group of Panax notoginseng polysaccharide: only a small amount of gastric mucosal epithelial cell shedding was present, and gastric mucosal congestion and glandular structure disorder were milder, with less inflammatory cell infiltration.

[0041] Effects of Panax notoginseng polysaccharide on GAS content and MPO activity in mouse gastric tissue

[0042] After dissecting the mice, the stomach tissue was removed, and blood and residual contents were washed away. Stomach tissue from each group of mice was collected, tissue lysis buffer was added, and the tissue was minced on ice using tissue scissors. The tissue was then homogenized twice in a tissue homogenizer, 5 minutes each time. The homogenate was then centrifuged at 12,000 rpm for 10 minutes to remove tissue fragments. The supernatant was then transferred to a centrifuge tube and centrifuged at 14,000 rpm for 15 minutes. The supernatant was collected, and the precipitate was discarded. Testing was performed using a commercially available test kit purchased from Linko Biotechnology (Beijing, China) according to the manufacturer's instructions.

[0043] like Figure 4 As shown, compared with the model group, the MPO content in both the high-dose group and the ranitidine group of Panax notoginseng polysaccharide was significantly reduced (P < 0.01); compared with the model group, the GAS content in both the high-dose group and the ranitidine group of Panax notoginseng polysaccharide was significantly reduced (P < 0.001, P < 0.001).

[0044] Effects of Panax notoginseng polysaccharide on the levels of IL-6, IL-10 and TNF-α in mouse gastric tissue

[0045] like Figure 5 As shown, compared with the model group, the IL-6 content in different dose groups of Panax notoginseng polysaccharide and the ranitidine group was significantly reduced (P < 0.05); compared with the model group, the IL-10 content in the high-dose group of Panax notoginseng polysaccharide and the ranitidine group was significantly reduced (P < 0.01); compared with the model group, the TNF-α content in the high-dose group of Panax notoginseng polysaccharide and the ranitidine group was significantly reduced (P < 0.01). The results suggest that Panax notoginseng polysaccharide can reduce the level of inflammatory factors in tissues and exert a protective effect on the gastric mucosa.

Claims

1. Application of Panax notoginseng polysaccharide in the preparation of drugs for the prevention or treatment of alcoholic gastric ulcers.

2. The application according to claim 1, wherein the drug is an injectable or oral dosage form.

3. The application according to claim 2, wherein the drug is a tablet, capsule, oral liquid, syrup, granule or drop pill.

4. The application according to claim 2, wherein the drug is a liquid injection or a powder injection.

5. The application according to claim 1, wherein the drug comprises pharmaceutically acceptable excipients.

6. The application according to claim 5, wherein the pharmaceutically acceptable excipient is selected from one or more of fillers, binders, lubricants, disintegrants, coating agents, capsule shells, solvents, antioxidants, cosolvents, adsorbents, osmotic pressure regulators, and pH regulators.

7. The application according to claim 1, wherein the drug reduces the area of ​​gastric ulcers and alleviates mucosal edema and congestion.

8. The application according to claim 1, wherein the drug reduces the GAS content and MPO activity in gastric tissue.

9. The application according to claim 1, wherein the drug reduces the levels of IL-6, IL-10 and TNF-α in gastric tissue.

10. The application according to claim 1, wherein the minimum dose unit of the drug contains 200-800 mg of Panax notoginseng polysaccharide.

11. The application according to claim 1, wherein Panax notoginseng polysaccharide is the only active ingredient in the drug.

12. The application according to claim 1, wherein the medicament further comprises other medicaments for treating gastric ulcers.

13. The application according to claim 12, wherein the other drug for treating gastric ulcers is selected from one or more of aluminum magnesium carbonate, colloidal bismuth pectin, and omeprazole.

14. The application according to any one of claims 1-13, wherein the method for preparing the Panax notoginseng polysaccharide is as follows: adding the Panax notoginseng sample to 6-8 times its mass of pure water and boiling to extract for 0.5-3 hours; Cool, centrifuge, and collect the supernatant; add the precipitate back into pure water at 6-8 times the mass of the Panax notoginseng sample, and boil to extract for 0.5-3 hours; Cool, centrifuge, and collect the supernatant; mix the supernatants collected twice and concentrate to 1 / 4-1 / 2 volume; add 0.7-1.3 times the volume of the supernatant collected twice with 95% ethanol for alcohol precipitation; after alcohol precipitation, rotary evaporate the supernatant to recover the ethanol and collect the Panax notoginseng polysaccharide.

15. The application according to claim 14, wherein the preparation method of the Panax notoginseng polysaccharide is as follows: after washing the Panax notoginseng sample, add it to 6-7 times the mass of the Panax notoginseng sample in pure water, and boil to extract for 1-2 hours; Cool, centrifuge, and collect the supernatant; add the precipitate back into 6-7 times the mass of the Panax notoginseng sample in pure water, and boil to extract for 1-2 hours; Cool, centrifuge, and collect the supernatant; mix the supernatants collected twice and concentrate to 1 / 3-1 / 2 volume; add 0.9-1.1 times the volume of the supernatant collected twice to 95% ethanol for alcohol precipitation; after alcohol precipitation, rotary evaporate the supernatant to recover the ethanol and collect the Panax notoginseng polysaccharide.

16. The application according to claim 15, wherein the preparation method of the Panax notoginseng polysaccharide is as follows: accurately weigh 8g of Panax notoginseng sample and dissolve it in 50mL of pure water; vortex for 3min to wash away impurities, and centrifuge at 3000rpm / min for 10min; collect the residue, then add 50ml of pure water and boil to extract for 1.5h; let stand and cool, centrifuge at the same speed, collect the supernatant, and repeat the above steps; mix the supernatants collected twice, concentrate to 35mL at 90℃; add 100mL of 95% ethanol to perform alcohol precipitation treatment, let stand overnight at room temperature, treat the supernatant by rotary evaporation in the same way, recover the ethanol and collect the Panax notoginseng polysaccharide.

17. Application of Panax notoginseng polysaccharide in the preparation of health products that have an auxiliary protective effect against gastric mucosal damage, wherein the gastric mucosal damage is gastric mucosal damage caused by alcoholic gastric ulcer.

18. The application according to claim 17, wherein the health product is an oral health product.

19. The application according to claim 17 or 18, wherein the preparation method of the Panax notoginseng polysaccharide is: adding the Panax notoginseng sample to 6-8 times its mass of pure water and boiling to extract for 0.5-3 hours; Cool, centrifuge, and collect the supernatant; add the precipitate back into pure water at 6-8 times the mass of the Panax notoginseng sample, and boil to extract for 0.5-3 hours; Cool, centrifuge, and collect the supernatant; mix the supernatants collected twice and concentrate to 1 / 4-1 / 2 volume; add 0.7-1.3 times the volume of the supernatant collected twice with 95% ethanol for alcohol precipitation; after alcohol precipitation, rotary evaporate the supernatant to recover the ethanol and collect the Panax notoginseng polysaccharide.

20. The application according to claim 19, wherein the preparation method of the Panax notoginseng polysaccharide is as follows: after washing the Panax notoginseng sample, add it to 6-7 times the mass of the Panax notoginseng sample in pure water, and boil to extract for 1-2 hours; Cool, centrifuge, and collect the supernatant; add the precipitate back into 6-7 times the mass of the Panax notoginseng sample in pure water, and boil to extract for 1-2 hours; Cool, centrifuge, and collect the supernatant; mix the supernatants collected twice and concentrate to 1 / 3-1 / 2 volume; add 0.9-1.1 times the volume of the supernatant collected twice with 95% ethanol for alcohol precipitation; after alcohol precipitation, rotary evaporate the supernatant to recover the ethanol and collect the Panax notoginseng polysaccharide.

21. The application according to claim 20, wherein the preparation method of the Panax notoginseng polysaccharide is as follows: accurately weigh 8g of Panax notoginseng sample and dissolve it in 50mL of pure water; vortex for 3min to wash away impurities, and centrifuge at 3000rpm / min for 10min; collect the residue, then add 50ml of pure water and boil to extract for 1.5h; let stand and cool, centrifuge at the same speed, collect the supernatant, and repeat the above steps; mix the supernatants collected twice, concentrate to 35mL at 90℃; add 100mL of 95% ethanol to it for alcohol precipitation, let stand overnight at room temperature, and treat the supernatant by rotary evaporation in the same way to recover ethanol and collect the Panax notoginseng polysaccharide.

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