CN1095366C - Application of N-aceto-D-aminoglucose in medicinal preparation for curing intestinal diseases - Google Patents

Abstract

The invention discloses an application of a compound N-acetyl-D-glucosamine (N-acetyl-D-glucosamine) in preparing a medicine for treating irritable bowel syndrome (Irritable Bowel Syndrome). By regulating the biological wave of intestinal smooth muscle, anti-bacterial latent organisms colonization and improving intestinal microecology, the preparation with it as the main active ingredient can be used to treat irritable bowel syndrome and produce significant curative effect.

Description

Application of N-acetyl-D-glucosamine in preparation of medicine for treating irritable bowel syndrome

The invention relates to the application of N-acetyl-D-glucosamine as medicine, in particular to the application of N-acetyl-D-glucosamine in the preparation of medicines for treating irritable bowel syndrome.

N-acetyl-D-glucosamine (N-acetyl-D-glucosamine) is a chemical agent that has been used in the treatment of periodontitis (W09102530A ₁ ) and as a periodontal tissue regeneration accelerator since the 1980s. (JP3083927A ₃ ), serum growth factor (US05281582), lipoprotein and cholesterol detection reagent (US05320968), shampoo preparation (JP2011505A ₂ ), plant growth promoter (JP63033310A ₂ ), etc.

During the research process of the "biological wave" theory, the present inventor established a bacterial wave growth model. After research, it is realized that this kind of fluctuation has its internal regulation mechanism: some chemical substances participate in the regulation of the biological fluctuation process, and transform the pathological periodic slow wave into a normal physiological chaotic fast wave. Such substances are called wave-promoting factors. . After separation, purification and identification, it is determined that there is a factor N-acetyl-D-glucosamine, and its wave-promoting effect is related to its lubricating and protecting effect on cells. Many biochemical and physiological processes in the human body require the participation of wave-stimulating factors, and when this wave-stimulating factor is lacking in the body, it will lead to an abnormal state.

Irritable bowel syndrome (IBS) is a functional intestinal disorder that is caused by abnormal periodic slow-wave manifestations of intestinal smooth muscle. Bacterial latent colonization, colonization and release of hydrolytic enzymes in the intestinal mucosa are one of the pathogenesis mechanisms of IBS. Observation of clinical treatment effects begins with clinical classification. Most doctors accept the classification based on etiology, which is mainly divided into three categories: mental factors, dietary factors and other incentives. Further classification combined with clinical manifestations is more conducive to treatment. Mainly diarrhea type, constipation type and diarrhea type. Diarrhea type is mainly based on diarrhea, frequent defecation, chronic attack, good and bad, protracted. The constipation type mainly manifests as decreased stool frequency, poor defecation, abdominal discomfort, and weakened bowel sounds; there is also a diarrhea type in which diarrhea and constipation alternate. Different symptoms show different characteristics. This disease is protracted and has a long course, and the patient's intestinal tract itself has no organic lesions. Its incidence rate is high, accounting for more than 50% of outpatient visits of digestive system diseases. Because the pathogenesis of the disease is not clear, the outpatient department is mostly treated as gastrointestinal dysfunction, that is, an incurable but not fatal disease. At present, there is no specific drug to treat irritable bowel syndrome. Generally, some antidiarrheals, laxatives, antibiotics and psychotropic drugs are given to the symptoms. Antibiotics are not only ineffective, but will further destroy the normal flora and affect the intestinal micro-ecosystem. Although there is a WO93/14765 patent (Use of N-acetyl-glucosamine for treating lower gastrointestinal tract disorders) mentioning that N-acetyl-D-glucosamine is used to treat organic lesions of the gastrointestinal mucosa and restore the integrity of the mucosa, but At present, no one has used it in the preparation of pharmaceutical preparations for treating irritable bowel syndrome (Irritable Bowel Syndrome).

The object of the present invention is: aiming at the pathogenesis of irritable bowel syndrome, utilize the new medicinal application that N-acetyl-D-glucosamine has, make the pharmaceutical preparation for treating irritable bowel syndrome, to overcome existing The shortcomings of conventional medicines for the treatment of irritable bowel syndrome.

The above-mentioned object of the present invention is achieved like this: promptly adopt structural formula to be (I) compound active ingredient, combine with multiple pharmaceutically acceptable excipients or/and carrier, adopt mixing, granulation, tableting, sugar packet It can be prepared into liquid or solid preparations by methods such as coating or film coating, and is used for treating irritable bowel syndrome.

Wherein, the chemical name of structural formula (I) is N-acetyl-D-glucosamine (N-acetyl-D-glucosamine), molecular formula: C ₈ H ₁₅ NO ₆ , and the structure is expressed as follows:

Test conclusion shows: formula (I) compound acute toxicity test dose exceeds 2g/kg, is 300 times of human injection dose, does not yet have acute poisoning reaction; Observe that no toxic reaction occurs; in the reproduction test, feed mice from conventional dose 7mg/kg, through three passages, prove that the compound of formula (I) has no effect on mouse conception, pregnancy, childbirth, lactation and pup development. Prove that the compound of formula (I) is a non-toxic substance.

The main pharmaceutical test of the compound of formula (I) is to treat irritable bowel syndrome. Animal models, to further test the effect of eliminating these symptoms, on the other hand, through the overall observation of clinical trials of irritable bowel syndrome, to solve the problem of lack of animal models of irritable bowel syndrome.

In addition to the aforesaid test for promoting bacterial fluctuation in vitro, the results of the test on the animal model of intestinal flora imbalance and the test for promoting bifidobacteria in vitro show that: the compound of formula (I) can adjust the relationship between intestinal anaerobic bacteria and demand The proportion of oxygen bacteria can improve the intestinal micro-ecological environment; it can promote the growth of bifidobacteria: it can make the intestinal flora irregular.

Formula (I) compound is clinically tested in 300 cases and is diagnosed as the treatment situation of irritable bowel syndrome patient as follows:

Apply formula (I) compound capsules to treat patients with clinical IBS, the dosage is 100mg/time, 3 times/day, and 7 days is a course of treatment. The course of the disease ranges from 3 to 20 years, and most of them are ineffective after being treated with multiple antibiotics and other drugs. From the aspect of inducement, these cases can be divided into the following three groups: mental factor group, dietary factor group and intestinal flora disorder group. See the attached table for the treatment results.

Judgment criteria for clinical treatment effect; it can be divided into three situations: cured, effective, and ineffective. After 1-2 courses of treatment, clinical symptoms disappear, appetite improves, stool samples are tested multiple times, and bacterial flora analysis shows diversity and irregular characteristics. The number of bifidobacteria is large (>108/g), and those who relapse at the end of half a month after stopping the drug are cured; after taking the drug, the self-reported symptoms improved or disappeared, but the intestinal flora still showed a single dominant bacterium or the number of bifidobacteria was small (<105 /g), after stopping the drug, the symptoms improved, or gradually improved until recovery was defined as effective; and if the patient’s symptoms did not improve or improved but relapsed within a short period of time (<15 days) after the medication, it was defined as invalid. Preliminary observation table of the therapeutic effect of oral liquid on irritable bowel syndrome Item content group Clinical symptoms Classification of flora disorder Number of cases treatment result Mental factors Diarrhea 2-5 times/day, loose stools, transient +～++ 178 113 52 13 dietary factors Diarrhea 2-3 times/day, often abdominal pain after eating +～++ 80 40 33 7 Gut flora disorder Diarrhea, 4-5 times/day, shapeless stool, fatigue +++～++++ 42 twenty one 17 4 Total 300 174 102 twenty four

As shown in the table, the curative effect results of 300 cases of patients after medication are counted, the cure rate is 58%, the effective rate is 34%, and the ineffective rate is 8%. Among them, more than half of the patients are cured or achieve effective results after using the drug for a course of treatment. .

The compound of formula (I) can be administered by usual routes, such as parenteral administration, such as intravenous injection or oral administration. The dose depends on the patient's age, weight, condition and route of administration. The suitable dosage is 150-300 mg/day for adults, one intravenous injection, three oral or intramuscular injections; seven days is a course of treatment, and 2-3 courses of treatment are adhered to.

Pharmaceutical compositions in the form of pharmaceutically suitable formulations can be prepared by conventional methods. For example, liquid form preparations for intravenous injection or oral administration may use sterile water or sterile saline as a carrier. The suspension or solution for intramuscular injection can use sterile water, olive oil, ethyl oleate, glycols and other medically acceptable carriers. Solid oral forms, such as tablets or capsules, may contain, in addition to the active compound of formula (I), excipients such as lactose, glucose, cellulose, starch; lubricants such as silicon, talc, magnesium stearate or Calcium and/or polyethylene glycol; binders such as starch, alginic acid, alginate, sodium starch glycolate; superfoam mixture; coloring agents; sweeteners; lubricants such as lecithin, polyethoxylated Fatty ethers, etc.; general non-toxic and pharmacologically inactive substances can be used in pharmaceutical preparations. Said pharmaceutical preparations can be prepared by known methods, for example by mixing, granulating, tableting, sugar coating or film coating.

The invention discloses a new medical application of the compound of formula (I) which is different from its known application, expands the application range of N-acetyl-D-glucosamine, and improves its development value. In addition to being used as an active substance for the preparation of medicines for treating irritable bowel syndrome, it can also be used as an additive in health products and food for the prevention of intestinal diseases and the health care of the intestinal tract. The invention has the advantages of unique and remarkable curative effect, simple preparation method and no toxic and side effects.

Claims (1)

1, the application of N-acetyl-D-amino glucose in preparation treatment irritable bowel syndrome medicine.