CN115634236B - Multi-tungstate compound for relieving colonitis and preparation method and application thereof - Google Patents
Multi-tungstate compound for relieving colonitis and preparation method and application thereof Download PDFInfo
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- CN115634236B CN115634236B CN202110810895.5A CN202110810895A CN115634236B CN 115634236 B CN115634236 B CN 115634236B CN 202110810895 A CN202110810895 A CN 202110810895A CN 115634236 B CN115634236 B CN 115634236B
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Abstract
The invention discloses a multi-tungstate compound for relieving colonitis, and a preparation method and application thereof. The multi-tungstate compound consists of 76-88% of multi-tungstate and 12-24% of dispersing agent according to mass percentage; wherein the dispersing agent is at least one of polypeptide, surfactant and polysaccharide. The polytungstate complex is dissolved in an aqueous solution and administered orally to mice. After oral administration of the polytungstate complex to a mouse suffering from colitis for a period of time, the symptoms of colitis can be alleviated, wasting due to colitis can be alleviated, and the unbalanced intestinal microflora can be restored to an equilibrium state. The poly-tungstate compound has no obvious influence on mammals, does not directly produce anti-inflammatory effect on animals, but acts on intestinal bacteria in the bodies of the animals, so that adverse side effects on the animals can be avoided.
Description
Technical Field
The invention belongs to the field of biotechnology for veterinary use, and particularly relates to a multi-tungstate compound for relieving colonitis, and a preparation method and application thereof.
Background
Inflammatory bowel disease is one of the most common diseases in pets that cause abdominal pain, cramps, and weight loss of unknown origin. Inflammatory bowel disease has increased significantly over the past decades due to genetic, environmental, geographic, psychological and many other factors. Colitis is an inflammatory bowel disease that causes inflammation and ulceration of the colon and rectum. The chronic and unhealed colonic cancer of human is likely to cause colorectal cancer, so that the inflammatory bowel disease needs to be treated in time, and the progress of the disease is closely concerned.
The current common method for clinically treating colonitis mainly comprises the step of inhibiting the immune response of a host through immune inhibition drugs such as small molecule drugs or biological agents. Although immunosuppressant drugs can reduce inflammatory response in colitis patients, these therapies neither repair damage to intestinal mucus layers nor address the imbalance of intestinal microflora. Alterations in gut microbiota composition and function are associated with a number of major chronic diseases including inflammatory, metabolic, autoimmune and neurodegenerative diseases. One of the symptoms of colitis is the outbreak of opportunistic pathogens in the gut, altering the sensitivity of the host to inflammation and microbial irritation. During the onset of colitis, intestinal microorganisms affect the composition of host intestinal bioactive molecules, thereby modulating the function of host immune cells, triggering an inflammatory response.
Nanotherapy achieves positive effects in stabilizing the environment in the intestinal tract and treating inflammatory diseases. In order to make substantial progress, more effort is required to develop nanosystems that are capable of modulating intestinal microbiota, while at the same time improving inflammatory response to colitis. Polytungstates are a class of sub-nanoscale metal oxides that are widely used in materials, chemistry and bioscience. The living body utilizes the characteristics of metal ions to complete a series of life processes which cannot be replaced by other organic matters. Tungsten is involved in biochemical activities within cells such as oxygen transport, electron transport, regulation of protein structure and function, ion transport, isomerization, catalytic degradation of DNA and RNA, and the like. Tungsten has been used in the chemical industry to prepare tungsten complexes and to further build a set of catalytic systems to simulate nitrogen fixation enzymes. The nitrogen is protonated on the tungsten complex and ammonia is produced at one atmosphere under reaction conditions similar to those of nitrogen-fixing enzymes produced by nitrogen-fixing bacteria. Thus, the present invention employs sub-nanometer-scale polytungstate to ameliorate inflammatory response to colitis.
Disclosure of Invention
To solve the disadvantages and shortcomings of the prior art, the primary object of the present invention is to provide a multi-tungstate complex for relieving colitis.
The invention provides an alternative nano-complex for targeting inflammatory colon and regulating intestinal microbiota, namely a multi-tungstate complex for relieving colonitis. The poly-tungstate compound is prepared by assembling the poly-tungstate and the dispersing agent together, and can be administered to animals through a drinking water way to exert the activity of the poly-tungstate to inhibit bacterial nitrate reductase, limit the malignant expansion of bacteria of the family anaerobic enterobacteriaceae, enable the intestinal microorganisms of a host to restore the balance state and alleviate the adverse effects of intestinal bacteria imbalance.
Another object of the present invention is to provide a method for preparing the above-mentioned complex of polytungstate for relieving colitis. The preparation method is simple.
It is still another object of the present invention to provide the use of the above-mentioned polytungstate complex for relieving colitis in food additives and for preparing pharmaceutical preparations.
The invention aims at realizing the following technical scheme:
the multi-tungstate compound for relieving colonitis consists of 76-88% of multi-tungstate and 12-24% of dispersing agent according to mass percentage;
The sum of the mass percentages of the components is 100 percent;
the molecular composition of the polytungstate is K nNa14-n[NaP5W30O110]·mH2 O;
the dispersing agent is at least one of polypeptide, surfactant and polysaccharide.
Preferably, the multi-tungstate compound for relieving the colonitis consists of 83-87% of multi-tungstate and 13-17% of dispersing agent in percentage by mass.
Preferably, the polytungstate K nNa14-n[NaP5W30O110]·mH2 O, n=10 to 13, m=5 to 20, has a molecular weight of 8.0 to 8.4kDa.
More preferably, the polytungstate K nNa14-n[NaP5W30O110]·mH2 O, n=11 to 13, m=5 to 8.
Preferably, the polypeptide is at least one of a natural polypeptide sequence and an artificially synthesized artificial polypeptide.
More preferably, the polypeptide has a molecular weight of 2.1 to 2.7kDa.
Most preferably, the amino acid sequence of the polypeptide is GIGKFLHSAKKFGKAFVGEIMNS.
Preferably, the surfactant is at least one of ditetradecyl dimethyl ammonium bromide and ditetradecyl dimethyl ammonium bromide; more preferably, it is dicetyl dimethyl ammonium bromide.
Preferably, the polysaccharide is chitosan.
More preferably, the viscosity of the chitosan is <200mpa.s and the molecular weight is 10-50 kDa; still more preferably 30kDa.
The preparation method of the multi-tungstate compound for relieving colonitis comprises the following steps:
Uniformly mixing the aqueous solution of the polytungstate and the aqueous solution of the dispersing agent, incubating for 2-8 hours at the temperature of 0-10 ℃, and removing the solvent and the dispersing agent which are not combined to obtain the polytungstate compound.
Preferably, the concentration of the aqueous solution of the poly-tungstic acid is 0.5-2.0 mg/mL, and the concentration of the aqueous solution of the dispersing agent is 0.2-1.2 mg/mL. The solvent of the dispersant aqueous solution is at least one of acetic acid buffer solution, PBS buffer solution and water.
Preferably, the incubation is at a temperature of 0 to 10℃for a period of 2 to 6 hours.
Preferably, the removal of the solvent means removal of water; the method for removing the solvent comprises the following steps: filtering the product mixture through a 0.22 mu m water phase filter membrane, collecting filtrate, adding ethanol to precipitate a complex, washing the product with ethanol, collecting the precipitate complex, and freeze-drying at-20-5 ℃ for 8-24 hours to obtain the poly-tungstate complex.
Preferably, the colitis-alleviating polyglutamate complex is stored in dry powder form.
The application of the polytungstate compound for relieving colonitis in food additives and preparing pharmaceutical preparations.
Preferably, the use of the colitis-alleviating poly-tungstate complex in the preparation of an animal food; more preferably in the preparation of pet treats.
The technical principle of the invention is as follows: the higher tungsten readily polymerizes to form anions having sub-nanometer dimensions, which behave somewhat like phosphates but unlike phosphorus, tungsten can mediate oxygen atom transfer reactions like molybdenum. Tungsten inhibits periplasmic nitrate reductase activity of plant and anaerobically grown enterobacteria by replacing molybdenum atoms in molybdenum cofactors in metalloenzymes, and has no obvious effect on mammalian enzyme systems. This is one of the possible reasons why tungsten can inhibit respiration of anaerobically growing intestinal bacteria in the intestinal tract, thereby inhibiting malignant proliferation of pathogenic intestinal bacteria, and finally realizing balance of the intestinal ecosystem of the organism.
Compared with the prior art, the invention has the following advantages:
(1) The synthesis process of the multi-tungstate compound for relieving the colonitis is simple, raw materials are easy to obtain, the quality of products is easy to control, and the mass production is facilitated.
(2) The multi-tungstate compound for relieving the colonitis can be supplemented into a body in a drinking water mode, so that the generation of drug resistance psychology for patients is avoided.
(3) The polytungstate in the polytungstate compound for relieving the colonitis achieves the aim of relieving the colonitis mainly by balancing intestinal microorganism groups, does not directly act on the immune system of an organism, does not directly inhibit the immune response of the organism, and therefore, does not interfere the immune system of the organism and does not generate corresponding side effects.
Drawings
Fig. 1 is a schematic illustration of the preparation of a multi-tungstate complex for relieving colitis according to the invention.
FIG. 2 is a thermogravimetric analysis of the polytungstate of example 1.
FIG. 3 is a 31 P nuclear magnetic resonance spectrum of the polytungstate-polypeptide complex of example 1.
FIG. 4 is an infrared spectrum of the polytungstate-DCTAB complex of example 2.
FIG. 5 is an ultraviolet-visible spectrum of the polytungstate-chitosan complex of example 3.
FIG. 6 is a physical image of a solution of the polytungstate-polypeptide complex of comparative example 1 mixed with a solution of Dextran Sodium Sulfate (DSS), and a physical image of a gel formed after the polytungstate is mixed with a solution of Dextran Sodium Sulfate (DSS).
FIG. 7 is a graph comparing the decrease in inflammatory factor mRNA transcription levels of mice two weeks after administration of the polyglutamate-polypeptide complex of example 1 to mice in example 4.
FIG. 8 is a graph comparing the recovery of body weight of a colitis mouse 10 days after administration of the polytungstate-polypeptide complex of example 1 to the mouse in example 4.
FIG. 9 is a graph showing the inhibition of the activity of E.coli nitrate reductase in example 4 after anaerobic culture supplemented with the polytungstate-polypeptide complex of example 1 in the culture medium.
FIG. 10 is a graph comparing the number of abnormally amplified E.coli in a colitis mouse 10 days after administration of the polyglutamate-polypeptide complex of example 1 to the mouse in example 4.
FIG. 11 is a graph showing the comparison of liver and kidney tissue sections of mice given with the polytungstate-polypeptide complex (KPC) of comparative example 2 and the polytungstate-chitosan complex (DCC) of comparative example 3 for 10 days, respectively, in comparative examples 2 and 3.
FIG. 12 is a graph comparing the white blood cell count in the blood of mice 15 days after administration of the polytungstate-DCTAB complex of example 2 and 12 days after administration of the polytungstate-chitosan complex of example 3, respectively, in examples 5 and 6.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but embodiments of the present invention are not limited thereto.
The specific conditions are not noted in the examples of the present invention, and are carried out according to conventional conditions or conditions suggested by the manufacturer. The raw materials, reagents, etc. used, which are not noted to the manufacturer, are conventional products commercially available.
Example 1
0.002G of a polytungstate salt (molecular formula K 13Na1[NaP5W30O110]·5H2 O, synthetic method reference chem. Commun.,2020,56,5287) was weighed and dissolved in 2.0mL of sterile water to prepare a 1mg/mL aqueous polytungstate salt solution. 0.001g of the polypeptide (amino acid sequence: GIGKFLHSAKKFGKAFVGEIMNS) was weighed and dissolved in 1.0mL of sterile PBS buffer (pH 7.2) to prepare an aqueous polypeptide solution having a mass concentration of 1 mg/mL. Under ice bath conditions, to 2mL concentration of 1mg/mL aqueous solution of poly tungstate solution added to 0.3mL polypeptide aqueous solution, the two are fully mixed, and then incubated at 0 ℃ for 6 hours. After the incubation is completed, the product mixture is filtered through a 0.22 mu m water phase filter membrane, the filtrate is collected, the ethanol precipitation complex is added, the product is washed by using ethanol, the precipitation complex is collected, and the freezing drying is carried out for 16 hours at the temperature of minus 20 to 5 ℃ to obtain the poly tungstate-polypeptide complex. The preparation schematic diagram of the poly-tungstate-polypeptide complex in this embodiment, the thermogravimetric analysis diagram of the poly-tungstate and the characterization result of the 31 P nmr spectrum are shown in fig. 1,2 and 3, respectively.
Example 2
0.002G of a polytungstate salt (molecular formula K 12Na2[NaP5W30O110]·8H2 O, synthetic method reference chem. Commun.,2020,56,5287) was weighed and dissolved in 1.0mL of sterile water to prepare a 2mg/mL aqueous polytungstate salt solution. 0.001g of dicetyl dimethyl ammonium bromide (DCTAB) was weighed out and dissolved in 1.0mL of sterile water to prepare a DCTAB aqueous solution having a mass concentration of 2 mg/mL. Under ice bath conditions, to 2mL 1mg/mL aqueous solution of polytungstate salt water added with 0.4mLDCTAB aqueous solution, the two were thoroughly mixed, and then incubated at 0 ℃ for 4 hours. After the incubation is completed, the product mixture is filtered through a 0.22 mu m water phase filter membrane, the filtrate is collected, the ethanol precipitation complex is added, the product is washed by using ethanol, the precipitation complex is collected, and the freezing and drying are carried out for 12 hours at the temperature of minus 20 to 5 ℃ to obtain the poly tungstate-DCTAB complex. The preparation schematic diagram and the characterization result of the infrared spectrogram of the polytungstate-DCTAB compound are shown in figures 1 and 4 respectively.
Example 3
0.001G of a polytungstate salt (molecular formula K 11Na3[NaP5W30O110]·6H2 O, synthetic method reference chem. Commun.,2020,56,5287) was weighed and dissolved in 2.0mL of sterile water to prepare a 0.5mg/mL aqueous polytungstate salt solution. 0.001g chitosan (viscosity less than <200mPa.s, molecular weight about 30 kDa) was weighed and dissolved in 2.0mL sterile acetic acid buffer solution (pH 4.0) to make an aqueous chitosan solution with a mass concentration of 0.5 mg/mL. Under ice bath conditions, 0.2mL of chitosan aqueous solution was added to 1mL of aqueous polytungstate solution with a concentration of 0.5mg/mL, and after thoroughly mixing the two, the mixture was incubated at 0℃for 2 hours. After the incubation is completed, the product mixture is filtered through a 0.22 mu m water phase filter membrane, the filtrate is collected, the ethanol precipitation complex is added, the product is washed by using ethanol, the precipitation complex is collected, and the mixture is freeze-dried for 18 hours at the temperature of minus 20 to 5 ℃ to obtain the poly tungstate-chitosan complex. The preparation schematic diagram and the characterization result of the ultraviolet-visible spectrum of the poly-tungstate-chitosan complex are shown in fig. 1 and 5 respectively.
Comparative example 1
0.005G of a polytungstate salt (molecular formula K 13Na1[NaP5W30O110]·5H2 O, synthetic methods reference chem. Commun.,2020,56,5287) was weighed and dissolved in 1.0mL of sterile water to prepare a stock solution of a polytungstate salt aqueous solution having a mass concentration of 5.0 mg/mL. 0.05g of Dextran Sodium Sulfate (DSS) was weighed and dissolved in 100mL of sterile water to prepare a 5% strength by mass aqueous dextran sodium sulfate solution. To 10mL of aqueous sodium dextran sulfate solution was added 6.67mL of aqueous poly tungstate solution at room temperature, and incubated at 25℃for 6 hours. After the incubation is completed, the poly tungstate-sodium dextran sulfate gel is obtained. A photograph of the polytungstate-dextran sodium sulfate gel of this comparative example is shown in FIG. 6. Because of gel formation, the sample has poor flowability, cannot be given to animals by a drinking water way, and is difficult to reduce colonitis symptoms of the animals in an effective way.
Example 4
The effect of the polytungstate-polypeptide complex prepared in example 1 on the alleviation of colitis by balancing the intestinal microbial population of mice is specifically illustrated.
The construction of the colitis mouse model adopts female C57BL/6J mice purchased from Shanghai Jieshijie laboratory animal Co., ltd., 6-8 weeks old. After two weeks of adaptive feeding, C57BL/6J mice were continuously given 3% aqueous dextran sodium sulfate solution via the drinking water route for at least one week (i.e., provided continuously daily, the water in the drinking bottle of the mice was changed to 3% aqueous dextran sodium sulfate solution) to induce the mice to develop colitis.
Control group: healthy mice were continuously given aqueous PBS (pH 6.8) via the drinking water route (i.e., supplied continuously daily, with the water in the drinking bottle of the mice replaced with aqueous PBS), and the other conditions were the same as those of the experimental group, which was C57BL/6J mice as a blank group.
Experimental group: healthy mice were tested for their ability to develop colitis by simultaneous continuous administration of 3% aqueous dextran sodium sulfate and 0.3% aqueous polytungstate-polypeptide complex or continuous administration of only 0.3% aqueous polytungstate-polypeptide complex (i.e., provided continuously daily, water in the drinking bottle of the mice was replaced with a mixed aqueous solution containing 3% sodium dextran sulfate and 0.3% polytungstate-polypeptide complex) via the drinking water route. After two weeks of continuous replenishment of the aqueous solution of the polytungstate-polypeptide complex by the drinking water route, the colon and cecum tissues of the mice were removed, snap frozen and mRNA extracted. The transcription level of the inflammatory factor mRNA related to inflammation was measured by reverse transcription PCR technique, and the result is shown in FIG. 7. The mRNAs tested corresponded to the inflammatory factors iNOS, TNF-. Alpha., IL-6, LCN2, IFN-. Gamma., CXCL1 and CXCL2, and the corresponding genes encoding these inflammatory factors were Nos2, tnf, IL6, lcn2, ifng, cxcl1 and Cxcl. After continuous supplementation of the aqueous solution of the polytungstate-polypeptide complex by the drinking water route for 10 days, the weight loss of the mice due to colitis was somewhat alleviated, as shown in fig. 8.
Tungsten can inhibit periplasmic nitrate reductase activity of plant and anaerobically grown enterobacteria by replacing molybdenum atoms in molybdenum cofactors in metalloenzymes, and has no obvious effect on mammalian enzyme systems. Coli E.coli (GDMCC 1.708.708) and E.coli K-12 (GDMCC 1.43.43) (strain was derived from the Cantonese collection of microorganisms) were anaerobically cultured in vitro on LB medium and tested for nitrate reductase activity, and as a result, it was found that the activity of anaerobically cultured E.coli nitrate reductase gradually decreased with increasing amounts of poly-tungstate addition, as shown in FIG. 9. Correspondingly, the number of the enterobacteria accompanied with the increase of the colonitis is also controlled to a certain extent, as shown in figure 10.
Comparative example 2
0.005G of a polytungstate salt (molecular formula: na 3[PW12O40]·12H2 O, purchased from Sigma-Aldrich) was weighed and dissolved in 5.0mL of sterile water to prepare a 1.0mg/mL aqueous polytungstate salt solution. 0.001g of the polypeptide (amino acid sequence: GIGKFLHSAKKFGKAFVGEIMNS) was weighed and dissolved in 1.0mL of sterile PBS buffer (pH 7.2) to prepare an aqueous polypeptide solution having a mass concentration of 1 mg/mL. Under ice bath conditions, to 1mL concentration of 1mg/mL aqueous solution of poly tungstate solution added to 0.15mL polypeptide aqueous solution, the two are fully mixed, and then incubated at 0 ℃ for 12 hours. After the incubation is completed, the product mixture is filtered through a 0.22 μm aqueous phase filter membrane, the filtrate is collected, the ethanol precipitation complex is added, and the product is washed by using ethanol, and the precipitation complex is collected, and is freeze-dried for 16 hours at the temperature of-20 to 5 ℃, so as to obtain the poly tungstate-polypeptide complex (Keggin-peptide complexes, KPC).
The results of the above-prepared polytungstate-polypeptide complex (KPC) on mouse health are specifically described as an example. The construction of the mouse model of colitis was identical to the method described in example 4. Healthy mice of the control group were continuously given aqueous PBS (pH 6.8) by the drinking water route, and the group of C57BL/6J mice served as a blank control group. Healthy mice of the experimental group were simultaneously and continuously administered 3% aqueous dextran sulfate sodium and 0.3% aqueous polytungstate-polypeptide complex (KPC) or only 0.3% aqueous polytungstate-polypeptide complex (KPC) via the drinking water route to test the ability of the polytungstate-polypeptide complex (KPC) to protect the mice from developing colitis. After 10 days of continuous supplementation of the aqueous solution of the polytungstate-polypeptide complex by the drinking water route, the weight loss of the mice due to colonitis is not effectively relieved, and the dissected tissue sections show that partial organ cells of the mice are edematous, the volume of liver cells is increased, and the volume of the intracellular cavity is increased, as shown in fig. 11. At the same time, the glomeruli are significantly deformed with a small amount of capillary damage.
Comparative example 3
0.004G of a polytungstate (molecular formula K 6[P2W18O62]·3H2 O, method of synthesis reference J.Am.chem.Soc.,113 (1991), p.7209) was weighed out and dissolved in 4.0mL of sterile water to prepare an aqueous polytungstate solution having a mass concentration of 1.0 mg/mL. 0.002g of chitosan (viscosity less than <200mPa.s, molecular weight of about 30 kDa) was weighed and dissolved in 2.0mL of sterile acetic acid buffer solution to prepare an aqueous chitosan solution with a mass concentration of 1.0 mg/mL. Under ice bath conditions, to 2mL concentration of 1.0mg/mL aqueous solution of polytungstate salt added with 0.3mL chitosan water solution, the two after fully mixing, at 0 ℃ incubation for 2 hours. After the incubation is completed, the product mixture is collected by centrifugation, washed three times with water, freeze-dried for 18 hours at the temperature of-20-5 ℃ and ground into powder, thus obtaining the poly tungstate-chitosan complex (Dawson-chitosan complexes, DCC).
The results of the above-prepared polytungstate-chitosan complex (DCC) on mouse health are specifically described as an example. The construction of the mouse model of colitis was identical to the method described in example 4. Healthy mice of the control group were continuously given aqueous PBS (pH 6.8) by the drinking water route, and the group of C57BL/6J mice served as a blank control group. Healthy mice of the experimental group were simultaneously and continuously administered with 3% aqueous dextran sodium sulfate solution and 0.3% aqueous polytungstate-chitosan complex (DCC) solution or only 0.3% aqueous polytungstate-chitosan complex (DCC) solution via the drinking water route to test the ability of the polytungstate-chitosan complex (DCC) to protect the mice from colitis. After continuous supplementation of the aqueous solution of polytungstate-chitosan complex (DCC) by the drinking water route for 10 days, the weight loss of the mice due to colitis was not effectively alleviated, and the dissected tissue sections showed that edema occurred in a part of organ cells of the mice, as shown in fig. 11. Also, the kidney is damaged by capillary vessels. Although the polytungstate-chitosan complex (DCC) causes edema in the visceral cells of mice, it is lighter than the polytungstate-polypeptide complex (KPC), but it causes irreversible liver and kidney damage after long-term use.
Example 5
The effect of the polytungstate-DCTAB complex prepared in example 2 on the alleviation of colitis by balancing the mouse intestinal microbiota is specifically illustrated.
The construction of the mouse model of colitis was identical to the method described in example 4. Colitis mice served as positive control group. Healthy mice of the control group were continuously given aqueous PBS (pH 6.8) by the drinking water route, and the group of C57BL/6J mice served as a blank control group. Healthy mice of the experimental group were simultaneously and continuously administered with 3% aqueous dextran sodium sulfate solution and 0.3% aqueous polytungstate-DCTAB complex solution via the drinking water route to test the ability of polytungstate-chitosan complex (DCC) to protect mice from developing colitis symptoms. After 15 days of continuous replenishment of the aqueous solution of the polytungstate-DCTAB complex by the drinking water route, the blood leukocyte count of the colitis mice was reduced, indicating that the increase in leukocytes due to colitis was alleviated to some extent, as shown in fig. 12.
Example 6
The effect of the polytungstate-chitosan complex prepared in example 3 on the alleviation of colitis by balancing the intestinal microbial population of mice is specifically illustrated.
The construction of the mouse model of colitis was identical to the method described in example 4. Colitis mice served as positive control group. Healthy mice in the control group were continuously given aqueous PBS by the drinking water route, and the group of C57BL/6J mice served as a blank control group. Healthy mice of the experimental group were simultaneously and continuously administered with 3% aqueous dextran sodium sulfate solution and 0.3% aqueous polytungstate-chitosan complex solution via the drinking water route to test the ability of polytungstate-chitosan complex (DCC) to protect mice from developing colitis symptoms. After 12 days of continuous replenishment of the aqueous solution of the polytungstate-chitosan complex by the drinking water route, the blood leukocyte count of the colitis mice was reduced, indicating that the increase in leukocytes due to colitis was alleviated to some extent, as shown in fig. 12.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (8)
1. The multi-tungstate compound for relieving the colonitis is characterized by comprising 76-88% of multi-tungstate and 12-24% of dispersing agent by mass percent;
The sum of the mass percentages of the polytungstate and the dispersing agent is 100%;
The molecular composition of the polytungstate is K nNa14-n[NaP5W30O110]•mH2 O; n=10 to 13, m=5 to 20, and the molecular weight is 8.0 to 8.4 kDa;
the dispersing agent is at least one of polypeptide, surfactant and polysaccharide; the molecular weight of the polypeptide is 2.1-2.7 kDa, and the amino acid sequence of the polypeptide is GIGKFLHSAKKFGKAFVGEIMNS; the surfactant is at least one of ditetradecyl dimethyl ammonium bromide and ditetradecyl dimethyl ammonium bromide; the polysaccharide is chitosan.
2. The multi-tungstate compound for relieving colonitis according to claim 1, wherein the compound comprises 83-87% of multi-tungstate and 13-17% of dispersing agent by mass percent.
3. The multi-tungstate complex for relieving colitis according to claim 1, wherein the multi-tungstate K nNa14-n[NaP5W30O110]•mH2 O, n=11-13, m=5-8.
4. The multi-tungstate complex for relieving colitis according to claim 1, wherein the surfactant is dicetyl dimethyl ammonium bromide; the viscosity of the chitosan is less than 200 mPa.s, and the molecular weight of the chitosan is 10-50 kDa.
5. The method for preparing the polytungstate complex for relieving colonitis according to any one of claims 1 to 4, wherein the polytungstate salt aqueous solution and the dispersing agent aqueous solution are uniformly mixed, incubated for 2 to 8 hours at the temperature of 0 to 10 ℃, and the solvent and the unbound dispersing agent are removed to obtain the polytungstate complex.
6. The method for preparing a polytungstate complex for alleviating colitis of claim 5, wherein the concentration of said aqueous solution of polytungstate is 0.5-2.0 mg/mL and the concentration of said aqueous solution of dispersant is 0.2-1.2 mg/mL.
7. The method for preparing a complex of polytungstate for alleviating colitis according to claim 6, wherein the incubation is carried out at a temperature of 0-10 ℃ for a period of 2-6 hours.
8. Use of a polytungstate complex according to any one of claims 1 to 7 for the preparation of a pharmaceutical formulation.
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| GB700132A (en) * | 1950-08-16 | 1953-11-25 | Basf Ag | Improvements in the manufacture of sodium sulphide |
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| WO2014200929A1 (en) * | 2013-06-10 | 2014-12-18 | The Regents Of The University Of California | Tungstate treatment of the dysbiosis associated with gastrointestinal inflammation |
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| GB700132A (en) * | 1950-08-16 | 1953-11-25 | Basf Ag | Improvements in the manufacture of sodium sulphide |
Non-Patent Citations (4)
| Title |
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| Amelioration of enteric dysbiosis by polyoxotungstates in mice gut;Kun Chen等;Journal of Inorganic Biochemistry;20211027;第226卷;1-8 * |
| Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance;Kun Chen等;Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance;第1-7页摘要、3-4部分 * |
| Precision editing of the gut microbiota ameliorates colitis;Wenhan Zhu等;Nature;20180711;第553卷(第7687期);208-211 * |
| 蛙源抗菌肽Magainin Ⅱ对畜禽常见病原菌抑菌活性与体外稳定性测定;徐欣欣等;饲料工业;第39卷(第20期);第34-39页摘要、2-3部分 * |
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