Application of yolk immunoglobulin in preparation of medicine for preventing and treating digestive tract inflammatory diseases

Abstract

The invention provides an application of yolk immunoglobulin in preparation of a medicine for preventing and treating digestive tract inflammatory diseases, and belongs to the technical field of biological medicines. The egg yolk immunoglobulin is used for preventing and treating inflammatory diseases of digestive tracts, can relieve inflammatory response of the digestive tracts, inhibit disease progression, relieve hemafecia, diarrhea and tissue edema and hyperemia, and can also regulate the immune function of the intestinal tracts, enhance the barrier effect of intestinal mucosa, promote repair of damaged intestinal mucosa, improve the environment in the intestinal tracts from the source and improve the immunity of the intestinal tracts. The intestinal structure is complete, and the phenomenon of sparse villus in the intestinal tract is avoided. Moreover, the egg yolk immunoglobulin is derived from eggs, belongs to a natural bioactive substance, and compared with a chemical synthesis medicine, the egg yolk immunoglobulin is mild in component, does not easily cause strong rejection reaction of an organism, greatly reduces the occurrence probability of allergy and other adverse reactions, is also very friendly to patients with weak gastrointestinal functions, and provides a new thought for prevention and treatment of digestive tract inflammation.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to application of egg yolk immunoglobulin in the preparation of medicines for preventing and treating digestive tract inflammatory diseases. Background Art

[0002] Gastrointestinal inflammation is an inflammatory response triggered by damage to the digestive tract mucosa. The causes of this disease are complex, with common types including gastroenteritis, inflammatory bowel disease (IBD, including Crohn's disease and ulcerative colitis), and infectious enteritis. Causes include infection with food or water contaminated by bacteria (such as Salmonella and Escherichia coli), viruses (such as norovirus and rotavirus), or parasites; dietary and lifestyle factors such as an irritating diet, unclean food, and irregular sleep and rest schedules; autoimmune disorders and genetic susceptibility; medication damage; and chronic diseases. All of these factors result in inflammatory symptoms. Prevention and treatment strategies typically involve dietary management, good hygiene habits, and immune system enhancement. Treatment options typically include antibiotics for bacterial gastroenteritis, antidiarrheal drugs and probiotics to restore the intestinal flora, and immunomodulatory biologics for Crohn's disease. However, unauthorized discontinuation of medications can easily lead to relapses or "rebound inflammation," and complete cure is rarely achieved. The following describes IBD's symptoms and current treatment options, using the example of IBD.

[0003] Ulcerative colitis (UC) is a chronic inflammatory disease driven by multiple mechanisms: intestinal barrier disruption, dysbiosis, and immune imbalance. Its pathological process involves a vicious cycle of "dysbiosis-immune abnormalities-intensified inflammation." It is a highly recurrent inflammatory disease, and, along with Crohn's disease, is collectively referred to as inflammatory bowel disease (IBD). The peak age of IBD patients is between 20 and 40 years old, with women more likely than men. Ulcerative colitis lesions are characterized by continuous, diffuse inflammation of the mucosa and submucosa. Involvement of the muscularis and serosa is rare. Lesions of UC are superficial and less prone to intestinal strictures or perforations. Lesions typically begin in the rectum and spread proximally. Severe cases can involve the entire colon and even the terminal ileum. Lesions are diffuse, continuous, and lack skip zones. Furthermore, with the increasing global incidence of IBD, its treatment has become a major challenge in the field of digestive diseases. IBD has many characteristics: [Gross Features] ① During the active phase, the mucosa is congested, edematous, and punctately hemorrhaged, with superficial ulcers of varying sizes visible. In severe cases, the muscularis mucosa may be destroyed and adhere to each other to form mucosal bridges. ② Inflammatory pseudopolyps may be present between ulcers. In late-stage lesions, the intestinal tract becomes fibrotic, narrowed, and shortened. ③ Pancolonic forms may be accompanied by inflammatory lesions in the terminal ileum, known as "backflow ileitis." [Microscopic Features] ① Crypt abscesses and cryptitis are common. ② Inflammatory pseudopolyps (relatively elevated residual mucosa surrounded by ulcers) are common. ③ Shallow ulcers (primarily in the mucosa). Diffuse acute and chronic inflammatory cell infiltration of the mucosa and submucosa is present, along with vascular congestion and edema. ④ A significant increase in basal plasma cells (an important criterion for distinguishing infectious colitis). ⑤ Chronic changes include crypt deformation and epithelial regenerative changes. ⑥ No granulomas are seen.

[0004] Currently, there are many therapeutic drugs for IBD, such as aminosalicylic acid preparations, glucocorticoids, immunosuppressants, and biologics. Current clinical treatments for IBD primarily rely on immunosuppressants such as aminosalicylic acid anti-inflammatory drugs and corticosteroids, but long-term use of these drugs can easily lead to drug resistance and significant adverse reactions. While glucocorticoids can quickly control inflammation, they cannot prevent disease progression, and long-term use can lead to systemic side effects such as osteoporosis and increased risk of infection. Immunosuppressants have a slow onset of action, a narrow therapeutic window, and require frequent monitoring of blood levels. They also carry risks such as liver and kidney damage. The emergence of biologics has brought new breakthroughs in the treatment of IBD, working by targeting key cytokines or signaling molecules in inflammatory pathways. However, biologics are expensive, and some patients experience primary or secondary non-response. Long-term use can also induce the production of anti-drug antibodies, reducing efficacy and increasing the risk of infection, and even leading to serious adverse events such as tumors.

[0005] Surgical treatment plays an irreplaceable role in treating IBD complications (such as intestinal perforation, intestinal obstruction, cancer, etc.), but surgical resection of the diseased intestinal segment cannot cure the disease. The recurrence rate after surgery is high, and it will affect the patient's intestinal function and nutrient absorption, leading to complications such as short bowel syndrome, which seriously affects the patient's quality of life. In addition, existing treatment methods are difficult to accurately regulate the balance of intestinal microecology. Although traditional fecal microbiota transplantation and probiotic therapy can partially regulate the intestinal microecology, it is difficult to achieve accurate inhibition of pathogens and targeted enrichment of beneficial bacteria due to problems such as low colonization efficiency of the bacterial flora (<20%) and the destruction of active ingredients by the gastric acid environment.

[0006] Yolk immunoglobulin (IgY) is an immunoglobulin present in the yolk of birds and reptiles. It is widely present in the yolk and is abundant. IgY is formed by the immune system in response to specific antigens and can be obtained by immunizing hens with specific antigens. It has the advantages of high yield, low cost, stable properties, and can withstand a certain degree of acid-base environment and high temperature treatment. It has been widely used in disease prevention and control, immunoassays and biotechnology, and has become a green alternative to antibiotics. The wide application of IgY can deal with diseases caused by various viral infections, and can also be used to prevent and treat many diseases in aquaculture production, such as bursal disease, duck hepatitis, and gosling plague. However, there is currently no research on the use of IgY to treat human gastrointestinal inflammation, especially IBD.

[0007] Since the pathogenesis of IBD has not been fully elucidated, existing treatment technologies are difficult to achieve precise treatment and individualized intervention. There is an urgent need to develop new treatment strategies and technologies to overcome the limitations of existing treatments and improve the treatment effect of IBD and the quality of life of patients. Summary of the Invention

[0008] The purpose of the present invention is to provide an application of egg yolk immunoglobulin in the preparation of drugs for preventing and treating inflammatory diseases of the digestive tract. The egg yolk immunoglobulin can reduce inflammatory reactions including colitis, inhibit disease progression, relieve blood in the stool, diarrhea, and tissue edema and congestion, and can also regulate intestinal immune function, enhance the barrier function of the intestinal mucosa, promote the repair of damaged intestinal mucosa, improve the intestinal environment from the root, make the intestinal structure intact, and eliminate the sparse villi in the intestine.

[0009] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0010] The present invention provides an application of egg yolk immunoglobulin in the preparation of medicines for preventing and treating digestive tract inflammatory diseases.

[0011] Preferably, the drug for treating and preventing digestive tract inflammatory diseases contains egg yolk immunoglobulin as an active ingredient.

[0012] Preferably, the digestive tract inflammatory diseases include: IBD, colon cancer, chronic enteritis, duodenal ulcer, acute gastroenteritis, and diarrhea.

[0013] Preferably, the drug for preventing and treating digestive tract inflammatory diseases further comprises one or more pharmaceutically acceptable auxiliary materials, carriers, excipients, diluents, adjuvants or vehicles.

[0014] Preferably, the dosage form of the drug for preventing and treating digestive tract inflammatory diseases includes liquid preparations, solid preparations or semisolid preparations.

[0015] Preferably, the dosage of the egg yolk immunoglobulin is 1 to 3 g / d.

[0016] Preferably, the egg yolk immunoglobulin can reduce the inflammatory response of the digestive tract.

[0017] The beneficial effects of the present invention compared with the prior art are:

[0018] The present invention utilizes egg yolk immunoglobulin to prevent and treat inflammatory diseases of the digestive tract. It can reduce inflammatory reactions in the digestive tract, inhibit disease progression, alleviate blood in the stool, diarrhea, and tissue edema and congestion. It can also regulate intestinal immune function, enhance the barrier function of the intestinal mucosa, promote the repair of damaged intestinal mucosa, and fundamentally improve the intestinal environment, maintaining an intact intestinal structure and eliminating sparse villi. Furthermore, egg yolk immunoglobulin, derived from eggs, is a natural bioactive substance. Compared to chemically synthesized drugs, its composition is milder and less likely to trigger strong rejection reactions in the body, significantly reducing the incidence of allergies and other adverse reactions. It is also very friendly to patients with weak gastrointestinal function. Long-term use is less likely to damage liver and kidney function. It also avoids the problems of osteoporosis, increased infection risk, and drug resistance caused by existing therapeutic drugs. This provides a reliable and safe, effective treatment for inflammatory diseases of the digestive tract, and offers new ideas for the treatment of inflammatory diseases of the digestive tract. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0020] Figure 1 The graph shows the results of oral administration of mice in each treatment group of Example 1 of the present invention, wherein A is the weight of the mouse, B is the disease activity index of the mouse, C is a photo of the mouse colon, and D is the length of the mouse colon; Con: normal control mouse, Model: IBD model mouse, AC: positive control, Western medicine (mesalazine), IgY: egg yolk immunoglobulin;

[0021] Figure 2 This is a HE staining picture of the intestine of normal mice in the blank group in Example 1 of the present invention;

[0022] Figure 3 This is a HE staining image of the intestine of the IBD model group mice in Example 1 of the present invention;

[0023] Figure 4 This is a HE staining image of the intestine of mice in the positive control group in Example 1 of the present invention;

[0024] Figure 5 This is a picture of HE staining of the intestine of the IBD model mice in the experimental group of Example 1 of the present invention after oral administration of anti-inflammatory egg yolk immunoglobulin. DETAILED DESCRIPTION

[0025] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0026] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0027] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0028] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0029] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0030] Example 1

[0031] Example 1 of the present invention provides a method for treating inflammatory bowel disease (IBD) using egg yolk immunoglobulin, the specific steps of which are as follows:

[0032] (1) Construction of IBD model:

[0033] 6-8 week old C57 mice were purchased and adaptively fed for 1 week. The mice were divided into 4 groups (blank group, IBD model group, positive control group, and experimental group), with 6 mice in each group. 2.5% DSS drinking water was prepared with sterile water and used as the only drinking water for the IBD model group, positive control group, and experimental group. The blank group mice used sterile water as drinking water. The mice were fed for 7 days to obtain an IBD model.

[0034] Modeling criteria: Clinical manifestations: Weight loss: Mice experience significant weight loss after DSS induction, typically reaching 20%-30% within 3-4 days of DSS administration. Bloody stools and diarrhea: Mice experience bloody stools and diarrhea, key clinical manifestations of the DSS-induced UC model. Mice also exhibit tissue edema, congestion, and significant inflammation. Behavioral changes: Mice exhibit symptoms of discomfort, such as arched backs, erect piloerection, and decreased activity.

[0035] (2) Drug treatment:

[0036] On the third day after modeling, the drug was administered orally at a dose of 0.25 g / kg / day for 7 days. The weight of the mice was recorded and the colon was removed for observation. The results were as follows: Figure 1 The positive control group was gavaged with mesalazine, the experimental group was gavaged with egg yolk immunoglobulin, and the blank group and IBD model group were gavaged with an equal amount of normal saline.

[0037] Figure 1 The results showed that after mice were gavaged with egg yolk immunoglobulin, their weight increased significantly, and their disease activity index decreased, returning to a level comparable to that of the blank control group after 7 days. The feces in the mouse colon were also significantly more than those in the IBD model group and the positive control group that took the oral Western medicine mesalazine, which was basically the same as that of the normal group of mice. This indicates that the food intake of mice was normal after gavage with egg yolk immunoglobulin. The length of the mouse colon was significantly longer than that of the IBD model group, which was basically the same as that of the normal mice in the blank control group.

[0038] (3) Staining observation

[0039] 1) Tissue fixation: The mouse colon tissue obtained in step (2) was quickly placed in 10% neutral buffered formalin fixative for 24 hours.

[0040] 2) Dehydration: Dehydrate the fixed tissue in a gradient of alcohol (e.g., 70%, 80%, 95%, 100%) to remove water from the tissue.

[0041] 3) Transparency: Use a transparent agent such as xylene to replace the alcohol in the tissue to facilitate subsequent wax immersion.

[0042] 4) Wax immersion: Place the tissue in melted paraffin and allow the paraffin to fully penetrate the tissue.

[0043] 5) Embedding and sectioning: Place the wax-soaked tissue in an embedding box, pour in melted paraffin, and form a wax block after cooling and solidification, which is then sectioned.

[0044] The sections were stained with HE, and the results were as follows Figures 2 to 5 shown.

[0045] Figure 2 The results showed that the intestinal structure of mice in the normal group was intact, but 3-5% of them had missing or sparse intestinal villi (indicated by the thin scissors). Figure 3 The results showed that the intestinal structure of mice in the IBD model group was incomplete, with concentrated inflammation areas covering approximately 30% of the area (indicated by the cut head), and the affected areas had no intact villi. Figure 4 The mesalazine group showed improved intestinal structure, but with concentrated inflammation affecting approximately 5% of the total area (indicated by the rough cutout), and a few areas with sparse villi. However, the effects were not consistent within the groups. Some groups showed relatively intact structures and less inflammation. Figure 5 The results showed that two-thirds of the mice in the egg yolk immunoglobulin group had intact intestinal structures, no different from the normal group. One-third of the mice had concentrated areas of inflammation, with a large number of plasma cell infiltrates at the base, affecting approximately 25% of the area (indicated by the rough cut head). However, the inflamed area still had a large number of villi and intact muscle tissue. There was essentially no sparse villi in the entire intestine.

[0046] Example 2

[0047] Example 2 of the present invention tested the preventive and therapeutic effects of egg yolk immunoglobulin on digestive tract inflammatory diseases, and the specific contents are as follows:

[0048] (1) Colon cancer

[0049] User: Qin, female, 58 years old.

[0050] Symptoms: He had been suffering from gastrointestinal discomfort for two years. When it was serious, hospitalization could only provide relief. He was diagnosed with colon cancer before the Chinese New Year in 2017. He underwent resection surgery after the Spring Festival and received two chemotherapy sessions.

[0051] Yolk immunoglobulin: Before the diagnosis, I was treated for gastric problems, taking gastric medication and yolk immunoglobulin (0.3g, morning and evening), which had a relieving effect. After the diagnosis and surgery, I continued to take yolk immunoglobulin and the cancer cell-suppressing drugs prescribed by the doctor. After two follow-up visits and chemotherapy, I recovered very well. I ate significantly more than before the surgery, no longer had constipation, and my complexion improved.

[0052] (2) Chronic enteritis

[0053] User: Yuan, female, 60 years old.

[0054] Symptoms: chronic enteritis, diarrhea, going to the toilet 4-5 times a day.

[0055] Yolk immunoglobulin usage: Take 0.3g of yolk immunoglobulin once in the morning and evening for 2 consecutive months. Effect: Chronic enteritis is now basically under control, I go to the toilet 1-2 times a day, and my stool is formed.

[0056] (3) Duodenal ulcer

[0057] User: Yuan, male, 35 years old, from Suzhou.

[0058] Symptoms: Suffering from duodenal ulcer for many years, abdominal pain when hungry, and vomiting blood in severe cases.

[0059] Yolk immunoglobulin usage: twice a day (total 0.3g), take continuously for about 12 days.

[0060] Effect: There is no recurrence of duodenal ulcer, no more abdominal pain when hungry, and I can now drink some red wine and beer instead of alcohol.

[0061] (4) Stress-induced diarrhea

[0062] User: Wei, male, 43 years old, from Anhui Province, salesperson of a feed company.

[0063] Symptoms: The nature of my job requires frequent business trips, but I get diarrhea wherever I go.

[0064] Usage of egg yolk immunoglobulin: Take egg yolk immunoglobulin once in the morning and once in the evening (total 0.3g) when traveling.

[0065] Effect of use: Now when I travel to a new place on business, I basically don’t have diarrhea anymore.

[0066] (5) Acute gastroenteritis

[0067] User: Dai, male, 38 years old, from Taizhou, fishery medicine dealer.

[0068] Symptoms: Acute gastroenteritis, vomiting, diarrhea, abdominal pain, and fever.

[0069] Use of egg yolk immunoglobulin: One day of infusion treatment was ineffective. On the second day, egg yolk immunoglobulin was started at the same time as the infusion, 0.6g / day. There was obvious improvement. On the third day, the infusion was stopped and egg yolk immunoglobulin was continued to be taken. The acute gastroenteritis was completely cured.

[0070] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. Use of egg yolk immunoglobulin in the preparation of medicines for preventing and treating inflammatory diseases of the digestive tract.

2. The application according to claim 1, characterized in that The medicine for preventing and treating digestive tract inflammatory diseases uses egg yolk immunoglobulin as an active ingredient.

3. The application according to claim 1, characterized in that The digestive tract inflammatory diseases include: IBD, colon cancer, chronic enteritis, duodenal ulcer, acute gastroenteritis, and diarrhea.

4. The application according to claim 1, characterized in that The drug for preventing and treating digestive tract inflammatory diseases further comprises one or more pharmaceutically acceptable auxiliary materials, carriers, excipients, diluents, adjuvants or vehicles.

5. The application according to claim 1, characterized in that: The dosage form of the drug for preventing and treating digestive tract inflammatory diseases includes liquid preparations, solid preparations or semisolid preparations.

6. The application according to claim 1, characterized in that: The dosage of the egg yolk immunoglobulin is 1 to 3 g / d.

7. The use according to claim 1, characterized in that The egg yolk immunoglobulin can reduce the inflammatory response of the digestive tract.

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