CN100333787C

CN100333787C - YG and YGG for use as medicaments for maintaining and improving immune response

Info

Publication number: CN100333787C
Application number: CNB2004100561623A
Authority: CN
Inventors: 麦瑞斯·高特莱布
Original assignee: Individual
Current assignee: Individual
Priority date: 2004-08-17
Filing date: 2004-08-17
Publication date: 2007-08-29
Anticipated expiration: 2024-08-17
Also published as: HK1075209A1; CN1644214A

Abstract

The invention discloses an application of YG and YGG in maintaining and improving immune response, which mainly relates to YG and YGG and other substances as medicines for diagnosing and treating individuals with the risk of cell-induced immune abnormality so as to improve the cell-induced immune function. The introduction of cells into an immunocompromised patient presents the patient with an increased risk of disease and opportunistic disease caused by infection with viruses, bacteria, fungi or protozoa, or by exposure to other antigenic materials, or by an increased risk of developing and spreading malignant tumors. Maintenance of immune function allows the patient's own immune system to destroy pathogens, other microbial or environmental antigens prior to onset of disease, and to destroy abnormal cells leading to the appearance of malignant tumors. The medicine of the present invention can improve the efficiency of antimicrobial medicine and prevent diseases, and compared with common antimicrobial diagnosis and treatment methods, the present invention has the advantages of fast speed and less development of treatment antagonism.

Description

YG and YGG are as keeping and improving application in the immunoreactive medicine

Invention field

The present invention relates to two kinds of materials: tyrosyl-glycine (tyrosylglycine) and tyrosyl glycylglycine (tyrosylglycylglycine), and relative chemical compound and material; The usefulness of these materials immunity be subjected to challenge (immunologically challenged), immunity to be subjected to suppress (immunologically suppressed) or because of be under pressure (psychology or physiological), certain environmental factors (comprising payable contact), the disease condition that has existed, use certain medicine and/or touch some pathogen (the especially never contacted pathogen of those individualities) when facing weak dangerous of immunologic function, the individual effect that keeping is arranged and/or increase cell importing immunologic function of order.Above-mentioned pathogen comprises new appearance, and/or the pathogen that is not identified as yet, and the existence of these pathogen is that the increase by the disease number of times that can't explain the cause of disease embodies (AIDS that for example, has occurred in history or the SARS that takes place recently).The present invention especially can be applicable to keep the balance of function of immune system or the immune system of change (hyperactivity or activity are low excessively) is restored balance, thereby can ward off disease, alleviate or prevent owing to contacting the disease that causes with following pathogen thereby perhaps be used with specific microbial medicine.These pathogen comprise fungus (for example candidiasis), antibacterial (for example pulmonary tuberculosis bacterium), virus (HIV virus for example, hepatitis A, B, C virus or the like), the contact of protozoacide pathogen such as (for example interstitial pneumonia, malaria), and some pathogen that are not identified as yet (for example SARS before being confirmed to be coronavirus) that can cause not having the infectious disease of definite therapeutic scheme.This protective effect also strengthens the development of opposing malignant tumor, and this is because the normal immune system of health can detect and remove the undesired cell that those may develop and cause uncontrolled canceration in vivo.Simultaneously, immunity loses effective function and balance is considered to playing the part of with a role in diseases such as similar metabolic syndrome and old people's aging.

The background of invention technology

The present invention relates to correct cell and import the function of immune system obstacle.This dysfunction can finally cause owing to infected) virus, antibacterial, the pathogenic microorganism of character such as fungus or protozoacide and the disease that causes.In addition, under this handicapped state, also may be because of the infection that is subjected to other organism cause the generation of disease, and this organism infection is the generation that can not cause disease under the normal situation of immunologic function.For example, candidiasis and reticuloendothelial cytomycosis are to be caused by fungus, and pulmonary tuberculosis is to be caused by antibacterial, and herpes zoster is that the adult herpes (Herpeszoster) that infected the water bean is in the past reproduced, and it is viral relevant with this childhood mainly demonstrating.In the individuality of an immune system kakergasia (perhaps uneven), the individuality that the caused disease of candidiasis is more sound than function of immune system is serious.In addition, the normal crowd of immune system when touching the dried Pseudomonas pulmonary tuberculosis of branch (Mycobacterium tuberculosis), can be caused phthisical bacterial infection by this, but this infects the generation of the pulmonary tuberculosis that can not cause.It is reported that Mycobacterium tuberculosis is present in the population in the whole world 1/3.In the infected individuality of major part, this antibacterial is controlled by under the normal immune system.When immune system is subjected to " pressure ", this control will lose and disease will occur.In addition, cell imports immune dysfunction, and some cancer is developed, if normal immune system can be discerned and kill or be reduced those and do not eliminated then undesired (external) cell that can develop and continue to grow into malignant tumor.No matter for some is the individuality that contact has mutation or carcinogenic material from environmental exposure or medicine, and the ability of identification and the improper cell of elimination/minimizing seems and is even more important.

Immune dysfunction is caused by multiple factor, includes, but are not limited to: medicine and the aging used when physiology or mental pressure, disease (such as some cancer), some treatment cancer or other disease.In addition, when an individuality is exposed in the multiple microbial environment, and this microbial environment is never contacted before individual, for example: international travel, then this individual need has and is higher than the protective response that the general individual immune system had and tackles; This reaction just with in the ordinary course of things, be the same to the reaction that pathogen produced contacted or that directly or indirectly produced immune resistance before the individuality.

It is the delayed hypersensitivity (DH-Delayedtype Hyper-sensitivity) that skin produces existing antigen that classical cell imports immune case.By just observing this reaction to contacted antigen before the individual subcutaneous injection some.In 24-48 hour, local inflammation (erythema) and swelling, thicken when phenomenons such as (scleromas) can be carried out immunoreation at the individuality of a sensitivity and observe.Responsive (reaction) degree is weighed with the size and the seriousness of scleroma that antigen-reactive is formed.The DH reaction has histological characteristic---and the infiltration of leukocyte and mononuclear cell appears in blood vessel week (small artery) in the inflammation scope.At the next blood leucocyte of the observed cell of DH reactive site to periphery.This reaction provides a kind of mode with direct range estimation to detect the method that cell imports immunologic function, and in one was exempted from service handicapped individuality, this response strength can reduce, and therefore can be used as the index that is faced with the individuality that increases ill risk.

Cell imports the mechanism of immunity and is not still made clear fully.Known, regulated immunoreactive cell and can make the reaction of multiple mode antigenic challenge.These reactions comprise: the cell proliferation that the antigen that is provided is produced certain sensitive; Regulate the bringing out and breed of cell of a series of functions of exempting from service, comprise production of antibodies; External cell or tumor are created antagonism.

Gottlieb has disclosed from the human leukocyte dialysis solution isolating endogenous substance at United States Patent (USP) 4468379 can increase speed and the intensity that cell imports immune system response.In No. 4468379 United States Patent (USP)s, these materials are called " immunity amplify son (inmunoamplifier) " (being referred to as " immunomodulating (immunomodulators) " in other articles), and are meant " immunoregulation (immunoregulators) " here.These immunoregulations is with the distinctive points of so-called transfer factor (transferfactors): immune control can not transferred to some concrete mitogen or antigenic immunoreation on never contacted or simultaneously contacted their object, yet it is said can be so in transfer factor.In addition, immunoregulation is non-influence concretely cell import immune system to contacted or simultaneously contacted mitogen and/or antigenic object react, and transfer factor has specific reaction to some antibody.

In No. 4468379 United States Patent (USP)s indication " amplifying son 1 (amplifier1) ", the immunity of indication is amplified sub-β-1.0 and is confirmed to be the mixture of being made up of multiple material subsequently in the United States Patent (USP) 4751216,5081108 and 5100663.These materials comprise the YG product of indication in the United States Patent (USP) 5081108 and 5100663 of Gottlieb, and the YGG product in the United States Patent (USP) 5081108.YG is the tyrosyl-glycine dipeptides, YGG is a tyrosyl glycylglycine tripeptides, these products are except containing each peptide species, also comprise to these polypeptide carry out covalent modification and obtain can received homologue on the pharmacology, and can received dipeptides on the pharmacology, the salt of tripeptides and their covalent modification thing.

Point out in the United States Patent (USP) 4616079 of Gottleib that immunoregulation described herein (immunoregulator) acts on T cell (CD4+ cell), and makes them produce number of chemical medium (cytohormone) in physiologically balanced mode.These various kinds of cell hormones are the speed and the intensity of the reaction that takes place than using single cytohormone can improve effectively more that cell imports immune system antagonist or other activation.The sign of these reactions comprises that DH reacts and seeks out antigen, the generation of IL-2 and IFN-, the cell of sexual cell of enabling to kill virus strengthens, and peripheral blood dendritic cells reacts to the stimulation of antigen or mitogen (for example PHA and pokeweed mitogen (PWM)).

YG dipeptides that United States Patent (USP) 4699898 and 5100068 is pointed out and YGG tripeptides are that Gottleib has immunocompetent component in the partially purified dialysis solution described in the more early stage United States Patent (USP) (for example No. 4616079 patents).YG and YGG product make a difference to immunoreation and are confirmed by other people respectively and put down in writing:

1.B.Zacharie et al.，Thioamides：Synthesis，stability，and immunologic activities ofthioanalogues of Imreg.Preparation of new thioacylating agents using fluorobenzimidazolonederivatives，42 J.MED.CHEM.2046(1999)；

2.H.Kayser and H.Meisel，stimulation of human peripheral blood lymphocytes by bioactivepeptides derived from bovine milk proteins，383 FEBS LETT.18(1996)，

3.Robert Sizemore’s Laboratory Investigations，includng L.T.Moore et aL，Effect ofpeptides derived from enkephalin on delyed-type hypersensitivity(DTH)in hairless guinea pigs.EXPERIMENTAL BIOLOGY，ORLANDO，FLORIDA(2001).

At last also can thumb the following works of inventor M.S.Gottlieb to make reference background:

4.M.S Gottlieb，et al，Response to treatment with the leukocyte-derived immunomodulatorIMREG-l in momunocompromised patients with AIDS-related complex，115 ANNALS OFINTERNAL，MEDICINE 84，1991；

5.M.S Gottlieb，et al，Decrease in serum HIV RNA following treatment with a leukocytedialysate fraction(LDS)that contins N-terminal peptides of the enkephalins and enhancescell-mediated immunity，in INTERNATIONAL CONGRESS OF IMMUNOLOGY，NEW DELHI，INDIA 883-99(G.P.Talwar et al.eds.1998)(pub.Monduzzi Editore SpA，Bologna Italy).

Known, different diseases and pathologic situation (such as measles, HIV and AIDS) and chemotherapy, radiation, some drugs treatment (such as corticosteroid), old and feeble and pressure all can reduce immune reaction.A kind of result of this reduction can be more prone to obtain or produce opportunistic infection, malignant tumor and other pathological conditions, and in normal immune system, these can both be can be controlled.Usually the result of (in some cases, inevitable) immune dysfunction infects debilitating short-term or prolonged sickness, and finally causes death.

Chemical compound that material-tyrosyl-glycine as described herein (YG) is relevant with it with tyrosyl glycylglycine (YGG) and their application provide a brand-new method to strengthen cell and have imported immune adjusting function and prevent and/or control disease.

YG and YGG are sold as a kind of chemical reagent (L-tyrosyl-glycine and L-tyrosyl glycylglycine) by Sigma company (Sigma Chemical Co.), st. Louis companies such as (St.Louis).YG and YGG do not sell with the U.S.P grade, and under existing legal provisions, it is illegal that YG that obtains by commercial sources and YGG are sold to that human body uses.The YG of class of trade and YGG are considered to contain thermal source, and endotoxin and other can not received compositions.Contain these thermals source, endotoxin and some otherly on materia medica, can not make such product can not be applied to human body by received composition.

Know, thus synthetic YG, YGG and relevant chemical compound can be manufactured and purification its finished product is accepted be used to make the product that can be used for human body, include but not limited to: oral, subcutaneous medication and injection.

Know, if the bioactive molecule that will use certain to have therapeutical effect, also can be by dosing a patient with a kind of different molecular but contain the composition medicine of this bioactive molecule, this bioactive molecule can be released through the hydrolysis of body endoenzyme.The hetacillin is exactly an example.The hetacillin degradation in vivo is a penbritin.There is arguement in the world so whether the production of hetacillin, use and selling is accused of invading the patent right of penbritin.

Know (do not use " everybody knows ", selected bioactive molecule with therapeutic effect can be hydrolyzed enzymatic degradation, and simultaneously such situation can be utilized the steric hindrance principle and postponed or prevent.This mode is by laying a group at the hydrolytic enzyme action site, and for example methyl is realized.This principle is widely used in the synthetic penicillin produced of method of debugging and the medicine of other anti-hydrolysis.Equally, as you know, the tyrosine residue N terminal methylization of YG or YGG can prevent such enzymatic reaction.In addition, the esterification of C-terminal carboxyl or amidatioon can the restriction enzyme digestion activity also (replacing " everybody knows ") know.These modify the integrity that finally can keep bioactive molecule.

The invention describes from nature extraction and/or artificial synthetic, purification, can be applied to the purposes of the YG and/or the YGG of human body: the present invention also describes simultaneously in order to improve its medicine usefulness YG and YGG is carried out covalent modification and the trim that obtains, and can be used for improving immune function of human body and pharmaceutically can received YG salt and the purposes of YGG salt and related component.

The term that uses in the early stage patent of in recent years document and GOTTLIEB: " amplicon (amplifier) ", " immune amplicon (immunoamplifier) ", " immune amplicon (amplifier of the immune system) ", " regulon (modulator) ", " immunomodulating (immunmodulator) " and relevant title are unified yet so far.In the present patent application " immunoregulation (immunoregulator) " of indication all should be understood that with article of delivering in the past and patent application in other term be the same.Here, why the inventor selects " immunoregulation " this term for use, purpose is to emphasize: no matter the level of immunologic function is subjected to the effect of immunoregulation and increases or reduce, and material described in the invention all has the effect of regulating control immunologic function (balance).

The present invention's general introduction

One object of the present invention is to provide a kind of preventive, not enough and patient that the disease risk that causes taking a disease increases uses for being in immunologic function, these diseases are by some known or unknown virus, fungus, and antibacterial or protozoacide pathogen or environmental factors etc. are caused.

Another object of the present invention is to provide a kind of therapeutic agent, the symptom that is used to palliate a disease and causes.This therapeutic agent also can use with conventional medicine when being necessary simultaneously.The model of action of this symptom that causes of palliating a disease is by immunity support is provided, thereby the immune system that makes health can play a role and improve immunoregulation to reduce the pathogen combination, the death that reduces sickness rate or avoid causing by pathogen, especially effective to the individuality that those immune systems weaken.The support of these immunitys (balance) can from the therapeutic agent of independent usefulness or with its be added in other medicine such as the medicine of antimicrobial or chemotherapy and obtain to provide.

These purposes of the present invention are to be achieved by using the material with following characteristic: these materials can improve the interior living function of immune system that is in hypoimmunity and therefore faces the people in the ill danger, perhaps improve the interior living function of immune system because of the ill individuality of hypoimmunity.These materials import immunoreactive ability and are called as " immunomodulating " or " immunoregulation " owing to have the non-cell that strengthens concretely.Know, regulate, regulation and control or strengthen cell and import immunologic function and mean and makes these function normalization (balance), rather than make its enhancing or weaken.

Use tyrosyl-glycine and/or tyrosyl glycylglycine to improve and/or keep people's immune system balance, can make the human body generation meet cytohormone and other immune system compositions of physiological need quantity and proper proportion.These functions and other are taken the single cell hormone, for example cause the obviously interleukin-2 of poisoning, and some trials of carrying out immunoregulation form significant contrast.YG, YGG or other related component are undiscovered toxic in surpassing the use in 4 years of 300 patients.

The specific embodiment of the present invention

The human body effect experimental data of having taken the patient of the sub-material of immunoregulation has been collected as follows.

Embodiment 1

HIV causes the patient's of immunodeficiency opportunistic disease prevention

Control test center at a plurality of placebo

Use the endogenous leukocyte dialysis solution that is purified of Beta-1.0

Beta-1.0 (endogenous described in the United States Patent (USP) 5081108,5100068,5100663 and the leukocyte dialysis solution that is purified) at random, double blinding contains the placebo experiment and 8 experimental centers 141 ARC (syndrome relevant with AIDS) patient is carried out 6 months test.YG and YGG have immunocompetent component among the Beta-1.0.These patients are because acquired immune deficiency syndrome (hang down the CD4+ cell and do not have immunoreation [lacking the DTH reaction]), be faced with the threat of infection and cancer, above-mentioned these infection can be interstitial pneumonia, pulmonary tuberculosis, monilial infection, cytomegalovirus infects and other makes the weak and life-threatening infection of health.

93 patients that are diagnosed as ARC take the Beta-1.0 of a standard dose per fortnight, continue for 26 week.48 patients that are diagnosed as ARC take the placebo of same dosage per fortnight, continue for 26 week.And these patients are carried out clinical monitoring.

The Beta-1.0 of a standard dose is confirmed as the dialysis solution that obtains in this test from about 125000 human leukocyte.The Beta-1.0 of a standard dose contains the YG of 4.2fmol (approximately 1pg).In this research, adopted the administration of subcutaneous injection mode.(per two weeks carry out a standard dose administration and be considered to an effective dosage.Also be considered to an effective dosage or its mode that equates according to a different interval time or according to the medicine of different insecticide-applying way dispensing same doses.)

This test, those patients ARC that concentrate diagnosis to change AIDS into especially.The labelling of this transformation is the significant change of symptom and clinical condition, for example begins to suffer from opportunistic diseases such as interstitial pneumonia, bronchocandidiasis or Kaposi ' s Sarcoma.Such clinical effectiveness labelling the end of ARC and the beginning of AIDS, and more serious clinical symptoms occurs and be called " terminal point ".The opportunistic disease often occurs on the insufficient individuality of immunity.

When 26 weeks finished, (a) use among 48 patients of placebo 12 appearance " terminal point " are arranged, account for all 25%; (b) in 93 patients that take Beta-1.0,4 appearance " terminal point " are arranged, account for all 4%.The ARC/AIDS number turnover that adopts the patient of Beta-1.0 treatment approximately be take placebo patient the ARC/AIDS number turnover 20%.Since it is clearly clinically that ARC/AIDS changes, can illustrate that Beta-1.0 can delay the process of HIV disease so can be sure of above-mentioned experimental data.

Use placebo one group, its CD4+ cell on average descends 80 * 10 from the baseline meter ⁶Cell/patient L/, adopt Beta-1.0 decline 29 * 10 ⁶Cell/patient L/.

In these experiments, the patient who adopts Beta-1.0 to treat also is observed the improvement of clinical symptoms simultaneously, and for example increase of body weight, fever are releived, coughed and suffer from diarrhoea minimizing.These clinical experiments are at Gottlieb, et al.ANNALS OFINTERNAL MEDICINE, and 115:84-91 (1990) has detailed description.

In other infects, lose weight, have a fever, cough and diarrhoea are universal phenomenon very.Some infection not only appear on one's body HIV (AIDS or the ARC) patient like this, also can appear on one's body the individuality of some immunodeficiencies that caused by other reason (diagnosis diagnosis or non-).Therefore, other infection that can control patient HIV with these immunoregulation is exactly that an evidence proves that it has the effect that prevents and control to the infection that immunodeficiency caused that is caused by the other reasons beyond the HIV disease.

Embodiment 2

Viral load is identified (Viral Load Assays)

Experimental test from embodiment 1 clinical experiment, obtain and 14 patients' that cold preservation is standby serum sample, to observe the influence of Beta-1.0 to the quantity of HIV RNA (virus).7 patients that accept Beta-1.0 treatment are as one group, its initial CD+ cell number average out to 299, and accept 7 patients' of placebo treatment initial CD+ cell number average out to 303; Two groups relatively, not significantly difference.

CD+ cell number destination data just is collected in the clinical experiment of carrying out embodiment 1.Serum finishes (perhaps clinical " terminal point " is when occurring) in incipient stage, the 9th week and the experiment that clinical experiment is carried out, and respectively these samples is carried out the quantity detection of HIV RNA.All accept Beta-1.0 treatment patient viral load (HIV RNA) from mid-term of experiment to end, be downward trend, and accept to have only among the patient of placebo three people's viral load to reduce.

Generally, the viral load of Beta-1.0 treatment group has reduced 30%, and the viral load of placebo treatment group has increased by 239%.In experimentation, the patient's of Beta-1.0 treatment group CD4+ cell on average descends 23.4 * 10 ⁶Individual cell/L/ patient, and the patient of placebo treatment group has descended 32.4 * 10 ⁶Individual CD4+ cell/L/ patient.

Embodiment 2 has described the ability (with immune serum HIV-RNA level as metering system) of control HIV that main active is the sub-Beta-1.0 of immunoregulation of YG and YGG, and to threatening function of immune system to weaken or disorderly patient's the virus or the potential control ability of pathogen.In addition, HIV is in conjunction with entering in the cellular genome (DNA) and can't detect by augmentation detection method (Amplicor assay), but can recombinant expressed there (Re-expressed).Expressing again of virus combined or dormancy taken place when the immunocompromised host of individuality usually.By keeping enough immunologic functions, express again and will be restricted.In addition, if virus is expressed, individual good interior living function of immune system then can be controlled the active and diffusion of virus better.Beta-1.0 can control that virus is considered to because immune system has the function of differentiating new virion that produces or the new cell that infects, and the ability that can remove them in the infected individuality.

Embodiment 3

The improvement of metabolic syndrome and the result of chronic antigenic stimulus

Metabolic syndrome or syndrome " X " are the diseases of usually reporting recently, its principal character is that impaired, the polycystic ovary syndrome of too high, the sugared patience of triglyceride in obesity, insulin resistance, hypertension, dyslipidemia, the serum, acute phase protein increase (comprising C-reactive protein and Fibrinogen), and cause diabetes and crown arterial disease.It is reported that in the crowd who is exposed to contaminated air or dioxin, coronary heart disease and diabetes are increasing.The extended patient of AIDS is developed the lipodystrophy of formation, has very similarly feature with metabolic syndrome.

From the data kind that above-mentioned patient's HIV clinical experiment has been gathered, some research as immunoregulation also of no use, but they are useful on the current theory of metabolic syndrome.Some toxicity assessment data of collecting in the clinical experiment process is carried out and reexamines, the result shows at those and accepts in the individuality of placebo (P＜0.015), concentration of glucose in the serum raises, apparently higher than the individuality of accepting immunoregulation (P＜0.043) treatment.If all individualities of accepting immunoregulation are all added up, then the concentration of glucose in these individual serum is to reduce, and as only to those when initial, the normal individuality of concentration of glucose is added up, then the concentration of glucose in the serum only raise a little (seeing Table 1).

Same, accept that platelet reduces in the individuality of immunoregulation treatment, and it is little to accept in the individuality of placebo treatment blood

Plate then obviously increases (P＜0.038).Difference between two groups is very significant (p=0.032) (seeing Table 1).

All patients of table 1 a

Serum component	The treatment group					Placebo group					P-value between two groups ^d
	The treatment group					Placebo group						N ^t	Initially ^a	Δ ^b	±s.d	The p-value ^c	N	Initially ^a	Δ ^b	±s.d	The p-value ^c
	Glucose	94	84.89	-5.67	±32.28±	0.066	50	81.95	+7.99	±33.25		N ^t	Initially ^a	Δ ^b	±s.d	The p-value ^c	N	Initially ^a	Δ ^b	±s.d	The p-value ^c	0.186	0.043
Platelet * (10 ³)	Glucose	94	84.89	-5.67	±32.28±	0.066	50	81.95	+7.99	±33.25	97	204.81	-1.81	46.17	0.381	50	208.16	+8.76	±39.54	0.038	0.032	0.186	0.043

The normal patient of table 1b initial value

	The treatment group					Placebo group					P-value between two groups ^d
	The treatment group					Placebo group						Serum component	N ^a	Initially ^a	Δ ^b	±s.d	The P-value ^c	N	Initially ^a	Δ ^b	±s.d	The P-value ^c
Glucose	54	73.42	+2.77	±15.73	0.556	31	72.07	+8.61	±18.86	0.015		Serum component	N ^a	Initially ^a	Δ ^b	±s.d	The P-value ^c	N	Initially ^a	Δ ^b	±s.d	The P-value ^c	0.059
Glucose	54	73.42	+2.77	±15.73	0.556	31	72.07	+8.61	±18.86	0.015	Platelet * (10 ³)	94	208.36	-2.58	±46.24	0.304	49	210.56	+7.78	±39.33	0.054	0.036	0.059

Annotate: ^aNumerical value when initial value is meant the treatment beginning;

^bFrom the initial change in value when treatment finishes;

^cThe P-value is according to Wilcoxon Signed Rank experiment statistics;

^dThe P-value is according to Mann-Whitney (Stratified Wilcoxon Rank Sum) experiment statistics;

^eRefer to those in the starting stage, the normal patient of component value.

These find to support a kind of like this supposition: because the not controlled antigenic stimulus that the pollutant or the infection of environment cause, relevant immune bad, and owing to too much pathogen is loaded, cause to remove toxin, all can cause metabolic syndrome and insulin to be resisted.Metabolic syndrome and insulin resistant are the active interferential results of active and relevant with the glucose metabolism enzyme of insulin.Correct so immune bad or immunely out of controlly can cure metabolic syndrome and the lipogenous diabetes relevant with the HIV disease with immunoregulation of the present invention.According to these discoveries, treating those with the mode of the immunologic function of one or more immunoregulation of the present invention by improving patient, to face metabolic syndrome patient dangerous or that suffer from metabolic syndrome be feasible, and therefore can prevent world merchant increasing, especially in the high pollution place, the diabetes relevant with metabolic syndrome.

Embodiment 4

Treatment of cancer

Patient N is diagnosed as the colon metastatic carcinoma in January, 1985, and 1986 just dies from this disease the most finally.We have gathered relevant data on one's body from this patient.Since on May 8th, 1985, per two weeks of patient N are taken a dosage (about 400, the extract of 000 leukocyte cell) the sub-LDS of immunoregulation (Beta-1.0), this immunoregulation, extract from general 400000 leukocyte cells as immune active ingredient with YG and YGG.This treatment lasts till in February, 1986 of patient death always from May 8th, 1985.This pharmaceutical quantities once was used on one's body patient AIDS/ARC, improving function of immune system, and found that this is one is the efficacious agents amount to this disease.Patient N also accepts fluorouracil widely simultaneously

Chemotherapy with 9-methylpteroylglutamic acid.

In the meantime, the NK cytoactive of patient N is all measured with standard method before with the LDS treatment and in the periodically mensuration behind the begin treatment.This NK cell activity.Before treatment, the NK cytoactive of patient N is lower than normal value.After adopting the LDS treatment the 8th day, his NK cytoactive obviously raises, and rises to 70% of normal value from 30% of about normal value.His NK cytoactive all remains on higher level in some months.Can be on one's body the patient who accepts a large amount of chemotherapy, it is beyond thought keeping high-caliber NK cytoactive like this.

By this treatment, though the NK cytoactive of patient N does not return to normal level, his NK cytoactive has been improved significantly.We be sure of to have only when the NK cell activity and return to the propagation that normal 70-75% could suppress tumor cell effectively at least.

The NK cell activity is measured from the mode of the K562 cell of American Type Culture Collection acquisition with effector lymphocyte's (lymphocyte populations that contains the NK cell of the 10-15%) dartboard that obtains on one's body from patient.Said determination has used the intercellular four kinds of typical different ratios of effector lymphocyte and dartboard (common 100: 1,50: 1,25: 1 and 10: 1) to measure, and the cytolysis rate tabulation that causes.Though continue to treat with LDS, the NK cytoactive is improved, not significantly difference of appraising datum after the different treatments.The contrast that reaches treatment back (treating a back week) before the treatment is as shown in the table:

Effector lymphocyte/target cell	Cytolysis rate %
	Cytolysis rate %		Before the treatment	After the treatment
	100∶1 50∶1 25∶1 10∶1	54.3％ 41.7％ 22.1％ 7.9％	Before the treatment	After the treatment	69.6％ 58.6％ 51.4％ 31.8％

A.Arthur Gottlieb doctor thinks and causes the life of patient N to be extended 3 to 6 months with LDS treatment, and because his immunoreactive improvement, at 1985 and 1986, the health status that his health status is not all received treatment than suffering from this disease was good.

Above-mentioned experimental data has been supported a kind of like this hypothesis: taking immunoregulation that contains YG and YGG can increase the NK cell activity, and the raising of NK cytoactive can prevent or stop the propagation of malignant cell, and the latter is useful to the treatment of malignant tumor.Animal and human data are all supported this hypothesis.

Embodiment 4 has further disclosed the sub-pair cell of the immunoregulation that contains YG and YGG and has imported Immune Effects, even and this immunoregulation still has the ability of this immunologic function of regulation and control under the situation of immunity challenge or other factors (chemotherapy that can suppress the cellular immunity function for example) existence.

Individual because old, cancer, surgical operation, serious burn, chemotherapy, radiation, viral or other microorganism disease or immune other unknown challenge caused function of immune system decline.To such individuality, functions of immune system can be rebuild and keep to YG and/or YGG and relevant chemical compound, thereby can be used as the preventive that prevents microbial diseases.Cell imports immune decline can be with in the delaying type hypersensitivity skin experiment identification antigen not being reacted as index.Whether the recovery that cell imports immunity then can recover with the test immunoreation with same experiment.

Embodiment subsequently is used for showing and summarizing the conclusion that obtains from above case.These cases have been described from surpassing the clinical practice data that 300 AIDS and patient ARC obtain on one's body, and the true clinical data that obtains on one's body from the patient who suffers from certain cancer, rheumatic arthritis and sarcoidosis.

Be based on the similar terms of the sharp face of the early stage United States Patent (USP) of the Gottlieb described in the background technology and come with the term of lower part.These terms comprise that the molecular modification thing of YG and YGG (being respectively tyrosyl-glycine and tyrosyl glycylglycine), YG and YGG and these molecules can be for the salt of human body use.

" YG product " refers to only have the YG amino acid residue and do not have a kind of in the molecular group of other amino acid residue.But these molecule synthetic, also extract from nature.This molecule both can single YG sequence form exist, also can be methylated, amidatioon, dealing with alcohol, acetyl groupization, thioacetylization or be substituted or by the molecule of covalent modification.The YG product does not comprise tripeptides or the above polypeptide of tripeptides.Yet two kinds of YG products (for example two kinds of YG molecules) can (YG) Zn ⁺⁺(YG) form combines, and perhaps becomes a dimer.Such polymer or dimer are not considered to tetrapeptide, and only are two combinations or two dipeptides that condense together." YG product " comprises that also these chemical compounds are pharmaceutically can received salt.

" YGG product " refers to only have the YGG amino acid residue and do not have a kind of in the molecular group of other amino acid residue.But these molecule synthetic, also extract from nature.This molecule both can single YYG sequence form exist, also can be methylated, amidatioon, dealing with alcohol, acetyl groupization, thioacetylization or be substituted or by the molecule of covalent modification.The YGG product does not comprise dipeptides or tetrapeptide and the above polypeptide of tetrapeptide.Yet two YGG products (for example planting the YGG molecule) or YG product and YGG product can be combined or two get together.Such polymer or dimer are not considered to pentapeptide or six peptides." YGG product " comprises that also these chemical compounds are pharmaceutically can received salt.

" repressed YG product " refers to be ruptured by interior living enzyme for the molecular link that suppresses YG, and mixed with certain form, in conjunction with, constraint, link or be substituted or the YG product of covalent modification or by the YG product of gang; Yet these materials still must contain the YG amino acid residue sequence, and do not contain other aminoacid sequence.Puromycin and bacitracin (bacitracin) are exactly the example that can be used as with the blended inhibitor of YG product.Know that also the N-of tyrosine residue methylates and can suppress this enzyme reaction, and the esterification of the carboxyl of C-end or amidatioon also can suppress this enzymatic decomposition.Repressed YG product does not comprise the following YG product that is expanded that will define; These two terms here do not comprise mutually, lay down a definition at this.

" the YG product that is expanded " refers to the molecule that exists with the Tyr-X-Gly form, and the X here refers to D-aminoacid (for example D-Ala).The product of this definition also comprises amidate, carboxylate, salt and other covalent modification thing of above-mentioned molecule.Insertion D-aminoacid is given birth to the enzymatic cleavage of enzyme to the Tyr-Gly key in helping to suppress between Tyr-Gly.YG product and these two terms of YG product that are expanded are not comprise mutually, because the former is a dipeptides and the latter is a tripeptides, and the former has the Tyr-Gly key and the latter does not have.

" repressed YGG product " refers to be disconnected by interior living enzyme for the Tyr-Gly or the Gly-Gly key that suppress molecule, and mixed with certain form, in conjunction with, constraint, link or be substituted or the YGG product of covalent modification, or produced by the YGG of gang; Yet these materials still must contain the Tyr-Gly-Gly amino acid residue sequence, and do not contain other amino acid residue sequence.Puromycin and bacitracin (bacitracin) be exactly can with the blended inhibitor example of YGG product; The N-of tyrosine (Tyr) residue methylates and can suppress this enzyme reaction, and esterification of the carboxyl of C-end (esterfy) or amidatioon (amidify) also can suppress this enzymatic decomposition.Repressed YGG product does not comprise the following YGG product that is expanded that will define; These two terms here do not comprise mutually.

The molecule that " the YGG product that is expanded " refers to have Tyr-X-Gly-Gly or Tyr-Gly-S-Gly form, here, X refers to D-aminoacid (for example D-Ala).The product of this definition also comprises amidate, carboxylate, salt and other covalent modification thing of above-mentioned molecule.Insertion D-aminoacid is given birth to the enzymatic cleavage of enzyme to Tyr-Gly key or Gly-Gly key in helping to suppress between Tyr-Gly-Gly.YGG product and these two terms of YGG product that are expanded are not comprise mutually, because the former is a tripeptides and the latter is a tetrapeptide, and Tyr-Gly-Gly has Tyr-Gly and Gly-Gly key and the latter may not have.

" endogenous YG product " refers to the YG product of generation in the human body.

" synthetical YG product " refers to the YG product in the laboratory manufacturing.

" endogenous YGG product " refers to the YGG product of generation in the human body.

" synthetical YGG product " refers to the YGG product in the laboratory manufacturing.

" irrelevant polypeptide amino acid residue sequence " refers to all amino acid residue sequences except that YG and YGG.In addition, employed here " sequence " refers to a plurality of residues, and it has got rid of the molecule that only has an amino acid residue, for example glycine (Glycine).

Embodiment 5

Owing to pressure is in individuality among the immune insufficient danger

It is new factory's erection unit that the lineup is transferred a far community by their employer.The suffered pressure of these people is single because will transfer to a new environment, and wants for a long time the family away from them.In addition, they are exposed in the new microbial environment, and this new microbial environment is different with the microbial environment that they were contacted in the past.Be exposed in the new local microbial environment, can cause respiratory symptom and/or the intestines and stomach symptom usually, this is called as " traveler's diarrhea " sometimes.

Week before they set out, the health doctor of the said firm advises that everyone begins a medical course of treatment in the last week of setting out, take effective dose endogenous or synthetical Tyr-Gly product (for example every day oral one time 25 μ g, perhaps per fortnight is carried out intradermal injection one time), keeping immunologic function, and help to resist the disease that the interior sick substance of this remote community causes.Setting out preceding and during in new place, these employees' immune state all passes through the laboratory experiment of standard and monitors, and adjusting dose as required and keep suitable immunologic balance.New facility is finished under minimum disease is disturbed.

The use of immunological enhancement material can produce endogenous protection.In addition, even when use is antibiotic, normally functioning immune system also is necessary to curing some disease situation.

Embodiment 6

Payable exposure

One group of workman in the factory constantly is exposed in organic solvent and other reactant.Even the doctor of this company recognizes long term exposure in low-level above-mentioned environment, prolong open-assembly time, also can weaken immunologic function.This doctor tests a plurality of workmans, finds that the DH effect reduces.He takes the YG product (for example per fortnight is taken 10 μ gYG) of effective dose for these workmans, and workman's DH reaction is followed the tracks of, and finds that it has improvement.In addition, this doctor also follows the tracks of workman's immunologic function with the laboratory propagation chemical examination of standard, and test peripheral blood dendritic cell (PeripheralBlood Mononuclear Cell) is to the respond of antigen or mitogen.It is few that he realizes that also the workman calls in sick simultaneously.

Embodiment 7

The appearance of controlled virus

Herpes zoster has several times appearred in an old patient.In the time of each the morbidity, suitably use antiviral therapy, situation can both take a turn for the better, and reaches very uncomfortable process for a long time but will experience one.This doctor concludes that this patient's immunity is damaged, and asserts that this patient also can continue the reason herpes zoster.Chickenpox (varicella zoster virus) appearred in known this patient as a child, and now, this is present in the patient body always and the virus that is controlled reappears, and has caused painful erythra.Herpes zoster usually and other disease occur together, for example, through the cancer of chemotherapy and be in pressure big during, these diseases can cause the decline of cell importing immunologic function, or cause those diseases because of its decline.In addition, herpes zoster occurs on one's body the old people usually.Just because of the decline of cell importing immunologic function, cause virus to lose and control and reappear.

This patient has adopted the effective antiviral drugs of herpes zoster (for example Zovirax) has been carried out suitable treatment, and is aided with the YG treatment to shorten therapeutic process.This patient takes a tablet (asublingual tablet) that is placed on the Sublingual every morning and carries out the YG treatment.This doctor tests the immune state of monitoring patient with DH.The reaction that he finds patient still a little less than, so patient's YG product dosage is brought up to 25ug every day.After fortnight, the DH reaction is improved.After herpes zoster is cured one month, this patient comes back to the YG dosage that begins to take, and continues monitoring DH and react.Immunologic function continues to keep, and does not occur herpes zoster again.

Embodiment 8

The immunosuppressant relevant (immunosuppression) with chemotherapy

A patient has accepted chemotherapy because of carcinoma of prostate.According to investigations, this patient as a child once must cross chickenpox, so he is faced with the danger of suffering from herpes zoster.This patient also is faced with the threat of other chance disease (opprtunistic illness) simultaneously, for example candidiasis, fungal infection (for the patient of immunocompromised host, this infection is to be difficult to treatment) or other situations (for example pneumonia).

Accepting chemotherapeutic period, this patient has also adopted the YG product to treat (for example per fortnight is made an intradermal injection 1ug), and his immunologic function is monitored.In four week after chemotherapy is finished, still adopt YG to continue treatment and carry out.The opportunistic disease does not take place on one's body this patient.

Implement sharp 9

Prevention

A patient is suffered from carcinoma of prostate by diagnosis, must carry out surgical operation and chemotherapy.The doctor knows that the immunologic function of cancered individuality normally weakens.The person, the stimulation of surgical operation and chemotherapeutant can cause immune dysfunction, and finally causing increases the infection chance of microbial pathogens.Take place if infect, adopt the therapy of standard to treat the difficulty more that to become, infect because immune system can not assist to remove.The doctor is chosen in and carries out earlier patient having been carried out the treatment of YG product to improve his cell importing immunologic function before the surgical operation.Patient continues to accept this treatment in behind convalescent period, chemotherapeutic period and end of chemotherapy one month.By measuring patient's immunologic function is monitored in retardance hypersensitivity reaction (delayedhypersensitvity response) or the lymphopoiesis reaction (lymphocyte proliferative response) of antigen or mitogen again, thereby adjust the dosage of YG as required.The final infection that does not have to comprise opportunistic infection.

Embodiment 10

Extended prevention

The old woman at 80 years old advanced age is admitted to hospital and carries out the dish bone that surgical operation has ruptured with treatment.As everyone knows, be accompanied by wound in the operation process, anaesthetize and lose blood, can make her be faced with very high streptococcus pneumoniae (or staphylococcus or streptococcus) infection risk, and secondary becomes pneumonia.Used effective antibiotic even her surgeon knows, the infection that forms in this hospital has very high pathogenicity rate, and hospital stay is prolonged and/or patient death.As you know, antibiotic effectiveness is limited, and in order to control pathogenic microorganism effectively, the immune system of a normal function is necessary.In addition, the immunologic function decline that causes with age, the damage that contaminated hospital environment, especially surgical operation cause all can increase the risk of infection.

After her surgeon is chosen in patient admission, adopt YG, YG product, YGG or YGG product to come for patient treats, tackling with the immune system that promotes patient has high chance to be exposed to infection and thing followed disease that pathogenic microorganism causes in this environment.In addition, because of hospital can provide further rehabilitation and recovery from illness nursing facility, this doctor is chosen in whole convalescent period continuation and uses such treatment.In addition, her doctor is carefully monitoring her immunologic function, makes it keep normal immunologic balance.

Everybody be sure of, if can guarantee to have enough immunoreation just can reduce infection rate to these or other fatal pathogen, promote the effectiveness of administration of antibiotics, minimizing is to antibiotic dependence, can shorten the essential treatment phase of antibiotic therapy when needed, and reduce the formation of the pathogen that antibiotic is developed immunity to drugs.

Embodiment 11

Prevention

A patient who suffers from the chronic asthma disease uses suction corticosteroid therapy for treating every day.As everyone knows, corticosteroid has especially used long period of time, can produce immunosuppressant, and have side effects, for example the candidiasis of mucosa skin.This patient's doctor notices patient's immunologic function degression.

Reduce the candidiasis of the mucosa skin that causes or the formation of other side effect for fear of immunologic function, adopted the YG product of effective dose to treat to this patient, candidiasis does not take place in the result.

Embodiment 12

Keeping of immunologic function

Cell importing immune system with normal function is very important, because it can be resisted by disease external or that endogenous infective micro-organisms or infective pathogen body etc. cause, comprises the disorderly or uneven relevant disease with human immunity.Above-mentioned these diseases comprise cancer or by autoimmune disorder that communicable organism triggered or other disease relevant with communicable organism or the complicated more disease that is caused by double infection.

A patient has family history I type (insulin-dependent) diabetes.This patient's genotype is detected, and the result shows that he is faced with to be infected by virus (or other) and causes and suffer from this disease danger.This patient's doctor imports immune ability to patient's cell and has carried out periodic monitoring, monitored patient and whether had the ability that test shows suitable reaction to DH, and patient's lymphocyte is to the respond of the stimulation of antigen or mitogen.This doctor thinks if cell imports immunologic function can be maintained, and then the outbreak of type i diabetes can prevent.

When king-sized period of pressure of patients undergo, it is normal that this doctor notices that patient's DH reaction is lower than, and this is the danger that a signal indicating patient is faced with infection, and may therefore cause the outbreak of diabetes.The doctor has opened a treatment prescription for patient, and this prescription comprises the YG product of dosage every day one.

It is normal that this therapeutic scheme lasts till that always the DH reaction is returned to.The result infects and disease (diabetes) does not all have to occur, and periodic monitoring patient's immunologic function continues.

Implement 13

The treatment of diseases that causes by the pathogen of the unknown

People takes the travelling of having finished him from the international flight in Hong Kong.In several days, this people has a high fever, dry cough and serious dyspnea.These symptoms conform to SARS, and at that time, the pathogen of SARS is undiscovered.SARS has hyperinfection, and it is caused by coronavirus, and to this virus, does not also have special Therapeutic Method and vaccine at present.

This doctor recognizes that this patient is in the serious pathogenic infection that is difficult to by himself immune system control, so except the Drug therapy of routine, also patient is treated with the YG of effective dose, and last till patients ' recovery always.This patient gets soon than the rehabilitation of expecting of wanting as a result.

Embodiment 14

SARS (Severe Acute Respiratory Syndrome) (SARS)

A patient suffers from SARS.SARS is caused by coronavirus, at present this virus is not also had special Therapeutic Method (medicine or vaccine).The doctor treats controlling virus with virazole Ribavirim (a kind of anti-viral nucleoside), and controls serious inflammation with corticosteroid.Though corticosteroid can be used for controlling inflammation, they also can suppress cell and import immunologic function.Therefore, the doctor has adopted YG to regulate and control patient's immunologic function.This regulation and control are for following some purpose:

(a) this regulation and control can make the pathogen of patient's self interior living immune system antagonism invasion;

(b) because corticosteroid that this patient's oneself immune system is taken and pathogen combination suppress, this regulation and control make patient's immune system can remove other pathogen that can cause the chance disease (infection of secondary).

(c) this regulation and control make patient's immune system can more normally bring into play function, to differentiate and remove the abnormal cell that produces in fission process, especially during being under pressure and being in certain Drug therapy.

Embodiment 15

Protection to biological weapons

An army is deployed in the combat zone.Will not be used though know what pathogen, its enemy of having known for sure will use this army of biological weapons attack.Know that also the soldier who is in the combat environment is subjected to the pressure of physiology and psychology, and these two kinds of pressure can make immunologic function weaken, make be exposed to know or ignorant pathogen in the soldier easier to be ill.

The doctor of army recognizes that this army is disposed under this condition, thus allow each soldier continue to take the YG product or the YGG product of effective dose, to keep the effectively immunologic function of (normally) level of soldier.This medical officer monitors several chosen soldiers, to judge their immunologic function level.This army performs competent preparation, makes them can finish set task.

Embodiment 16

Control the sequela that long-term antigenic stimulus produces

A) patient is just accepting the HIV treatment of diseases.His viral load has reduced, but he begins to occur other disease of lipodystrophy and metabolic syndrome.The glucose patience that his doctor especially is concerned about patient is unusual, and this shows with the related type ii diabetes of metabolic syndrome and may fall ill.

The doctor recognizes that patient's immunologic function suffers damage, antigenic stimulus seems to have disturbed insulin performance usefulness for a long time, this can cause insulin resistant (insulin resistance), therefore and cause the formation of metabolic syndrome, so per fortnight of this doctor give the YG product of patient 10ug.As a result, the HIV disease still keeps being controlled, and the opposing of patient's glucose returns to normal.

B) weight increase 50 pounds the women of youth go to see and her doctor carry out annual health check-up, found that hypertension, and pruritus of vagina arranged.In the past few years, she stays near the main traffic congestion district (oil plant).The doctor has carried out health check-up for this women, in the wrinkle of her neck, found abnormal melanin district (nigrifactin of sour jujube shape), and carried out a series of chemical examination, these chemical examinations comprise fast and 2-hour blood glucose, S-TG, serum insulin, cholesterol distribution (cholesterl profile), C-reactive protein, Fibrinogen and vaginal candida smear.

It is impaired that this women is found glucose endurance, and triglyceride raises, the c reactive protein and the Fibrinogen of low HDL and high ldl receptor, high concentration.Her vaginal smear candida mycoderma (candida albicans) positive that is white in color.

The doctor judges that this women is the metabolic syndrome that a regular meeting develops into diabetes and coronary heart disease, and leaves following prescription for patient: slimming diabetic diet, physical training, ACE inhibitor and Fluconazole.Patient's weight loss but reply in the past.

The doctor returns patient and has taken YG (sublingual) except above-mentioned treatment, and per fortnight once.

The doctor regularly detects patient's blood glucose, c reactive protein, S-TG, serum cholesterol and body weight.

Through the therapeutic process in 1 year, her blood sugar concentration was recovered normally gradually, c reactive protein reduces, cholesterol levels reduces.Patient continues her Diet Therapy and physical training, has made weight loss.But patient need accept a spot of hypertension therapeutic.The doctor continues to monitor patient's cell importing immunologic function, blood sugar concentration, oils and fats distribution, inflammation, and corresponding her medication of suitable adjustment.

Patient's body weight continues to descend and arrive target weight, and blood pressure is controlled, and blood sugar recovery is normal, and the risk that she suffers from diabetes and coronary heart disease reduces.

Embodiment 17

The raising of vaccine potency

The vaccine that in a vaccine intermixture, contains a carrier and inoculum concentration, this vaccine is relevant with a certain disease antigen or pathogen, amount of vaccine is only enough challenged individual immune system, make it cause the few immunoreation vaccine of malaria (as prevent), improvement method of the present invention comprises compatibly with in right amount and adding, chemistry is connected or use the object of following listed one or more simultaneously with antigen vaccine, and the immune system that above-mentioned inoculum concentration antigen or pathogen vaccines can be challenged individuality because of the existence of this object makes it cause a plurality of few immunoreation:

YG；

Methylated (methylated), the YG of acetyl groupization (acetylated), thioacetylization (thioacylated), amidatioon (amidified), esterification (esterified) or dealing with alcohol (alcoholated);

For hydrolysis that suppresses YG or the biological activity that improves YG, the YG that has carried out covalent modification or covalency addition (covalentadditiou);

YGG：

Methylated (methylated), the YGG of acetyl groupization (acetylated), thioacetylization (thioacylated), amidatioon (amidified), esterification (esterified) or dealing with alcohol (alcoholated);

For hydrolysis that suppresses YGG or the biological activity that improves YGG.Carried out the YGG of covalent modification or covalency addition (covalentaddition);

The YG product;

The YGG product;

The YG product of expansion;

The YGG product of expansion;

Downtrod YG product;

Downtrod YGG product;

The salt that the suitable human body of aforementioned product uses;

Purified leukocyte dialysis component (Leukocyte Dialysate).

The concrete case study on implementation that improves vaccine is as follows:

A) to be used for the effectiveness of prevention of malaria be very little to vaccine, and 5 to 50pg synthetic YG (or respective substance, for example YG product) is dissolved in 100 milliliters of physiological saline solution, and to adopt the subcutaneous injection mode to inject body weight be in 70 kilograms the human body.Simultaneously, the doctor finally makes this individuality produce immunity use malaria vaccine for this human body according to conventional method.

B) vaccine is used to prevent what effectiveness histoplasmosis from not having yet.1 to the synthetic YGG of 10pg (or relevant material, for example YGG product) be with 100 milliliters normal saline dilution, and and histoplasma capsulatum's antigen mixing (U.S.P) of 100 milliliters.It is 70 kilograms adult that the mixture of this vaccine-immunoregulation is administered to an individual weight according to conventional method, and this human body produces the antigenic immunity of histoplasma capsulatum.

Sum up

Former, treatment of diseases and prevention all adopted disease had narrow spectrum vaccine or microbial infection is had narrow spectrum antibiosis usually treat.And in the reality, have numerous disease can not adopt this method to treat, the especially disease that those Institute of Micro-biology that can not at once determine are caused, for example SARS.So core of the present invention is, adopts following a kind of product as medicine, influences human immune system, thereby further reach the purpose of prevention, control or treatment disease.

As above-mentioned case and discussion, the present invention can realize that these products are characterised in that and have Tyr (Y) and Gly (G) amino acid residue, especially have the dipeptides or the tripeptides of Y or G amino acid residue with following a kind of product.Above-mentioned selectivity of product ground mixes with other products also can make the present invention be achieved, and in addition, some part of these structures is carried out selective modification also can be used for realization of the present invention.

The present invention is described by some detailed most preferred embodiments, but it still can not be further improved not breaking away from the spirit and scope of the present invention.The protection domain of the present patent application has comprised any variation, use or the application of making according to General Principle of the present invention: be also included within the affiliated technical field of the present invention, done any improvement according to explanation of the present invention and in conjunction with prior art.Should be realized that scope of the present invention should not terminate in this detailed description for making for example, example just is used to help to explain following claim.

Employed in the claims sentence, " select (typo error) property immunoregulation " refer to a kind of of following immunoregulation, or a kind of in the mixture of these immunoregulation: YG (generation or synthetic) naturally; Methylated (methylated), the YG of acetyl groupization (acetylated), thioacetylization (thioacylated), amidatioon (amidified), esterification (esterified) or dealing with alcohol (alcoholated); For hydrolysis that suppresses YG or the biological activity that improves YG, the YG that has carried out covalent modification or covalency addition (covalentaddition); YGG (nature or synthetic); Methylated (methylated), the YGG of acetyl groupization (acetylated), thioacetylization (thioacylated), amidatioon (amidified), esterification (esterified), dealing with alcohol (alcoholated); For hydrolysis that suppresses YGG or the biological activity that improves YGG, carried out the YGG of covalent modification or covalency addition (covalent addition); Or the salt of the suitable human body use of aforementioned product; Purified leukocyte dialysis component (Leukocyte Dialysate); The YG product; The YGG product; The YG product of expansion; The YGG product of expansion; Downtrod YG product; And/or downtrod YGG product.

Claims

1.YG or YGG or its are combined in preparation and improve cell and import the application of immunologic function with the medicine of treatment metabolic syndrome.