Application of organic lycium barbarum polysaccharide in prevention and treatment of colorectal adenoma type polyps
By preparing and purifying organic wolfberry polysaccharides, the problem of the lack of safe and sustainable prevention and treatment strategies for colorectal adenomatous polyps in existing technologies has been solved, and the effect of significantly reducing the incidence of polyps has been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- LANZHOU UNIV SECOND HOSPITAL
- Filing Date
- 2026-06-04
- Publication Date
- 2026-07-10
AI Technical Summary
Current technologies lack suitable long-term oral medication or nutritional intervention strategies that target mucosal homeostasis and offer better safety and sustainability to reduce the risk of occurrence or recurrence of colorectal adenomatous polyps.
Organic wolfberry polysaccharides were extracted and purified. Animal experiments showed that they could significantly reduce the volume of colorectal adenomatous polyps. The preparation method included crushing organic wolfberry raw materials, water extraction, deproteinization, alcohol precipitation and dialysis purification, to obtain organic wolfberry polysaccharides with a total sugar content of 58.60-58.76%.
Organic wolfberry polysaccharides significantly reduce the incidence and progression risk of colorectal adenomatous polyps, with better effects than ordinary wolfberry polysaccharides.
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Figure CN122351284A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biology, specifically relating to the application of a type of Lycium barbarum polysaccharide in the prevention and treatment of colorectal adenomatous polyps. Background Technology
[0002] Colorectal adenomatous polyps are a common type of proliferative lesion of the colorectal mucosa. Pathologically, they are mainly characterized by abnormal expansion of glandular structures, which may be accompanied by varying degrees of epithelial cell abnormalities. Because polyps vary significantly in location, morphology, atypia, and number, clinical assessment typically employs a multifactorial approach, categorizing individuals into different follow-up and management levels. Generally, lesions with larger volume, more complex glandular structures, or higher degrees of atypia are often classified as higher-risk and require more intensive follow-up and management strategies.
[0003] Similar to many mucosal lesions detectable endoscopically, a prominent characteristic of adenomatous polyps is that detection often relies on screening opportunities, and their formation and recurrence are not necessarily accompanied by clear symptoms. Even after endoscopic resection, a certain percentage of recurrences or metachronous new lesions may still occur. For populations requiring long-term management, if there is a lack of more easily adhered, lower-risk, and long-term oral intervention options, the overall prevention strategy often reverts to a model that solely relies on endoscopic follow-up, highlighting practical burdens and adherence issues. Furthermore, the formation of adenomatous polyps is not determined solely by a single event of local hyperplasia. Increasing evidence suggests that inflammatory mediator networks can affect the balance of epithelial cell proliferation and differentiation, increased oxidative stress and DNA damage load can increase the probability of abnormal clonal expansion, and alterations in barrier function and local immune tone can, in turn, amplify unfavorable conditions in the mucosal microenvironment. This multi-faceted coupling means that simply removing the lesion endoscopically does not necessarily equate to reducing the risk of subsequent recurrence from the source.
[0004] Current pharmacological and nutritional intervention strategies for reducing the risk of adenoma occurrence or recurrence face long-term practical limitations: while some anti-inflammatory drugs have shown reduced adenoma-related outcomes in certain studies, their adverse reaction profiles and specific systemic risks make routine use in the general population unacceptable as long-term preventative measures. In other words, what is truly lacking in clinical practice is a candidate substance that is more suitable for long-term oral administration, targets mucosal homeostasis, and has advantages in safety and sustainability, to help reduce the occurrence or recurrence tendency of adenomatous polyps.
[0005] Lycium barbarum polysaccharides (LBP) are one of the important natural active ingredients of Lycium barbarum. However, currently available information still lacks a complete system of applications for the clear and systematic use of Lycium barbarum polysaccharides from organic Lycium barbarum in the prevention of colorectal adenomatous polyps. Summary of the Invention
[0006] To address the aforementioned technical problems, this invention extracts organic wolfberry polysaccharides. Animal experiments have shown that, compared to ordinary wolfberry polysaccharides, organic wolfberry polysaccharides can serve as a natural agent for the prevention and treatment of colorectal adenomatous polyps, significantly reducing the lesion volume of colorectal adenomatous polyps. Specifically, this includes the following: In a first aspect, the present invention provides the application of Lycium barbarum polysaccharide in the preparation of drugs for the prevention and treatment of colorectal adenomatous polyps.
[0007] Preferably, the wolfberry polysaccharide is organic wolfberry polysaccharide; the organic wolfberry conforms to the GB / T 19630 standard, and the organic product certification certificate number is 6540P2200007.
[0008] Preferably, the total sugar content of the organic wolfberry polysaccharide is 50-65%.
[0009] Preferably, the total sugar content of the organic wolfberry polysaccharide is 58.60-58.76%.
[0010] Preferably, the molar ratio of glucose, mannose, glucosamine, rhamnose, galactose, xylose, arabinose and galacturonic acid in the organic wolfberry polysaccharide is 1:0.03-0.05:0.004-0.05:0.009-0.02:0.01-0.03:0.005-0.01:0.04-0.1:0.03-0.11.
[0011] Preferably, the molar ratio of glucose, mannose, glucosamine, rhamnose, galactose, xylose, arabinose and galacturonic acid in the organic wolfberry polysaccharide is 1:0.0323:0.0043:0.0096:0.0126:0.0058:0.0437:0.0328.
[0012] Preferably, the preparation method of the organic wolfberry polysaccharide includes the following steps: (1) Organic wolfberry raw materials are pulverized and degreased and impurities are removed; (2) Water extraction: Add purified water at a solid-liquid ratio of 1:30 (g:mL) for extraction, and concentrate the extract; (3) Deproteinization: Deproteinization was performed using the Sevag method; (4) Alcohol precipitation: Add anhydrous ethanol to the concentrated solution after deproteinization for alcohol precipitation, and collect the precipitate; (5) Resolution and dialysis purification: Dissolve the precipitate in purified water and perform dialysis purification.
[0013] (6) Freeze-drying: Concentrate the dialysate and dry it to obtain organic wolfberry polysaccharide powder.
[0014] Preferably, step (1) is as follows: the organic wolfberry raw material is crushed to 40-80 mesh, and extracted by reflux with 95% ethanol at a solid-liquid ratio of 1:15 (g:mL) for 2 h, repeated 1-2 times, the organic phase is discarded, and the residue is kept for later use.
[0015] Preferably, step (2) is as follows: add purified water to the residue at a solid-liquid ratio of 1:30 (g:mL), extract at 70-95℃ for 3 h, repeat 1-3 times, combine the extracts and filter; concentrate the extract to 1 / 10 of the original volume to obtain concentrated water extract.
[0016] Preferably, step (3) is as follows: add a chloroform and n-butanol solution with a volume ratio of 4:1 to the concentrated water extract, shake and separate the layers repeatedly 3-6 times until the supernatant has a negative protein reaction, and take the supernatant to obtain the deproteinized concentrate.
[0017] Preferably, step (4) is as follows: add anhydrous ethanol to the deproteinized concentrate to make the final concentration reach 70-85% (v / v), let it stand at 4°C for 8-24 h, then centrifuge and collect the precipitate; Preferably, the precipitate is washed with 70% ethanol 1-2 times to remove small molecule impurities.
[0018] Preferably, step (5) is as follows: dissolve the precipitate in purified water, dialyze for 24-72 hours using a 3.5-10 kDa dialysis bag, change the water 3-6 times during dialysis, and remove salt, monosaccharides and other small molecules.
[0019] Preferably, step (6) is: the dialysate is concentrated under reduced pressure and then freeze-dried for 24-48 h to obtain wolfberry polysaccharide powder.
[0020] Preferably, the organic wolfberry polysaccharide is formulated into any pharmaceutically acceptable dosage form by adding pharmaceutically acceptable excipients.
[0021] The beneficial effects of this invention are as follows: This invention extracts organic wolfberry polysaccharides from organic wolfberries that meet the GB / T 19630 standard and have obtained organic product certification; the total sugar content of the organic wolfberry polysaccharides is 58.60-58.76%, wherein the molar ratio of glucose, mannose, glucosamine, rhamnose, galactose, xylose, arabinose and galacturonic acid is 1:0.0323:0.0043:0.0096:0.0126:0.0058:0.0437:0.0328; the organic wolfberry polysaccharides can effectively improve colorectal adenomatous polyps, and are used to reduce the incidence and progression risk of colorectal adenomatous polyps, with significantly better effects than ordinary wolfberry polysaccharides. Attached Figure Description
[0022] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0023] Figure 1 The therapeutic effect of Lycium barbarum polysaccharide LBP on an animal model of colorectal adenomatous polyps (HE pathological staining results).
[0024] Figure 2 Statistical results on the preventive and therapeutic effects of Lycium barbarum polysaccharide LBP on an animal model of colorectal adenomatous polyps. Detailed Implementation
[0025] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1: Preparation process of organic wolfberry polysaccharide LBP-2 and ordinary wolfberry polysaccharide LBP-1
[0026] The preparation scheme of wolfberry polysaccharides will be described in detail below with reference to this embodiment. The "organic wolfberry" and "ordinary wolfberry" mentioned in this embodiment differ only in the source of raw materials; the remaining preparation steps, key parameters, and quality control requirements are the same. The organic wolfberry raw material can be sourced from the organic wolfberry planting base of Gansu Hengtaize Biotechnology Co., Ltd., and a valid "Organic Product Certification Certificate" can be provided, certificate number 6540P2200007, certified according to GB / T 19630 "Requirements for Organic Product Production, Processing, Labelling and Management System". The ordinary wolfberry raw material comes from planting bases or suppliers that have not obtained organic product certification and is used as a control for ordinary wolfberry polysaccharides. In this embodiment, ordinary wolfberries of the same variety, origin, and harvesting season as organic wolfberries are selected to reduce raw material differences.
[0027] 1. Raw material preparation and pretreatment: Select the above-mentioned organic goji berries and ordinary goji berries, remove impurities such as mud and fruit stems, and dry them; grind the above-mentioned goji berry raw materials into 40-80 mesh for later use.
[0028] 2. Degreasing and impurity removal: To remove fat-soluble impurities, reflux extraction with 95% ethanol at a solid-liquid ratio of 1:15 (g:mL) for 2 h, repeating 1-2 times; discard the organic phase, and allow the residue to evaporate the solvent naturally for later use.
[0029] 3. Water extraction: Add purified water to the residue at a solid-liquid ratio of 1:30 (g:mL), extract at 70–95℃ for 3 h, repeat 1–3 times; combine the extracts and filter.
[0030] 4. Concentration: The filtrate is concentrated to about 1 / 10 of its original volume under reduced pressure to obtain concentrated aqueous extract.
[0031] 5. Deproteinization: Use the Sevag method (chloroform: n-butanol = 4:1, v / v) to repeatedly shake and separate the layers 3-6 times until the supernatant has a negative protein reaction. Take the supernatant for later use.
[0032] 6. Alcohol precipitation: Slowly add anhydrous ethanol to the deproteinized concentrate to achieve a final concentration of 70-85% (v / v), let stand at 4°C for 8-24 h, then centrifuge and collect the precipitate; the precipitate can be washed 1-2 times with 70% ethanol to further remove small molecule impurities.
[0033] 7. Resolution and dialysis purification: Dissolve the precipitate in purified water and dialyze for 24-72 h using a dialysis bag (MWCO 3.5-10 kDa) (changing the water 3-6 times during the process) to remove salts, monosaccharides and other small molecules.
[0034] 8. Freeze-drying and physicochemical characterization The dialysate was concentrated under reduced pressure and then freeze-dried for 24–48 h to obtain organic wolfberry polysaccharide LBP-2 and ordinary wolfberry polysaccharide LBP-1 powders, respectively.
[0035] The obtained samples were subjected to physicochemical characterization, including total sugar content, infrared spectroscopy, monosaccharide composition and molecular weight analysis.
[0036] (1) Total sugar content (phenol-sulfuric acid method): The total sugar content of the prepared ordinary wolfberry polysaccharide LBP-1 was 43.04%±0.41, and the total sugar content of the organic wolfberry polysaccharide LBP-2 was 58.68%±0.08. This indicates that both powders are mainly composed of polysaccharides, and the sugar content of the organic wolfberry polysaccharide LBP-2 is significantly higher than that of the ordinary wolfberry polysaccharide LBP-1.
[0037] (2) FT-IR: Both samples were measured at 3400 cm⁻¹. -1 An OH stretching vibration peak appears at 2930 cm⁻¹. -1 A CH stretching peak appears at 1000-1200 cm⁻¹. -1 The peaks at 1600-1740 cm⁻¹ are characteristic of glycosidic bonds and pyranose rings. Organic wolfberry polysaccharide LBP-2 shows peaks at 1600-1740 cm⁻¹. -1 The more pronounced absorption peaks nearby indicate a higher proportion of acidic polysaccharides.
[0038] (3) Monosaccharide composition analysis (PMP-derived HPLC): Both common wolfberry polysaccharide LBP-1 and organic wolfberry polysaccharide LBP-2 are mainly composed of glucose (Glc), with cosaccharides including mannose (Man), glucosamine (GlcN), rhamnose (Rha), galactose (Gal), xylose (Xyl), arabinose (Ara), and galacturonic acid (GalA). Among them, the molar ratio of cosaccharides in common wolfberry polysaccharide LBP-1 is relatively high and the distribution is dispersed, while the molar ratio of cosaccharides in organic wolfberry polysaccharide LBP-2 is relatively low, but the proportion of acidic polysaccharide components (GalA + Ara) is prominent.
[0039] (4) Molecular weight analysis (GPC-HPLC): Common wolfberry polysaccharide LBP-1 showed three peaks of 1.8 kDa, 0.6 kDa and 0.2 kDa, with a relatively dispersed molecular weight distribution; organic wolfberry polysaccharide LBP-2 had the main peaks of 1.8 kDa and 0.2 kDa, with smaller intermediate peaks and a concentrated molecular weight distribution.
[0040] The results are shown in Table 1. Both common wolfberry polysaccharide LBP-1 and organic wolfberry polysaccharide LBP-2 are wolfberry polysaccharide products with polysaccharides as the main component. Among them, the organic wolfberry polysaccharide LBP-2 described in this application has a high total sugar content, a high proportion of acidic polysaccharides, and a concentrated molecular weight distribution.
[0041] Table 1 Physicochemical characterization data of common wolfberry polysaccharide LBP-1 and organic wolfberry polysaccharide LBP-2 powders
[0042] 9. Consistency statement: Without changing the properties and uses of Lycium barbarum polysaccharides, the parameters in the above steps can be adjusted within a reasonable range; however, when used for comparison, it is preferred that LBP-1 and LBP-2 be prepared by the same operator under the same equipment conditions and with the same parameters. Example 2: The preventive and therapeutic effect of Lycium barbarum polysaccharide LBP on colorectal adenomatous polyps
[0043] 1. Select AC (Apc) flox / flox A colorectal adenomatous polyp model was constructed using Vil1-iCre mice.
[0044] Both types of single-gene mice used were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd., with a genetic background of C57BL / 6J. Before the experiment, the mouse genotypes were identified by PCR to confirm that they carried the target allele. Apc... flox / flox After hybridization with Vil1-iCre mice, genomic DNA was extracted from the tail tips of offspring and subjected to PCR amplification to confirm the genotype. Offspring with the Apc genotype were selected. flox / floxThe offspring mice of Vil1-iCre were used as an animal model of colorectal adenomatous polyps for subsequent experiments.
[0045] 2. Once the AC mice reach 3 months of age, they will be divided into groups and given the drug.
[0046] 3. Dosing regimen and groups: (1) Control group: treated with physiological saline by gavage; (2) LBP-1 group: ordinary wolfberry polysaccharide LBP-1 prepared in Example 1 was administered by gavage at a dose of 50 mg / kg / day; (3) LBP-2 group: Organic wolfberry polysaccharide LBP-2 prepared in Example 1 was administered by gavage at a dose of 50 mg / kg / day.
[0047] 4. Observe the mice once a day to assess their overall condition. After one month of drug administration, all mice can be sacrificed, and the colorectal tissue of the mice can be removed, fixed, dehydrated, and embedded in paraffin.
[0048] 5. The paraffin-embedded sample was sectioned, then graded hydration was performed followed by hematoxylin-eosin staining to obtain HE sections.
[0049] The results are as follows Figure 1 and Figure 2 As shown, compared with the control group and ordinary wolfberry polysaccharide LBP-1, the organic wolfberry polysaccharide LBP-2 described in this application can significantly reduce the lesion area of colorectal adenomatous polyps.
[0050] The results in summary indicate that the organic Lycium barbarum polysaccharide LBP-2 described in this application can effectively improve colorectal adenomatous polyps and reduce the incidence and progression risk of colorectal adenomatous polyps, with significantly better effects than ordinary Lycium barbarum polysaccharides.
Claims
1. Application of Lycium barbarum polysaccharides in the preparation of drugs for the prevention and treatment of colorectal adenomatous polyps.
2. The application as described in claim 1, characterized in that, The goji berry polysaccharide is an organic goji berry polysaccharide; the organic goji berries comply with GB / T 19630 standard, and the organic product certification certificate number is 6540P2200007.
3. The application as described in claim 2, characterized in that, The total sugar content of the organic wolfberry polysaccharide is 50-65%.
4. The application as described in claim 3, characterized in that, The total sugar content of the organic wolfberry polysaccharide is 58.60-58.76%.
5. The application as described in claim 4, characterized in that, The molar ratio of glucose, mannose, glucosamine, rhamnose, galactose, xylose, arabinose, and galacturonic acid in the organic wolfberry polysaccharide is 1:0.03-0.05:0.004-0.05:0.009-0.02:0.01-0.03:0.005-0.01:0.04-0.1:0.03-0.
11.
6. The application as described in claim 5, characterized in that, The molar ratio of glucose, mannose, glucosamine, rhamnose, galactose, xylose, arabinose and galacturonic acid in the organic wolfberry polysaccharide is 1:0.0323:0.0043:0.0096:0.0126:0.0058:0.0437:0.0328.
7. The application as described in any one of claims 2-6, characterized in that, The preparation method of the organic wolfberry polysaccharide includes the following steps: (1) Organic wolfberry raw materials are pulverized and degreased and impurities are removed; (2) Water extraction: Add purified water at a solid-liquid ratio of 1:30 (g:mL) for extraction, and concentrate the extract; (3) Deproteinization: Deproteinization was performed using the Sevag method; (4) Alcohol precipitation: Add anhydrous ethanol to the concentrated solution after deproteinization for alcohol precipitation, and collect the precipitate; (5) Resolution and dialysis purification: Dissolve the precipitate in purified water and perform dialysis purification; (6) Freeze-drying: Concentrate the dialysate and dry it to obtain organic wolfberry polysaccharide powder.
8. The application as described in claim 7, characterized in that, The preparation method of the organic wolfberry polysaccharide includes the following steps: (1) Pulverize the organic wolfberry raw material to 40-80 mesh, and extract it by reflux with 95% ethanol at a solid-liquid ratio of 1:15 (g:mL) for 2 h. Repeat 1-2 times, discard the organic phase, and keep the residue for later use. (2) Add purified water to the residue at a solid-liquid ratio of 1:30 (g:mL), extract at 70-95℃ for 3 h, repeat 1-3 times, combine the extracts and filter; concentrate the extract to 1 / 10 of the original volume to obtain concentrated aqueous extract; (3) Add chloroform and n-butanol solution with a volume ratio of 4:1 to the concentrated water extract, shake repeatedly to separate the layers 3-6 times until the supernatant has a negative protein reaction, and take the supernatant to obtain the protein-free concentrated solution; (4) Add anhydrous ethanol to the concentrated solution after deproteinization to make the final concentration reach 70-85% (v / v), let it stand at 4℃ for 8-24 h, then centrifuge and collect the precipitate; (5) Dissolve the precipitate in purified water and dialyze for 24-72 h using a 3.5-10 kDa dialysis bag. Change the water 3-6 times during dialysis to remove salt, monosaccharides and other small molecules. (6) The dialysate was concentrated under reduced pressure and then freeze-dried for 24-48 h to obtain wolfberry polysaccharide powder.
9. The application as described in claim 8, characterized in that, The precipitate in step (4) is washed with 70% ethanol 1-2 times to remove small molecule impurities.
10. The application as described in any one of claims 2-6, characterized in that, The organic wolfberry polysaccharide is formulated into any pharmaceutically acceptable dosage form by adding pharmaceutically acceptable excipients.