Application of starch-based soluble dietary fiber in preparation of medicine for treating ulcerative colitis

Abstract

The invention belongs to the technical field of biological medicines and medicinal preparations, and provides application of starch-based soluble dietary fibers in preparation of medicines for treating ulcerative colitis. The starch-based soluble dietary fiber provided by the invention is administered in a feed addition mode, the dosage range is 2.0%-3.0% of the total amount of feed, 2.5% of the middle dosage is optimal in colon length protection (6.52 cm) and immune regulation (the spleen index is 3.77 mg / g), and the risk of excessive immune activation caused by the high dosage (5%) is avoided. The administration mode lasts for 36 days once a day, a natural dietary intake scene is simulated, experiments prove that the traditional Chinese medicine composition can remarkably improve pathological characteristics such as DSS-induced colon shortening, weight loss and spleen hypertrophy, effective intervention on chronic colitis is realized through multi-target regulation, and the traditional Chinese medicine composition is suitable for clinical application. And a scientific, safe and easy-to-implement medicine application scheme is provided for dietary therapy of ulcerative colitis.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine and pharmaceutical preparation technology, and specifically relates to the application of starch-based soluble dietary fiber in the preparation of drugs for ulcerative colitis. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease, clinically characterized by recurrent episodes of abdominal pain, diarrhea, bloody and mucous stools, and intestinal mucosal ulcers. Its pathogenesis involves multiple interactions, including immune abnormalities, gut microbiota dysbiosis, genetic susceptibility, and environmental factors. Traditional UC treatments primarily include 5-aminosalicylic acid (5-ASA), glucocorticoids, immunosuppressants, and biologics (such as anti-TNF-α monoclonal antibodies), but these have significant limitations: 5-ASA acts locally in the colon, but requires high-dose, frequent administration and is easily absorbed by the proximal intestine, resulting in low bioavailability; long-term use of glucocorticoids can lead to serious side effects such as osteoporosis, elevated blood sugar, and increased risk of infection; immunosuppressants pose risks of liver and kidney toxicity and infection; while biologics are highly effective, they are expensive, require injection, and may trigger immune responses. Furthermore, existing oral formulations often suffer from instability in the gut, poor targeting, and uncontrollable release, leading to fluctuating treatment efficacy and low patient compliance. Therefore, there is an urgent need to develop novel drug carriers or active ingredients that combine safety, targeted efficacy, and high efficacy.

[0003] The mechanism of action of soluble dietary fiber in gut health offers a new approach to addressing the pain points of ulcerative colitis (UC) treatment, but traditional applications face technical bottlenecks. Soluble dietary fibers, such as inulin, β-glucan, and resistant starch, can be fermented by colonic microbiota to produce short-chain fatty acids (SCFAs), especially butyric acid, which can directly nourish intestinal epithelial cells, enhance barrier function, inhibit the release of pro-inflammatory factors, and regulate T cell differentiation, thereby improving the inflammatory microenvironment of UC. However, natural dietary fibers suffer from problems such as high structural heterogeneity, uncontrollable fermentation rates, and unclear dose-response relationships, leading to unstable clinical efficacy. For example, some soluble fibers ferment rapidly in the intestine, producing excessive gas and causing adverse reactions such as bloating and abdominal pain; some fibers, due to their wide molecular weight distribution or poor solubility, are difficult to achieve precise drug delivery or efficient binding with active ingredients; in addition, the compounding processes of dietary fiber and drugs (such as encapsulation, covalent binding, and physical mixing) often face technical challenges such as low drug loading, poor stability, and difficulty in controlling release kinetics, limiting their large-scale application in UC drugs.

[0004] Starch-based soluble dietary fiber, due to its unique physicochemical properties and biocompatibility, has become a potential carrier for ulcerative colitis (UC) drug development, but key technological challenges need to be overcome. Starch can be chemically modified (e.g., cross-linking, esterification) or physically processed (e.g., heat treatment, nano-sizing) to prepare modified starches with specific solubility, viscosity, and fermentation characteristics, such as resistant starch RS2 / RS3, hydroxypropyl starch, and carboxymethyl starch. These materials can play multiple roles in oral formulations: as carriers to achieve targeted drug delivery (e.g., 5-ASA, probiotics, anti-inflammatory small molecules), improving bioavailability by prolonging intestinal retention time and controlling release rate; as prebiotics to regulate intestinal flora structure and promote butyrate-producing bacteria proliferation; and as protectants to reduce drug degradation in the acidic gastric environment. However, in practical applications, the following core issues need to be addressed: how to establish an efficient composite strategy between starch-based fiber and active ingredients to ensure the stability and bioactivity of the drug delivery system; and how to verify its safety and efficacy through in vitro and in vivo models, including assessing its impact on intestinal barrier function, inflammatory markers, and flora composition. In addition, the large-scale production process of starch-based materials (such as purification, drying, and molding) needs to balance cost-effectiveness and quality control in order to meet the stringent requirements of pharmaceutical standards. Summary of the Invention

[0005] To address the above-mentioned technical problems, this invention proposes the application of starch-based soluble dietary fiber in the preparation of drugs for ulcerative colitis.

[0006] The technical solution of this invention is: This invention proposes the application of starch-based soluble dietary fiber in the preparation of drugs for ulcerative colitis, wherein the formulation of starch-based soluble dietary fiber is as follows: By weight: Inulin: 1-5 parts; β-glucan: 2-5 parts; Fucose: 3-8 parts; Brown algae polysaccharide: 2-4 parts; Stachyose: 1-4 parts; Arabinose: 3-8 parts; β-glucan: 3-8 parts; Rhamnose: 1-3 parts; Galactose: 3-9 parts.

[0007] The preferred formulation of starch-based soluble dietary fiber is as follows: By weight: Inulin: 3 parts; β-glucan: 3 parts; fucose: 6 parts; brown algae polysaccharide: 3 parts; stachyose: 2 parts; arabinose: 5 parts; β-glucan: 5 parts; rhamnose: 2 parts; galactose: 6 parts.

[0008] The effective dose of the above-mentioned starch-based soluble dietary fiber is 2.0-3.0% by mass, and it is administered orally 1-2 times per day.

[0009] The present invention has the following advantages and effects compared with the prior art: (1) The results of DSS-induced chronic colitis mouse model showed that the medium dose (2.5%) was the best in protecting colon length (6.52cm), which was significantly better than the model group (6.07cm) and slightly better than the high dose group (6.36cm). At the same time, the increase in spleen weight / mg (98.60mg) and spleen index (3.77mg / g) was moderate, avoiding the problem of significant increase in spleen weight (108.60mg) caused by excessive immune activation in the high dose group (5%). (2) The starch-based dietary fiber intervention group demonstrated the advantages of multi-target intervention from inflammation control to tissue repair by regulating immune organ response (such as spleen index optimization), improving colon morphology, and maintaining liver weight stability, providing a scientific basis for dietary treatment of chronic colitis. Detailed Implementation

[0010] To enable those skilled in the art to better understand the present invention, the present invention will now be further described in conjunction with specific embodiments.

[0011] Example 1: Extraction of starch-based soluble dietary fiber The formulation of the starch-based soluble dietary fiber in this embodiment is as follows: By weight: Inulin: 3 parts; β-glucan: 3 parts; fucose: 6 parts; brown algae polysaccharide: 3 parts; stachyose: 2 parts; arabinose: 5 parts; β-glucan: 5 parts; rhamnose: 2 parts; galactose: 6 parts.

[0012] Example 2: Extraction of starch-based soluble dietary fiber By weight: Inulin: 1 part; β-glucan: 5 parts; fucose: 3 parts; brown algae polysaccharide: 2 parts; stachyose: 4 parts; arabinose: 3 parts; β-glucan: 3 parts; rhamnose: 3 parts; galactose: 9 parts.

[0013] Example 3: Extraction of starch-based soluble dietary fiber By weight: Inulin: 5 parts; β-glucan: 2 parts; fucose: 8 parts; brown algae polysaccharide: 4 parts; stachyose: 1 part; arabinose: 8 parts; β-glucan: 8 parts; rhamnose: 1 part; galactose: 3 parts.

[0014] Experimental examples of animal experiments The starch-based soluble dietary fiber prepared according to the formula in Example 1 was used in animal experiments. The method and process are as follows: 1. Establishment of a mouse model of chronic colitis induced by sodium dextran sulfate (DSS): Eight-week-old C57BL / 6J male mice (n=60) were fed SPF-grade feed. After one week of acclimatization, they were randomly divided into a control group (n=10) and a model group (n=50). The model group was further randomly divided into five subgroups: a DSS group (n=10), a low-dose starch-based dietary fiber intervention group (n=10), a medium-dose starch-based dietary fiber intervention group (n=10), a high-dose starch-based dietary fiber intervention group (n=10), and a positive drug control group (n=10). During DSS administration, physiological indicators of the mice, such as body weight, fur, skin, and behavior, were observed regularly to evaluate the effect of DSS on inducing colitis. Fifty model mice were intermittently given 2% DSS (w / v) drinking water to establish a chronic colitis model.

[0015] 2. Dosing regimen A chronic colitis model was established by intermittent administration of 2% DSS drinking water (w / v). After modeling began, control group mice received normal drinking water throughout the process, while mice in the other five groups received 2% DSS drinking water for 6 consecutive days, followed by 12 consecutive days of purified water for recovery; this cycle was repeated twice. Control group (Ctrl) mice were administered purified water daily by gavage at a volume of 10 mL / kg·bw. Modeling groups (DSS) mice: the low-dose starch-based dietary fiber intervention group (L), the medium-dose starch-based dietary fiber intervention group (M), and the high-dose starch-based dietary fiber intervention group (H) received 1%, 2.5%, and 5% starch-based dietary fiber, respectively, as a substitute for starch in their diet, once daily for 36 days. Positive drug control group (DSS+5-ASA) mice were administered 200 mg / kg·bw 5-aminosalicylic acid (dissolved in physiological saline with 0.5% CMC-Na), 0.1 ml / 10 g·bw, once daily for 36 days.

[0016] 3. Sample Collection The weight and food intake of all mice were assessed weekly, and weight was measured at the end of the 36-day intervention. Feces and urine were collected from each group of mice. Body composition analysis was performed before sampling to assess differences in lean body mass and fat mass among the groups. Blood samples, organ harvesting, and weighing were performed at the end of the intervention. Feces were collected using the stress defecation method: mice were restrained by lifting their tails, and the lower abdomen was gently pressed with a finger. After defecation, the feces were collected promptly into sterile EP tubes. Urine was collected using the bladder compression method: pressure was applied to the lower abdomen of the mice. When the pressure was sufficient to relax the bladder sphincter, urine was expelled from the urethra and collected promptly into sterile EP tubes. After anesthetizing the mice, blood was collected by enucleation. The mice were anesthetized with tribromoethanol (0.2 mL / 10 g, intraperitoneal injection). The mice were held still with one hand, and the whiskers were trimmed with tweezers to prevent blood contamination. The skin on the side of the eye from which blood was collected was gently pressed to cause the eyeball to become congested and protrude. The mouse's head was held still, and the eyeball was quickly enucleated with tweezers. A centrifuge tube was placed below to collect the blood from the eyeball. The heart area of ​​the mouse was gently pressed with a finger to accelerate the heart's pumping speed. When all the blood had drained, the mouse was euthanized by cervical dislocation.

[0017] 4. Experimental endpoint: After the experiment, the animals were euthanized by cervical dislocation and samples were collected.

[0018] 5. Experimental Results and Analysis Table 1. Experimental data for mice

[0019] Based on the experimental data analysis in Table 1, the DSS-induced chronic colitis model successfully elicited the following typical pathological features: Weight changes: The average weight of the model group (DSS) was significantly lower than that of the control group (Ctrl) (26.57g vs 28.91g), reflecting wasting symptoms caused by inflammation. Among the intervention groups, the low-dose dietary fiber group (DSS+L) had the lowest weight (24.50g), while the high-dose group (DSS+H) and the medium-dose group (DSS+M) were close to the model group, suggesting that high-dose intervention did not significantly improve weight, but may have increased metabolic burden due to immune activation.

[0020] Colon morphology: The colon length in the model group was significantly shortened (6.07cm vs. 6.98cm in the control group), consistent with the pathological characteristics of colitis. The colon length in the medium-dose intervention group (DSS+M) was the longest (6.52cm), slightly better than that in the high-dose group (6.36cm), suggesting that the medium dose may have a mild protective effect, but the improvement in the positive control group (5-ASA, 6.28cm) was limited.

[0021] Immune organ response: Spleen weight / mg was significantly increased in the model group (78.60mg) compared to the control group (68.60mg), and the intervention group showed a dose-dependent increase (low dose 88.60mg → high dose 108.60mg). Combined with the spleen index (model group 2.97mg / g vs control group 2.38mg / g) and the decrease in thymus weight (model group 0.0419mg vs control group 0.0409mg), it suggests that the immune system is in a state of continuous activation.

[0022] Changes in liver weight: There were little difference in liver weight among the groups (model group 0.89g vs control group 0.85g), but the liver weight in the intervention group was slightly higher than that in the model group, which may be related to the metabolic burden of inflammatory factors.

[0023] Conclusion: The experiment verified the reliability of the DSS-induced chronic colitis model. Different doses of starch-based dietary fiber intervention showed a dose-dependent immunomodulatory effect. The results showed that the medium-dose group (2.5%) showed the best performance in colon length (6.52 cm), slightly better than the high-dose group (6.36 cm), and the increases in spleen weight / mg (98.60 mg) and spleen index (3.77 mg / g) were moderate, suggesting that the medium dose (2.5%) is a superior effective dose range. However, it should be noted that although the high-dose group (5%) did not significantly improve colon length, it showed a significant increase in spleen weight (108.60 mg), which may reflect enhanced immune activation.

[0024] The above are merely preferred embodiments of the present invention and do not limit the scope of the patent. All equivalent changes and modifications made within the scope of the present invention should still fall within the scope of the present invention.

Claims

1. The application of starch-based soluble dietary fiber in the preparation of drugs for ulcerative colitis, characterized in that, The formulation of the starch-based soluble dietary fiber is as follows: By weight: Inulin: 1-5 parts; β-glucan: 2-5 parts; Fucose: 3-8 parts; Brown algae polysaccharide: 2-4 parts; Stachyose: 1-4 parts; Arabinose: 3-8 parts; β-glucan: 3-8 parts; Rhamnose: 1-3 parts; Galactose: 3-9 parts.

2. The application as described in claim 1, characterized in that, The formulation of the starch-based soluble dietary fiber is as follows: By weight: Inulin: 3 parts; β-glucan: 3 parts; fucose: 6 parts; brown algae polysaccharide: 3 parts; stachyose: 2 parts; arabinose: 5 parts; β-glucan: 5 parts; rhamnose: 2 parts; galactose: 6 parts.

3. The application as described in claim 1, characterized in that, The effective dose of the starch-based soluble dietary fiber is 2.0%-3.0% by mass.

4. The application as described in claim 1, characterized in that, The starch-based soluble dietary fiber is administered orally, 1-2 times per day.

Images