Application of mannose in preparation of medicine for treating silicosis

Abstract

The invention belongs to the technical field of biological medicine, and particularly discloses application of mannose in preparation of medicine for treating or preventing silicosis. The invention discloses application of mannose in preparation of medicines for treating or preventing silicosis for the first time. Tests show that the mannose has a good curative effect on relieving diseases of silicosis, has outstanding potential for treating silicosis, has no obvious toxic action on cells, is relatively good in safety, has a good medicinal value prospect, and can be developed into a novel medicine for treating silicosis.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of mannose in the preparation of drugs for treating silicosis. Background Art

[0002] Free silica dust, also known as silica dust, is widely present in the fields of national economic construction such as construction manufacturing and transportation. Silicosis is a systemic disease mainly characterized by pulmonary fibrosis caused by long-term inhalation of a large amount of free silica-containing dust during labor, and it is an occupational disease that seriously endangers human physical and mental health. After the patient stops contacting silica dust, the disease still progresses. The main symptoms include cough, expectoration, chest tightness, shortness of breath, and dyspnea. The pathogenesis of silicosis is complex, and the current understanding of the occurrence and development mechanisms of silicosis is not very clear. Research has found that the onset of silicosis is the result of the combined action of the body's immune function disorder and various cytokines. Recent studies have shown that dust-induced lung injury is mainly achieved through the following five pathways: ① direct cytotoxicity; ② formation of reactive chemical substances; ③ production of some cytokines and chemokines; ④ pulmonary fibrosis; ⑤ cell death induced by the apoptotic pathway. After dust particles enter the respiratory tract, they are recognized and phagocytosed by alveolar macrophages through surface receptors. During this process, alveolar macrophages can release a large number of bioactive substances mainly composed of inflammatory factors, including tumor necrosis factor (tumor necrosis factor-α, TNF-α), transforming growth factor-β (transforming growth factor-β, TGF-β), etc. These inflammatory factors are not only directly related to the degree of damage to the respiratory system, but also participate in the immune response process in the lung tissue and regulate the activity of other related cells in the lung. TNF-α and TGF-β can promote collagen deposition and promote the epithelial-mesenchymal transition of lung epithelial cells, ultimately leading to interstitial lung disease and the progression of silicosis. There is currently no specific treatment method for silicosis and it cannot be cured completely. Clinical treatment mainly focuses on symptomatic treatment and comprehensive treatment for complications. Therefore, it is urgent to find a reasonable and effective way to treat silicosis, and drug treatment, as the main means of treating silicosis, has attracted increasing attention.

[0003] Mannose (D-(+)-Mannose), abbreviated as Mannose, is an epimer of glucose at the C2 position, and its molecular formula is C6H 12 O6, and its molecular structure is It mainly exists in the form of the sweet α or bitter β isomers of pyranose. Mannose is widely distributed in body fluids and tissues such as nerves, skin, liver, and intestines. Mannose can serve as a source of cell energy and is involved in the synthesis and modification of glycoproteins on the cell surface. The mannose receptor is an atypical pattern recognition receptor (PRR), mainly distributed in human macrophages and dendritic cells, and its expression is related to the activation of macrophages. The mannose receptor can bind both endogenous molecules and pathogens; the mannose receptor can clear these two types of substances, making it a bridge between homeostasis and immune defense. After mannose binds to its receptor, it can induce these cells to uptake and antigen presentation, affect the tumor microenvironment by regulating the host immune response, and thus affect the development of cancer; at the same time, it can also affect intracellular signal transduction through specific sensitivity pathways and regulate cell growth, differentiation, and apoptosis. Clinically, there have been attempts to use mannose in antibacterial, anti-tumor, obesity, and diabetes treatments and certain results have been achieved. However, there has been no report on the use of mannose in the treatment of silicosis or other occupational diseases. Summary of the Invention

[0004] An object of the first aspect of the present invention is to provide the use of mannose in the preparation of a drug for treating or preventing silicosis.

[0005] An object of the second aspect of the present invention is to provide the use of mannose in promoting macrophage proliferation or in the preparation of a product for promoting macrophage proliferation.

[0006] An object of the third aspect of the present invention is to provide the use of mannose in alleviating cytotoxicity or in the preparation of a product for alleviating cytotoxicity.

[0007] An object of the fourth aspect of the present invention is to provide the use of mannose in the preparation of a product for promoting macrophages to clear silica.

[0008] An object of the fifth aspect of the present invention is to provide a method for promoting macrophage proliferation.

[0009] In order to achieve the above objects, the technical solutions adopted by the present invention are as follows:

[0010] The first aspect of the present invention provides the use of mannose in the preparation of a drug for treating or preventing silicosis.

[0011] In some embodiments of the present invention, the mannose achieves the purpose of treating or preventing silicosis by promoting macrophage proliferation and alleviating silica-induced cytotoxicity.

[0012] In some embodiments of the present invention, the mannose achieves the purpose of treating or preventing silicosis by promoting macrophage clearance of silica.

[0013] In some embodiments of the present invention, the drug further comprises a pharmaceutically acceptable excipient or any one or more other active ingredients.

[0014] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, antiadhesives, chelating agents, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoaming agents, thickening agents, clathrates, humectants, absorbents, diluents, flocculants and deflocculants, filter aids, release retardants, carriers.

[0015] In some embodiments of the present invention, for the convenience of administration, the active ingredient mannose can be processed into a specific dosage form with any one or several pharmaceutically acceptable excipients. These excipients can be diluents (such as starch, pregelatinized starch, dextrin, sucrose, lactose, mannitol, microcrystalline cellulose, etc.), absorbents (such as calcium sulfate, calcium hydrogen phosphate, light magnesium oxide, calcium carbonate, etc.), wetting agents (such as water, ethanol, etc.), binders (such as hydroxypropyl methylcellulose, povidone, starch paste, syrup, etc.), disintegrants (such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, effervescent disintegrants, cross-linked povidone, etc.), lubricants (such as magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, colloidal silica, etc.), colorants (such as titanium dioxide, sunset yellow, methylene blue, medicinal iron oxide, etc.), coating materials (such as acrylic resin, hydroxypropyl methylcellulose, povidone, etc.), solvents (such as water for injection, ethanol, propylene glycol, glycerol, etc.), acid-base regulators (such as hydrochloric acid, lactic acid, sodium hydroxide, tartaric acid, sodium tartrate, etc.), antioxidants (such as sodium sulfite, sodium metabisulfite, sodium thiosulfate, etc.), bacteriostatic agents (such as phenol, benzyl alcohol, thimerosal, etc.), or can also be isotonicity regulators (such as sodium chloride, glucose, etc.).

[0016] In some embodiments of the present invention, the dosage form of the drug includes a gastrointestinal administration dosage form or a non-gastrointestinal administration dosage form.

[0017] In some embodiments of the present invention, the gastrointestinal administration dosage forms include at least one of powders, tablets, granules, capsules, sustained-release agents, solutions, dry suspensions, effervescent tablets, emulsions, suspensions, syrups, drops, chewable tablets.

[0018] In some embodiments of the present invention, the gastrointestinal dosage forms include, but are not limited to, enteric-coated tablets, coated tablets, film-coated tablets, sugar-coated tablets, dispersible tablets, sucking tablets, chewable tablets, effervescent tablets, scored tablets, sustained-release and controlled-release dosage forms such as sustained-release tablets, sustained-release coated tablets, controlled-release tablets, orally disintegrating tablets, lozenges, oral patches, etc.

[0019] In some embodiments of the present invention, the non-gastrointestinal dosage forms include at least one of injection dosage forms, respiratory dosage forms, skin dosage forms, mucosal dosage forms, and cavity dosage forms.

[0020] In some embodiments of the present invention, the injection dosage forms include, but are not limited to, injection solutions, solution for injection, injection solutions for intravenous drip, injection suspensions, sterile powders for injection, intravenous injection needles, aqueous injections, emulsion for injection, powder injections, injections, sterile powder injections, lyophilized powder injections, etc.

[0021] In some embodiments of the present invention, the effective dose of mannose in the drug is 1% (w / w) to 20% (w / w).

[0022] In some embodiments of the present invention, the effective dose of mannose in the drug is 1% (w / w) to 10% (w / w).

[0023] The second aspect of the present invention provides the use of mannose in promoting macrophage proliferation or in the preparation of a product for promoting macrophage proliferation.

[0024] In some embodiments of the present invention, the effective dose of mannose is 1 to 15 mM.

[0025] In some embodiments of the present invention, the effective dose of mannose is 1 to 10 mM.

[0026] In some embodiments of the present invention, the effective dose of mannose is 5 to 10 mM.

[0027] In some embodiments of the present invention, the product includes a reagent, a kit, or a drug.

[0028] The third aspect of the present invention provides the use of mannose in alleviating cytotoxicity or in the preparation of a product for alleviating cytotoxicity.

[0029] In some embodiments of the present invention, the cytotoxicity includes the cytotoxicity caused by silica.

[0030] In some embodiments of the present invention, the effective dose of mannose is 1 to 15 mM.

[0031] In some embodiments of the present invention, the effective dose of mannose is 1 to 10 mM.

[0032] In some embodiments of the present invention, the effective dose of mannose is 5-10 mM.

[0033] In some embodiments of the present invention, the product includes a reagent, a kit or a drug.

[0034] The fourth aspect of the present invention provides the use of mannose in the preparation of a product for promoting macrophages to remove silica.

[0035] In some embodiments of the present invention, the effective dose of mannose is 1-15 mM.

[0036] In some embodiments of the present invention, the effective dose of mannose is 1-10 mM.

[0037] In some embodiments of the present invention, the effective dose of mannose is 5-10 mM.

[0038] In some embodiments of the present invention, the product includes a reagent, a kit or a drug.

[0039] The fifth aspect of the present invention provides a method for promoting macrophage proliferation, including the step of treating cells with mannose.

[0040] In some embodiments of the present invention, macrophages are treated with a mannose solution of 1-15 mM.

[0041] In some embodiments of the present invention, macrophages are treated with a mannose solution of 1-10 mM.

[0042] The beneficial effects of the present invention are as follows:

[0043] The present invention firstly discloses the use of mannose in the preparation of a drug for treating or preventing silicosis. Experiments of the present invention show that mannose has a good curative effect on alleviating the lesions of silicosis, has outstanding potential for treating silicosis, and mannose itself has no obvious toxic effect on cells, has good safety, has good prospects for medicinal value, and can be developed into a new drug for treating silicosis. Description of the Drawings

[0044] Figure 1Cell proliferation-toxicity detection results of human monocytic leukemia cell line (THP-1 cells) stimulated to differentiate into THP-1-derived macrophages and mannose acting on THP-1-derived macrophages; among them, A shows that THP-1 cells differentiate into THP-1-derived macrophages after stimulation with phorbol 12-myristate 13-acetate (PMA), and the scale bar is 100 μm. B shows the cell viability results after treating THP-1-derived macrophages with mannose at four concentrations of 0 mM, 5 mM, 10 mM, and 20 mM; in the figure, * represents p < 0.05, ** represents p < 0.01, and *** represents p < 0.001.

[0045] Figure 2 Cell proliferation-toxicity detection results of mannose acting on silica-exposed THP-1-derived macrophages; among them, after silica exposure, THP-1-derived macrophages are treated with mannose at four concentrations of 0 mM, 5 mM, 10 mM, and 20 mM. A shows the cell viability results, and B shows the cell toxicity results; in the figure, * represents p < 0.05, and *** represents p < 0.001.

[0046] Figure 3 Transmission electron microscopy results of mannose stimulating THP-1-derived macrophages after silica exposure; among them, THP-1-derived macrophages after silica exposure are treated with mannose at four concentrations of 0 mM, 5 mM, 10 mM, and 20 mM. The scale bar in the upper figure (magnified 6000 times) is 5 μm, and the scale bar in the lower figure (magnified 15000 times) is 2 μm.

[0047] Figure 4 Hematoxylin-eosin (H&E) staining results of mannose acting on lung tissues of mouse silicosis conventional model and silicosis extended model; among them, A shows the H&E staining results of lung tissues of the silicosis conventional model with free drinking water of control group and mannose at two concentrations (2% (w / w), 10% (w / w)), and B shows the H&E staining results of lung tissues of the silicosis extended model with free drinking water of control group and mannose at two concentrations (2% (w / w), 10% (w / w)), and the scale bar is 10 μm. Detailed implementation manners

[0048] The content of the present invention will be further described in detail below through specific examples.

[0049] It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention.

[0050] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specified in the embodiments, they are carried out according to conventional conditions or the conditions recommended by the manufacturer. For reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0051] The features and performance of the present invention will be further described in detail below in conjunction with the embodiments.

[0052] Example 1 Low-concentration mannose can promote macrophage proliferation in vitro and reduce the cytotoxicity caused by silica

[0053] This example examines the effect of mannose on macrophages exposed to silica, specifically as follows:

[0054] (1) Take THP-1 cells in good growth condition and culture them in a complete medium prepared from Roswell Park Memorial Institute (RPMI) 1640 medium (USA, Gibco, 11875093) and 10% (v / v) fetal bovine serum (China, ExCell Bio, FSD050).

[0055] (2) By counting, seed 1×10 4 cells per well in a 96-well plate. Add 150 nM PMA (China, Selleck, S7791) to each well and stimulate for 24 h to differentiate THP-1 cells into THP-1-derived macrophages.

[0056] (3) Prepare the silica solution and mannose solution: Dissolve 2.5 g of silica powder (USA, sigma-aldrich, SLCF2432) in 10 mL of physiological saline to prepare a 250 g / L suspension. Autoclave at 120 °C for 30 min and then cool to room temperature. After ultrasonic treatment for 20 min, seal and store. Dissolve 1.8 g of mannose powder (China, Meilun Bio, J0724D) in 10 mL of complete medium, filter with a 0.22 μm sterile needle filter, and then seal and store. Mix the solution before use and dilute it to the corresponding concentration.

[0057] (4) Experimental grouping: Set two major groups, namely the mannose group and the silica + mannose group, and set 4 treatment groups in each major group.

[0058] 1) Mannose group

[0059] A. Control group: THP-1-derived macrophages are cultured in complete medium.

[0060] B. 5 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 5 mM mannose;

[0061] C. 10 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 10 mM mannose;

[0062] D. 20 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 20 mM mannose;

[0063] 2) Silicon Dioxide (SiO2) + Mannose Group

[0064] A. SiO2 Group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2;

[0065] B. SiO2 + 5 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 5 mM mannose;

[0066] C. SiO2 + 10 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 10 mM mannose;

[0067] D. SiO2 + 20 mM Mannose Group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 20 mM mannose;

[0068] (5) After culturing for 24 h, a certain proportion of CCK-8 reagent (DOJINDO, CK04, Japan) was added according to the instructions;

[0069] (6) After incubating in the incubator for 2 h, the absorbance of each group was measured at a wavelength of 450 nm using a microplate reader. Set As as the experimental well (medium containing cells, CCK-8, and toxic substance), Ac as the control well (medium containing cells, CCK-8, and no toxic substance), and Ab as the blank well (medium without cells and toxic substance, CCK-8). Calculate the cell survival rate and inhibition rate according to the instructions. Cell survival rate = [(As - Ab) / (Ac - Ab)] × 100%, inhibition rate = [(Ac - As) / (Ac - Ab)] × 100%, and perform statistical analysis on the results.

[0070] The experimental results are shown in Figure 1 and Figure 2 as follows. As shown in Figure 1, after being stimulated by PMA, THP-1 cells differentiated from suspension cells into adherent THP-1-derived macrophages. Compared with the control group, low concentrations (5 mM, 10 mM) of mannose could promote macrophage proliferation, while high concentration (20 mM) inhibited macrophage proliferation. As Figure 2 , after silica exposure, adding 10 mM mannose could alleviate the cytotoxicity caused by silica. It is suggested that low-concentration mannose can promote macrophage proliferation in vitro, reduce the cytotoxicity induced by silica, and thus achieve the purpose of treating silicosis.

[0071] Example 2 Mannose Promotes THP-1-derived Macrophages to Clear Silica Crystal Particles

[0072] This example investigated the mechanism by which mannose alleviates the cytotoxicity of THP-1-derived macrophages exposed to silica, as follows:

[0073] (1) THP-1 cells in good growth condition were cultured in complete medium;

[0074] (2) By counting, 2×10 7 cells were seeded in a 15 mm culture dish. PMA was added and stimulated for 24 h to differentiate THP-1 into THP-1-derived macrophages;

[0075] (3) Experimental grouping: Four treatment groups were set up;

[0076] A. SiO2 group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2;

[0077] B. SiO2 + 5 mM mannose group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 5 mM mannose;

[0078] C. SiO2 + 10 mM mannose group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 10 mM mannose;

[0079] D. SiO2 + 20 mM mannose group: THP-1-derived macrophages were cultured in complete medium containing 100 μg / mL SiO2 + 20 mM mannose;

[0080] (4) Sample collection and fixation: After 24 h of culture, the cell precipitate was collected by centrifugation. The complete medium was discarded, and an appropriate amount of electron microscopy fixative (China, Sevier Bio, G1102-100 mL, and the following experimental steps all used Sevier transmission electron microscopy-related reagent products) was added. The cells were resuspended and fixed at 4°C for 2 - 4 h, and stored and transported at 4°C for fixation;

[0081] (5) Agar pre-embedding: Centrifuge, discard the supernatant, add 0.1M phosphate buffer PB (pH 7.4), mix well and rinse for 3 min, then centrifuge again. Repeat the washing 3 times. Prepare a 1% (w / w) agarose solution by heating and dissolving in advance. After slightly cooling, add it into the EP tube. Before the agarose solidifies, pick up the precipitate with forceps and suspend it in the agarose for wrapping;

[0082] (6) Post-fixation: Fix in the dark at room temperature for 2 h with 1% (v / v) osmium tetroxide prepared with 0.1M phosphate buffer PB (pH 7.4). Rinse 3 times with 0.1M phosphate buffer PB (pH 7.4), 15 min each time;

[0083] (7) Dehydration at room temperature: The samples are successively dehydrated in 30% (v / v) - 50% (v / v) - 70% (v / v) - 80% (v / v) - 95% (v / v) - 100% (v / v) - 100% (v / v) alcohol for 20 min each time, and twice in 100% (v / v) acetone for 15 min each time;

[0084] (8) Infiltration and embedding: Acetone: 812 embedding agent = 1:1, at 37°C for 2 - 4 h, acetone: 812 embedding agent = 1:2, infiltrate overnight at 37°C, and pure 812 embedding agent at 37°C for 5 - 8 h. Pour the pure 812 embedding agent into the embedding plate, insert the samples into the embedding plate and incubate overnight in an oven at 37°C;

[0085] (9) Polymerization: Place the embedding plate in an oven at 60°C for polymerization for 48 h, take out the resin block for standby;

[0086] (10) Ultra-thin sectioning: Ultra-thin section the resin block at 60 - 80 nm on an ultra-microtome, and pick up the sections with a 150-mesh Fanghua film copper grid;

[0087] (11) Staining: Stain the copper grid with a saturated alcohol solution of 2% (w / w) uranyl acetate in the dark for 8 min; Wash 3 times with 70% (v / v) alcohol; Wash 3 times with ultrapure water; Stain with a 2.6% (w / w) lead citrate solution in the absence of carbon dioxide for 8 min; Wash 3 times with ultrapure water and gently blot dry with filter paper. Place the copper grid sections in a copper grid box and dry overnight at room temperature;

[0088] (12) Observe under a transmission electron microscope and collect images for analysis.

[0089] The experimental results are as Figure 3 shown. It can be seen from the experimental results that compared with the control group, under the stimulation of 10 mM mannose, the silica crystal particles in THP-1-derived macrophages are significantly reduced. This is consistent with the results of Figure 2 , indicating that mannose may reduce the toxicity of silica to macrophages by promoting macrophages to clear silica particles, thereby achieving the therapeutic effect on silicosis.

[0090] Example 3: Mannose has a preventive treatment effect in a conventional mouse silicosis model

[0091] This example examines the therapeutic effect of mannose in a conventional mouse silicosis model. The specific experiment is as follows:

[0092] (1) Twenty-four 8-week-old male C57BL / 6J mice were selected and randomly divided into 3 groups. Five days before modeling, they were given free access to water and 2% (w / w) and 10% (w / w) mannose solution in water for 5 days respectively;

[0093] (2) On day 0, they were treated with intratracheal injection of 20 μL of SiO2 suspension with a mass concentration of 250 g / L, and then continued to be given free access to water and mannose solution in water;

[0094] (3) On day 28, the mice were sacrificed, and their lungs were isolated for H&E staining.

[0095] The experimental results are as shown in Figure 4 A in the figure. It can be seen from the experimental results that the silicosis nodules in the mice that had ingested mannose in advance were significantly reduced, and compared with 2% (w / w) mannose, after ingesting 10% (w / w) mannose, the number of silicosis nodules was even less. This indicates that mannose has a preventive treatment effect in the mouse silicosis model, and ingesting mannose in advance can prevent silicosis and slow down the progression of silicosis.

[0096] Example 4: Mannose has a therapeutic effect in an extended mouse silicosis model

[0097] To observe the drug treatment effect and the effect of delayed administration, on the basis of Example 3, relevant experiments on an extended mouse silicosis model were further carried out as follows:

[0098] (1) Twenty-four 8-week-old male C57BL / 6J mice were selected and randomly divided into 3 groups;

[0099] (2) On day 0, they were treated with intratracheal injection of 20 μL of SiO2 suspension with a mass concentration of 250 g / L;

[0100] (3) Starting from day 28, they were given free access to water and 2% (w / w) and 10% (w / w) mannose solution in water respectively;

[0101] (4) On day 56, the mice were sacrificed, and their lungs were isolated for H&E staining.

[0102] The experimental results are as shown in Figure 4As shown in B, it can be seen from the experimental results that the silicosis nodules in mice with delayed mannose intake were significantly reduced, and compared with 2% (w / w) mannose, after using 10% (w / w) mannose, the number of silicosis nodules was less, indicating that mannose intake can alleviate the progression of silicosis, and mannose has a therapeutic effect in the mouse silicosis model.

[0103] The embodiments of the present invention have been described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the scope of knowledge possessed by those of ordinary skill in the art. In addition, the embodiments of the present invention and the features in the embodiments can be combined with each other without conflict.

Claims

1. The use of mannose in the preparation of medicines for treating or preventing silicosis.

2. The use according to claim 1, characterized in that: The mannose achieves the purpose of treating or preventing silicosis by promoting macrophage proliferation and alleviating silicon dioxide-induced cytotoxicity.

3. The use according to claim 1, characterized in that: The mannose achieves the purpose of treating or preventing silicosis by promoting the removal of silicon dioxide by macrophages.

4. The use according to any one of claims 1 to 3, characterized in that: The drug may also include pharmaceutically acceptable excipients or any one or more other active ingredients; Preferably, the pharmaceutically acceptable excipients include at least one of solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesives, integrities, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, release retardants, and carriers.

5. Use of mannose in promoting macrophage proliferation or preparing products promoting macrophage proliferation.

6. The use according to claim 5, characterized in that: The effective dosage of mannose is 1-15 mM.

7. Use of mannose in alleviating cytotoxicity or in preparing products for alleviating cytotoxicity.

8. The use according to claim 7, characterized in that: The cytotoxicity includes cytotoxicity caused by silicon dioxide.

9. Application of mannose in the preparation of products for promoting macrophages to clear silicon dioxide.

10. A method for promoting macrophage proliferation, comprising the step of treating cells with mannose.

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