Application of glycerine enema in treatment of respiratory tract infection in children

Abstract

The invention relates to application of glycerine enema to treatment of respiratory tract infection in children. Specifically, the invention relates to application of glycerine enema in preparation of a medicine for treating respiratory tract infections in children, and the respiratory tract infections are especially infections caused by bacteria and viruses, such as novel coronavirus infections and influenza.

Description

Technical Field

[0001] This application relates to the fields of biomedicine and infectious disease prevention and control. Specifically, this application relates to the use of glycerol enema in the treatment of children's respiratory tract infections. Background Art

[0002] Respiratory tract infection is a common disease of the respiratory system, caused by bacteria, viruses, fungi, non-specific pathogens, mycoplasma, chlamydia, etc., and is prone to occur in infants, the elderly, and patients with low immunity in hospital for treatment. Due to the lack of a mature immune system, the infection of the novel coronavirus and seasonal influenza virus has caused great trouble to infants, and a small number of patients even have severe symptoms.

[0003] Currently, the main treatments for respiratory tract infections are antiviral and antibiotic drugs. Commonly used antiviral drugs include ribavirin, arbidol, ganciclovir, oseltamivir, zanamivir, peramivir, ritonavir, etc. These drugs often have strong toxic and side effects, and are prone to cause digestive tract and central nervous system reactions, especially more harmful to children with underdeveloped liver and kidney functions. Severe and above patients need to use glucocorticoids, which have an adverse impact on the growth and development of children. Therefore, there is an urgent need for an effective and body-friendly new treatment method to solve the problem of difficult medication after children's respiratory tract infections.

[0004] Whether antiviral or antibiotic drugs used clinically can only partially kill pathogenic microorganisms. In the case of complete immune deficiency, the proliferation rate of viruses and bacteria in the body is extremely astonishing. Therefore, the real power to control infection in the body is the body's own immune system, and drugs play an auxiliary role by reducing the load of pathogenic bacteria. Compared with adult immune cells, infant immune cells are more perfect. They are newly developed and have extremely strong killing and clearance abilities against germs. However, the nervous and endocrine systems of infants are not yet fully developed, resulting in weak overall coordination ability of the immune system, and immune cells are easily affected by the surrounding environment and their functions are easily inactivated. On the contrary, once exposed to adverse environmental factors, the functions of infant immune cells can quickly recover, thereby effectively controlling the infection.

[0005] Current medical research reveals that the human immune system and the gut microbiota have co-evolved. The immune system allows the colonization of symbiotic bacteria, inhibits the colonization and spread of pathogenic microorganisms; at the same time, the symbiotic bacteria produce a variety of small molecule substances such as short-chain fatty acids, indole derivatives, polyamines, and secondary bile acids, etc., to achieve positive regulation of innate immunity and adaptive immunity. Therefore, the imbalance of the gut microbiota has a negative impact on the body's anti-infection immune response. The gut microecology of infants and young children is still in the establishment stage. Improper diet or indigestion will affect the microecology, and then affect the immune cells of the system, including the natural immune cells and their T cells and B cells in the respiratory tract, reducing the resistance of the respiratory tract to pathogenic bacteria and leading to the occurrence of respiratory tract infections.

[0006] The gut microbiota is distributed throughout the intestine, but most of it aggregates in the large intestine mainly composed of the colon. Changing the gut microbiota by emptying the intestine and then regulating the immune system of infants and young children is a potential strategy for treating respiratory tract infections.

[0007] Glycerol enema is an over-the-counter drug that can be used to treat constipation, and its main ingredient is the chemical molecule glycerol. When glycerol enters the rectum, glycerol uses its high osmotic pressure characteristics to quickly absorb water molecules from the intestinal epithelial tissue into the intestinal lumen. The expansion of the intestinal lumen fluid volume causes intestinal wall contraction and defecation, clearing the gut microbiota. Such a method of emptying the intestine based on physical principles has no toxic side effects, and at the same time promotes the normalization of the gut microecology, and this normalization in turn normalizes the function of the respiratory immune cells of infants and young children, stimulating the control of respiratory tract infections. There have been literature reports suggesting that the gut microbiota can prevent infections and regulate pulmonary inflammatory responses.

[0008] The liver and kidney functions of children are not yet fully developed, and chemical drugs often have obvious toxic side effects on children. Glycerol enema is an ideal treatment option for children with respiratory tract infections because of its high safety, easy administration to infants and young children, and extremely low cost. The inventors found that glycerol enema can regulate the immune system by regulating the gut microbiota and become a new and effective drug for children to resist respiratory tract infections. Summary of the Invention

[0009] In order to overcome the lack of treatment means for children with respiratory tract infections, the present invention is specifically proposed.

[0010] The present invention relates to the use of glycerol enema in the preparation of a drug for treating children with respiratory tract infections.

[0011] Common glycerol enemas include two preparations. One is a glycerol preparation, and the other is a mannitol and magnesium sulfate preparation. The two preparations have different ingredients, but the principles are basically the same. The glycerol enema used in this application is a glycerol preparation. Unless otherwise specified, the glycerol enema mentioned hereinafter is a glycerol preparation.

[0012] The main component of Kaisailu is the chemical molecule glycerol, also known as glycerin. When glycerol enters the rectum, it utilizes its high osmotic pressure characteristics to rapidly draw water molecules from the intestinal epithelial tissue into the intestinal lumen. The expansion of the intestinal lumen fluid volume causes intestinal wall contraction and defecation, clearing the intestinal flora. Kaisailu clears the intestine based on physical principles and simultaneously promotes the normalization of the intestinal microecology, which in turn normalizes the functions of immune cells in the infant respiratory tract and stimulates the control of respiratory tract infections.

[0013] In a particular embodiment, Kaisailu contains 52.8 - 58.3% (weight / weight) of glycerol and purified water, or consists of 52.8 - 58.3% (weight / weight) of glycerol and purified water.

[0014] In a particular embodiment, the childhood respiratory tract infection is a childhood respiratory tract infection caused by microorganisms.

[0015] In a particular embodiment, in the childhood respiratory tract infection caused by microorganisms, the microorganisms are selected from bacteria, viruses, fungi, mycoplasmas, and chlamydias.

[0016] In a particular embodiment, in the childhood respiratory tract infection caused by microorganisms, the microorganisms are selected from bacteria and viruses.

[0017] In a particular embodiment, in the childhood respiratory tract infection caused by microorganisms, the microorganisms are selected from the SARS-CoV-2 virus and influenza virus. In a particular embodiment, the childhood respiratory tract infection is selected from coronavirus disease 2019 (COVID-19) and influenza.

[0018] In a particular embodiment, the child is 14 years old or younger.

[0019] The inventors found through experimental research that using Kaisailu has a significant curative effect on treating childhood respiratory tract infections. After using Kaisailu, the patient's body temperature drops to normal; the viral load detected by throat swab decreases; the levels of inflammation-related cytokines and C-reactive protein (CRP) in the blood decrease. Therefore, it can be shown that using Kaisailu has a therapeutic effect on childhood respiratory tract infections. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Showing that Kaisailu can restore the body temperature of febrile children to normal within a short time.

[0021] Figure 2 Showing that Kaisailu reduces the viral load in children.

[0022] Figure 3 Showing that Kaisailu decreases the levels of IL-6, TNFα, and IFNγ in the serum of children.

[0023] Figure 4It is shown that Kaisailu can reduce the CRP level in the serum of children. Specific Embodiments

[0024] Example 1. Kaisailu can normalize the body temperature of febrile children in a short time.

[0025] 1. Experimental Procedures

[0026] Measure the body temperatures of 20 children infected with the novel coronavirus (SARS-CoV-2 virus) and 20 children with influenza respectively. The measurement method is to use a digital thermometer placed under the tongue of the child to measure the oral body temperature.

[0027] Administer Kaisailu to 10 children infected with the novel coronavirus and 10 children with influenza as the sole treatment method. The Kaisailu used in this application is Kaisailu (containing glycerol) produced by Guangdong Hengjian Pharmaceutical Co., Ltd. Each vial is 10 mL and contains 52.8 - 58.3% (weight / weight) of the main component glycerol. The excipient is purified water. The usage and dosage are to remove the outer cap at the top of the container, apply a little grease, slowly insert it into the anus, and then squeeze the liquid medicine into the rectum. For children, 0.5 vials are used once. The children admitted to the hospital only received Kaisailu treatment once after admission. Unless otherwise specified, the same treatment method is used in subsequent treatments.

[0028] At the same time, take 10 children infected with the novel coronavirus and 10 children with influenza and treat them with a placebo.

[0029] Measure the body temperature every 6 hours after treatment with Kaisailu, record the body temperature, take the average value of the body temperatures of all children, and make a line graph ( Figure 1 ).

[0030] The children admitted in this experiment are between 2 and 13 years old, both male and female. They were sent to the hospital for admission after presenting fever symptoms and had not received treatment before. The children in subsequent experiments were all selected from the same batch of children.

[0031] 2. Experimental Results

[0032] (1) Kaisailu can normalize the body temperature of febrile children infected with the novel coronavirus in a short time, while there is no obvious change after using the placebo ( Figure 1 A in).

[0033] (2) Kaisailu can normalize the body temperature of febrile children with influenza in a short time, while there is no obvious change after using the placebo ( Figure 1 B in).

[0034] Example 2. Kaisailu reduces the viral load in children.

[0035] 1. Experimental Procedures

[0036] The viral loads of 15 children infected with novel coronavirus and 16 children with influenza were detected using throat swabs at the time of admission. 8 children infected with novel coronavirus and 8 children with influenza were treated with glycerin suppositories respectively, and 7 children infected with novel coronavirus and 8 children with influenza were treated with placebo. The tests were repeated 24 hours after treatment. The changes in the viral loads of the children before and after treatment were compared.

[0037] The method of throat swab detection was to use a sterilized long cotton swab to wipe the secretions on both palatine arches, pharynx, and tonsils of the children, collect the samples for real-time fluorescence RT-PCR, and confirm the viral nucleic acid content in the secretions. The CT value of PCR was used to measure the viral load.

[0038] 2. Experimental results

[0039] After treatment with glycerin suppositories, the viral loads of children infected with novel coronavirus and influenza decreased significantly, while there was no significant change after treatment with placebo ( Figure 2 ).

[0040] Example 3. Glycerin suppositories decrease the levels of IL-6, TNFα, and IFNγ in children's serum.

[0041] 1. Experimental procedures

[0042] The levels of cytokines IL-6, TNFα, and IFNγ in the sera of 15 children infected with novel coronavirus and 16 children with influenza were detected at the time of admission. 8 children infected with novel coronavirus and 8 children with influenza were treated with glycerin suppositories respectively, and 7 children infected with novel coronavirus and 8 children with influenza were treated with placebo. The levels of cytokines IL-6, TNFα, and IFNγ in the sera were detected again 24 hours after treatment, and the changes in the cytokine levels before and after treatment were compared.

[0043] The levels of cytokines IL-6, TNFα, and IFNγ in the sera were detected using methods well-known in the art, and the average values of all children were taken.

[0044] 2. Experimental results

[0045] (1) Glycerin suppositories can decrease the levels of IL-6, TNFα, and IFNγ in the sera of children with novel coronavirus infection-induced fever in a short time, while there is no significant change after treatment with placebo ( Figure 3 A in).

[0046] (2) Glycerin suppositories can decrease the levels of IL-6, TNFα, and IFNγ in the sera of children with influenza-induced fever in a short time, while there is no significant change after treatment with placebo ( Figure 3 B in).

[0047] Example 4. Glycerin enema reduces the CRP level in children's serum.

[0048] 1. Experimental procedure

[0049] Detect the levels of C-reactive protein (CRP) in the sera of 15 children infected with novel coronavirus and 16 children with influenza at the time of admission. Treat 8 children infected with novel coronavirus and 8 children with influenza with glycerin enema respectively, and treat 7 children infected with novel coronavirus and 8 children with influenza with placebo. Detect the levels of CRP in the sera again 24 hours after treatment, and compare the changes in CRP levels before and after treatment.

[0050] The levels of CRP in the sera are detected by methods well-known in the art, and the average values of all children are taken.

[0051] 2. Experimental results

[0052] After treatment with glycerin enema, the CRP levels in children infected with novel coronavirus and influenza decreased significantly, while there was no obvious change after treatment with placebo ( Figure 4 ).

[0053] In summary, the solution of this application has the following effects:

[0054] 1. The novel treatment strategy of using glycerin enema to treat children's respiratory tract infections mentioned in this application utilizes physical factors to empty the intestine, improve the intestinal flora, stimulate the body's immune system, and stimulate the immune system to control respiratory tract infections.

[0055] 2. Using glycerin enema to treat children's respiratory tract infections can quickly improve the infection symptoms of children, significantly reduce the inflammatory response of children, and has no obvious side effects, showing good clinical application prospects.

[0056] 3. The glycerin enema in this application is a common drug, and its safety and reliability have been verified, and it can be directly applied to the human body. Moreover, glycerin enema is safe, easy to operate, has extremely low cost, and has a medium adjustment effect, making it an ideal treatment option for children with respiratory tract infections.

Claims

1. Use of enema in preparing medicine for treating respiratory tract infection in children.

2. The use according to claim 1, wherein the pediatric respiratory tract infection is a pediatric respiratory tract infection caused by microorganisms.

3. The method according to claim 2, wherein the microorganism is selected from bacteria, viruses, fungi, mycoplasmas and chlamydia.

4. The method according to claim 3, wherein the microorganism is selected from bacteria and viruses.

5. The use according to claim 4, wherein the microorganism is selected from the group consisting of SARS-CoV-2 virus and influenza virus.

6. The method according to claim 1, wherein the respiratory tract infection in children is selected from the group consisting of novel coronavirus infection COVID-19 and influenza.

7. The use according to claim 1, wherein the child is 14 years old or younger.

Images