CN106722972A - For immunoregulation ability related gene individuation formula food and preparation method thereof - Google Patents

Abstract

Immunoregulation ability related gene individuation formula food is directed to the invention provides one kind, the Individual treatment formula food is made as follows：1) individual interleukin 1 beta acceptor encoding gene, CTL antigen 4 encoding gene, the variation of tumor necrosis factor α encoding gene is detected；2) risk of the variation of detected gene is assessed；3) raw material in selection food square foundation, according to the raw material in the risk selection gene side for being assessed, is made described for immunoregulation ability related gene individuation formula food.Individual treatment formula food provided by the present invention can improve the immunity of tumor patient.

Description

For immunoregulation ability related gene individuation formula food and preparation method thereof

Technical field

Immunoregulation ability related gene is directed to the present invention relates to a kind of Individual treatment formula food, more particularly to one kind Individuation formula food.

Background technology

According to《China's tumour registration annual report in 2012》Latest data shows that the annual de novo malignancy case of China is about 3120000, it is per minute just to there are 6 people to be diagnosed as malignant tumour；It is annual because the case of mortality of malignant tumors is about 2,700,000, it is per minute Just there are 5 people to die from malignant tumour.Tumor patient needs more nutrition because of the special of its metabolic condition, tumour cell, performs the operation, puts The discomfort that chemotherapy is brought aggravates the reasons such as the apocleisis of patient, easily occurs malnutritive.Malnutrition can cause patient's body Decline, immunity degradation, tolerance reduction, can greatly shorten life span again.If ignoring nutrition problem, nutrition is missed On the opportunity for giving, 1/4 tumor patient will be caused directly to die from malnutrition.The de novo malignancy patient in the whole world 20% exists China, 24% malignant tumor patient death is in China.In China, the underfed incidence of tumor patient is up to 65%, dislikes Property the underfed incidence of disease of tumor patient be about 31%-87%, wherein about 35% colorectal cancer patients, 40% lung cancer suffer from There is malnutrition in person, 45% incidence cancer patient, 49% upper gastrointestinal cancer patient, 80% Pancreas cancer patients, often The tumor patient that year there are about 22% directly dies from malnutrition, and malnutrition has turned into common concurrent of China's malignant tumor patient One of disease.

Substantial amounts of evidence and clinical practice show that nutritional support has very for the therapeutic effect and rehabilitation speed of patient Important and irreplaceable effect.How the malnutritive problem of tumor patient is just avoided thatAt present, special medicine purposes formula Food is the main method for clinically implementing nutritional support, common metabolic feature according to tumour and to some specific nutrition compositions Demand, manually changes its ratio, causes internal certain predetermined substance superfluous or lacks, the expansion for making it be unfavorable for tumour cell Increase, or improve sensitiveness of the tumour to antineoplaston, or the toxicity for reducing other treatment.Correct nutrition treatment is not only The nutritional status of malignant tumor patient can be improved can also be played a part of to treat tumour.

Tumour is substantially genopathy, and various environment and heredity carcinogenic factors etc. are caused with collaboration or sequential mode DNA damage, so as to activate proto-oncogene and (or) inactivation tumor suppressor gene, adds apoptosis gene and (or) DNA is repaired The change of gene, and cause the exception of expression, normal cell is converted, ultimately result in tumour and formed.

Vicious transformation is caused due to genetic change.The albumen of some abnormal gene expressions can cause siberian crabapple The reaction of system, so that body can eliminate the transformed cells of these " non-".If without this immune surveillance mechanism, tumour Generation it is more much more than what is actually occurred.Antineoplastic immunological effect mechanism includes：Tumor immunity is with cellular immunity Based on, supplemented by humoral immunity.The effector cell for participating in cellular immunity mainly has cytotoxic T cell (CTL), NK And macrophage (NK).

The gene related to immunoregulation ability includes interleukin 1 beta acceptor encoding gene (IL1 β), cytolytic T lymphs The encoding gene of cell-associated antigens 4 (CTLA4), tumor necrosis factor-alpha encoding gene (TNF-α), wherein IL1 β genetic mutations shadow The expression of inflammatory factor is rung, inflammatory factor is locally generated excessive and/or generation and reduces, and increased the generation wind of cancer Danger；CTLA4 genetic mutations cause various disease risks increases such as T cell immune tolerance ability exception, tumour；TNF-A bases Because variation causes internal immunologic cellular activity regulating power to be damaged, various disease susceptibilities increase.

The content of the invention

Basis of the present invention《Special medicine purposes formula food general rule》Related request, for tumor patient immunoregulation base The Individual treatment formula food that the feature of cause is prepared from, it is made as follows：1) genetic test tumor patient Interleukin 1 beta acceptor encoding gene, CTL antigen 4 encoding gene, tumor necrosis factor-alpha coding base The variation situation of cause；2) assessment detects the risk of genetic mutation；3) raw material in selection food square foundation, according to what is assessed Raw material in risk selection gene side, is made described for immunoregulation ability related gene individuation formula food.This hair Bright is the Individual treatment formula food designed for this kind of special population of the weak tumor patient of immunoregulation ability, can be met Demand of the neoplastic disease states crowd of malnutritive, immunologic hypofunction and metabolic disorder to various nutritional ingredients.

The corresponding site of immunoregulation gene of the present invention is：

Interleukin 1 beta acceptor encoding gene is site one：rs1143627；CTL antigen 4 is encoded Gene is site two：rs4553808；Tumor necrosis factor-alpha encoding gene is site three：rs1800629.

The variation risk of immunoregulation gene of the present invention is：

When the genotype in site one is CC, CT, TT, the risk of site one is respectively 0.53,0.53,3.65；

When the genotype in site two is AA, AG, GG, the risk of site two is respectively 0.32,2.56,2.56；

When the genotype in site three is AA, AG, GG, the risk of site three is respectively 0.32,4.35,4.35.

The variation risk of gene is equal to the product of the risk of site one, the risk of site two and the risk of site three, according to Product is classified as low-risk, risk and excessive risk.

The composition of inventive formulation is：

1. square foundation necessity raw material is：Pea protein, shitosan, green starch, lactalbumin, agropyron；Wherein：

Pea protein：Pea protein is with non-transgenic, without anaphylactogen, low protease inhibitor, high-absorbility, perfect The advantage such as Amino acid profile and meals and healthcare function is famous.Pea protein is rich in lysine, arginine and branched-chain amino acid, Wherein arginine content about 8.7%, and help lend some impetus to muscle growth." hypo-allergenic " and " without transgenosis " of pea protein is special Property differentiates it from global vegetable egg white matter product.

Shitosan：Have substantial amounts of lymphocyte (such as NK cells, LAK cells) in human organism, it can decompose normal cell and Cancer cell.Lymphocyte kills the effect of cancer cell, the most active in pH=7.4 or so.But in cancer cell and around, due to The key enzyme of the glycolysis in cancer cell --- disaccharides kinases, phosphofructokinase activity it is very high, can produce more Calculation so that pH value deflection is acid, and lymphocyte function is blunt, and immunologic function declines.Therefore in the acyclic acidic of carcinoma cells There is the lymphocyte for killing tumour to be suppressed under border.Shitosan is combined with bile to be made one internal pH value and is partial to alkalescence, is created The environment of lymphocyte attacks cancer cells, strengthens immunocompetent cell quality and quantity, suppresses tumor vascular endothelial cell Growth, suppresses metastases, mitigates the side effect of radiotherapy chemotherapy, and strengthening immune system suppresses tumour.He Xuebin etc. is with 200mg/ (kgd) water soluble chitosan gavage, can significantly inhibit the growth of lotus S180 and Ehrlich ascites carcinoma tumour.Chitosan oligosaccharide is swollen Effective inhibitor of knurl angiogenesis, and suppress ehrlich ascites tumor cell growth with soluble chitosan in contrast chitosan oligosaccharide Found during with Tumor Angiongesis, 50 μ g chitosan oligosaccharides have stronger inhibition than 100 μ g soluble chitosans.Wang etc. with Human umbilical vein epithelial cell does experiment in vitro and shows that COS can suppress the angiogenesis triggered by VEGF, 1000 μ G/mL effects are best.The research such as Qinghua LIU, Huang, Pae, Hasegawa finds, after chitosan oligosaccharide effect sarcoma cell, cell resistance It is stagnant, while Apoptosis increases, hence it is evident that improve the expression of Bax, to reduce the expression of Bcl-2 in the G0/G1 phases, point out chitosan oligosaccharide to press down The growth of sarcoma processed simultaneously promotes its apoptosis.Xu etc. is to having found that COS can significantly mediate this thin in the research of HCC SMMC-7221 The apoptosis of born of the same parents, and raised and efficiency increase with COS concentration.After processing 72h with 0.8mg/mL COS, the apoptosis rate of initiation is reachable 38%.The research of Maeda etc. shows that chitosan oligosaccharide can activate enteric epithelium lymph thin while tumor-bearing mice tumour growth is suppressed Born of the same parents and the NK cells of spleen, and the toxic action of enteric epithelium lymphocyte and SPL to S180 cells can be strengthened, it is believed that it Mainly play a part of by strengthening body's immunity suppression tumour.Zhu Wanping thinks that chitosan oligosaccharide is small by improving lotus knurl The transformation function of mouse T lymphocytes, the killing activity of NK cells, the content of IL-2, IFN-Y and the phagocytic function of macrophage come Play antitumor action.

Green starch：Contain a considerable amount of oligosaccharide (pentosan, galactan etc.) in green starch.These oligosaccharide Because human gastrointestinal tract is difficult to be digested absorption without hydrolysis enzyme system accordingly, so the energy value that green starch is provided is than it His cereal is low, plays the role of auxiliary treatment for overweight people and diabetic.And oligosaccharide is beneficial in human body intestinal canal The MF of bacterium --- Bifidobacterium, frequent edible mung bean starch can improve gut flora, reduce harmful substance and absorb, prevention Some cancers.

Lactalbumin：Lactalbumin is class protein present in milk whey, its essential amino acid A wide selection of colours and designs, number Amount is sufficient and ratio is appropriate, is a kind of nutritive value high-quality protein higher, maintain body enteron aisle, the health of musculature and GSH quantity, antioxidant system health aspect in added body plays an important role.In lactalbumin also containing beta lactoglobulin, α- The multiple biological activities albumen such as lactoalbumin, seralbumin, immunoglobulin, lactotransferrin and milk peroxidase. These materials participate in constituting body nonspecific defense barrier, are played at the aspect such as antibacterial, antiviral, immunological regulation and actively made With.

Agropyron：Containing abundant abscisic acid in agropyron, abscisic acid has been found to effectively to suppress the growth of cancer cell, Tumour gradually atrophy can be promoted simultaneously, be the effective weapon to inhibiting tumor cell.

Described square foundation necessity raw material can be commercially available by commercially available, and pea protein of the present invention selects Yantai The gold of east albumen Science and Technology Ltd. production is preced with auspicious pea protein powder, and shitosan is limited from Guangzhou Li Yuan food additives The chitosan powder of company's production, the good fortune bridge green starch that green starch is produced from Hengshui Fu Qiao starch Co., Ltd, whey , from the lactalbumin of Shijiazhuang Chun Xin bio tech ltd production, agropyron is from the Zhejiang limited public affairs of Bai Yuan food for albumen Take charge of the dehydrated wheat grass of production.

Described square foundation necessity raw material, its component for including following weight portion：2~5 parts of pea protein, shitosan 0.5 ~2 parts, 0.4~0.6 part of green starch, 0.4~0.7 part of lactalbumin, 0.3~0.6 part of agropyron.

Preferably, square foundation necessity raw material includes the component of following weight：It is 3 parts of pea protein, 1 part of shitosan, green 0.5 part of beans starch, 0.5 part of lactalbumin, 0.5 part of agropyron.

2. square foundation supplement raw material is：Rice protein, kudzu-vine root powder, probiotics, prebiotics；Wherein：

Rice protein：The value of rice protein is mainly reflected in its low antigenicity, non-pigment interference, with it is soft without The taste and its high nutritive value of stimulation.The low antigenicity of rice protein is the important spy that it is different from other vegetable proteins Point.Contain ANFs in many vegetable proteins, such as in soybean and peanut containing to body be harmful to trypsase suppress because Son and agglutinin etc., also contain the gaseous distention factor (such as raffinose, stachyose) in soybean；Also some animal protein are former The ANFs contained in material, such as beta lactoglobulin and some egg albumins, make user there may be allergy or in Poison reaction, particularly neonate is extremely sensitive to this.It is safe and reliable and rice protein is free of similar sensitizing factor, therefore, rice Being uniquely can be from the cereal of allergic experiment.Rice protein amino acid Compositional balance is reasonable, the essential amino acid rich in body, especially Its lysine content is higher than other cereals.It is slightly not enough containing lysine, isoleucine, threonine compared with ideal protein, but Compared with aleuronat, in addition to isoleucine is less, its various essential amino acid is all relatively abundanter, and nutritive value is higher than Aleuronat and close to ideal protein.Molita etc. shows rice separated protein (RPI) result of study, feeds rice Dimethylbenzanthracene (DMBA) the induction Female small white mouse tumor weight for separating albumen is less than fed casein small white mouse, rice point From albumen there is anti-DMBA inductions canceration to act on.

Kudzu-vine root powder：The Puerarin extracted from the root of kudzu vine has the effect of coronary artery dilator and cerebral artery, it is possible to decrease blood Pressure, can dramatically increase the blood supply amount of ischemic tissue, have B1 receptor blockings to act on, and it is overworked substantially to slow down the heart, reduce myocardium oxygen Consumption, can mitigate myocardial ischemia, limitation and diminution myocardial infarct size, Antitachycardiac agents, can reduce cholesterol and blood is viscous Degree, suppresses platelet aggregation, improves microcirculation.Kudzuvine root starch is contained within ten several amino acids and the ten lot of trace unit of human body needs Element, wherein calcium, zinc, the content highest of phosphorus, richness " solarization " element contained by kudzuvine root starch, the effect of with certain cancer-resisting.Han Ping Found Deng research, the suppression ED-SCLC H446 cells propagation of pueraria crude extract and Puerarin sterling concentration dependence, its machine System may be relevant in G0/G1 phases, rise Bax expression, downward Bel-2 expression with arresting cell cycle.

Probiotics：Probiotics can optimize the combination of gut flora, suppress the growth of the spoilage organisms of generation carcinogen；Produce Raw anti-inducer matter and cancer-resisting substance；Strengthen the immune system of host, preventing chronic recurrent inflammatory；Associated proteins mutagenesis Material and carcinogen；The expression of influence tumor cell gene and enzyme, plays a role in the preventing and treating of tumour.

Prebiotics：To promote probiotics intestinal colonisation, enteron aisle convergence, intestinal pH environment be reduced, also not by most enteron aisle Spoilage organisms is utilized, but can promote the growth and breeding of beneficial bacteria-lactobacillus, Bifidobacterium in human body, such that it is able to suppress rotten Bacteria growing is lost, helps to improve and maintain enteron aisle normal function；Long-term consumption can with anti-aging, defaecation, enhance immunity, subtract Light burden of liver, the absorptivity for improving nutrient, can particularly improve absorption of the body to metal ions such as calcium, iron, zinc；Can Selectively promote outside the growth and breeding of beneficial bacterium (bifid, lactic acid), also metabolizable is the organic acids such as acid product such as lactic acid, is made The reduction of colon pH value, suppresses the growth of intestinal harmful bacillus；Small enteral Water-Electrolyte is trapped in enteric cavity, produce hypertonic effect Really, enterocinesia is stimulated to cause laxative, so as to promote intestinal endotoxin and the discharge of other toxicants, lactulose can also directly go out Endotoxin, reduction gut pH, have been widely applied to the treatment of hepatic encephalopathy in enteron aisle living.

Described square foundation necessity raw material can be commercially available by commercially available, and rice protein of the present invention is selected The rice protein powder of Krauterhaus Sanct Bernhard KG companies production, kudzu-vine root powder is had from Xinghua City Jiahe food The kudzu-vine root powder of limit company production, the lactic acid bacteria freeze drying powder that probiotics is produced from Shandong sunflower bio tech ltd, benefit Prebiotics powder of the raw unit from the production of Shanghai Nai Jin Industrial Co., Ltd.s.

Described square foundation supplement raw material, its component for including following weight portion：1~4 part of rice protein, kudzu-vine root powder 1~3 Part, 0.3~1 part of probiotics, 0.4~0.7 part of prebiotics.

Preferably, the square foundation supplement raw material includes the component of following weight：2 parts of rice protein, 2 parts of kudzu-vine root powder, benefit 0.5 part of raw bacterium, 0.5 part of prebiotics.

3. necessity raw material in gene side's is：Barrenwort, astragalus polyose, glutamine, arginine, leucine, zinc；Wherein：

Barrenwort：Icariin (ICA) is the principle active component for drying stem-leaf extract, being barrenwort of barrenwort, It is the very promising traditional Chinese medicine monomer of a class.ICA cardio-cerebrovascular, internal system, skeletal system, immune system and There is important pharmacological action in tumour system.Zhao Lianmei etc. (2009) research displays, icariin can promote TNF-α to produce It is raw, and then play immunologic enhancement；Shorthorned Epimedium P.E culture simultaneously can raise M1 type macrophages IL-10, CTLA-4 Deng the scorching gene expression of suppression, pathogen is promoted to remove and tissue repair, so as to play multiple-effect immunoregulation effect.

Astragalus polyose：Astragalus polyose has cardiovascular immunological regulation, protection, protection enteron aisle, anti-aging, anti-inflammatory, antiviral etc. Various pharmacological activity.The research display such as Ren Meiping (2010), astragalus polyose energy stimulating expression of macrophage activity promotes T cell propagation, Can also promote expression of the surface antigen in lymphocyte, induce stronger humoral and cellular immune response response, non-specific and Played a significant role in specific immune response.Meanwhile, Xiao Shunhan etc. (2009) research displays, astragalus polyose can raise macrophage Cell factor IL-1 β in cell, the level of TNF-α, strengthen the immunoregulation function of body and give full play to antitumor activity.

Glutamine：Glutamine is a kind of most abundant nonessential amino acid of body content, is protein and nucleotides The required substrate of synthesis.Tumor patient Oral glutamine supplementation can slow down the loss of musculature GLN, can While the incidence of disease and the death rate is reduced, making the cytotoxicity of the antineoplastics such as ammonia first throat purine strengthens twice.Radiotherapy and change Treatment is the important means of oncotherapy, but its many side effect directly affects tumor patient to the tolerance for the treatment of and controls curative effect Really.There is provided glutamine can substantially mitigate the incidence and the order of severity of above-mentioned complication.Glutamine can not only improve Tumor patient function of intestinal canal, additionally aids improvement patient's decomposing state, promotes body nitrogen retention and protein synthesis, improves patient It is chemicotherapy wound advantage, and do not influence chemicotherapy to the lethality of tumour cell to the tolerance of chemicotherapy.Grind and make internal disorder or usurp into one Step find for tumor patient, glutamine in addition to nutritious benefit, also important therapeutic action.Additionally, paddy ammonia Acid amides can also act on immune system, improve patient's immune response, strengthen immunity.Glutamine is a kind of main being immunized Nutrient, is the energy source of immunocyte, improves tumor patient body's immunity, lowers infection risk.Glutamine is The precursor of nucleic acid, lipoid and other amino acid, and nitrogen can be improved store, alleviate the degraded of muscle protein.In tumor patient Glutamine is supplemented during postoperative chemotherapy can improve the proteinaceous nutrient level of body, and on the one hand its reason may answer with body The negative nitrogen balance of glutamine is relevant under sharp state；On the other hand it is probably protective effect of the glutamine to gut barrier, Body is set to improve digesting and assimilating for nutriment；It is also likely to be that glutamine can reduce inflammatory factor TNF-α, IL-1 The level of β, reduces body itself Expression of Inflammatory Media, reduces gastrointestinal reaction, promotes the increase of diet.

Arginine：Arginine belongs to nonessential amino acid for normal person, but under some special pathological states then into It is essential amino acid, therefore also referred to as semi-dispensable amino acid.Its active configuration in vivo is L-type, arginine medicinal at present Also it is L-type.The method of traditional treatment tumour is surgery excision knurl body and Radiotherapy chemotherapy, and has research confirmation in recent years, is increased Suppression and apoptosis-induced effect of the amount arginine to tumour cell are notable, therefore external own someone is begun attempt to tumour using not Amino acid therapy, i.e., by adjusting in tumor host body the content of certain or certain several essential amino acid, interference tumour is thin The metabolism of born of the same parents and function, and then suppress the growth of tumour or induce its apoptosis.Additionally, arginine also participates in the generation in lymphocyte Apologize for having done sth. wrong journey, therefore, immune defense and immunological regulation, maintain and the specific immunity of protection intestinal mucosa function and tumour in terms of Play a significant role.Arginine mainly includes passing through NO inducing apoptosis of tumour cell and suppression to the suppression mechanism of tumour cell The polyamines synthesis of tumour cell, polyamines is putrescine, spermine and spermidine/general name.Polyamines can promote tumour thin in vivo and in vitro Born of the same parents' protein synthesizes.Explain this paulownia etc. (2005) research to be displayed in endothelial cell, L-arginine can be turned by the effect of NO synthase It is changed into Cit and generates NO, NO is the Endothelium der ived relaxation factor, with the poly- of vasodilator, suppression blood platelet and leucocyte The effect such as collection and scavenging activated oxygen.The supply of L-arginine increases NO generations, may on the one hand inhibit leucocyte Aggregation and platelet activation, on the other hand increased the blood flow of enteron aisle blood vessel makes its ischemic conditions be improved, so that enteron aisle Endotoxin greatly reduces into blood circulation, and then reduces pro-inflammatory cytokine TNF-α, the release of IL-1 β.

Leucine：The decomposition of the visceral proteins such as muscle protein and liver is reduced, promotes albumen synthesis, reduce the mistake of protein Degree consumption, corrects negative nitrogen balance, alleviates tumor patient dyscrasia, slows down the loss of body weight.Su Quansheng etc. (2014) is studied and shown, Supplement leucine can suppress proinflammatory cytokine TNF-α, the rising of IL-1 β expression to a certain degree, with delaying body aging Effect.Supplementing high expression of the bright ammonia combination aerobic exercise for suppressing mouse aging liver proinflammatory cytokine has good Have there is inflammatory senile symptom in 5 monthly age mouse, show TNF-α, IL-1 β, IL-6 and CRP and increase.

Zinc：Zinc can improve immunity of organisms, maintain normal scotopia ability, keep the normal sense of taste and appetite.Zinc It is the important component of many enzymes and coenzyme containing zinc fingers in organism, electron transmission, body be anti-oxidant, DNA is repaiied Played a significant role in many bioprocess such as multiple.Have numerous studies at present to show, when body is chronically at zinc deficiency state When, body anti-oxidation function and cellular repair mechanisms may be made impaired, the destruction even mutation of gene of DNA are caused, make to be immunized Monitoring network imbalance, the enzyme function reduction related to zinc fingers, the reverse failure of canceration bio signal is sent out as tumour Vital factor in exhibition.Prasad AS etc. (2010) researchs find, after giving zinc supplement, cytokine TNF-α, IL-1 β Reduced with the level such as NF-kB, while zinc can strengthen DNA Specific binding proteins A20, its activation that can suppress NF-kB, knot Fruit prompting supplement zinc can lower inflammatory Cytokines Expression by raising the negative-feedback regu- lation of A20, so as to play anti-inflammatory and anti-oxidant Effect.

Described square foundation necessity raw material can be commercially available by commercially available, and barrenwort of the present invention is met from Guangdong The HERBA EPIMEDII barrenwort Chinese medicine of spring pharmaceutical Co. Ltd's production, astragalus polyose is given birth to from Xi'an Bai Chuan bio tech ltd The astragalus extraction powder of product, the Glu powder that glutamine is produced from the taste bio tech ltd of Hebei hundred, essence , from the L-arginine powder of Zhejiang oasis Bioisystech Co., Ltd production, leucine is from the western Tang's biotechnology in Shandong for propylhomoserin The L-Leu powder of Co., Ltd's production, gluconic acid zinc powder of the zinc from the production of the taste bio tech ltd of Hebei hundred End.

Described gene side's necessity raw material, its component for including following weight portion：1~4 part of barrenwort, astragalus polyose 0.5 ~2 parts, 1~3 part of glutamine, 0.5~2 part of arginine, 0.6~1.2 part of leucine, 0.3~1 part of zinc.

Preferably, gene side's necessity raw material includes the component of following weight：2 parts of barrenwort, 1 part of astragalus polyose, paddy 2 parts of glutamine, 1 part of arginine, 1 part of leucine, 0.5 part of zinc.

4. supplement raw material in gene side's is：Glycyrrhizin, GL-B, n-3 aliphatic acid, selenium；Wherein：

Glycyrrhizin：Glycyrrhizic acid, glycyrrhizin, potenlin are called, are the active ingredient of Radix Glycyrrhizae sweet taste, sugariness is about sugarcane 80~300 times of sugar, are a kind of very promising pure natural sweeteners.Because low calorie, safety non-toxic and stronger medical treatment are protected Strong effect, is most preferable sweetener that hypertension, obesity, diabetes, cardiac use, and it can make up sucrose essence etc. The drawbacks of sweetener induces above-mentioned disease.Wang Xiaoli etc. (2014) research shows that it is thin that glycyrrhizin can significantly increase macrophage The ability of intracrine IL-1 β and TNF-α, the cell factor of these activation can play immunoregulation effect, and further activation NK is thin Born of the same parents, inducing T cell differentiation, reach antineoplastic effect.

GL-B：It is the main composition extracted from ganoderma lucidum, the various pharmacological activity with ganoderma lucidum are relevant, Ke Yiti Body immunity high, antitumor, anticancer, anti-aging, regulation blood fat, radioresistance, raising body's hypoxia tolerance etc..Jiang Miao The research of seedling (2013) and season wise man (2014) shows that GL-B with activated lymphocyte, and can specifically stimulate pouring Bar B cell proliferation, increases the activity of NK cells, and antagonism tumour cell is to lymphocytic emiocytosis cell factor IL-1 β, TNF-α Inhibitory action, reaching full activation immunologic function carries out antineoplastic purpose.

Polyunsaturated fatty acid (PUFA)：N-3 and the classes of n-6 two can be divided into.Linoleic acid is one kind of n-6PUFA, and α-Asia Numb acid category n-3PUFA.The exogenous oxidable energy supplies of PUFA, can also be stored in adipose tissue or further branch saturation, be extended for each Long-chain PUFA is planted, selectively into cell.Some include prostate with shock, infection and the relevant inflammatory mediator of organ failure Element, leukotriene and platelet activating factor are n-6PUFA metabolites.N-3PUFA has promotion immunologic function, weakens acute and chronic The effect of inflammatory reaction, can increase exogenous n-3PUFA, such as fish oil in the application.Additionally, n-3PUFA also has regulation fat The function of fat, sugar and protein metabolism, it is possible to decrease blood triglyceride, cholesterol and FFA concentrations, mitigates protein point Solution, promotes protein synthesis, maintains nitrogen balance.High content n-3 aliphatic acid in meals, can increase cell membrane n-3 content of fatty acid Plus, so as to reduce the mobility of cell membrane, reduce the generation of the scorching medium of potent cause and cell factor.Therefore, in former nutrient formulation On the basis of add n-3 aliphatic acid, the effect of immunity nourishment can be played.(1989) such as Barton RG etc. (1991), Endres S Show with Furukawa K etc. (1999) researchs, high content n-3 aliphatic acid in meals, can increase cell membrane n-3 content of fatty acid Plus, so as to reduce the mobility of cell membrane, reduce the scorching medium of potent cause and cytokine TNF-α, IL-1 generation.Therefore, in original N-3 aliphatic acid is added on the basis of nutrient formulation, the effect of immunity nourishment can be played.

Selenium：Selenium can reduce Tumor incidence and the death rate, suppress animal induction property tumour and growth of tumour cell, and Mitigate the toxic and side effect of tumor chemotherapeutic drug.Therefore, selenium has very important effect in the preventing and treating of tumour.King eggplant etc. (1990) research shows that selenium is a kind of important immune response modifier, can adjust immune response by multiple links, is maintaining Play an important roll in normal immunological function, selenium may indirectly promote the generation of IL-2 by promoting macrophages secrete IL-l With the expression of acceptor, and then promote T lymphocytes propagation and function, play immunoregulation effect.

Described gene side's supplement raw material can be commercially available by commercially available, and glycyrrhizin of the present invention selects Xiamen The glycyrrhizin of Heng Rui health bio tech ltd production, GL-B selects Yancheng City Zhi Qingtang bio tech ltd The GL-B of production, the EPA powder that n-3 aliphatic acid is produced from Xi'an Tong Ze bio tech ltd, selenium selects Rizhao City The selenide of carragheen of Qian Mu bio tech ltd production.

Described gene side's supplement raw material, its component for including following weight portion：0.5~1.5 part of glycyrrhizin, ganoderma lucidum are more Sugared 0.5~2 part, 0.2~1.5 part, selenium 0.3-1 parts of n-3 aliphatic acid.

Preferably, gene side's necessity raw material includes the component of following weight：1 part of glycyrrhizin, 1 part of GL-B, 0.5 part of n-3 aliphatic acid, 0.5 part of selenium.

It is of the present invention as follows according to the personalized intervention formula food of the situation of genetic mutation selection：

If the risk of the genetic mutation for being detected is low-risk, selection square foundation necessity raw material, reselection gene side Necessary raw material；

If the risk of the genetic mutation for being detected is risk, selection square foundation necessity raw material, reselection gene side Necessary raw material and gene side's supplement raw material；

If the risk of the genetic mutation for being detected is excessive risk, selection square foundation necessity raw material and square foundation supplement are former Material, reselection gene side necessity raw material and gene side's supplement raw material.

The making of Individual treatment formula food：

The making of above-mentioned Individual treatment formula food can be completed by automating low temperature sampling machine device.

Preferably, the preparation unit of the automation low temperature sampling machine includes sample addition zone, microwave sterilization component, low temperature drying Shredder assemblies, screening plant pipeline, separation storage electric hybrid module, batch mixing component, control panel.Preferred square foundation is necessary former Material is put into the first sample room of sample addition zone, square foundation supplement raw material and is put into the second sample room of sample addition zone, gene side's necessity raw material The 4th sample room that the 3rd sample room of sample addition zone, gene side's supplement raw material are put into sample addition zone is put into, each component raw material is through microwave Sterilizing component sterilizing；By low temperature drying shredder assemblies, dried fine powder raw material is filled each component raw material by screening after sterilizing Enter separation storage electric hybrid module after putting pipeline；Gravity sensor installed in screening plant pipeline controls different component raw material Quality proportioning, basis of formation side's composition, square foundation supplement side composition, gene side's composition, supplement side of gene side composition It is separately stored in first to fourth storage room and is sufficiently mixed；Gravity sensor installed in storage separation assembly can basis Can need to control the quality proportioning of different storage room compositions fully to be mixed into removable batch mixing component, said process leads to Control panel is crossed to be controlled.The composition is collected, Vacuum Package is as of the present invention related for immunoregulation ability Genetic entities formula food.Specific preparation method is as follows：

(1) selected quality raw materials；

(2) weight proportion for needing is set by control panel；

(3) component raw material of each formula is added in corresponding sample room, through microwave sterilization, sterilizing power is 750W, Continue 90s；

(4) each component of upper step is carried out into vacuum dehydrating at lower temperature crushing, vacuum is below -0.08MPa, and temperature is no more than 4 DEG C, the time is about 5 hours；

(5) by upper step each component raw material by 60~90 mesh sieves point, each component original powder is obtained final product；

(6) quality of different component is controlled to match somebody with somebody by installed in the gravity sensor of screening plant pipeline in above-mentioned former powder Than basis of formation side's composition, square foundation supplement side composition, gene side's composition, supplement side of gene side composition are stored up respectively In the presence of in first to fourth storage room；

Composition in (7) first to fourth storage rooms is under conditions of rotating speed is 60r/min~100r/min in storage Indoor fully to mix, the time is 30~60s；

(8) the above-mentioned each compound composition for being stored in different storage rooms controls the quality of different formulations by gravity sensor Proportioning, has respectively entered in the different product room of batch mixing component, is fully mixed under the conditions of rotating speed is 60r/min~100r/min Even, the time is 15~20s；

(9) collect corresponding product room in above-mentioned batch mixing component composition obtain final product it is of the present invention for immunoregulation ability Related gene individuation formula food.

Present invention also offers a kind of preparation method for immunoregulation ability related gene individuation formula food, institute Preparation method is stated to comprise the following steps：

1) detect individual interleukin 1 beta acceptor encoding gene, CTL antigen 4 encoding gene, The variation of tumor necrosis factor-alpha encoding gene；

2) risk of the variation of detected gene is assessed；

3) raw material in selection food square foundation, according to the raw material in the risk selection gene side for being assessed, is made described For immunoregulation ability related gene individuation formula food.

Beneficial effects of the present invention are：On the basis of genetic test, for the genotypic variation situation of patient, provide suitable The special medicine purposes formula food of Patient genotype is closed, for tumor patient provides rational nutritional supplementation, prevention of tumor patient The generation of malnutrition, improves the immunity of tumor patient.

The technique effect of design of the invention, concrete structure and generation is described further below with reference to accompanying drawing, with It is fully understood from the purpose of the present invention, feature and effect.

Brief description of the drawings

Fig. 1 is composition preparation system schematic diagram in a preferred embodiment of the present invention.

Specific embodiment

Embodiment 1

The individual mouth epithelial cells sample of collection, genomic DNA is extracted with silica gel adsorption, verifies laggard through electrophoresis detection Row quantitative fluorescent PCR reacts.

Individual specimen is respectively put into 3 reacting holes, while detecting the site one of 3 sites, i.e. IL1 β genes： rs1143627；The site two of CTLA4 genes：rs4553808；The site three of TNF-α gene：rs1800629.According further to reality Test needs and set up the NTC blank control wells without DNA profiling；

It is quantitative fluorescent PCR reaction system that reagent is added in each reacting hole, and cumulative volume is 10 μ L, i.e. concentration is The μ L of DNA profiling 2 of 20ng/ μ L, 10 × quantitative fluorescent PCR reaction bufferMGB1 μ L, 25mM dNTP are closed Into four kinds of deoxynucleotide substrates 0.1 μ L, 25mMMgCl of DNA₂The μ L of solution 0.5, (5units/ μ L) Taq DNA polymerase 0.02 μ L, the μ L of deionized water 4.98,3 sites be respectively adopted different forward primers (20 μM, 0.225 μ L), reverse primer (20 μM, 0.225 μ L), VIC fluorescence probes (10 μM, 0.25 μ L) and FAM fluorescence probes (10 μM, 0.25 μ L)；3 sites using primer and Probe is as shown in table 1 below.

13 sites of table use primer and probe

Reacting hole and blank are reacted in PCR amplification instrument, is first preheated：50 DEG C, 2 minutes, 95 DEG C, 10 points Clock, then carry out 60 circulation 95 DEG C, 30 seconds, 60 DEG C, 1 minute, reaction terminate after take out reaction system place into fluorescence determine Fluorescent amount is read in amount PCR instrument, three the three of gene figures are obtained.

The figure of the final sample fluorescence signal that will be shown on quantitative real time PCR Instrument compares with NTC blanks, each site The one kind in three kinds of different signals is likely to occur, i.e., pure VIC fluorescence signals, VIC and FAM heterozygosis fluorescence signal and pure FAM Fluorescence signal, represents the different genotype in three kinds of the site respectively.

Embodiment 2

Molecular epidemiology correlative study achievement in extensive Chinese population is consulted, three measured by embodiment The risk of the different genotype in site is as shown in table 2 below：

Table 2 without genotype risk

Each gene polymorphism sites related to immunoregulation ability has three kinds of hypotypes respectively, by all Asias in selected site The possibility that type occurs carries out permutation and combination；Then the risk that the risk multiplication of these hypotypes obtains different permutation and combination is multiplied Product；The risk product of acquisition is arranged from small to large or from big to small, merges the equal group of risk product；Finally press risk The size for spending product determines the height of each group risk.

The above method is to be weighted treatment using each site as independent factor, and risk product is bigger, assesses risk It is bigger；The Polymorphism type heredity excessive risk individuality for calculating in aforementioned manners can be expressed as it because of autoimmunity ability of regulation and control Difference and trigger the genetic risk factors of tumour more or result certainty is stronger.

Further, it is a, b, c ... by related polymorphic site-tag, different hypotypes is labeled as 1,2,3, that is, takes Haplotype with the hypotype 1 of 1 hypotype 1+ sites of site, 2 hypotype 1+ sites 3 is expressed as a1b1c1；This preferred embodiment is detected Site rs1143627 (IL1 β), rs4553808 (CTLA4) and rs1800629 (TNF-α) are respectively labeled as a, b, c, according to upper State listed single-gene risk calculation risk degree result of product in form as shown in table 3：

The genetic mutation risk product of table 3

Preferably, risk product is programmed using PHP, after each single-gene risk angle value is then input into a computer Calculated.

Then the haplotype in upper table 3 is arranged and is grouped from low to high by risk product, as shown in table 4；Risk etc. Level is higher, and risk product is bigger, i.e., individual to trigger the genetic risk of tumour to get over because of itself mutation immunoregulation capacity variance It is high.

The genetic mutation risk grade classification of table 4

Three site Polymorphism type risk class I-IV are defined as low-risk, risk class V-VII is defined as risk, Risk class VIII is defined as excessive risk.

Embodiment 3

Prepare square foundation necessity raw material：3 parts of pea protein, 1 part of shitosan, 0.5 part of green starch, 0.5 part of lactalbumin, 0.5 part of agropyron.

Square foundation supplements raw material：2 parts of rice protein, 2 parts of kudzu-vine root powder, 0.5 part of probiotics, 0.5 part of prebiotics.

Gene side's necessity raw material：2 parts of barrenwort, 1 part of astragalus polyose, 2 parts of glutamine, 1 part of arginine, 1 part of leucine, 0.5 part of zinc.

Gene side supplements raw material：1 part of glycyrrhizin, 1 part of GL-B, 0.5 part of n-3 aliphatic acid, 0.5 part of selenium.

Embodiment 4

By automating quality proportioning of the low temperature sampling machine by the square foundation of embodiment 3 necessity raw material, the non-of embodiment 4 is obtained Individual treatment formula food.

Embodiment 5

It is by automating quality proportioning of the low temperature sampling machine by embodiment 3, square foundation necessity raw material and gene side is necessary Raw material is blended, and obtains the Individual treatment formula food of embodiment 5.

Embodiment 6

It is by automating quality proportioning of the low temperature sampling machine by embodiment 3, square foundation necessity raw material, gene side is necessary former Material and the supplement raw material blending of gene side, obtain the Individual treatment formula food of embodiment 6.

Embodiment 7

It is by automating quality proportioning of the low temperature sampling machine by embodiment 3, square foundation necessity raw material, gene side is necessary former Material, gene side's supplement raw material and square foundation supplement raw material blending, obtain the Individual treatment formula food of embodiment 7.

Embodiment 8

The making of embodiment 4~7 can be completed by automating low temperature sampling machine device.

As shown in figure 1, the preparation unit of the automation low temperature sampling machine includes sample addition zone 1, microwave sterilization component 2, low Warm drying and crushing component 3, screening plant pipeline 4, separation storage electric hybrid module 5, batch mixing component 6, control panel 7.Will be preferred Square foundation necessity raw material is put into the A sample rooms of sample addition zone, raw material is put into the B sample rooms of sample addition zone to square foundation supplement, gene side must Want raw material to be put into the C sample room of sample addition zone, gene side's supplement raw material and be put into the D sample rooms of sample addition zone, each component raw material is through microwave Sterilizing component sterilizing；By low temperature drying shredder assemblies, dried fine powder raw material is filled each component raw material by screening after sterilizing Enter separation storage electric hybrid module after putting pipeline；Gravity sensor installed in screening plant pipeline controls different component raw material Quality proportioning, basis of formation side's composition, square foundation supplement side composition, gene side's composition, supplement side of gene side composition It is separately stored in A, B, C, D storage room and is sufficiently mixed；Gravity sensor installed in storage separation assembly can be according to can Fully mixed into removable batch mixing component with the quality proportioning for needing to control different storage room compositions, said process passes through Control panel is controlled.The composition is collected, Vacuum Package is as of the present invention for immunoregulation ability dependency basis Because of individuation formula food.Specific preparation method is as follows：

(1) square foundation necessity raw material of embodiment 3 is put into the A sample rooms of sample addition zone, square foundation supplement raw material to be put into and add The B sample rooms of specimen chamber, gene side's necessity raw material are put into the C sample room of sample addition zone, gene side's supplement raw material and are put into the D samples of sample addition zone Product room, each component raw material sterilizes through microwave sterilization component 2, and sterilizing power is 750W, continues 90s；

(2) it is configured according to each component weight proportion in embodiment 3 by control panel；

(3) by low temperature drying shredder assemblies 3, vacuum is below -0.08MPa to each component raw material, and temperature is not after sterilizing More than 4 DEG C, the time is about 5 hours；

(4) dried fine powder raw material separates storage mixing by entering after the screening plant pipeline 4 of 60~90 mesh sieves point Component 5；

(5) gravity sensor installed in screening plant pipeline controls the quality proportioning of different component raw material, is formed and implemented Example 3 square foundation necessity raw material, square foundation supplement raw material, gene side necessity raw material and gene side supplement raw material be separately stored in A, In B, C, D storage room and it is sufficiently mixed, the composition in storage room is under conditions of rotating speed is 60r/min~100r/min in storage Indoor fully mixing is deposited, the time is 30~60s；

(6) controlling the quality proportioning of different storage room compositions to enter installed in the gravity sensor for storing separation assembly can Mobile batch mixing component 6 is fully mixed；

(7) mixture is collected, 20g/ bag Vacuum Packages are distributed into, is obtained final product of the present invention immune for tumor patient Non-individuals formula food (embodiment 4) and Individual treatment formula food (embodiment 5, embodiment 6, the implementation of controlling gene Example 7).

Embodiment 9

Random selection Post operation low-risk, risk and some names of high-risk grade tumour patient, according to the number in table 5 below Intervene formula food or Individual treatment formula food according to non-individualsization made above are taken, wherein, it is daily 3 times, early Middle evening is each once, every time a bag, after being dissolved with (45 degree) of about 150ml warm waters, directly drinks.Detect that NK is thin after taking 1 month Cytoactive (nature killing efficiency), takes every group of average value of the nature killing efficiency of (20) as testing result, and detect its body weight Change, it is as a result as shown in table 5 below.

The NK cytoactives and changes of weight of the patient of table 5

Be can be seen that for tumor patient by the data of table 5, compared to non-individuals formula food, Individual treatment More preferably, to different types of tumor patient, different individuation formula foods have the effect of formula food to the activity of NK cells It is variant.For low-risk patient, embodiment 5 is the activity for being remarkably improved NK cells；For centering risk patients, implement Example 6 is remarkably improved the activity of NK cells；, it is necessary to embodiment 7 significantly improves the activity of NK cells for excessive risk patient. Different individuation formula foods disclosure satisfy that the nutritional need of different type tumor patient, contrast statistically significant (P< 0.05)。

Preferred embodiment of the invention described in detail above.It should be appreciated that one of ordinary skill in the art without Need creative work just can make many modifications and variations with design of the invention.Therefore, all technologies in the art Personnel are available by logical analysis, reasoning, or a limited experiment on the basis of existing technology under this invention's idea Technical scheme, all should be in the protection domain being defined in the patent claims.

Claims (10)

1. it is a kind of to be directed to immunoregulation ability related gene individuation formula food, it is characterised in that the Individual treatment is matched somebody with somebody Square food is made as follows：

1) individual interleukin 1 beta acceptor encoding gene, CTL antigen 4 encoding gene, tumour is detected The variation of necrosis factor-alpha encoding gene；

2) risk of the variation of detected gene is assessed；

3) raw material in selection food square foundation, according to the raw material in the risk selection gene side for being assessed, is made described pin To immunoregulation ability related gene individuation formula food.

2. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 1, it is characterised in that in institute State step 1) in, the site of the interleukin 1 beta acceptor encoding gene of detection is site one：rs1143627；The cytolytic T of detection The site of lymphocyte-associated antigen 4 encoding gene is site two：rs4553808；The tumor necrosis factor-alpha coding base of detection The site of cause is site three：rs1800629.

3. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 2, it is characterised in that in institute The step of stating 2) in, the risk of the variation of the gene for being detected is equal to the risk of site one, the risk of site two and the wind of site three The product of dangerous degree；

As genotype respectively CC, CT, the TT in the site one for detecting, the risk of site one is respectively 0.53,0.53, 3.65；

As genotype respectively AA, AG, the GG in the site two for detecting, the risk of site two is respectively 0.32,2.56, 2.56；

As genotype respectively AA, AG, the GG in the site three for detecting, the risk of site three is respectively 0.32,4.35, 4.35。

4. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 1, it is characterised in that in institute State step 3) in, the raw material in square foundation includes square foundation necessity raw material, and square foundation necessity raw material includes by weight：Pea egg White 2~5 parts, 0.5~2 part of shitosan, 0.4~0.6 part of green starch, 0.4~0.7 part of lactalbumin, agropyron 0.3~0.6.

5. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 4, it is characterised in that in institute State step 3) in, the raw material in square foundation also includes that square foundation supplements raw material, and square foundation supplement raw material includes by weight：Rice 1~4 part of albumen, 1~3 part of kudzu-vine root powder, 0.3~1 part of probiotics, 0.4~0.7 part of prebiotics.

6. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 5, it is characterised in that in institute State step 3) in, the raw material in gene side includes gene side's necessity raw material, and gene side's necessity raw material includes by weight：Barrenwort 1~4 part, 0.5~2 part of astragalus polyose, 1~3 part of glutamine, 0.5~2 part of arginine, 0.6~1.2 part of leucine, zinc 0.3 ~1 part.

7. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 6, it is characterised in that in institute State step 3) in, the raw material in gene side also includes that gene side supplements raw material, and gene side's supplement raw material also includes by weight：It is sweet 0.5~1.5 part of careless glucin, 0.5~2 part of GL-B, 0.2~1.5 part, selenium 0.3-1 parts of n-3 aliphatic acid.

8. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 7, it is characterised in that in institute State step 3) in,

If the risk of the genetic mutation for being detected is low-risk, selection square foundation necessity raw material, reselection gene side is necessary Raw material；

If the risk of the genetic mutation for being detected is risk, selection square foundation necessity raw material, reselection gene side is necessary Raw material and gene side's supplement raw material；

If the risk of the genetic mutation for being detected is excessive risk, selection square foundation necessity raw material and square foundation supplement raw material, Reselection gene side necessity raw material and gene side's supplement raw material.

9. immunoregulation ability related gene individuation formula food is directed to as claimed in claim 8, it is characterised in that used Automation low temperature sampling machine is made described for immunoregulation ability related gene individuation formula food, and the automation is low The preparation unit of warm sampling machine includes sample addition zone, microwave sterilization component, low temperature drying shredder assemblies, screening plant pipeline, separation Storage electric hybrid module, batch mixing component, control panel, square foundation necessity raw material is put into the first sample room, the square foundation of sample addition zone Supplement raw material is put into the second sample room of sample addition zone, gene side's necessity raw material and is put into the 3rd sample room of sample addition zone, gene side and mends The 4th sample room that raw material is put into sample addition zone is filled, each component raw material sterilizes through microwave sterilization component；Each component raw material warp after sterilizing Low temperature drying and crushing component is crossed, dried fine powder raw material separates storage electric hybrid module by entering after screening plant pipeline；Peace Gravity sensor mounted in screening plant pipeline controls the quality proportioning of different component raw material, basis of formation side's composition, basis Side's supplement side composition, gene side's composition, supplement side of gene side composition are separately stored in first to fourth storage room simultaneously It is sufficiently mixed；The composition is collected, Vacuum Package is as described for immunoregulation ability related gene individuation formula food Product.

10. a kind of preparation method for immunoregulation ability related gene individuation formula food, it is characterised in that the system Preparation Method comprises the following steps：

1) individual interleukin 1 beta acceptor encoding gene, CTL antigen 4 encoding gene, tumour is detected The variation of necrosis factor-alpha encoding gene；

2) risk of the variation of detected gene is assessed；

3) raw material in selection food square foundation, according to the raw material in the risk selection gene side for being assessed, is made described pin To immunoregulation ability related gene individuation formula food.