阅读说明：本技术 海参多糖在抗新型冠状病毒中的应用 (Application of sea cucumber polysaccharide in resisting novel coronavirus ) 是由 朱蓓薇 宋爽 董秀萍 周大勇 温成荣 刘正奇 祁立波 陶帅妃 于 2020-06-18 设计创作，主要内容包括：本发明公开了海参多糖在抗新型冠状病毒中的应用,属于生物医学技术领域。本发明通过假病毒和真病毒模型证实了海参多糖能够通过与SARS-CoV-2病毒表面的S蛋白结合,防止机体细胞的细胞膜对SARS-CoV-2病毒进行吸附和内化,从而阻止SARS-CoV-2病毒感染机体细胞,表明海参多糖具有预防和治疗新型冠状病毒所致肺炎的效果。海参多糖可制备吸入剂,进入鼻腔、气管、肺部,防止病毒的感染机体组织,用于预防和治疗新型冠状病毒；海参多糖加入护手乳液配方,可增加护手乳液抗新型冠状病毒的效果；海参多糖制成的口服液可抑制SARS-CoV-2病毒从消化系统侵入,起到预防和辅助治疗新型冠状病毒所致肺炎的作用,并具有增强免疫力、降血脂、减肥、改善肠道菌等作用。(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.)

1. Application of sea cucumber polysaccharide in preparing medicine or daily chemical product for treating or preventing coronavirus infection is provided.

2. Use according to claim 1, wherein the coronavirus comprises the novel coronavirus SARS-CoV-2.

3. The use of claim 1, wherein the anti-coronavirus is for preventing or treating pneumonia caused by coronavirus, and the anti-coronavirus binds to S protein on the surface of SARS-CoV-2 virus to prevent SARS-CoV-2 virus from invading cells in the body.

4. The use according to any one of claims 1 to 3, wherein the sea cucumber polysaccharide is derived from sea cucumber, including sea cucumber varieties of the families Stichopus tenosynovitis, Stichopus tenosynovium, Protoviridae and Cucumaria gigas, containing sea cucumber fucoidan sulfate and sea cucumber fucosylated chondroitin sulfate.

5. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable excipient; the dosage form of the medicament comprises: spray, aerosol, powder spray, lotion, ointment, liniment, nasal spray, effervescent tablet, gargle, powder, emulsion, suspension, solution.

6. The use according to claim 1, wherein said commodity comprises: hand lotion, hand sanitizer and mouthwash.

7. A medicine for treating or preventing coronavirus infection, or inhalant, nasal spray, hand lotion, hand sanitizer or mouthwash is characterized in that sea cucumber polysaccharide is used as an active ingredient for inhibiting coronavirus from entering cells of a body.

8. An inhalant for preventing coronavirus infection 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 respectively stirred and dissolved by 8-50 times of purified water in a sterile environment; stirring and dissolving 5-20 g of sea cucumber polysaccharide by using 500mL of purified water; mixing the above solutions, diluting with purified water to 5-20L, microfiltering, and canning.

9. An oral liquid for preventing coronavirus infection is characterized in that 1-2 kg of wolfberry fruits and 1-2 kg of longan are boiled with 12-20 liters of water, kept for 0.5-3 hours by slow fire, filtered to obtain filtrate, concentrated to 8-15 liters, added with 40-100 g of sea cucumber polysaccharide, 8-16 g of pectin and 500-1000 g of honey, stirred uniformly, cooled naturally and kept stand for 2-6 hours to ensure complete precipitation; filter pressing is adopted to obtain filtrate, 500-1500 g of white sugar, 35-80 g of citric acid, 3-10 g of salt and 15-60 g of vitamin C are added and mixed uniformly, diatomite is used for pressure filtration, the mixture is filtered through two stages of microporous filter membranes, and then the filtrate is subjected to bus sterilization and can be canned.

10. The hand lotion for preventing coronavirus infection is characterized by comprising 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.

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, 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