Application of ziziphus jujuba in preparation of medicine for regulating intestinal permeability

Abstract

The invention discloses application of ziziphus jujuba in preparation of a medicine for regulating intestinal permeability, and belongs to the technical field of medicines. The application refers to the application of the ziziphus jujube, the extract of the ziziphus jujube or the pharmaceutical composition of the ziziphus jujube in preparation of a medicine for regulating intestinal permeability, a medicine for preventing and treating intestinal barrier function injury, a medicine for treating intestinal leakage and a medicine for preventing and treating related diseases of the intestinal leakage. In an immunity investigation process, the invention accidentally finds that the intestinal permeability of rats which are molded by cyclophosphamide and have low immunity is increased, and the intestinal barrier function is severely damaged. After intestinal permeability increase and inflammatory injury caused by low immunity of cyclophosphamide molding, the Chinese ixeris dates can efficiently remove intestinal inflammation, repair intestinal villus and crypt form, remarkably reduce DAO, ET, LPS and LN levels of rats with low immunity of cyclophosphamide molding, and realize rapid reduction of intestinal permeability, repair of intestinal leakage and treatment of intestinal barrier function injury. The influence of body immunosuppression on intestinal lesions is reversed.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicines, and relates to the preparation of a medicine for regulating intestinal permeability, in particular to the application of Alhagi camel thorn, an extract thereof or a pharmaceutical composition thereof in the preparation of a medicine for regulating intestinal permeability, the preparation of a medicine for preventing and treating damage to intestinal barrier function, the preparation of a medicine for treating intestinal leakage, and the preparation of a medicine for preventing and treating intestinal leakage-related diseases. BACKGROUND

[0002] Alhagi camel thorn, also known as porcupine date, is a rare and precious traditional Chinese medicinal material, and is derived from a secretion stone in the body of an Alhagi camel thorn. When an Alhagi camel thorn is injured or ill, it will search for medicinal herbs to treat the injury. After the medicinal herbs are digested and decomposed in the body of the Alhagi camel thorn, a secretion is formed to dissolve viruses in the body and rapidly recover. Some secretion still remaining in the body of the Alhagi camel thorn is converted into the Alhagi camel thorn.

[0003] The Alhagi camel thorn has the effect of improving immunity and is widely used in Southeast Asia. Many clinical tests have confirmed that the Alhagi camel thorn can play a good preventive and therapeutic role on cancer, liver disease, diabetes and various inflammations.

[0004] Leaky gut, also known as leaky gut syndrome, refers to dysfunction in the tight junctions of the intestinal epithelium, which triggers an enhanced inflammatory immune response and leads to various health problems. Leaky gut can be caused by many factors and can manifest in a variety of different clinical manifestations or diseases. Known diseases associated with leaky gut include inflammatory bowel disease (IBD), coeliac disease (also known as celiac disease), irritable bowel syndrome, acute pancreatitis, non-alcoholic fatty liver disease (NAFLD), alcoholic cirrhosis, type 1 and type 2 diabetes mellitus, obesity, chronic kidney disease, cardiovascular disease, multiple organ failure syndrome (shock, burns, and trauma), HIV / AIDS, asthma, eczema, psoriasis, autism, depression, anxiety, schizophrenia, bipolar disorder, and Alzheimer's disease. disease), Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), ankylosing spondylitis, fibromyalgia, chronic sleep fragmentation, insomnia, etc.

[0005] At present, there is no discovery of the use of porcupine date in the treatment of intestinal leakage. Summary of the Invention

[0006] The purpose of the present invention is to provide the use of porcupine date in preparing a drug for regulating intestinal permeability.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions: In a first aspect, the present invention provides the use of porcupine date, an extract thereof or a pharmaceutical composition thereof in the preparation of a drug for regulating intestinal permeability.

[0008] In a second aspect, the present invention provides the use of porcupine date, an extract thereof or a pharmaceutical composition thereof in the preparation of a drug for preventing and treating intestinal barrier function damage.

[0009] In some embodiments, the intestinal barrier function damage includes at least one of intestinal mechanical barrier damage, biological barrier damage, chemical barrier damage, immune barrier damage and microbial barrier damage.

[0010] In some embodiments, the intestinal barrier function damage includes at least one of intestinal mucosal ischemia damage, oxygen free radical damage, cytokine production damage, inflammatory damage, increased intestinal permeability, and imbalance of intestinal microecological balance.

[0011] In some embodiments, the intestinal barrier function damage is caused by at least one of low immunity, tumors and drugs.

[0012] In a third aspect, the present invention provides the use of porcupine date, an extract thereof or a pharmaceutical composition thereof in the preparation of a drug for treating intestinal leakage.

[0013] In a fourth aspect, the present invention provides the use of porcupine date, an extract thereof or a pharmaceutical composition thereof in the preparation of a drug for preventing and treating diseases related to intestinal leakage.

[0014] In some embodiments, the leaky gut-related diseases include intestinal diseases, acute pancreatitis, non-alcoholic steatohepatitis, alcoholic cirrhosis, type 1 diabetes, type 2 diabetes, obesity, chronic kidney disease, cardiovascular disease, multiple organ dysfunction, AIDS, asthma, eczema, psoriasis, autism, depression, anxiety, schizophrenia, bipolar disorder, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, ankylosing spondylitis, fibromyalgia, chronic sleep fragmentation or insomnia.

[0015] In some embodiments, the intestinal disease comprises at least one of inflammatory bowel disease, celiac disease, irritable bowel syndrome, infectious diarrhea, chronic diarrhea, irritable bowel, colon cancer, colon cancer, and esophageal cancer.

[0016] In some embodiments, the inflammatory bowel disease comprises at least one of Crohn's disease, ulcerative colitis, colitis, and proctitis.

[0017] The extraction methods of the porcupine date described in the present invention include percolation, water extraction, alcohol extraction, ultrasonic extraction and supercritical extraction.

[0018] The pharmaceutical composition of the present invention comprises the aforementioned porcupine date or its extract and pharmaceutically acceptable excipients.

[0019] The oral forms of the porcupine date, its extract or its pharmaceutical composition in the present invention include tablets, capsules, granules, pills, powders, syrups, oral solutions, oral suspensions, oral emulsions or mixtures.

[0020] The beneficial effects of the present invention are: During the study of immunity, the present invention unexpectedly discovered that the intestinal permeability of cyclophosphamide-induced immunocompromised rats increased and their intestinal barrier function was severely impaired. After the increased intestinal permeability and inflammatory damage caused by cyclophosphamide-induced immunocompromised rats, porcupine date can effectively eliminate intestinal inflammation, repair the morphology of intestinal villi and crypts, and significantly reduce the levels of DAO, ET, LPS, and LN in cyclophosphamide-induced immunocompromised rats, thereby rapidly reducing intestinal permeability, repairing intestinal leakage, treating intestinal barrier function damage, and reversing the effects of low immunity on intestinal lesions. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 Figure 3. Effects of porcupine date on the levels of immunoglobulins in the serum of rats induced by cyclophosphamide modeling. A represents the IgG level in rat serum, and B represents the IgA level in rat serum. Compared with the Mod group, ns indicates no significant difference, ****P<0.0001.

[0022] Figure 2 Figure 3. Effects of porcupine date on serum cytokine levels in cyclophosphamide-induced rat model. A is the IL-6 level in rat serum, and B is the TNF-α level in rat serum. Compared with the Con group, **P < 0.01, and compared with the Mod group, ##P < 0.01.

[0023] Figure 3 Figure 3 Effects of porcupine date on serum DAO and ET levels in cyclophosphamide-induced rat modeling rats. A is the DAO content in rat serum, and B is the ET content in rat serum. Compared with the Con group, *P < 0.05, ***P < 0.001; compared with the Mod group, #P < 0.05, ##P < 0.01.

[0024] Figure 4 Figure 3 Effects of porcupine date on the levels of LPS and LN in the serum of rats induced by cyclophosphamide modeling. A is the LPS level in rat serum, and B is the LN level in rat serum. Compared with the Con group, **P < 0.01; compared with the Mod group, #P < 0.05, ##P < 0.01.

[0025] Figure 5 HE staining of colon sections of rats induced by cyclophosphamide model.

[0026] Figure 6 Statistical graphs of the effect of porcupine date on colon sections of cyclophosphamide-induced rat models, A is the statistical graph of colon villus length, and B is the statistical graph of crypt depth; compared with the Con group, **P < 0.01, compared with the Mod group, ##P < 0.01. DETAILED DESCRIPTION

[0027] The following describes the embodiments of the present invention through specific examples. Those skilled in the art will readily understand the other advantages and benefits of the present invention from the disclosure herein. The present invention may also be implemented or applied through various other specific embodiments, and the details in this specification may be modified or altered based on different viewpoints and applications without departing from the spirit of the present invention.

[0028] Before further describing the specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terms used in the examples of the present invention are for describing specific embodiments rather than for limiting the scope of protection of the present invention.

[0029] When numerical ranges are given in the examples, it should be understood that, unless otherwise specified herein, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present invention belongs.

[0030] The "pharmaceutical composition" described in the present invention comprises porcupine date or an extract thereof and a pharmaceutically acceptable excipient. In a specific embodiment, the porcupine date or an extract thereof described in the present invention is provided in the pharmaceutical composition in an effective amount (e.g., a therapeutically effective amount).

[0031] As used herein, "pharmaceutically acceptable" ingredients are substances suitable for use in humans and / or animals without undue adverse side effects (such as toxicity, irritation, and allergic reactions), that is, substances with a reasonable benefit / risk ratio. "Pharmaceutically acceptable excipients" include inert diluents, dispersants, granulating agents, surfactants, emulsifiers, disintegrants, binders, preservatives, buffers, lubricants, and / or oils. Excipients (such as cocoa butter and suppository waxes), colorants, coating agents, sweeteners, and flavoring agents may also be present in the pharmaceutical composition.

[0032] The "pharmaceutical composition" and "medicament" described in the present invention can be prepared by any method known in pharmacy. Generally speaking, these preparation methods include associating the porcupine date or its extract (i.e., the sole active ingredient) with a carrier or excipient and / or one or more other auxiliary ingredients, and then, if necessary and / or desired, shaping and / or packaging the product into a desired single-dose or multi-dose unit.

[0033] The pharmaceutical compositions and medicaments of the present invention can be prepared according to known methods, such as those described in the general rules for preparation of the Chinese Pharmacopoeia (2020 edition), the Japanese Pharmacopoeia (16th edition), the United States Pharmacopoeia (USP), and the European Pharmacopoeia (EP), 9th edition. Depending on the dosage form, the pharmaceutical compositions and medicaments of the present invention can be appropriately administered to patients.

[0034] The sole active ingredient, pharmaceutically acceptable excipient, in the "pharmaceutical composition" described herein will vary depending on the identity, size, and / or condition of the subject being treated and further depending on the route of administration of the composition. The pharmaceutical composition may contain between 0.1% and 100% (w / w) of the first active ingredient.

[0035] As used herein, "treating," unless otherwise indicated, means reversing, alleviating, inhibiting the progression of, or preventing the condition or disorder to which the term applies, or one or more symptoms of such condition or disorder. The term "treating," as used herein, refers to the act of treating, as "treating" is defined immediately above.

[0036] The present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all common commercial products in the field of the present technology. It is worth noting that the porcupine date used in the examples of the present invention was purchased from Miracle Medicine King Co., Ltd.

[0037] Example 1 Porcupine Date The preparation method of porcupine date is as follows: crush the porcupine date and pass it through an 80-mesh sieve.

[0038] Example 2 Efficacy Test 1. Experimental Animals 60 male SD rats, weighing 100-130 g.

[0039] 2. Experimental methods Sixty experimental animals were housed in an SPF-grade barrier animal room with a constant temperature (22±2°C), stable humidity (50±10%), and a 12-hour light / dark cycle. After three days of acclimatization, the SD rats were divided into six groups (n=10) based on the absence of significant differences in body weight between groups: a blank control group (Con group), a model group (Mod group), a positive drug spleen aminopeptide oral lyophilized powder group (POS or Pos), a low-dose porcupine date group (JZZ-L group), a medium-dose porcupine date group (JZZ-M group), and a high-dose porcupine date group (JZZ-H group).

[0040] The JZZ-L, JZZ-M, and JZZ-H groups were given porcupine date 2.1 mg / 100 g / d, 4.2 mg / 100 g / d, and 8.4 mg / 100 g / d by gavage, respectively. The POS group was given spleen aminopeptide oral lyophilized powder solution 0.042 mg / 100 g / d by gavage. The Con and Mod groups were given the same volume of water by gavage for 15 consecutive days.

[0041] On days 11, 12, and 13, except for the Con group, rats in other groups were intraperitoneally injected with 3.5 mg / 100 g / d of cyclophosphamide (CTX) to establish immunocompromised rat models.

[0042] Twenty-four hours after the end of dosing on day 15, rats were weighed. All rats were anesthetized with isoflurane. Blood was collected from the abdominal aorta, incubated at 4°C for 1 hour, and centrifuged at 3500 rpm for 15 minutes. The supernatant was collected and stored at -80°C for subsequent use. After blood collection, the spleen, thymus, heart, intestine, and their contents were rapidly removed.

[0043] 3. Detection indicators 3.1 General indicators During the experiment, the rats were weighed once a day, the food intake was calculated by weighing the weight of the food every day, and the changes in general indicators were observed. 3.2 Detection of biological related indicators in serum Under isoflurane anesthesia, blood was collected from the abdominal aorta, stored in EDTA-anticoagulant tubes, incubated at 4°C for 1 hour, and centrifuged at 3500 rpm for 15 minutes. The supernatant was collected and serum levels of immunoglobulins (IgA, IgG), diamine oxidase (DAO), endothelin (ET), D-lactic acid, and cytokines were determined according to the ELISA kit instructions from Shanghai ELISA Biotechnology Co., Ltd. 3.3 Histomorphological observation of jejunum and colon After the jejunum and colon tissues were peeled off, they were quickly rinsed several times with PBS buffer and placed in a test tube containing 4wt% paraformaldehyde solution for fixation at room temperature for 24 hours. The samples were then paraffin-embedded, sectioned, and stained with hematoxylin-eosin (HE). The samples were photographed and the pathological changes of the tissues were observed. The remaining jejunum and colon tissues were quickly frozen in liquid nitrogen and stored in a -80°C refrigerator. 3.4 Statistical methods The experimental data were processed using Graphpad, and the measurement data were expressed as mean ± standard deviation. The independent sample t test was used for comparison between two groups, and ANOVA analysis of variance was used for comparison between multiple groups. p < 0.05 was considered statistically significant.

[0044] 4. Experimental results 4.1 Effect of Porcupine Dates on Body Weight in Cyclophosphamide-Induced Rats The results are shown in Table 1.

[0045] Table 1 Effects of porcupine date on body weight in cyclophosphamide-induced rats (n=10)

[0046] The results showed that on day 15 of the experiment, the weight of rats in the Mod group showed a downward trend compared to the Con group. After the drug intervention, the weight of rats in each group increased to varying degrees compared to the Mod group, and the effect of porcupine date on improving the weight of immunocompromised rats was comparable to that of positive drugs.

[0047] 4.2 Effects of Porcupine Dates on Serum-Related Indicators in Cyclophosphamide-Induced Rats (1) Effect of Porcupine Dates on the Level of Immunoglobulin in the Serum of Rats Induced by Cyclophosphamide The results are as follows Figure 1 shown.

[0048] The results showed that compared with the Mod group, the IgG and IgA levels in the serum of rats in the Con group were significantly different (P < 0.0001), indicating that cyclophosphamide modeling led to a significant decrease in the IgG and IgA levels in the serum of rats and a decline in the body's immune function.

[0049] After drug intervention, compared with the Mod group, the IgG content in the serum of rats in each group was significantly increased (P < 0.0001), and the IgA content in the serum of rats in the POS group, JZZ-M group and JZZ-H group was significantly increased (P < 0.0001), indicating that porcupine date can increase the levels of IgA and IgG in the serum of cyclophosphamide model rats and improve the body's immune function.

[0050] (2) Effect of Porcupine Dates on Serum Cytokine Content in Cytoxan-Induced Rats The results are as follows Figure 2 shown.

[0051] The results showed that compared with the Con group, the levels of IL-6 and TNF-α in the serum of rats in the Mod group were significantly decreased (P < 0.01). After the drug intervention, the levels of IL-6 and TNF-α in the serum of rats in all groups were significantly increased (P < 0.01). This suggests that porcupine date can improve serum cytokine levels and enhance the body's immune capacity.

[0052] (3) Effect of porcupine date on the levels of DAO and ET in the serum of cyclophosphamide-induced rats The results are as follows Figure 3 shown.

[0053] like Figure 3 As shown in Figure A, compared with the Con group, the serum DAO content of rats in the Mod group was significantly increased (P < 0.001), indicating that cyclophosphamide-induced damage to the intestinal epithelial cells, compromised intestinal integrity, and increased permeability in immunocompromised rats. Following intervention, serum DAO levels in rats in all treatment groups were significantly decreased (P < 0.01 or P < 0.05). This suggests that porcupine date can effectively reduce damage to intestinal epithelial cells and maintain intestinal integrity, thereby positively improving intestinal permeability and leaky gut symptoms.

[0054] like Figure 3 As shown in Figure B, compared with the Con group, the serum ET content of rats in the Mod group was significantly increased (P < 0.05), indicating that cyclophosphamide-induced intestinal microcirculatory impairment in immunocompromised rats was caused by increased intestinal permeability. After the intervention, serum ET levels in rats in all treatment groups were significantly decreased (P < 0.01 or P < 0.05). This suggests that porcupine date can regulate the release of vasoactive substances, improve intestinal microcirculation, and alleviate intestinal ischemia and hypoxia caused by increased intestinal permeability, thus having a positive effect on improving intestinal permeability and leaky gut symptoms.

[0055] (4) Effects of porcupine date on serum LPS and LN levels in cyclophosphamide-induced rats The results are as follows Figure 4 shown.

[0056] When intestinal permeability increases, the intestinal mucosal barrier function is impaired, allowing lipopolysaccharide (LPS) to enter the bloodstream and stimulate an immune response. Measuring LPS and its antibody levels in the blood can indirectly reflect intestinal permeability and bacterial translocation. Laminin (LN) is a protein that regulates intestinal tight junctions and plays an important role in maintaining the integrity of the intestinal mucosal structure and processes such as cell adhesion and migration. Its level is closely related to intestinal permeability. When intestinal permeability increases, LN levels in the blood typically increase. Studies have shown that the release of LN can lead to the opening of intestinal tight junctions, increasing intestinal permeability, and thus playing an important role in the pathogenesis of intestinal-related diseases such as inflammatory bowel disease, celiac disease, and metabolic syndrome.

[0057] like Figure 4 As shown in Figure A, compared with the Con group, the serum LPS content of immunocompromised rats in the Mod group was significantly increased (P < 0.01). After drug intervention, compared with the Mod group, the serum LPS content of rats in each drug group was significantly decreased (P < 0.01 or P < 0.05), indicating that porcupine date can repair damaged intestinal barrier, improve intestinal permeability, and prevent LPS from entering the blood from the intestine.

[0058] like Figure 4As shown in Figure B, compared with the Con group, the serum LN content of immunocompromised rats in the Mod group, which was induced by cyclophosphamide, was significantly increased (P < 0.01). After drug intervention, the serum LN content of rats in each drug group was significantly decreased compared with the Mod group (P < 0.01 or P < 0.05), indicating that porcupine date can promote the repair of intestinal mucosal basement membrane structure and maintain the integrity of intestinal mucosal structure, thereby having a positive effect on improving intestinal permeability and intestinal leakage symptoms.

[0059] (5) Effect of porcupine date on colon tissue morphology in cyclophosphamide-induced rats The results are as follows Figure 5 shown.

[0060] like Figure 5 As shown in the results, the colonic tissue structure of rats in the Con group was basically normal, with regular arrangement of mucosal epithelial cells, no thickening or collagen fiber deposition in the submucosal layer, clear crypt morphology, no inflammatory cell infiltration, and no obvious tissue damage. The colonic tissue structure of the Mod group was severely damaged, with atrophy of the small intestinal villi and shedding or damage of the mucosal epithelial cells; thickening of the submucosal layer and increased collagen fiber deposition were observed; the crypts were atrophied or absent, and inflammatory cells accumulated and infiltrated severely in the crypts. After drug intervention, the colonic tissue structure of rats in all groups was basically restored, as shown by increased height of the small intestinal villi, no shedding of mucosal epithelial cells, no thickening or collagen fiber deposition in the submucosal layer, partial repair of crypt morphology, reduced aggregation of inflammatory cells in the crypts, and reduced infiltration. The overall recovery of the porcupine date-treated group was better than that of the Pos group, as shown by less inflammatory cell infiltration.

[0061] Villi are the primary structures for intestinal absorption, and their height reflects the maturity and absorptive capacity of epithelial cells. Increased villus length indicates active intestinal epithelial cell proliferation and an expanded absorptive surface area; decreased villus length may lead to nutrient absorption impairment. Crypts are the areas where intestinal glands are located, and crypt depth reflects the rate of epithelial cell renewal. Increased crypt depth indicates accelerated cell proliferation, but excessive proliferation may lead to the migration of immature cells into the villi, disrupting barrier function.

[0062] Image J was used to measure the villus length (VH) and crypt depth (CD) of colon tissue. Figure 6 shown.

[0063] The results showed that compared with the Con group, the colon villus length of the cyclophosphamide-induced immunocompromised rats in the Mod group was significantly reduced (P < 0.01), and the crypt depth was significantly increased (P < 0.01). After drug intervention, the colon villus length of the rats in each drug group was significantly increased (P < 0.01), and the crypt depth was significantly shallower (P < 0.01) compared with the Mod group, indicating that porcupine date can promote the proliferation and repair of intestinal mucosal cells, effectively reduce intestinal permeability, repair intestinal leakage, enhance intestinal wall protection, and reverse the effects of low immunity on intestinal lesions.

[0064] The above further describes the present invention in conjunction with specific embodiments. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the technical solutions of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, and such modifications and replacements shall fall within the scope of protection of the present invention.

Claims

1. Use of porcupine date, its extract or its pharmaceutical composition in the preparation of drugs for regulating intestinal permeability.

2. Use of porcupine date, its extract or its pharmaceutical composition in the preparation of drugs for preventing and treating intestinal barrier function damage.

3. The use according to claim 2, characterized in that The intestinal barrier function damage includes at least one of intestinal mucosal ischemia damage, oxygen free radical damage, cytokine production damage, inflammatory damage, increased intestinal permeability, and imbalance of intestinal microecological balance.

4. The use according to claim 2, characterized in that The intestinal barrier function damage is caused by at least one of low immunity, tumors and drugs.

5. Use of porcupine date, its extract or its pharmaceutical composition in the preparation of drugs for treating intestinal leakage.

6. Use of porcupine date, its extract or its pharmaceutical composition in the preparation of drugs for preventing and treating intestinal leakage-related diseases.

7. The use according to claim 6, characterized in that The diseases related to leaky gut include intestinal diseases, acute pancreatitis, non-alcoholic steatohepatitis, alcoholic cirrhosis, type 1 diabetes, type 2 diabetes, obesity, chronic kidney disease, cardiovascular disease, multiple organ dysfunction, AIDS, asthma, eczema, psoriasis, autism, depression, anxiety, schizophrenia, bipolar disorder, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, ankylosing spondylitis, fibromyalgia, chronic sleep fragmentation or insomnia.

8. The use according to claim 7, characterized in that The intestinal disease includes at least one of inflammatory bowel disease, celiac disease, irritable bowel syndrome, infectious diarrhea, chronic diarrhea, irritable bowel, colon cancer, colon cancer and esophageal cancer; the inflammatory bowel disease includes at least one of Crohn's disease, ulcerative colitis, colitis and proctitis.

9. The use according to any one of claims 1 to 8, characterized in that The extraction method of the porcupine date includes at least one of percolation, water extraction, alcohol extraction, ultrasonic extraction and supercritical extraction.

10. The use according to any one of claims 1 to 8, characterized in that The pharmaceutical composition comprises the porcupine date or its extract and pharmaceutically acceptable excipients.

Images