CN111658664B - Application of sea cucumber polysaccharide in resisting novel coronavirus - Google Patents
Application of sea cucumber polysaccharide in resisting novel coronavirus Download PDFInfo
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- CN111658664B CN111658664B CN202010560842.8A CN202010560842A CN111658664B CN 111658664 B CN111658664 B CN 111658664B CN 202010560842 A CN202010560842 A CN 202010560842A CN 111658664 B CN111658664 B CN 111658664B
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- sea cucumber
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- polysaccharide
- sars
- cucumber polysaccharide
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Abstract
The invention discloses application of sea cucumber polysaccharide in resisting novel coronavirus, belonging to the technical field of biomedicine. The invention proves that the sea cucumber polysaccharide can prevent the cell membrane of organism cells from adsorbing and internalizing SARS-CoV-2 virus by combining with S protein on the surface of the SARS-CoV-2 virus through a pseudovirus and a euvirus model, thereby preventing the SARS-CoV-2 virus from infecting the organism cells, and showing that the sea cucumber polysaccharide has the effect of preventing and treating pneumonia caused by novel coronavirus. The Stichopus japonicus polysaccharide can be made into inhalant, and can enter nasal cavity, trachea, and lung to prevent virus infection of organism tissue, and can be used for preventing and treating novel coronavirus; the formula of the hand protection emulsion added with the sea cucumber polysaccharide can improve the effect of the hand protection emulsion on resisting novel coronavirus; the oral liquid prepared from sea cucumber polysaccharide can inhibit SARS-CoV-2 virus from invading from digestive system, has effects of preventing and adjunctively treating pneumonia caused by novel coronavirus, and has effects of enhancing immunity, reducing blood lipid, reducing weight, improving intestinal bacteria, etc.
Description
Technical Field
The invention relates to application of sea cucumber polysaccharide in resisting novel coronavirus, belonging to the technical field of biomedicine.
Background
The novel coronavirus (2019-nCoV) is formally classified and named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and is called novel coronavirus (novel coronavirus) for short. After people are infected with coronavirus, the common signs of the person are respiratory symptoms, fever, cough, shortness of breath, dyspnea and the like. In more severe cases, the infection can lead to pneumonia, severe acute respiratory syndrome, renal failure, and even death.
After entering into the body through the skin mucosa, the new coronavirus is combined with angiotensin converting enzyme 2 (ACE 2 for short) receptors on cells through spike protein (S protein for short) on the surface of the virus, then the virus is adsorbed and internalized by cell membranes, and the virus enters cytoplasm and is unshelled to release genome. After the genome is released into the cytoplasm, the viral RNA binds to the ribosomes of the host cell, translating into two sets of proteins, which are subsequently cleaved by proteolytic enzymes to produce enzymes and proteins for the continued assembly and replication of the virus. The newly produced enzyme includes RNA-dependent RNA polymerase (RdRp), which functions to replicate and form new viral RNA. The new viral RNA will bind to the protein produced by the hydrolase, assemble into a new virus, release the original host cell, and continue to infect other cells. According to the infection mechanism of the new coronavirus, the research and development of the anti-new coronavirus mainly start from two aspects, namely, the combination of the virus and host cells is prevented, and the action target is S protein or ACE 2; secondly, the generation of new viruses in host cells is prevented, and the acting target is RdRp or proteolytic enzyme.
The sea cucumber polysaccharide is an important nutrient component of the sea cucumber body wall, and the content of the sea cucumber polysaccharide can account for more than 6 percent of the total organic matters of the dried sea cucumber. The sea cucumber polysaccharide is composed of sea cucumber fucosan sulfate and sea cucumber fucosylated chondroitin sulfate. Sea cucumber fucosan sulfate is a sulfated polysaccharide formed by polymerizing L-fucose; sea cucumber fucosylated chondroitin sulfate is a sulfated polysaccharide with a fucosyl branched chain, wherein the main chain structure of the sulfated polysaccharide is composed of glucuronic acid-acetylgalactosamine repeating units. The sea cucumber polysaccharide has the effects of enhancing immunity, reducing blood fat, losing weight, improving intestinal flora and the like.
Disclosure of Invention
[ problem ] to
The technical problem to be solved by the present invention is the lack of effective substances for inhibiting novel coronaviruses.
[ solution ]
The invention provides application of sea cucumber polysaccharide in resisting coronavirus, wherein the coronavirus comprises novel coronavirus SARS-CoV-2. The anti-coronavirus is used for preventing or treating pneumonia caused by coronavirus, and comprises S protein combined with SARS-CoV-2 virus surface to prevent SARS-CoV-2 virus from invading organism cells. The application of sea cucumber polysaccharide can be used for preparing medicines, foods and daily chemical products for preventing or treating coronavirus infection.
The Stichopus japonicus polysaccharide is derived from Stichopus japonicus, including Stichopus japonicus species of Stichopus japonicus family of tenosynovia, Apostichopus japonicus family of tenosynovia, Oenothera acuminata nojirimaceae family and Cucumaria japonica family of Claritiales, and comprises Stichopus japonicus fucoidan sulfate and Stichopus japonicus fucosylated chondroitin sulfate. Sea cucumber fucoidan is a sulfated polysaccharide formed by polymerizing L-fucose; sea cucumber fucosylated chondroitin sulfate is a sulfated polysaccharide with a fucosyl branched chain, wherein the main chain structure of the sulfated polysaccharide is composed of glucuronic acid-acetylgalactosamine repeating units.
The invention provides application of sea cucumber polysaccharide in preparing a medicament for preventing or treating coronavirus infection, wherein the medicament takes the sea cucumber polysaccharide as an active ingredient for inhibiting coronavirus from entering cells of an organism.
The medicine also comprises pharmaceutically acceptable auxiliary materials, including: solvents, propellants, solubilizers, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integration agents, permeation promoters, pH regulators, buffers, plasticizers, surfactants, foaming agents, antifoaming agents, thickeners, coating agents, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants, and the like.
The dosage form of the medicament may be: spray, aerosol, powder spray, lotion, ointment, liniment, nasal spray, effervescent tablet, gargle, powder, emulsion, suspension, and solution.
The invention provides application of the sea cucumber polysaccharide in preparing a protective product for preventing coronavirus infection, wherein the protective product comprises the following components in parts by weight: hand lotion, hand sanitizer and mouthwash.
The invention provides a method for preparing a coronavirus infection protective product by utilizing sea cucumber polysaccharide, which is characterized in that the sea cucumber polysaccharide is added in the process of preparing the protective product.
The invention provides a preparation method of an inhalant for preventing coronavirus infection, which is characterized in that 30-50 g of sodium chloride, 70-120 g of citric acid, 70-120 g of sodium citrate and 0.5-2 g of benzalkonium chloride are stirred and dissolved by 8-50 times of purified water in an aseptic environment. 5-20 g of sea cucumber polysaccharide is stirred and dissolved by 500mL of purified water. Mixing the above solutions, diluting with purified water to 5-20L, filtering with 0.5 μm filter membrane, and packaging.
The invention provides a preparation method of an oral liquid for preventing coronavirus infection, which comprises the steps of taking 1-2 kg of wolfberry fruits and 1-2 kg of cassia seeds, adding 12-20 liters of water to boil, keeping the mixture for 0.5-3 hours with slow fire, filtering to obtain filtrate, concentrating the filtrate to 8-15 liters, adding 40-100 g of sea cucumber polysaccharide, 8-16 g of pectin and 500-1000 g of honey, uniformly stirring, naturally cooling, and standing for 2-6 hours to ensure that the precipitate is complete. Taking a filtrate by adopting filter pressing, adding 500-1500 g of white sugar, 35-80 g of citric acid, 3-10 g of salt and 15-60 g of vitamin C, uniformly mixing, performing pressure filtration by using diatomite, filtering by using two-stage microporous filter membranes with the pore diameter of 5 microns and 0.5 micron, performing bus sterilization on the filtrate (at 70-90 ℃ for 20-50 minutes), and canning.
The invention provides a preparation method of hand lotion for preventing coronavirus infection, which comprises the following components in percentage by mass: oil phase: 3-6 parts of stearic acid, 1-4 parts of stearic acid monoglyceride, 1-5 parts of isopropyl palmitate, 1-4 parts of vaseline, 5-10 parts of white mineral oil, 1-4 parts of hexadecanol, 0.1-0.5 part of essence, 0.1-0.4 part of methyl paraben and 0.1-0.4 part of propyl paraben; water phase: 5-10 parts of glycerol, 0.1-0.5 part of urea capsule, 0.1-0.4 part of dimethyl parachlorophenol, 0.5-1 part of triethanolamine, 0.05-0.5 part of sea cucumber polysaccharide and 65-75 parts of water;
heating and stirring oil phase (stearic acid, monoglyceride stearate, isopropyl palmitate, vaseline, white mineral oil, cetyl alcohol, methyl hydroxybenzoate, and propyl hydroxybenzoate) to dissolve; dissolving sea cucumber polysaccharide in water, adding glycerol and triethanolamine, heating, stirring and dissolving; then slowly pouring the water phase into the oil phase under vigorous stirring; after the treatment of the homogenizer, starting heating and stirring, cooling to 45-55 ℃, adding allantoin, dimethyl-p-chlorophenol and essence, continuing stirring and cooling to 25-35 ℃, and discharging; and (5) ageing for 2-3 days without change, and packaging after the inspection is qualified.
[ advantageous effects ]
The invention proves that the sea cucumber polysaccharide can prevent the cell membrane of organism cells from adsorbing and internalizing SARS-CoV-2 virus by combining with S protein on the surface of SARS-CoV-2 virus at the concentration of 3.9 mu g/mL or more through a true virus model experiment, thereby preventing the SARS-CoV-2 virus from infecting the organism cells and showing that the sea cucumber polysaccharide has the effect of resisting novel coronavirus.
The sea cucumber polysaccharide has the effects of moisturizing after external application, enhancing immunity, reducing blood sugar and blood fat, losing weight, improving intestinal flora and the like after eating the sea cucumber polysaccharide, and is beneficial and harmless to human bodies after external application and oral administration. Therefore, the sea cucumber polysaccharide can be prepared into inhalant (nasal spray) to enter nasal cavity, trachea and lung to prevent virus from infecting organism tissues, and is used for preventing and treating novel coronavirus; the formula of the hand lotion added with the holothurian polysaccharide can improve the effect of the hand lotion on resisting novel coronavirus and prevent the novel coronavirus infection; the oral liquid prepared from sea cucumber polysaccharide can inhibit SARS-CoV-2 virus invasion from digestive system, has effects of preventing and adjunctively treating pneumonia caused by novel coronavirus, and has effects of enhancing immunity, reducing blood sugar and blood lipid, reducing weight, and improving intestinal bacteria.
The sea cucumber polysaccharide is derived from food, has no toxicity, and has no adverse side effects when used for preventing and treating new coronavirus.
Drawings
FIG. 1 is a cellular immunofluorescence chart of SARS-CoV-2 virus mixed with sea cucumber polysaccharide of different concentrations. The final concentration of holothurian polysaccharide is 500, 250, 125, 62.5, 31.3, 15.6, 7.8 and 3.9 mug/mL. The negative control was blank medium.
Detailed Description
Example 1 method for preparing sea cucumber polysaccharide
The specific method comprises the following steps:
cleaning Stichopus japonicus, decocting in water, draining, cutting into small pieces, and lyophilizing. And (3) soaking the freeze-dried sample in acetone at 4 ℃ for 24h, and airing at room temperature. Taking 1g of freeze-dried sample as an example, 30mL of 0.1mol/L sodium acetate buffer solution (pH 6.0), 100mg of papain (specific enzyme activity is 2units/mg), 48mg of ethylenediamine tetraacetic acid and 18mg of cysteine are added, vortex mixing is carried out, water bath oscillation and enzymolysis at 60 ℃ are carried out for 24 hours, the reaction mixture is centrifuged (6000g, 15min, room temperature), and supernatant is taken. To the supernatant was added 1.6mL of a 10% cetylpyridinium chloride solution, and after standing at room temperature for 24 hours, the precipitate was centrifuged (8000g, 15min, room temperature). Dissolving the precipitate in 15mL of 3mol/L NaCl-ethanol (100: 15v/v) solution, adding 30mL of 95% ethanol solution, standing at 4 deg.C for 24h, and centrifuging (8000g, 15min, room temperature) to obtain precipitate. Washing the precipitate with 10mL 80% ethanol for 2-3 times, washing with 10mL 95% ethanol for 2-3 times, air drying at room temperature, dissolving with distilled water, desalting with dialysis bag (3500Da), and lyophilizing to obtain Stichopus japonicus polysaccharide.
The embodiment can also comprise pretreatment steps such as solution preparation, ultrapure water preparation and the like.
Example 2 determination of structural characteristics and composition of the sea cucumber polysaccharide prepared in example 1
The specific method comprises the following steps:
by using1H NMR is carried out to detect the structural characteristics and the purity of the sea cucumber polysaccharide;
detecting the molecular weight of the sea cucumber polysaccharide by adopting a gel permeation chromatography;
detecting the sulfate radical content of the sea cucumber polysaccharide by adopting a gelatin turbidimetry method;
detecting the monosaccharide composition of the sea cucumber polysaccharide by adopting a high performance liquid chromatography and PMP derivatization method;
and detecting the polysaccharide functional groups of the sea cucumber by adopting Fourier infrared.
The result shows that the sea cucumber polysaccharide contains fucoidan sulfate and fucosylated chondroitin sulfate, the molecular weight of the fucoidan sulfate is more than 670kDa, and the molecular weight of the fucosylated chondroitin sulfate is more than 179 kDa; the sulfate radical content is 26-28%; the molar ratio of fucose, glucuronic acid and galactosamine is 9:0.8: 1.
Example 3 evaluation of the Effect of sea cucumber polysaccharides against novel Corona Virus Using a pseudovirus model
The full-length sequence of the gene encoding the HCoV-19 spike protein was cloned into the pCAGGS vector for pseudovirus production, and the resulting recombinant vector was constructed and designated pCAGGS-HCoV-19-S. The success of construction of pCAGGS-HCoV-19-S was confirmed by DNA sequencing. pCAGGS-HCoV-19-S and pNL4-3 plasmid were co-transfected into HEK 293T cells, after 48h of culture, the supernatants containing SARS-CoV-2 pseudovirus were collected and 50% of the Tissue Cell Infectivity (TCID) of the pseudovirus was determined by infecting Huh7 cells50)。
The SARS-CoV-2 pseudovirus model is used for evaluating the effect of sea cucumber polysaccharide on resisting novel coronavirus, and the specific steps are as follows:
(1) selecting Huh7 cells with good growth state, after trypsinization, laying plates with 96 holes, culturing overnight until the cells reach 80-100% after 18-24 h;
(2) 100TCID per well50Pseudovirus, mixed with serum-free medium containing Stichopus japonicus polysaccharide, the final concentration of Stichopus japonicus polysaccharide after mixing is 0.01mg/mL, 0.1mg/mL and 1mg/mL, and incubating at 37 deg.C for 30 min. The EK1 peptide served as a positive control, and blank serum-free medium served as a negative control.
(3) After washing Huh7 cells with PBS to remove serum, the mixture of virus and sea cucumber polysaccharide was diluted 3 fold and Huh7 cells were infected with 100 μ L of each well, three parallel wells were set for each sample, and after 4-6h, 100 μ L of medium containing 5% FBS serum was supplemented.
(4) The Luciferase value was measured at 48 h. Refer to the Protocol System of the scientific Assay or the Dual scientific Assay System of Promega. The method comprises the following specific operations: the 96-well plate was inverted, washed 2 times with PBS to ensure that PBS was blotted dry, then 30. mu.L of lysate was added, lysed at room temperature for 30min, 10. mu.L of lysate was blotted onto a white plate, 50. mu.L of substrate was added, and the luciferase value was determined, and the results are shown in Table 1 below.
TABLE 1
The results show that the SARS-CoV-2 virus can be effectively inhibited from entering cells when the final concentration of the sea cucumber polysaccharide is 0.1mg/mL and 1 mg/mL. And because the used model is SARS-CoV-2 pseudovirus with S protein, the action target point of the sea cucumber polysaccharide can be deduced to be S protein.
EXAMPLE 4 Effect of Stichopus japonicus polysaccharides on DuSARS-CoV-2 Euvirus
SARS-CoV-2 Euvirus (from second Legionnaire university) and Stichopus japonicus polysaccharide were mixed in DMEM medium containing 5% fetal bovine serum to give final concentration of Stichopus japonicus polysaccharide of 500, 250, 125, 62.5, 31.3, 15.6, 7.8, 3.9. mu.g/mL, and left at 37 deg.C for 1 hr, and 96-well plate inoculated with Vero E6 cells 12 hr earlier (and stock cell culture solution was added), cultured for 24 hr, and then virus protein was detected by immunofluorescence, and cell nucleus was stained with DAPI. The inhibitory action of eight concentration gradients of 500, 250, 125, 62.5, 31.3, 15.6, 7.8 and 3.9 mu g/mL of holothurian polysaccharide on viruses is observed by using an immunofluorescence microscope, and the result is shown in figure 1, and the holothurian polysaccharide can remarkably inhibit the infection of new coronavirus on cells within the concentration range of 500-3.9 mu g/mL.
Example 5 preparation method of Stichopus japonicus polysaccharide nasal spray
In a sterile environment, 40 g of sodium chloride, 100 g of citric acid, 100 g of sodium citrate and 1g of benzalkonium chloride are respectively dissolved by 10 times of purified water with stirring. 10 g of sea cucumber polysaccharide is stirred and dissolved by 500mL of purified water. Mixing the above solutions, diluting with purified water to 10L, filtering with 0.5 μm filter membrane, and packaging.
Example 6 preparation method of sea cucumber polysaccharide hand lotion
The formulation of the hand lotion is shown in table 2 below:
TABLE 2
Dissolving oil phase (stearic acid, monoglyceride stearate, isopropyl palmitate, vaseline, white mineral oil, cetyl alcohol, methyl hydroxybenzoate, and propyl hydroxybenzoate) under heating and stirring. Dissolving sea cucumber polysaccharide in water, adding glycerol and triethanolamine, heating, stirring, and dissolving. The aqueous phase was then slowly poured into the oil phase with vigorous stirring. After the treatment of the homogenizer, heating and stirring are started, allantoin, dimethyl-p-chlorophenol and essence are added when the temperature is cooled to 50 ℃, and the mixture is continuously stirred and cooled to 30 ℃ and discharged. And (5) ageing for 2-3 days without change, and packaging after the inspection is qualified.
Example 7 preparation method of sea cucumber polysaccharide oral liquid
Taking 1.6 kg of medlar and 1.6 kg of longan, adding 16 liters of water to boil, keeping the mixture for 1 hour by slow fire, filtering the mixture to obtain filtrate, concentrating the filtrate to 12 liters, adding 60 grams of sea cucumber polysaccharide, 12 grams of pectin and 840 grams of honey, stirring the mixture evenly, naturally cooling the mixture, and standing the mixture for 3 hours to ensure that the precipitate is complete. Filter pressing is adopted to take filtrate, 910 g of white sugar, 52 g of citric acid, 6.5 g of salt and 26 g of vitamin C are added and mixed evenly, pressure filtration is carried out by diatomite, then filtration is carried out by two stages of microporous filter membranes with the aperture of 5 microns and 0.5 micron, and then the filtrate is sterilized by bus (80 ℃ for 30 minutes) and can be filled.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (5)
1. The application of sea cucumber polysaccharide in preparing medicine or daily chemical product for inhibiting SARS-CoV-2 infection is characterized by that,
the sea cucumber polysaccharide contains fucosan sulfate and fucosylated chondroitin sulfate, the molecular weight of the fucosan sulfate is more than 670kDa, and the molecular weight of the fucosylated chondroitin sulfate is more than 179 kDa; the sulfate radical content is 26-28%; the molar ratio of fucose, glucuronic acid and galactosamine is 9:0.8: 1;
the preparation method of the sea cucumber polysaccharide comprises the following steps: cleaning sea cucumber, boiling in water, draining, cutting into blocks, freeze-drying, soaking a freeze-dried sample in acetone at 4 ℃ for 24 hours, airing at room temperature, adding 30mL of 0.1 mol/LpH 6.0.0 sodium acetate buffer solution, 100mg of papain with the specific enzyme activity of 2units/mg, 48mg of ethylenediamine tetraacetic acid and 18mg of cysteine into 1g of the freeze-dried sample, mixing by vortex, carrying out water bath oscillation at 60 ℃ for 24 hours for enzymolysis, centrifuging a reaction mixture, and taking a supernatant; adding 1.6mL of 10% cetylpyridinium chloride solution into the supernatant, standing at room temperature for 24h, and centrifuging to obtain a precipitate; dissolving the precipitate in 15mL of 3mol/L NaCl-ethanol solution, adding 30mL of 95% ethanol solution, standing at 4 ℃ for 24h, and centrifuging to obtain the precipitate; washing the precipitate with 80% ethanol for 2-3 times, washing with 95% ethanol for 2-3 times, air drying at room temperature, dissolving in distilled water, desalting with dialysis bag, and lyophilizing to obtain sea cucumber polysaccharide.
2. The use of claim 1, wherein the inhibition of infection by the novel coronavirus SARS-CoV-2 is inhibition of pneumonia caused by infection by the novel coronavirus SARS-CoV-2, and comprises binding to S protein on the surface of SARS-CoV-2 virus, and preventing SARS-CoV-2 virus from invading cells of the body.
3. The use of claim 1 or 2, wherein the sea cucumber polysaccharide is derived from a sea cucumber species, including the species Stichopus japonicus of the families Conus nojirimus and Cucumaria gigas.
4. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable excipient.
5. The use according to claim 1, wherein said commodity comprises: hand lotion, hand sanitizer and mouthwash.
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| PCT/CN2020/112597 WO2021253643A1 (en) | 2020-06-18 | 2020-08-31 | Application of sulphated polysaccharides against novel coronavirus |
| US17/567,945 US20220125827A1 (en) | 2020-06-18 | 2022-01-04 | Application of Sulfated Polysaccharides in Resisting novel Coronavirus |
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| CN112220799A (en) * | 2020-11-02 | 2021-01-15 | 江苏泰德医药有限公司 | Product for inhibiting virus and application |
| CN113150178B (en) * | 2021-04-14 | 2023-05-02 | 大连工业大学 | Sulfated abalone polysaccharide and application thereof in inhibiting new coronavirus |
| CN113372459B (en) * | 2021-05-07 | 2022-05-31 | 中国科学院上海药物研究所 | Oroxylum indicum polysaccharide, preparation method and application thereof |
| CN113647630B (en) * | 2021-08-24 | 2024-03-15 | 大连工业大学 | Application of sea cucumber sulfated polysaccharide and weak acid degradation product thereof in promoting lactobacillus proliferation |
| CN114316081B (en) * | 2021-12-07 | 2023-03-28 | 大连工业大学 | A sulfated polysaccharide of Botrytis longipedicularis with SARS-CoV-2 inhibiting activity, and its preparation method and application |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741810A (en) * | 2002-08-30 | 2006-03-01 | 鲁汶天主教大学研究开发部 | Glycopeptide antibiotic derivatives |
| CN101356984A (en) * | 2007-07-31 | 2009-02-04 | 邓洁 | High-calcium sea-slug (sea-slug peptide, sea-slug polysaccharide) milk and preparation method thereof |
| CN110357983A (en) * | 2019-08-14 | 2019-10-22 | 中国海洋大学 | A kind of preparation method of sea cucumber fucoidan and chondroitin sulfate oligosaccharide |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106490086A (en) * | 2016-10-17 | 2017-03-15 | 咀香园健康食品（中山）有限公司 | One main laminaria bubble cake and preparation method thereof |
| CN110384722A (en) * | 2019-08-27 | 2019-10-29 | 吉林省禹王生物医药有限公司 | A kind of antiviral nasal douche agent of releiving |
-
2020
- 2020-06-18 CN CN202010560842.8A patent/CN111658664B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1741810A (en) * | 2002-08-30 | 2006-03-01 | 鲁汶天主教大学研究开发部 | Glycopeptide antibiotic derivatives |
| CN101356984A (en) * | 2007-07-31 | 2009-02-04 | 邓洁 | High-calcium sea-slug (sea-slug peptide, sea-slug polysaccharide) milk and preparation method thereof |
| CN110357983A (en) * | 2019-08-14 | 2019-10-22 | 中国海洋大学 | A kind of preparation method of sea cucumber fucoidan and chondroitin sulfate oligosaccharide |
Non-Patent Citations (4)
| Title |
|---|
| Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives;Ritesh Tandon et al.;《bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.140236》;20200608;摘要部分；figure 2部分 * |
| Fucanomics and galactanomics: Current status in drug discovery, mechanisms of action and role of the well-defined structures;Vitor H. Pomin et al;《Biochimica et Biophysica Acta》;20120903;第1971-1979页 * |
| Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2;Shuang Song et al;《Food Funct》;20200923;第11卷;第7415-7420页 * |
| The COVID 19 novel coronavirus pandemic 2020: seaweeds to the rescue? Why does substantial, supporting research about the antiviral properties of seaweed polysaccharides seemto go unrecognized by the pharmaceutical community in these desperate times?;Leonel Pereira et al.;《Journal of Applied Phycology》;20200601;摘要部分 * |
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