CN115040513B - Application of vitamin B6 and preparation thereof in preparation of medicines for preventing and/or treating infection or inflammation-related diseases - Google Patents

Application of vitamin B6 and preparation thereof in preparation of medicines for preventing and/or treating infection or inflammation-related diseases Download PDF

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CN115040513B
CN115040513B CN202210726507.XA CN202210726507A CN115040513B CN 115040513 B CN115040513 B CN 115040513B CN 202210726507 A CN202210726507 A CN 202210726507A CN 115040513 B CN115040513 B CN 115040513B
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infection
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pyridoxine
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文雯
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Hefei Han Microorganism Technology Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415Pyridoxine, i.e. Vitamin B6
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides application of vitamin B6 in preparing medicines for preventing and/or treating infection or inflammation-related diseases, researches on new application of VB6 in preventing and/or treating infection or inflammation-related diseases, and discovers that VB6 has the effects of preventing and/or treating infection or inflammation-related diseases, especially has the effects of resisting infection, slowing down the development of inflammatory symptoms of body tissues and preventing and protecting body tissues from being influenced by inflammation. Meanwhile, the inventor discovers that the vitamin B6 can improve the expression of related antibacterial peptide, which indicates that the vitamin B6 can realize anti-infection and alleviate the inflammatory symptoms of body tissues by changing the antibacterial peptide.

Description

Application of vitamin B6 and preparation thereof in preparation of medicines for preventing and/or treating infection or inflammation-related diseases
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of vitamin B6 (VB 6) in preparing a drug system for resisting bacterial infection, and application of the vitamin B6 in preparing a drug or a preparation for preventing and/or treating inflammatory diseases.
Background
Vitamin B6 (Vitamin B6, VB 6), also known as pyridoxine, is commonly known as C 8 H 10 NO 5 P, which includes pyridoxine (C 8 H 11 NO 3 ) Pyridoxal (pyridoxal, C) 8 H 9 NO 3 ) And pyridoxamine (C) 8 H 12 N 2 O 2 ) In vivo, in the form of phosphate esters, including pyridoxine (PNP), pyridoxal-5'phosphate, PLP, and pyridoxamine-5' phosphate, PMP, are water-soluble vitamins that are easily destroyed by light or alkali and are not resistant to high temperatures.
Vitamin B6 is a soluble trace element obtained from food, is a necessary substance for metabolism of fat and sugar of human body, and lack of vitamin B6 can cause inappetence, low food utilization rate, weightlessness, emesis, diarrhea and other manifestations, and severe deficiency can cause acne, anemia, arthritis, infantile spasm, depression, headache, hair loss, easy inflammation, learning disorder, weakness and other symptoms. Meanwhile, vitamin B6 is used as a clinical medicine for the treatment of various diseases, including: arteriosclerosis, alopecia, hypercholesterolemia, hypoglycemia, mental disorder, muscular disorder, neurological disorder, emesis in early pregnancy, postoperative emesis, etc. With the intensive research of clinical application, the vitamin B6 also has a certain treatment effect in the aspects of rescuing isoniazid poisoning, treating anemia, treating leukopenia and the like.
Disclosure of Invention
At present, no research on preventing and/or treating infection or inflammation-related diseases by vitamin B6 exists, and the application finds that the vitamin B6 has the effect of preventing and/or treating infection or inflammation-related diseases, especially protecting organisms from being invaded or damaged by inflammation and the like through the research on animal models such as mice, nematodes and the like, and can be used for preparing medicines/preparations for preventing and/or treating the inflammation or inflammation-related diseases.
In one aspect, the invention provides the use of vitamin B6 in the manufacture of a medicament for the prevention and/or treatment of infection or inflammation-related disorder, wherein the vitamin B6 comprises at least one of the following: pyridoxine, pyridoxal, pyridoxamine, or a pharmaceutically acceptable salt or ester thereof; the salts include hydrochloride, phosphate, and the like; the ester comprises at least one of pyridoxine phosphate, pyridoxal phosphate, pyridoxamine phosphate, pyridoxine dipalmitate.
The infection or inflammation-related disorder is inflammatory invasion or injury of tissues caused by infectious diseases or non-infectious diseases; the infectious disease may be an infection by a virus, chlamydia, mycoplasma, bacteria or parasite; the bacteria include at least one of: pseudomonas aeruginosa, salmonella, listeria, staphylococcus aureus, candida albicans, shigella, and the like. The non-infectious disease may be autoimmune hepatitis, arthritis, pancreatitis, gastroenteritis, familial hemophilus syndrome, systemic juvenile idiopathic arthritis, chimeric Antigen Receptor (CAR) -T cell therapy, or lupus erythematosus; the tissue in the inflammatory invasion or injury of tissue comprises at least one of: blood, lung, liver, kidney, heart, stomach, intestine, spleen.
In another aspect, the present invention also provides the use of vitamin B6 in the manufacture of a medicament for increasing expression of an antimicrobial peptide, wherein the vitamin B6 comprises at least one of: pyridoxine, pyridoxal, pyridoxamine, or a pharmaceutically acceptable salt or ester thereof; the salts include hydrochloride, phosphate, and the like; the ester comprises at least one of pyridoxine phosphate, pyridoxal phosphate, pyridoxamine phosphate, pyridoxine dipalmitate; the antimicrobial peptide comprises at least one of the following: ang4, defa5, bd3, lyz1, pla2g2a, reg3α, reg3β, reg3γ.
In still another aspect, the present invention also provides a use of a pharmaceutical composition in the prevention and/or treatment of infection or inflammation-related disorder, wherein the pharmaceutical composition comprises vitamin B6 and a pharmaceutically acceptable carrier or adjuvant; the vitamin B6 comprises at least one of the following: pyridoxine, pyridoxal, pyridoxamine, or a pharmaceutically acceptable salt or ester thereof; the salts include hydrochloride, phosphate, and the like; the ester comprises at least one of pyridoxine phosphate, pyridoxal phosphate, pyridoxamine phosphate, pyridoxine dipalmitate.
The pharmaceutical composition may also comprise other pharmaceutically acceptable drugs or other related active substances for preventing and/or treating infection or inflammation-related diseases.
The infection or inflammation-related disorder is inflammatory invasion or injury of tissues caused by infectious diseases or non-infectious diseases; the infectious disease may be an infection by a virus, chlamydia, mycoplasma, bacteria or parasite; the bacteria include at least one of: pseudomonas aeruginosa, salmonella, listeria, staphylococcus aureus, candida albicans, shigella, and the like. The non-infectious disease may be autoimmune hepatitis, arthritis, pancreatitis, gastroenteritis, familial hemophilus syndrome, systemic juvenile idiopathic arthritis, chimeric Antigen Receptor (CAR) -T cell therapy, or lupus erythematosus; the tissue in the inflammatory invasion or injury of tissue comprises at least one of: blood, lung, liver, kidney, heart, stomach, intestine, spleen.
The dosage forms of the pharmaceutical composition comprise oral preparations, injection preparations, transdermal administration preparations, mucous membrane administration preparations, pulmonary inhalation administration preparations or intestinal administration preparations; specifically, the dosage form of the pharmaceutical composition comprises: drops, oral liquid, tablet, capsule, granule, film, gel, powder, emulsion, self-emulsifying preparation, dripping pill, suppository, aerosol, spray, powder fog agent, patch, emplastrum, solution, ointment or cream.
The invention has the beneficial effects that:
the invention researches the new application of VB6 in preventing and/or treating infection or inflammation-related diseases, and discovers that VB6 has the effects of preventing and/or treating infection or inflammation-related diseases, especially has the effects of resisting infection, slowing down the development of inflammatory symptoms of body tissues and preventing and protecting the body tissues from being influenced by inflammation. Meanwhile, the inventor finds that the vitamin B6 can improve the expression of related antibacterial peptide, which indicates that the vitamin B6 can realize anti-infection and alleviate the inflammatory symptoms of the organism tissues by changing the antibacterial peptide.
Drawings
Figure 1 is a statistical graph of nematode survival in a model of nematode infection with pyridoxine. Fig. 1A and 1B are two independent replicates, respectively. Wherein the control group is nematodes which are added into a culture medium containing pseudomonas aeruginosa PA14 colonies and metabolites; pyridoxine group nematodes were added to the medium containing pyridoxine and pseudomonas aeruginosa PA14 colonies and metabolites.
FIG. 2 is a phenotypic analysis of pyridoxine in a mouse infection model. Fig. 2A shows the percentage change of the body weight of the mice, fig. 2B shows the colonization of the intestinal tract of the mice, fig. 2C shows the distribution of the pathogenic bacteria in the various organs and blood of the mice, fig. 2D shows the colon length of the mice, and fig. 2E shows the spleen size of the mice. Wherein the blank group is lavage PBS, and is not infected by pathogenic bacteria; the control group is lavage PBS, and is infected by salmonella; the pyridoxine group is lavage pyridoxine, administered with salmonella infection. Where p <0.05, p <0.01, p <0.001 all have significant differences.
Figure 3 phenotypic analysis of vitamin B6 in a mouse infection model. Fig. 3A shows the percentage change of the body weight of the mice, fig. 3B shows the statistical graph of the survival rate of the mice, fig. 3C shows the colonization of the intestinal tract of the mice, fig. 3D shows the distribution of the pathogenic bacteria in the various organs and blood of the mice, fig. 3E shows the colon length of the mice, and fig. 3F shows the spleen size of the mice. Wherein the blank group is lavage PBS, and is not infected by pathogenic bacteria; the control group is lavage PBS, and is infected by salmonella; the pyridoxine group is lavage pyridoxine, administered with salmonella infection. Where p <0.05 has significant differences.
FIG. 4qPCR verifies the expression of the antimicrobial peptide gene in the colon tissue of mice. Wherein the control group is lavage PBS, and Salmonella infection is administered; the vitamin B6 group is lavage vitamin B6 and is administered with salmonella infection. Where p <0.05, p <0.01 all have significant differences.
Figure 5 vitamin B6 is essential for the protection of enteritis. Fig. 5A shows the percentage change in the body weight of the mice, fig. 5B shows the colonization of the intestinal tract of the mice by pathogenic bacteria, fig. 5C shows the colon length of the mice, fig. 5D shows the statistics of the colon length of the mice, fig. 5E shows the spleen size of the mice, and fig. 5F shows the spleen weight statistics of the mice. Wherein the blank group is not infected by pathogenic bacteria; the control group was lavage PBS, which was given Salmonella infection. Where p <0.05 has significant differences.
Detailed Description
The following examples are further illustrative of the technical content of the present invention, but the essential content of the present invention is not limited to the examples described below, and those skilled in the art can and should know that any simple changes or substitutions based on the essential spirit of the present invention should fall within the scope of the present invention as claimed.
Example 1 pyridoxine has anti-infective effects in models of nematode infection
Nematodes live in animals and plants, or freely living in soil, fresh water and seawater environments, most of which live spontaneously, and very few of which live in the human body and cause diseases. The commonly known nematodes, in particular caenorhabditis elegans (Caenorhabditis elegans), are very small worms, larvae of roundworms and other parasitic nematodes, which are parasitic in the soil layer and active in the role of model organisms. Caenorhabditis elegans feed on bacteria, including pseudomonas aeruginosa, but pseudomonas aeruginosa is pathogenic and lethal to nematodes. Thus, P.aeruginosa can be used to feed caenorhabditis elegans and observe whether there is a difference in survival rate in nematodes with additional pyridoxine addition.
Pseudomonas aeruginosa PA14 (ATCC source) was streaked and selected for monoclonal into tubes containing LB medium (Soy pal, L1010) and incubated overnight at 37 ℃. 20 mu L of bacterial liquid is vertically dripped into the center of a 6cm NGM culture medium (MyBioSource, MBS 652720-C) flat plate, placed in a super clean bench for blow drying, placed in a 37 ℃ incubator for 12 hours of culture, and 100 mu L of prepared 1mmol/mL pyridoxine (sigma, P5669-5G) is uniformly dripped onto the surface of bacteria and blow dried for later use. Caenorhabditis elegans (provided by the institute of genetics and developmental biology Tian subject group of the academy of sciences of China) synchronizing the spawning period, collecting adults in the L4 period, adding the adults to NGM plates containing pseudomonas aeruginosa PA14 colonies and metabolites, and counting the survival rate of the nematodes every 12 hours until the nematodes are all dead. As shown in fig. 1, the results show that the nematodes fed with pyridoxine show greater anti-infective and viability at different times, indicating that pyridoxine has anti-infective and nematode longevity effects in a model of nematode infection.
Example 2 pyridoxine has anti-infective, enteritis-slowing effects in mice infection models
Mice (C57 BL/6 mice, male, 6-8 weeks, purchased from south-jing college ex-rakanka) were intragastrically perfused with pyridoxine every day 7 days in advance and continued until the end of the entire experiment. Salmonella typhimurium SL1344 (from ATCC) was streaked on LB plates of streptomycin 100. Mu.g/mL (BBI, A610494-0050), and the single clone was picked up and cultured overnight at 37℃in LB liquid medium containing streptomycin, and the next day inoculated into blank LB medium and cultured at 37 ℃. When OD is 600 During the period of 0.5-0.8, collecting appropriate amount of bacteria, washing twice with PBS, calculating bacterial dosage, and re-suspending in PBS for use. After 7 days of gastric pyridoxine infusion, the total amount of infection per mouse was 1X 10 6 Bacterial count of cfu mice were gastrected with salmonella typhimurium SL1344 dailyMice were monitored for body weight and infection status.
Mouse fecal salmonella colony count: the colony count of the salmonella in the mice reflects the infection condition of the intestinal tracts of the mice, and the more the colony count is, the more the colony count is planted in the intestinal tracts of the mice, and the more serious the infection is. Each mouse is put into a sterile box for collecting fresh feces of the mouse every day, PBS buffer solution (Saiweier, G4207) is added according to the proportion of 50mg/mL, glass beads are added, the mixture is ground by a tissue homogenizer, and a proper volume is taken for gradient dilution to 10 -2 ,10 -3 ,10 -4 . mu.L was uniformly spread on streptomycin LB plates, and the number of CFU was counted after overnight incubation.
Colon length: colon length reflects the conditions of intestinal infection and intestinal inflammation in mice. One week after infection, mice were sacrificed, the colon was removed, and the length of the colon was measured, with shorter colon length indicating more severe intestinal infection.
Spleen size: the spleen size reflects the inflammatory status of the mice, the larger the spleen, indicating that the more severe the inflammation of the mice. One week after infection, mice were sacrificed, spleens were removed, and spleens of the mice were photographed and weighed.
Organ colony count CFU: the CFU of each organ reflects the severe condition that bacteria evade immune invasion of intestinal mucosa into the body. Blood CFU is obtained by taking blood from eyeballs of mice, directly carrying out gradient dilution and then coating, organs such as spleen, liver, colon, cecum and the like are obtained by dissecting the mice after sacrificing the mice, PBS and glass beads/steel balls are added, then a tissue refiner is used for grinding, a proper amount of the mixture is taken for gradient dilution and coating, and CFU in the organs is calculated.
As shown in the result of figure 2, the mice infused with pyridoxine show more stable weight change, smaller spleen and longer colon length relative to the control group, and the number of CFU in each organ is smaller, which shows that pyridoxine has good protective effect on infectious enteritis, splenitis and the like and has preventive effect.
Example 3 vitamin B6 has anti-infective, enteritis-slowing effects in mice infection model
Mice (C57 BL/6 mice, males, 6-8 weeks) were intragastrically injected with vitamin B6 injection (national drug Co.) 7 days in advance and continued until the end of the entire experiment. Seven days later, infection with Salmonella typhimurium SL1344 was performed, and the method and dosage of infection were consistent with example 2, and the weight and survival of mice were counted daily. As shown in fig. 3, the statistical result shows that the effect of the intragastric vitamin B6 is consistent with that of the intragastric pyridoxine, the mice with the intragastric vitamin B6 show more stable weight change, smaller spleen and longer colon length, and the number of CFUs in each organ is smaller, which shows that the vitamin B6 plays a good protective role on infectious enteritis, splenitis and the like in various aspects, and has a preventive effect.
After the molding is finished, the mice are sacrificed, colon tissues of the mice are taken, RNA is extracted, and qPCR detection is carried out on the antibacterial peptide of the mice. As shown in the results of FIG. 4, the antimicrobial peptides ang4 and defa, etc. of the ileum of the vitamin B6 group mice are obviously changed. The angiogenin 4 (ang 4) is a novel antibacterial peptide, is mainly expressed in intestinal tissues of mammals, has antibacterial and angiogenesis promoting functions, and plays an important role in the immune process and the angiogenesis process of organisms on pathogens. Defa is a generic term for defensins, a class of endogenous antimicrobial peptides, also an important component of its own defensin system, and Defa5 is a defensin alpha 5 in the defensin family, playing an important role in combating pathogenic bacterial infections. The rise in the antimicrobial peptide in the colon of the mice suggests that vitamin B6 may be resistant to infection by altering the antimicrobial peptide.
The specific method comprises the following steps:
1. a1 cm section of colon was taken, transferred to a 1.5mL EP tube with Trizol containing steel beads, added with 0.2mL of chloroform (1/5 Trizol amount of chloroform) according to 1mL of Trizol, and then vigorously shaken for 15s, and left at room temperature for 5min. Centrifuging at 12000g for 15min at 4deg.C, transferring 200 μL supernatant into EP tube of new RNase free, adding equal amount of isopropanol, and precipitating; mixing the solution thoroughly, standing at 4deg.C for 10min to precipitate RNA (if RNA amount is large, not standing for 10 min); centrifuging at 12000g at 4deg.C for 15-30min, discarding supernatant, adding 1mL of 75% ethanol (prepared by DEPC water), washing RNA precipitate, centrifuging at 7500g at 4deg.C for 3min; drying the RNA. Carefully discarding the supernatant after centrifugation, centrifuging for 5s in a short time, collecting the liquid on the tube wall to the bottom of the tube, sucking the liquid by using an RNase free gun head, opening the tube cover of the centrifuge tube to dry RNA for 15min (careful RNase pollution), adding a proper amount of DEPC water after the RNA precipitate becomes transparent, fully dissolving, uniformly mixing, centrifuging, and preserving at-80 ℃ for a long time.
2. Reverse transcription (RNA-reverse transcription):
genomic gDNA was removed using a reverse transcription kit (Norflu, R323), and a reaction mixture (4. Mu.L system) was prepared as follows:
Figure BDA0003713438880000051
Figure BDA0003713438880000061
42℃2min/37℃5min
4℃∞
reverse transcription (5. Mu.L System)
The reaction solution of the previous step (genome removal step) 4μL
5x RT Enzyme Mix 1μL
Procedure for reverse transcription:
37℃15min
85℃5s
4℃5min
with ddH 2 The cDNA product was diluted 10-fold with O, stored at 4℃for short period and at-20℃for long period.
rt-PCR (real-time PCR):
and carrying out real-time fluorescence quantitative PCR detection by taking the cDNA extracted in the steps as a template. The following components are prepared in an 8-joint tube:
Figure BDA0003713438880000062
and (3) centrifuging for a short time, mixing uniformly, putting into a quantitative PCR instrument, setting a program, and amplifying by a two-step method. The procedure is: pre-denatured for 60 seconds, 95 ℃.45 reaction cycles: 95 ℃ for 10 seconds; 60℃for 30 seconds. Fluorescence is collected at the end of each cycle extension. Use 2 -ΔΔCt The analysis method processes the data.
4. Primer list
Figure BDA0003713438880000063
Figure BDA0003713438880000071
Example 4 vitamin B6 deficiency exacerbates infectious inflammation in mice
To verify the importance of vitamin B6 for enteritis we constructed a vitamin B6 deficiency/normal/additive model. We ordered pyridoxine deficient foods and constructed four groups of vitamin B6 deficient salmonella infection, normal food control group salmonella infection, vitamin B6 salmonella infection, normal food non-infection for experiments, salmonella infection with different foods being fed at the same time. As shown in fig. 5, the vitamin B6 deficient mice lost the most rapidly after salve infection, and the normal diet control group lost the most slowly with vitamin B6 addition. According to the field planting condition analysis of salmonella in the intestinal tract of mice, the addition of vitamin B6 can reduce the field planting of salmonella in the intestinal tract. Colon length also showed that vitamin B6 addition group had the least intestinal inflammation. In conclusion, vitamin B6 is important for protecting infectious enteritis, and the vitamin B6 can resist enteritis of mice and has therapeutic effect.
It should be noted that the foregoing technical disclosure is only for explanation and illustration to enable one skilled in the art to know the technical spirit of the present invention, and the technical disclosure is not intended to limit the scope of the present invention. The essential scope of the invention is as defined in the appended claims. Those skilled in the art should understand that any modification, equivalent substitution, improvement, etc. made based on the spirit of the present invention should fall within the spirit and scope of the present invention.

Claims (5)

1. Use of pyridoxine as sole active ingredient in the manufacture of a medicament for combating pseudomonas aeruginosa infection.
2. The use according to claim 1, wherein the medicament comprises pyridoxine and a pharmaceutically acceptable carrier or adjuvant.
3. The use according to claim 2, wherein the pharmaceutical is in a dosage form selected from the group consisting of oral, injectable, transdermal, mucosal, pulmonary or enteral formulations.
4. The use according to claim 3, wherein the pharmaceutical dosage form is selected from the group consisting of: oral liquid, tablet, capsule, granule, film, gel, powder, emulsion, dripping pill, suppository, aerosol, spray, powder fog, patch, ointment or cream.
5. The use according to claim 3, wherein the medicament is in the form of drops, patches, solutions.
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US5254572A (en) * 1987-11-27 1993-10-19 Vesta Medicines (Pty) Ltd. Method and composition for supplementing vitamin B6 where the PN-PLP pathway is disturbed
NZ222664A (en) * 1986-11-29 1990-06-26 Vesta Med Pty Ltd Pharmaceutical compositions containing pyridoxal as a source of vitamin b6
US20090215727A1 (en) * 2005-05-05 2009-08-27 Medicure International Inc. Inhibition of atp-mediated, p2x7 dependent pathways by pyridoxal-5-phosphate and vitamin b6 related compounds
WO2008046202A1 (en) * 2006-10-20 2008-04-24 Medicure International Inc. USE OF PYπDOXAL-5'-PHOSPHATE FOR IMPROVING THE IMMUNE RESPONSE AND TREATMENT AND PREVENTION OF POST-OPERATIVE INFECTIONS
US20170056381A1 (en) * 2014-02-20 2017-03-02 Nanometics Llc Pyridoxamine for the treatment of sickle cell disease, thalassemia and related blood diseases
US20190247360A1 (en) * 2018-02-09 2019-08-15 Edward Wick Pharmaceutical Composition for Treating Bacterial and Viral infections
CN116367823A (en) * 2020-10-28 2023-06-30 帝斯曼知识产权资产管理有限公司 Direct delivery of vitamins to inhibit microbial pathogens

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