阅读说明：本技术 N-乙酰-d-氨基葡萄糖的新用途及相关产品 (New application of N-acetyl-D-glucosamine and related products ) 是由 张平原 邓渝 庄贤韩 于 2020-07-01 设计创作，主要内容包括：本发明提供N-乙酰-D-氨基葡萄糖或其药物可接受的盐在制备防治肠易激综合征的微生态制剂或制备双歧杆菌活性改善剂的应用。本发明提出了N-乙酰-D-氨基葡萄糖的新用途,开拓了N-乙酰-D-氨基葡萄糖的应用领域,对引起肠易激综合征的多个因素产生好的效果,可以有效防、治肠易激综合征,明显改善症状,无毒副作用。(The invention provides application of N-acetyl-D-glucosamine or pharmaceutically acceptable salts thereof in preparing a microecological preparation for preventing and treating irritable bowel syndrome or preparing a bifidobacterium activity improver. The invention provides a new application of N-acetyl-D-glucosamine, develops the application field of the N-acetyl-D-glucosamine, has good effect on a plurality of factors causing irritable bowel syndrome, can effectively prevent and treat the irritable bowel syndrome, obviously improves symptoms and has no toxic or side effect.)

Use of N-acetyl-D-glucosamine or a pharmaceutically acceptable salt thereof for the preparation of a microecological preparation for the prevention and treatment of irritable bowel syndrome or for the preparation of an agent for improving the activity of bifidobacteria.

2. The use of claim 1, further comprising one or more of the following features:

1) the N-acetyl-D-glucosamine is an effective component or one of effective components of a microecological preparation or a bifidobacterium activity improver for preventing and treating irritable bowel syndrome;

2) the microecological preparation for preventing and treating irritable bowel syndrome further comprises a pharmaceutically acceptable carrier or auxiliary material;

3) the microecological preparation for preventing and treating irritable bowel syndrome also comprises probiotics, wherein the genera of the probiotics are selected from one or more of the following genera: lactobacillus, bifidobacterium, bacillus, lactococcus, propionibacterium and enterococcus;

4) the bifidobacterium activity improving agent is used for restoring, growing and proliferating or promoting activation of bifidobacterium after growing under in-vitro adverse conditions;

5) in the microecological preparation or the bifidobacterium activity improver, the content of the N-acetyl-D-glucosamine or the pharmaceutically acceptable salt thereof is 5 to 90 percent by weight;

6) the dosage form of the microecological preparation or the bifidobacterium activity improver is any one of capsules, tablets, granules, powder and enteric-coated preparations.

3. The use of claim 2, wherein the probiotic bacteria comprise any one or more of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis, bifidobacterium infantis.

4. The use according to claim 3, wherein the proportion of parts by weight of Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus bulgaricus, Bifidobacterium adolescentis and Bifidobacterium infantis in the probiotic, based on the total amount of the probiotic, is (0.01-1): (0.01-1): (0.01-1): (0.01-1): (0.01-1).

5. Use according to claim 2, further comprising one or more of the following features:

1) in feature 4), the bifidobacterium is selected from bifidobacterium adolescentis;

2) based on the total amount of the microecological preparation, the number of the live probiotics in the microecological preparation is 1 × 10⁹～1×10¹⁰CFU/g。

3) The adverse environment refers to an environment that enables the bifidobacteria to form spheroids or an aerobic environment at a temperature of less than 30 degrees celsius.

6. A microecological preparation for preventing and treating irritable bowel syndrome comprises N-acetyl-D-glucosamine and probiotic bacteria.

7. The micro-ecological formulation for the prevention and treatment of irritable bowel syndrome according to claim 6, wherein the genus of the probiotic bacteria is selected from one or more of the following genera: lactobacillus, Bifidobacterium, Bacillus, lactococcus, Propionibacterium and enterococcus.

8. The micro-ecological preparation for the prevention and treatment of irritable bowel syndrome according to claim 7, wherein said probiotic bacteria comprise any one or more of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis, bifidobacterium infantis.

9. The microecological preparation for preventing and treating irritable bowel syndrome according to claim 8, wherein the ratio of the parts by weight of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis and bifidobacterium infantis in the probiotics based on the total amount of the probiotics is (0.01-1): (0.01-1): (0.01-1): (0.01-1): (0.01-1).

10. The microecological preparation for treating irritable bowel syndrome according to claim 6, wherein the microecological preparation for treating irritable bowel syndrome further comprises a pharmaceutically acceptable carrier or excipient.

11. A method for improving the activity of bifidobacteria in vitro, comprising at least the steps of: N-acetyl-D-glucosamine is added to a culture containing Bifidobacterium, and the culture is carried out under culture conditions suitable for the growth of Bifidobacterium.

12. The method of improving the activity of a bifidobacterium as claimed in claim 11 wherein the bifidobacterium is a bifidobacterium grown under adverse conditions.

Technical Field

The invention relates to the field of biological medicine, in particular to a new application of N-acetyl-D-glucosamine and a related product.

Background

Irritable Bowel Syndrome (IBS) is a clinically common disorder of gastrointestinal dysfunction characterized by abdominal pain, abdominal discomfort, with changes in bowel habits and stool characteristics, with symptoms either persistent or intermittent. Irritable bowel syndrome is classified into IBS constipation type (IBS-C), IBS diarrhea type (IBS-D), mixed IBS (IBS-M) and uncertain IBS (IBS-U) according to stool characteristics, wherein diarrhea type irritable bowel syndrome (Diarroea-predominant IBS, IBS-D) is the most common IBS subtype and mainly shows recurrent abdominal pain and diarrhea. The disease symptoms are prolonged and repeated, and are often accompanied with psychopsychological abnormalities such as anxiety, depression and the like, the life quality of patients is influenced to different degrees, and the disease also brings great economic burden to the patients and the society.

At present, the pathogenesis of IBS-D is not yet clarified, and psychosocial stress, intestinal microecological change, gastrointestinal motility disorder, brain-intestinal axis dysfunction, visceral hypersensitivity, mucosa low-grade inflammation, intestinal barrier damage, genetic factors and the like are considered to participate. The single factor is difficult to explain the onset and symptom characteristics of IBS-D, and the status of each factor in onset is different, so that the disease has obvious heterogeneity in the aspects of onset characteristics, clinical manifestations, treatment response and the like. Currently, alosetron, rifaximin and the like are commonly used drugs for treating IBS-D. Alosetron is a 5-HT3 receptor antagonist with a severe adverse effect of ischemic enteritis. Rifaximin, as an antibacterial agent, is also common in cases of drug resistance during use.

Disclosure of Invention

In view of the above-mentioned drawbacks of the prior art, it is an object of the present invention to provide new uses of N-acetyl-D-glucosamine and related products.

In order to achieve the above objects and other related objects, the present invention provides, in a first aspect, use of N-acetyl-D-glucosamine or a pharmaceutically acceptable salt thereof for preparing a probiotic for the prevention and treatment of irritable bowel syndrome or for preparing an agent for improving activity of bifidobacterium.

In a second aspect, the present invention provides a micro-ecological preparation for the prevention and treatment of irritable bowel syndrome, comprising N-acetyl-D-glucosamine and a probiotic.

In a third aspect of the invention, there is provided a method for improving the activity of bifidobacteria in vitro, said method comprising at least the steps of: N-acetyl-D-glucosamine is added to a culture containing Bifidobacterium, and the culture is carried out under culture conditions suitable for the growth of Bifidobacterium.

As mentioned above, the new application of the N-acetyl-D-glucosamine and the related products have the following beneficial effects:

the invention provides a new application of N-acetyl-D-glucosamine, develops the application field of the N-acetyl-D-glucosamine, can improve the activity of bifidobacterium, has good effect on a plurality of factors causing irritable bowel syndrome, can effectively prevent and treat the irritable bowel syndrome, obviously improves symptoms and has no toxic or side effect. The preparation provided by the invention can improve intestinal micro-ecology of IBS-D patients, increase diversity of intestinal flora of the patients after treatment, increase probiotics, inhibit pathogenic bacteria and opportunistic pathogenic bacteria, correct intestinal flora imbalance, recover intestinal micro-ecology to be stable, and recover intestinal functions to be normal, thereby achieving the effect of treating IBS-D.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

Before the present embodiments are further described, it is to be understood that the scope of the invention is not limited to the particular embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments, and is not intended to limit the scope of the present invention; in the description and claims of the present application, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition to the specific methods, devices, and materials used in the examples, any methods, devices, and materials similar or equivalent to those described in the examples may be used in the practice of the invention in addition to the specific methods, devices, and materials used in the examples, in keeping with the knowledge of one skilled in the art and with the description of the invention.

Unless otherwise indicated, the experimental methods, detection methods and preparation methods disclosed in the present invention all employ conventional techniques in the art.

An embodiment of the present invention provides an application of N-acetyl-D-glucosamine or a pharmaceutically acceptable salt thereof in preparing a microecological preparation for the prevention and treatment of irritable bowel syndrome or in preparing an agent for improving activity of bifidobacteria.

The N-acetyl-D-glucosamine is an effective component or one of effective components of a microecological preparation or a bifidobacterium activity improver for preventing and treating irritable bowel syndrome.

Optionally, the microecological preparation for preventing and treating irritable bowel syndrome further comprises a pharmaceutically acceptable carrier or auxiliary material.

By "pharmaceutically acceptable" is meant that the molecular entities and compositions do not produce adverse, allergic, or other untoward reactions when properly administered to an animal or human.

The "pharmaceutically acceptable carrier or adjuvant" should be compatible with the active ingredient, i.e., capable of being blended therewith without substantially diminishing the effectiveness of the drug under ordinary circumstances. Specific examples of some substances that can serve as pharmaceutically acceptable carriers or adjuvants are sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium methylcellulose, ethylcellulose and methylcellulose; powdered gum tragacanth; malt; gelatin; talc; solid lubricants, such as stearic acid and magnesium stearate; calcium sulfate; vegetable oils such as peanut oil, cottonseed oil, sesame oil, olive oil, corn oil and cocoa butter; polyhydric alcohols such as propylene glycol, glycerin, sorbitol, mannitol, and polyethylene glycol; alginic acid; emulsifiers, such as Tween; wetting agents, such as sodium lauryl sulfate; a colorant; a flavoring agent; tabletting agents, stabilizers; an antioxidant; a preservative; pyrogen-free water; isotonic saline solution; and phosphate buffer, and the like. These materials are used as needed to aid in the stability of the formulation or to aid in the enhancement of the activity or its bioavailability or to produce an acceptable mouthfeel or odor upon oral administration.

In one embodiment, the adjuvant comprises a filler comprising one or more of inulin, erythritol, fructo-oligosaccharides, cranberry fruit powder, xylo-oligosaccharides, and galacto-oligosaccharides.

Further, the microecological preparation for preventing and treating irritable bowel syndrome also comprises probiotics, wherein the genera of the probiotics are selected from one or more of the following genera: lactobacillus (Lactobacillus), Bifidobacterium (Bifidobacterium), Bacillus (Bacillus), Lactococcus (Lactobacillus), Propionibacterium (Propionibacterium) and Enterococcus (Enterococcus).

The agent for improving the activity of Bifidobacterium is useful for promoting the growth or activation of the Bifidobacterium after growth under unfavorable conditions in vitro.

Optionally, the adverse environment is an environment that enables the bifidobacteria to form spheroids or an aerobic environment at a temperature of less than 30 degrees celsius.

For example, the temperature may be 4 degrees celsius.

The Bifidobacterium is capable of forming spheroids in an environment containing harmful substances or a low-nutrient environment, and the Bifidobacterium activity improver of the present invention has a function of promoting the resuscitation, growth and proliferation of the spheroids of Bifidobacterium. The harmful substance is a substance which is not beneficial to the growth of the bifidobacterium. Such as cefuroxime sodium.

Optionally, the Bifidobacterium is selected from Bifidobacterium adolescentis (Bifidobacterium adolescentis).

In the microecological preparation or the bifidobacterium activity improver, the content of the N-acetyl-D-glucosamine or the pharmaceutically acceptable salt thereof is 5 to 90 percent by weight.

Optionally, the formulation of the microecological preparation or the bifidobacterium activity improver is any one selected from capsules, tablets, granules, powder and freeze-dried powder.

The probiotic or the bifidobacterium activity improver may be an enteric preparation.

For example, the probiotic preparation or the bifidobacterium activity improver can be prepared into capsules with the N-acetyl-D-glucosamine content of 50-350 mg/capsule, and can be enteric-coated capsules. Or the microecological preparation or the bifidobacterium activity improver is prepared into tablets with the N-acetyl-D-glucosamine content of 50-350 mg/tablet, and is enteric-coated tablets.

In one embodiment, the probiotic comprises any one or more of Lactobacillus rhamnosus (Lactobacillus rhamnosus), Lactobacillus acidophilus (Lactobacillus acidophilus), Lactobacillus bulgaricus (Lactobacillus bulgaricus), Bifidobacterium adolescentis (Bifidobacterium adolescentis), Bifidobacterium infantis (Bifidobacterium infantis).

In one embodiment, in the microecological preparation for preventing and treating irritable bowel syndrome, the ratio of parts by weight of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis and bifidobacterium infantis in the probiotics based on the total amount of the probiotics is (0.01-1): (0.01-1): (0.01-1): (0.01-1): (0.01-1).

Furthermore, the number of the live probiotics in the microecological preparation is 1 × 10 based on the total amount of the microecological preparation⁹～1×10¹⁰CFU/g。

One embodiment of the present invention provides a micro-ecological preparation for preventing and treating irritable bowel syndrome, comprising N-acetyl-D-glucosamine and probiotics.

Further, the genus of the probiotic is selected from one or more of the following genera: lactobacillus, Bifidobacterium, Bacillus, lactococcus, Propionibacterium and enterococcus.

In one embodiment, the probiotic comprises any one or more of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis, bifidobacterium infantis.

In one embodiment, the ratio of parts by weight of lactobacillus rhamnosus, lactobacillus acidophilus, lactobacillus bulgaricus, bifidobacterium adolescentis and bifidobacterium infantis in the probiotics is (0.01-1): (0.01-1): (0.01-1): (0.01-1): (0.01-1).

Optionally, the microecological preparation for preventing and treating irritable bowel syndrome further comprises a pharmaceutically acceptable carrier or auxiliary material.

One embodiment of the present invention provides a method for improving the activity of bifidobacteria in vitro, comprising at least the following steps: N-acetyl-D-glucosamine is added to a culture containing Bifidobacterium, and the culture is carried out under culture conditions suitable for the growth of Bifidobacterium.

The bifidobacterium is bifidobacterium grown under adverse conditions.

Optionally, the adverse environment is an environment that enables the bifidobacteria to form spheroids or an aerobic environment at a temperature of less than 30 degrees celsius.