CN111202836A - Application of sturgeon protein peptide in preparation of immunoregulation preparation - Google Patents
Application of sturgeon protein peptide in preparation of immunoregulation preparation Download PDFInfo
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- CN111202836A CN111202836A CN202010082066.5A CN202010082066A CN111202836A CN 111202836 A CN111202836 A CN 111202836A CN 202010082066 A CN202010082066 A CN 202010082066A CN 111202836 A CN111202836 A CN 111202836A
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Abstract
The invention provides application of sturgeon protein peptide in preparation of an immunoregulation preparation, wherein the sturgeon protein peptide contains 1.2-1.5 mg/g of metallothionein peptide, and the average molecular weight is below 250 Da. Experiments prove that the preparation can stimulate immune cells to proliferate and start immune response, thereby playing a role in immune regulation, can be used for preparing an immunity enhancing preparation, can be used for adjuvant treatment of virus infection and malignant tumor, and plays a role in bidirectional regulation of immunity. Meanwhile, the health-care food has food-grade safety, and is also suitable for daily health care as food and health-care products with the function of immunoregulation.
Description
Technical Field
The invention belongs to the field of biological products, and particularly relates to application of sturgeon protein peptide in preparation of an immunoregulation preparation.
Background
Immunoregulatory agents refer to substances that regulate, enhance, excite and restore the immune function of the body. The immunoregulatory preparation includes hormone, such as dexamethasone and prednisone, alkylating agent, such as cyclophosphamide, antimetabolite, such as methotrexate, and natural preparations, such as antithymocyte globulin, immunoglobulin for resisting human lymphocyte, and certain fungus polysaccharide, such as lentinan.
However, the hormone immunoregulation preparation is not easy to control in dosage, and sequelae are common; alkylating agents and antimetabolites have obvious cytotoxicity and are used carefully; other immunomodulatory drugs also have the problem of significant side effects or inaccurate immunomodulatory effects.
More safe preparations with immunoregulation function, including medicines, foods, health products and the like, need to be developed.
Disclosure of Invention
Aiming at the defects or the improvement requirements of the prior art, the invention provides the application of the sturgeon protein peptide in the preparation of the immunoregulation preparation, and the aim is to discover that the application of the sturgeon protein peptide provided by the invention has an immunoregulation effect, has food-grade safety and can be applied to the preparation of the immunoregulation preparation, including oral food, medicines and health-care products.
To achieve the above objects, according to one aspect of the present invention, there is provided a use of sturgeon protein peptide for preparing an immunomodulating preparation.
Preferably, the sturgeon protein peptide is applied to preparing an immune enhancement preparation.
Preferably, the sturgeon protein peptide is applied to preparing a medicament for adjuvant therapy of viral infection.
Preferably, the sturgeon protein peptide is applied to preparing a medicament for adjuvant therapy of coronavirus infection.
Preferably, the sturgeon protein peptide is applied to preparing 2019-nCoV coronavirus infection adjuvant therapy medicines.
6. Preferably, the sturgeon protein peptide is applied to preparing an auxiliary therapeutic drug for malignant tumors.
Preferably, the sturgeon protein peptide contains 1.2-1.5 mg/g of metallothionein peptide.
Preferably, the sturgeon protein peptide is applied, wherein the average molecular weight of the sturgeon protein peptide is below 250 Da.
Preferably, the sturgeon protein peptide is prepared by the following method:
1) cleaning sturgeon, cutting into blocks, mincing, adding 1-3 times of water, heating to above 90 deg.C, maintaining for 10-20min, and steam-exploding under 2-2.5MPa for 3-5 min;
2) cooling the material obtained in the step 1) to below 60 ℃, adding a hydrochloric acid solution to adjust the pH value to 1.5-5, and then adding pepsinogen accounting for 0.2-0.3% of the mass of the sturgeon to perform an enzymolysis reaction for 2-5 hours;
3) adding an alkali solution into the material obtained in the step 2) to adjust the pH value to 7.5-8, and adding trypsin accounting for 0.1-0.2% of the mass of the sturgeon to perform an enzymolysis reaction for 1-3 hours;
3) heating the material obtained in the step 2) to above 90 ℃ and keeping for 10-20min, cooling to below 65 ℃, decoloring, desalting, sterilizing, filtering, concentrating the filtrate, and finally sterilizing and drying to obtain the protein peptide powder.
Preferably, the sturgeon protein peptide is applied to preparing oral food, medicines and health-care products with immunoregulation effect.
In general, compared with the prior art, the above technical solution contemplated by the present invention can achieve the following beneficial effects:
experiments prove that the sturgeon protein peptide provided by the invention can stimulate immune cell proliferation and start immune response, so that the sturgeon protein peptide plays a role in immune regulation, can be used for preparing an immune enhancing preparation, can be used for adjuvant therapy of virus infection and malignant tumor, and plays a role in bidirectional regulation of immunity. Meanwhile, the health-care food has food-grade safety, and is also suitable for daily health care as food and health-care products with the function of immunoregulation.
Drawings
FIG. 1 is a graph showing the results of the toxic effect of sturgeon protein peptides on Raw264.7 cells at different concentrations in example 1;
FIG. 2 is a graph showing the effect of different concentrations of sturgeon protein peptide on NO secretion from Raw264.7 cells in example 2;
fig. 3 is a chest image of the posterior anterior position of the subject patient of example 3.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The sturgeon protein peptide contains 1.2-1.5 mg/g of metallothionein peptide, and the average molecular weight is below 250 Da.
The sturgeon protein peptide is prepared according to the following method:
1) cleaning sturgeon, cutting into blocks, mincing, adding 1-3 times of water, heating to above 90 deg.C, maintaining for 10-20min, and steam-exploding under 2-2.5MPa for 3-5 min;
2) cooling the material obtained in the step 1) to below 60 ℃, adding a hydrochloric acid solution to adjust the pH value to 1.5-5, and then adding pepsinogen accounting for 0.2-0.3% of the mass of the sturgeon to perform an enzymolysis reaction for 2-5 hours;
3) adding an alkali solution into the material obtained in the step 2) to adjust the pH value to 7.5-8, and adding trypsin accounting for 0.1-0.2% of the mass of the sturgeon to perform an enzymolysis reaction for 1-3 hours;
4) heating the material obtained in the step 3) to above 90 ℃ and keeping for 10-20min, cooling to below 65 ℃, decoloring, desalting, sterilizing, filtering, concentrating the filtrate, and finally sterilizing and drying to obtain the protein peptide powder.
Cell experiments prove that the sturgeon protein peptide (trade name of Gooduning sturgeon protein peptide powder) provided by the invention can stimulate immune cell proliferation and start immune response, so that the effect of immunoregulation is achieved, and the sturgeon protein peptide can be used for preparing immune enhancement preparations, such as malignant tumor adjuvant therapy medicines. Meanwhile, human experiments show that the sturgeon protein peptide provided by the invention has the effect of inhibiting excessive immune response, and the sturgeon protein peptide provided by the invention has a bidirectional immune regulation effect and can be used for preparing a virus infection adjuvant therapy medicament, such as a coronavirus infection adjuvant therapy medicament.
Meanwhile, the sturgeon protein peptide provided by the invention is derived from natural food and has food-grade safety through inspection.
The following are examples:
in the examples, sturgeon protein peptides were prepared as follows:
1) cleaning sturgeon, cutting into blocks, mincing, adding 1-3 times of water, heating to above 90 deg.C, maintaining for 20min, and steam-exploding under 2.5MPa for 3 min;
2) cooling the material obtained in the step 1) to below 60 ℃, adding a hydrochloric acid solution to adjust the pH value to 1.5-5, and then adding pepsinogen accounting for 0.3 percent of the mass of the sturgeon to perform an enzymolysis reaction for 5 hours;
3) adding an alkali solution into the material obtained in the step 2) to adjust the pH value to 7.5-8, and then adding trypsin accounting for 0.1% of the mass of the sturgeon to perform an enzymolysis reaction for 2 hours;
4) heating the material obtained in the step 3) to above 90 ℃ for 20min, cooling to below 65 ℃, decoloring, desalting, sterilizing, filtering, concentrating the filtrate, and finally sterilizing and drying to obtain the protein peptide powder. The decolorizing agent is obtained by mixing active carbon and diatomite according to a mass ratio of 2:1, the adding amount of the decolorizing agent is 0.2-0.3% of the mass of the sturgeon, the decolorizing time is 30min, and the temperature is controlled at 60-70 ℃; fermenting by using bacillus subtilis to remove fishy smell; adopting reverse osmosis desalination treatment, wherein the parameters of the reverse osmosis desalination treatment are as follows: pressure 1MP, temperature 25 ℃, salt rejection rate 70%, cellulose acetate membrane; then, sterilizing and filtering by adopting a microfiltration membrane; concentrating the filtrate with nanofiltration membrane, and performing instantaneous high temperature disinfection and vacuum freeze drying to obtain protein peptide powder.
The sturgeon protein peptide contains 1.5mg/g of metallothionein peptide; the average molecular weight 243 is shown by the detection results of the polypeptide content and molecular weight distribution carried out by the research institute of light-analytical chemical technology in Beijing Zhongke (food laboratory).
Example 1 Effect of monocyte macrophage RAW264.7 cell viability assay
The immunoregulatory activity of sturgeon protein peptide is evaluated by taking mouse mononuclear macrophage RAW264.7 cultured in vitro as a cell model.
Macrophages are the main components of the mononuclear macrophage system, have multiple functions of phagocytosing foreign invaded pathogenic microorganisms and processing and presenting antigens, kill foreign pathogens by phagocytosis and secretion of cytokines, and play a key role in maintaining human health. RAW264.7 is a mononuclear macrophage including macrophages in tissues including tissues, pre-monocytes in bone marrow, monocytes in peripheral blood, which can eliminate various pathogenic substances and play an important role in body defense. Not only can start innate immunity (nonspecific immunity) response, but also can participate in cellular immunity (specific immunity) response, and plays an important role in resisting a plurality of disease processes such as microbial infection, tumor and the like in a body. Thus, RAW264.7 is often used as an ideal cell model to evaluate the immunomodulatory activity of bioactive substances.
LPS (lipopolysaccharide) is a substance that activates macrophages, and therefore this experiment was selected as a positive control.
The MTT experiment can be used for evaluating the toxic effect of a drug on cells, the cell viability is in negative correlation with the cytotoxicity, the cell viability is generally considered to be less than 90% to have certain cytotoxicity, and the cell viability is more than 90% to have no cytotoxicity.
MTT (methanol to transfer) experiment for determining influence of sturgeon protein peptide on cell survival rate
MTT (3- (4, 5-dimethylthiazole-2) -2, 5-diphenyl tetrazole bromide salt) can be reduced to blue-purple crystalline precipitate by succinate dehydrogenase in mitochondria in living cells and cannot be reduced by dead cells, dimethyl sulfoxide can dissolve the purple precipitate, and the absorbance value of the solution at 490nm can reflect the number of the living cells
Taking cells in logarithmic growth phase, adjusting cell concentration after cell counting, inoculating 100ul cells per well into a 96-well plate according to the ratio of 1 multiplied by 10^ 5/ml, culturing for 24h in 5% CO2 at 37 ℃, discarding supernatant, and adding 100ul DMEM basal medium (without serum) into a blank control group; the positive control group was added with 100ul LPS (diluted to 1ug/ml in basal medium); the experimental groups were given sturgeon protein peptide solutions (basal medium formulation) at different concentrations (12.5-1000ug/ml), continued for 24h, discarded supernatant, added 100ul of MTT solution (final concentration 0.5mg/ml with DMEM basal medium), and further incubated for 4 h. After aspirating the medium, 150ul of DMSO was added to each well to dissolve formazan crystals, and the absorbance value was measured at 490 nm. Cell viability ═ (OD experiment-OD blank)/(ODcontrol-OD blank).
The experimental results are shown in figure 1, the toxicity effect of sturgeon protein peptide on Raw264.7 cells is not toxic to the cells when the concentration of the sturgeon protein peptide is in the range of 12.5-500 mug/ml, and the proliferation activity of macrophages can be promoted to a certain extent, when the concentration of the sturgeon protein peptide is in the range of 12-250 mug/ml, the proliferation activity is increased along with the increase of the concentration of the sturgeon protein peptide, and is higher than that of a positive control group (118.76 +/-5.78%), and the maximum proliferation activity is 143.97 +/-8.6%.
The experiment shows that: the sturgeon protein peptide can promote the proliferation of Raw264.7 cells, and the maximum proliferation activity of the sturgeon protein peptide at 250 mu g/ml is 143.97 +/-8.6%.
EXAMPLE 2 cellular NO secretion Effect experiment
Taking RAW264.7 cells in logarithmic growth phase, adjusting the cell concentration to 1 x 10^ 6/ml after counting the cells, inoculating the cells into a 24-well plate, culturing the cells in 5% CO2 at 37 ℃ for 24 hours, then removing supernatant, and adding 100ul DMEM basal medium (without serum) into a blank control group; sturgeon protein peptide (prepared by a basic culture medium) with different concentrations (12.5-500ug/ml) is given to the experimental group, the culture is continued for 24h, the supernatant is collected and centrifuged for 10min at 2500r/min, 100ul of sturgeon protein peptide is respectively taken out and put into an enzyme label plate, then equivalent Griess reagent is added, the mixture is stood for 30min at room temperature, and the absorbance is measured at 540 nm. The nitrite (NO2-) content in the supernatant was calculated according to a standard curve.
NO is also an important cytokine in immune responses, can be secreted by activated macrophages, is a reactive nitrogen intermediate, and is a free radical with oxidative properties. Small amount of NO has strong killing power, and can be used for pathogen, tumor cell, etc. However, excessive NO secretion can also damage normal host cells, causing a systemic inflammatory response. Therefore, when the body is free from inflammation, a small amount of NO can improve the immune function of the body. 12.5-500. mu.g/ml was selected for the next step based on the results of the previous MTT assay. As shown in FIG. 2, the influence of sturgeon protein peptides of different concentrations on NO secretion of Raw264.7 cells is shown in FIG. 2, and the sturgeon protein peptides of each concentration can promote NO secretion of Raw264.7 cells, and the promoting effect is 12.04 +/-0.17 mu M when the concentration is 100 mu g/ml.
The experiment shows that: the sturgeon protein peptide can promote Raw264.7 to secrete NO and has an immunoregulation effect.
Cell experiments show that the sturgeon protein peptide can effectively improve the immunity and has the application prospect of adjuvant therapy of malignant tumors.
Example 3 human body experiment
The patient who is tested has been diagnosed with 2019-nCoV coronavirus infection accompanied with hypertension through checking at 23 g.1.2020/1.2020 of women, and the chest radiograph at the front position after the confirmed day is shown in the left picture of fig. 3, and the result is that the two lungs have a vitreous-like rising shadow. The sturgeon protein peptide provided by the invention is taken three times a day and 30 g once with warm water in addition to the supportive therapy from 24 days 1 month in 2020 to 29 days 1 month in 2020. After 29 months of 1 in 2020, the radiographic examination is performed again, and the result of the chest radiography at the back and front positions is shown in the right picture of fig. 3, so that the lung focus is obviously improved.
The sturgeon protein peptide provided by the invention has an auxiliary treatment effect on antiviral infection, particularly an auxiliary treatment effect on coronavirus infection. As coronavirus causes excessive immune response, the sturgeon protein peptide provided by the invention is suggested to have a bidirectional immune regulation effect.
Claims (10)
1. An application of sturgeon protein peptide is characterized in that the sturgeon protein peptide is applied to preparing an immunoregulation preparation.
2. Use of a sturgeon protein peptide according to claim 1 for the preparation of an immunopotentiating preparation.
3. The use of sturgeon protein peptides according to claim 1 for the preparation of a medicament for the adjuvant treatment of viral infections.
4. Use of a sturgeon protein peptide according to claim 3 for the preparation of a medicament for the adjuvant treatment of coronavirus infection.
5. The use of sturgeon protein peptide according to claim 4 for the preparation of a 2019-nCoV coronavirus infection adjuvant therapy drug.
6. The use of sturgeon protein peptide according to claim 1, characterized in that it is used for preparing a drug for adjuvant therapy of malignant tumors.
7. The use according to claim 1, wherein the sturgeon protein peptide comprises 1.2 to 1.5mg/g of metallothionein peptide.
8. Use according to claim 1, wherein the sturgeon protein peptide has an average molecular weight below 250 Da.
9. The use according to claim 1, wherein the sturgeon protein peptide is prepared according to the following method:
1) cleaning sturgeon, cutting into blocks, mincing, adding 1-3 times of water, heating to above 90 deg.C, maintaining for 10-20min, and steam-exploding under 2-2.5MPa for 3-5 min;
2) cooling the material obtained in the step 1) to below 60 ℃, adding a hydrochloric acid solution to adjust the pH value to 1.5-5, and then adding pepsinogen accounting for 0.2-0.3% of the mass of the sturgeon to perform an enzymolysis reaction for 2-5 hours;
3) adding an alkali solution into the material obtained in the step 2) to adjust the pH value to 7.5-8, and adding trypsin accounting for 0.1-0.2% of the mass of the sturgeon to perform an enzymolysis reaction for 1-3 hours;
3) heating the material obtained in the step 2) to above 90 ℃ and keeping for 10-20min, cooling to below 65 ℃, decoloring, desalting, sterilizing, filtering, concentrating the filtrate, and finally sterilizing and drying to obtain the protein peptide powder.
10. The use according to claim 1 for the preparation of an oral food, pharmaceutical, health product with immunomodulating properties.
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| CN112690460A (en) * | 2020-12-28 | 2021-04-23 | 湖北嫦娥药业有限公司 | Sturgeon protein peptide-containing sublingual tablet and preparation method and application thereof |
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