CN115920059B - FXR receptor inhibition composition, preparation method and application thereof in prevention and treatment of coronavirus - Google Patents
FXR receptor inhibition composition, preparation method and application thereof in prevention and treatment of coronavirus Download PDFInfo
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An FXR receptor inhibition composition, a preparation method and application thereof in preventing and treating coronaviruses, relates to the technical field of biological medicines, and comprises isoquercetin, tetrahydrocurcumin, piperine and vitamin K. According to the FXR receptor inhibition composition, through the synergistic effect of isoquercetin, tetrahydrocurcumin, piperine and vitamin K, the activity of inhibiting FXR receptors can be obviously reduced, the expression of FXR receptors can be inhibited, the invasion of coronaviruses can be lightened, the virus infection rate can be reduced, and the effect of preventing and treating coronavirus infection can be realized. Meanwhile, the FXR receptor inhibition composition disclosed by the invention has the characteristics of simple components, high safety, no toxic or side effect, quick response and definite curative effect.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to an FXR receptor inhibition composition, a preparation method and application thereof in preventing and treating coronaviruses.
Background
Novel coronavirus infections have extremely high infections and have been highly prevalent worldwide. According to the prior case data, the novel coronavirus infection mainly shows fever, dry cough, hypodynamia and the like, and a few patients are accompanied with symptoms of upper respiratory tract and digestive tract such as nasal obstruction, nasal discharge, diarrhea and the like. The severe cases often have dyspnea after 1 week, and severe patients rapidly progress to acute respiratory distress syndrome, sepsis shock, metabolic acidosis and coagulation dysfunction which are difficult to correct, multiple organ failure and the like, so that the life health of the human body is seriously threatened.
Currently, the main treatment regimens for novel coronavirus infections are: general viral treatment regimens, small molecule drugs, neutralizing antibodies, other monoclonal antibodies, and traditional Chinese medicine formulations. However, the clinical requirements of the traditional Chinese medicine cannot be met far away in the aspects of variety number, safety, curative effect and the like; it is important to develop safe and effective substances for preventing or treating new crown infections to meet clinical demands.
Preliminary studies have shown that the novel coronavirus is damaging to humans through the ACE2 (angiotensin converting enzyme 2) target; ACE2, which is present in the epithelium of the nose, mouth and lungs and most major tissue and organs of the human body, is the portal for infection of the human body by new coronaviruses; the new coronavirus causes a preliminary infection of the lungs, and after severe damage to the epithelial and endothelial tissues of the lungs, it causes heart and other important vascular lesions by blood diffusion. A recent study of "FXR inhibition may protect from SARS-CoV-2 infection by reducingACE2" has shown that the bile acid nuclear receptor (FXR receptor) is the control switch for AEC 2. Therefore, research on a safe and efficient FXR receptor inhibitor has great significance for preventing and treating the novel coronavirus clinically.
Disclosure of Invention
In order to overcome the defects in the prior art, one of the purposes of the invention is to provide an FXR receptor inhibition composition which can obviously inhibit the expression of FXR receptors, lighten the invasion of coronaviruses and reduce the virus infection rate.
The second object of the present invention is to provide a preparation method of FXR receptor inhibiting composition, which has simple preparation process and easy operation.
It is a further object of the present invention to provide the use of an FXR receptor inhibiting composition.
One of the purposes of the invention is realized by adopting the following technical scheme:
an FXR receptor inhibitor composition comprising isoquercetin, tetrahydrocurcumin, piperine, and vitamin K.
Further, the mass ratio of the isoquercetin to the tetrahydrocurcumin to the piperine to the vitamin K is (1-10): (1-3): (0.3-0.7): (0.08-0.15).
Further, the mass ratio of the isoquercetin to the tetrahydrocurcumin to the piperine to the vitamin K is (1-7): (1-2): (0.4-0.6): 0.1.
further, the mass ratio of the isoquercetin, the tetrahydrocurcumin, the piperine and the vitamin K is (5-7): (1-2): 0.5:0.1.
the second purpose of the invention is realized by adopting the following technical scheme:
a method of preparing an FXR receptor inhibitor composition comprising the steps of: uniformly mixing isoquercetin, tetrahydrocurcumin, piperine and vitamin K to obtain the FXR receptor inhibition composition.
The third purpose of the invention is realized by adopting the following technical scheme:
use of an FXR receptor inhibitor composition for the preparation of a product for the prevention or treatment of coronavirus infection.
Further, the product includes any one of food, medicine and health care product.
Further, the product is in any one of a tablet, a capsule, a granule, a powder, a spray or an oral liquid.
Further, the product comprises an FXR receptor inhibition composition, vitamin E and auxiliary materials acceptable in foods, medicines or health care products; the mass ratio of the FXR receptor inhibition composition to the vitamin E is 1 (0.5-10).
Further, the product also includes any one of skin care products, oral care products, and hygiene products.
Further, the skin care product comprises any one of facial mask, eye cream, face cream, essence, face cleaning milk, stock solution, toner and sun cream; the oral care product comprises any one of mouthwash, toothpaste, oral spray and paint; the sanitary article is any one of paper towel, wet paper towel, face towel, sanitary towel, paper diaper, mask and eye drop.
Compared with the prior art, the invention has the beneficial effects that:
according to the FXR receptor inhibition composition, through the synergistic effect of isoquercetin, tetrahydrocurcumin, piperine and vitamin K, the activity of inhibiting FXR receptors can be obviously reduced, the expression of FXR receptors can be inhibited, the invasion of coronaviruses can be lightened, the virus infection rate can be reduced, and the effect of preventing and treating coronavirus infection can be realized. Meanwhile, the FXR receptor inhibition composition disclosed by the invention has the characteristics of simple components, high safety, no toxic or side effect, quick response and definite curative effect.
The preparation method of the FXR receptor inhibition composition is simple in preparation process and easy to operate.
The FXR receptor inhibition composition has good application prospect in preparing foods, medicines and health-care products for preventing or treating coronavirus infection.
Drawings
FIG. 1 is a graph showing comparison of the results of relative expression amounts of FXR genes in a cell over-expression test using an FXR receptor-inhibiting composition of the present invention.
FIG. 2 is a graph showing the comparison of the results of the relative expression amounts of ACE2 gene in a cell over-expression test of an FXR receptor inhibiting composition of the present invention.
FIG. 3 is a graph showing comparison of the results of the inhibition of cell by FXR receptor in SARS-CoV-2Spike pseudovirus infection assay.
FIG. 4 is a graph showing a comparison of the results of cell activity of an FXR receptor-inhibiting composition of the invention in an experiment of SARS-CoV-2Spike pseudovirus infection.
Detailed Description
The present invention will be further described with reference to the following specific embodiments, and it should be noted that, on the premise of no conflict, new embodiments may be formed by any combination of the embodiments or technical features described below.
The raw material formulas of an FXR receptor-inhibiting composition of examples 1 to 4 of the invention are shown in Table 1.
A method of preparing an FXR receptor inhibitor composition of examples 1-4 of the invention comprises the steps of: uniformly mixing isoquercetin, tetrahydrocurcumin, piperine and vitamin K to obtain the FXR receptor inhibition composition.
Example 5
A capsule, a FXR receptor inhibitor composition according to application example 1, comprising the components: FXR receptor inhibiting composition 0.2 g, vitamin E0.1 g, corn starch 0.1 g.
The preparation method of the capsule comprises the following steps: mixing the above materials, granulating, sieving, encapsulating, and making into capsule.
Example 6
A tablet for use in the FXR receptor inhibitor composition of example 2, comprising: FXR receptor inhibiting composition 0.5 g, vitamin E0.5 g, magnesium stearate 0.3 g.
The preparation method of the tablet comprises the following steps: mixing the above materials, calculating tablet weight, and tabletting.
Example 7
A fondant, comprising the FXR receptor inhibitor composition of example 3, in combination: 10 g of white granulated sugar, 20 g of syrup, 2 g of dry gelatin, 0.2 g of FXR receptor inhibition composition, 2 g of vitamin E, 0.1 g of sodium benzoate and 0.1 g of sodium citrate. The soft sweet is prepared according to the conventional preparation process of soft sweet.
Example 8
A mouthwash, using the FXR receptor inhibition composition of example 4, comprising, in mass percent: 2% of FXR receptor inhibiting composition, 0.12% of sweetener, 0.1% of acidulant, 7.6% of humectant, 8% of alcohol, 0.6% of active ingredient stabilizer, 0.5% of essence and the balance of water. The mouthwash is prepared according to the conventional preparation process of mouthwash.
Example 9
A sanitary article, comprising the FXR receptor inhibitor composition according to application example 4, in mass percent: FXR receptor inhibiting composition 2-3%, pulp 80% and water in balance. The sanitary article is manufactured according to the conventional manufacturing process of the sanitary article.
The pulp can also be replaced by cotton, synthetic fiber and other different base materials to prepare different sanitary products with the effect of preventing and treating coronavirus infection.
Example 10
An eye drop, using the FXR receptor inhibitor composition of example 1, comprising, in mass percent: FXR receptor inhibiting composition 1-10%, borneolum Syntheticum 0.5%, and water in balance. Is prepared by the process of eyedrops.
Example 11
A skin care product, using the FXR receptor inhibitor composition of example 1, comprising, in mass percent: FXR receptor inhibiting composition 2-8%,12% polyethylene glycol, 0.1-1.2% soluble salts, 1-3.5% ferulic acid, and water in balance.
Example 12
A liquid mask, to which the FXR receptor inhibitor composition according to example 1 is applied, comprising, in mass percent: 5-15% of FXR receptor inhibiting composition, 0.5% of citric acid, 2.5% of sorbitol, 0.2-0.8% of butanediol and the balance of water.
Comparative example 1
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: isoquercetin is not added to the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: evenly mixing tetrahydrocurcumin, piperine and vitamin K to obtain the pharmaceutical composition.
Comparative example 2
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: tetrahydrocurcumin was not added to the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, piperine and vitamin K to obtain the pharmaceutical composition.
Comparative example 3
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: no piperine was added to the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, tetrahydrocurcumin and vitamin K to obtain the pharmaceutical composition.
Comparative example 4
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: vitamin K was not added to the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, tetrahydrocurcumin and piperine to obtain the pharmaceutical composition.
Comparative example 5
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: the pharmaceutical composition of this comparative example replaced isoquercetin with quercetin.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing quercetin, tetrahydrocurcumin, piperine and vitamin K to obtain the pharmaceutical composition.
Comparative example 6
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: the tetrahydrocurcumin was replaced with curcumin in the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, curcumin, piperine and vitamin K to obtain the pharmaceutical composition.
Comparative example 7
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: the pharmaceutical composition of this comparative example replaced piperine with capsaicin.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, tetrahydrocurcumin, capsaicin and vitamin K to obtain the pharmaceutical composition.
Comparative example 8
A pharmaceutical composition differing from the FXR receptor inhibitor composition of example 1 in that: vitamin K was replaced with vitamin E in the pharmaceutical composition of this comparative example.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps: and uniformly mixing isoquercitrin, tetrahydrocurcumin, piperine and vitamin E to obtain the pharmaceutical composition.
Performance testing
1. Cell overexpression experiments
And (3) performing cell over-expression experiments by using Vero E6 cell groups, wherein each group of cells is divided into a blank control group, an over-expression control group and an over-expression experiment group, the over-expression experiment group corresponds to the composition samples of the examples 1-4 and the comparative examples 1-8, and the specific groups comprise: group 1 (example 1), group 2 (example 2), group 3 (example 3), group 4 (example 4), group 5 (comparative example 1), group 6 (comparative example 2), group 7 (comparative example 3), group 8 (comparative example 4), group 9 (comparative example 5), group 10 (comparative example 6), group 11 (comparative example 7) and group 12 (comparative example 8); each group had 3 wells.
The experimental method comprises the following steps: sterile 24 well plates were taken and 500. Mu.L of 2X 10 concentration was added to each well 5 cells/mL of VeroE6 cells (normal VeroE6 cells, FXR overexpressed VeroE6 cells) were incubated at 37℃for 12 hours. After 12h, different culture media were added respectively, a blank control group (500. Mu.l), an over-expression control group (500. Mu.l), and an over-expression experimental group (drug content 50ug/ml, 500. Mu.l), incubated for 36h, and sampled. The QPCR method detects the expression of FXR and ACE2 genes.
As shown in the results of FIGS. 1-2, groups 1-4 all have good inhibition effect on FXR receptor; wherein the inhibition effect of group 1 is optimal; the results in groups 5-8 show that the composition is indispensable, indicating that the four substances synergistically act with a good degree of wedging to achieve the best effect. 9-12 groups of data show that quercetin, tetrahydrocurcumin, piperine and vitamin K have good effects in the same type of products; for example, 9 groups of quercetin replaced isoquercetin, and both compounds are homologous compounds, but the absorption of isoquercetin is better than that of quercetin, and the effect is also remarkable.
2. SARS-CoV-2Spike pseudovirus infection experiment
SARS-CoV-2 (2019-nCoV) Spike pseudovirus infection experiments were performed as specified.
The experimental method comprises the following steps: the group of Vero E6 cells was divided into groups similar to the above-described experimental groups for overexpression of Vero E6 cells, and the groups were 5X 10 4 Inoculating into 6-well plate at 37deg.C with 5% CO 2 Culturing in an incubator for 12 hours. Different culture mediums were added respectively, and the blank group (500. Mu.l), the experimental group (drug content 50ug/ml, 500. Mu.l)l), incubation for 36h. A medium containing SARS-CoV-2 (2019-nCoV) Spike pseudovirus was added, based on 24h of culture. The Cck8 method detects cell viability and detects virus infection ability.
As shown in FIGS. 3-4, pseudovirus infection resulted in decreased cell activity, and the compositions of the present invention enhanced cell activity; in another aspect, the composition inhibits infection by a pseudovirus.
3. Oral test
40 new crown positive patients and 20 closely connected subjects were enrolled, positive blank: from the occurrence of preliminary symptoms such as cold, myalgia, runny nose, headache or sore throat, the nucleic acid detection is positive, and conventional treatment (analgesic/antipyretic) is given; positive treatment group: from the occurrence of preliminary symptoms such as cold, runny nose, headache or sore throat, the nucleic acid detection is positive, and the composition obtained in the example 1 is orally taken after the conventional treatment is added twice a day, 500 mg/person/60 kg each time; the close-fitting subjects were orally administered to each person 3 times per day, 1500 mg/person/day/60 kg, 15 days each, starting from the close-fitting positive subjects on the same day. And recording the symptom change and the negative turning time during the period; the results are shown in Table 2.
As shown in Table 2, the new crown patients often have symptoms such as fever, headache, dry throat, sore throat, and gastrointestinal discomfort. After the composition is orally taken, the symptoms of dry throat and headache are relieved for patients who are positive, and most notably, the gastrointestinal discomfort is greatly reduced; for close-connected people, the composition reduces the positive turning rate, reduces the number of people suffering from fever, can well reduce other symptoms, and greatly reduces the time for turning negative.
The above embodiments are only preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, but any insubstantial changes and substitutions made by those skilled in the art on the basis of the present invention are intended to be within the scope of the present invention as claimed.
Claims (4)
1. An FXR receptor inhibition pharmaceutical composition is characterized by comprising isoquercetin, tetrahydrocurcumin, piperine and vitamin K in a mass ratio of 7:2:0.5:0.1.
2. A method of preparing the FXR receptor inhibitor pharmaceutical composition of claim 1, comprising the steps of: uniformly mixing isoquercetin, tetrahydrocurcumin, piperine and vitamin K to obtain the FXR receptor inhibition composition.
3. Use of a pharmaceutical composition for inhibiting FXR receptor according to any of claims 1-2, characterized in that: the FXR receptor inhibition pharmaceutical composition is applied to the preparation of medicines for preventing or treating coronavirus infection.
4. Use of a FXR receptor inhibitor pharmaceutical composition according to claim 3, characterized in that: the dosage form of the medicine is any one of tablets, capsules, granules, powder, spray or oral liquid.
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