CN1512890A - HCG formulation - Google Patents

Abstract

The invention relates to a pharmaceutical composition comprising a biologically active protein or a peptide formulated in water-in-oil emulsion with or without muramyl peptide. More specifically it relates to a preparation of human chorionic gonadotropin (hCG) and related hormones. Also provides are methods of making the composition; methods of using the same against viral infections, immune disorders, and cancer.

Description

The HCG preparation

Technical field

In general, the present invention relates to the pharmaceutical formulation of the bioactive water-solubility protein of tool or polypeptide such as hCG hormone, these albumen or polypeptide can be used for treating different diseases. The disease of combination treatment of the present invention is especially preferred to be immunity and the malignant disease that is caused by virus. More specifically, all be the object of considering by virus as the disease and the associated cancer that cause the human immunodeficiency virus (HIV) of aids (AIDS) to cause among the mankind.

The background knowledge of correlation technique and discussion

Human chorionic gonadotropin (hCG) belongs to glycoprotein hormones family, this hormone family comprise lutropin (luteotropin, LH), follicle-stimulating hormone (FSH) and thyrotropic hormone (TSH). Each subunit by two different non-covalent combinations of this parahormone, α subunit and β subunit form. These hormones have an identical α subunit, and the β subunit is then unique separately, and is variant on length and amino acid sequence. The most similar hormone is hCG and LH, and except hCG C end had one section amino acid sequence, they had 85% homogeneity. HCG and LH act on same acceptor. By traditional viewpoint, hCG and associated hormone play a role in normal human subject physiology. For example hCG has confirmed as progestational hormone well, has played the part of important role in the During Pregnancy of physiology of reproduction. Provide widely background knowledge about hCG (referring to Hernan F.Acevedo in one piece of summary that the inventor writes, " human chorionic gonadotropin: give birth to and dead hormone; summary " (Human chorionic gonadotropin (hCG): The hormone of life and death, a review) is incorporated by reference here).

Recently, the someone proposes, and the hCG hormone also can be used for the treatment of HIV/AIDS and cancer. Referring to such as U.S. Patent No. 5700781; 5811390; 5851997; 5997871; 5877148 and 5677275 or Bourinbaiar AS, the original work of Nagorny R. Human chorionic gonadotropin (hCG) can affect lymphocyte and monocyte to the effect effect of reverse transcriptase activity among the HIV-1. FEMS Microbiol Lett.1992 September 1,75 (1): 27-30, and Bourinbaiar AS, the original work of Nagorny R. The inhibition that human chorionic gonadotropin (hCG) is propagated from the lymphocyte to the vegetative cell HIV-1. FEBS Lett, on August 31st, 1992; 309 (1): 82-4, the content of this piece article is incorporated by reference here. Yet some researchers propose, pollution factor antagonism HIV and the active anticancer found in some commercially available hCG preparations are responsible for, and having refuted hCG can be antiviral and the viewpoint of active anticancer. For example with reference to Lee-Huangs, Huang PL, Sun Y, Huang PL, Kuang HF, Blithe DL, Chen HC. lysozyme and RNase are as the anti-HIV composition of human chorionic gonadotropin β-core goods. Proc Natl Acad Sci USA.1999 March 16,96 (6): 2678-81; Sairam MR, Antakly T.Debunking hCG.Nat Biotechnol, in November, 1997, (12): 1228, Albini A, Paglieri I, Orengo G, Carlone S, Aluigi MG, DeMarchi R, Matteucci C, MantovaniA, Carozzi F, Donini S, Benelli R. human chorionic gonadotropin β-core fragment suppress the growth of the Kaposi sarcoma clone of Kaposi sarcoma derived cell and new immortalization. AIDS.1997 May; 11 (6): 713-21; Lunardi-Iskandar Y, Bryant JL, B lattner WA, Hung CL, F lamand L, Gill P, Hermans P, Birken S, Gallo RC. is from early stage pregnant woman's urine factor pair HIV-1, the effect effect of SIV and relevant disease. Nat Med.1998 April, 4 (4): 428-34; Sipsas NV, Aroni K, Tsavaris N, Mavragani K, Paikos S, the skin Kaposi sarcoma that Kordossis T.AIDS is relevant: with the failure of human chorionic gonadotropin treatment. J.Chemother.1999 February; 11 (1): 78-9; Masood R, McGarvey ME, Zheng T, Cai J, Arora N, Smith DL, Sloane N, the antineoplastic urine albumen of Gill PS. all can suppress Kaposi sarcoma and angiogenesis with external in vivo. Blood, on February 1st, 1999,93 (3): 1038-44; Griffiths SJ, Adams DJ, Talbot SJ, ribalgilase suppresses Kaposi sarcoma. Nature, on December 11st, 1997,390 (6660): 568; Darzynkiewicz Z.butler can be used to search the composition that kills and wounds Kaposi sarcoma in the human chorionic gonadotropin goods. J Natl Cancer Inst.1999 January 20; 91 (2): 104-6 and Noonan D, the anti-KS activity of Albini A. remains a mystery. Nat Med.1998 July; 4 (7): 748; The summary of above article is incorporated by reference in the lump at this. Because the result is chaotic, some authors propose, and contain the factor of the anti-Kaposi sarcoma of different tools and HIV-resistant activity in pregnant woman's urine and the commercially available clinical grade hCG crude product. The researcher finds the neurotoxin (EDN) of deriving such as eosinophil in urine, anti-oncogenicity urine albumen (ANUP), inhibin, the factors such as activin A and angiostatin. In addition, some authors openly warn hCG that reverse effect may be arranged, and it may promote carcinogenesis, and instruction has just deviated from hCG effectively as anticancer and serviceability Anti-virus agent like this. For example, can be with reference to (Simonart T such as Simonart, Hermans P, Van Vooren JP, the self-contradictory front Kaposi sarcoma active (Paradoxical pro-Kaposi ' s sarcoma activity of preparation of human chorionic gonadotropin) of Meuris S. human chorionic gonadotropin goods. Blood, on July 1st, 1999; 94 (1): 367-7).

Whether although have antiviral about hCG or certain pollution factor on prior art and active anticancer still has very large arguement, from a practical viewpoint, it is inconvenient using hormone or pollution factor in the commercially available hCG goods. The same with many other water-soluble sugar protein hormoneses, hCG can be fallen by metabolism rapidly in vivo, so its half life is relatively short. So just must often inject the loading dosage of hormone or increase hCG, and these two kinds of ways all are unpractical, and are expensive. With reference to the US Patent No 5700781 of authorizing Harn " method that treatment Kaposi sarcoma and HIV infect " (Method for treating Kaposi ' s sarcoma and HIV infections), incorporated by reference here.

The modified forms that hCG carries, namely " slowly discharging " or " sustained release " form of so-called hCG namely are suggested in early days, but nobody successfully implements, because not about the specific assurance guide of the hormone of these special shapes. For example, with reference to the US Patent No 5851997 of authorizing Ham " human chorionic gonadotropin is as the antivirotic of tool immunocompetence " (use of human chorionic gonadotropin as an immune-potentiating antiviral agent). In this patent, Harris has enumerated the slow method for releasing of multi-form hCG. Especially, Harris has instructed the sustained release form that is used as through the hCG of skin hCG paster, and this paster is the DURAGESIC that continues^TMA kind of paster after the fentaryl paster is popular, it so that carrying and can be accomplished by the method for iontophoresis or electric osmose through skin of the albumen as hCG namely under the impact of electric field, carry out. The another kind of hCG sustained release form of Harris thinking is implantable hCG induction system. A kind of exemplary device NORPLANT with this category^TMThe Levonorgestrol implantation, this system carries out the passive conveying of hCG by a kind of membrane component of the nonbiodegradable speed limit that for example is comprised of hydrogel or micropore polymer. The hCG implantation of another type that Harris considers combines using with the pumping action function of hCG. The action of this pump is with being by osmotic drive or patient's activation. Like this, Harris has just instructed the selectable different mode that hCG uses. Yet the transport model of consideration all is the dosers that utilize some specific sustained releases, i.e. transdermal patch and dissimilar implantation or pumps. Not having other hCG transporting pattern to be apprised of is the reliable of administration and the pattern that practice significance is arranged.

According to these inventors and other people, only muramyl peptide just can suppress retrovirus and copies (Acevedo HF, Raikow RB, Acevedo HO, Delgado TF, Pardo M. prevents that with synthetic muramyl dipeptide analog CGP11637 oncogenic virus is to infection (the Prevention of oncogenic viral infectious in mice with CGP 11637 of mouse, a synthetic muramyl dipeptide analog), Antimicrob Agents Chemother, in November, 1985,28 (5): 589-96; Lazdins JK, Woods-Cook K., Walker M, the muramyl peptide MTP-PE of Alteri E. lipophilic is strong inhibition (The lipophilic muramyl peptide MTP-PE is a potent inhibitor of HIV replication in macrophages) AIDS Res Hum Retroviruses that HIV copies in the macrophage, October nineteen ninety, 6 (10): 1157-61; Masihi KN, Lange W, Rohde-Schulz B, Chedid L, muramyl dipeptide copies (Muramyl dipeptide inhibits replication of human immunodeficiency virus in vitro) .AIDS Res Hum Retroviruses external HIV inhibiting, March nineteen ninety, 6 (3): 393-9.

Yet, being used in combination with the current idea in this area of hCG and muramyl peptide fails to agree, because muramyl peptide mainly is as vaccine adjuvant, be used for strengthening to the antigen in the vaccine product is the immune response (referring to for example U.S. Patent No. 5840313 or 5876724) of hCG, therefore, this composition can make hCG inactivation or even the process that can aggravate disease effectively. According to others' observation, in fact some muramyl peptide can strengthen copying of HIV, therefore the clinical practice meeting of muramyl peptide increases the weight of the HIV state of an illness, especially troubling (the Schreck R of this prospect, Bevec D, Duror P, Baeuerle PA, Chedid L, Bahr GM. selects muramyl peptide as the potential adjuvant of AIDS vaccine (Selection of a muramyl peptide based on its lack of activation of nuclear-kappa B as a potential adjuvant for AIDS vaccines) based on the activation that lacks Nuclear factor kappa-B, Clin Exp Immunol, in November, 1992,90 (2): 188-93, Masihi KN, Lange W, Rohde-Schulz B. increases the weight of the human immunodeficiency virus to infection (Exacerbation of human immunodeficiency virus infection in promonocytic cells by bacterial immunomodulators) the J Acquir Immune Defic Syndr of premonocyte, 1990 by the bacterial immune modulator; 3 (3): 200-5). Up to now, no matter separate MDP or artificial synthetic MDP from natural origin, when being administered to mammal, all be accompanied by obvious toxicity. This toxicity has limited MDP use clinically significantly. Although when the combination of muramyl peptide and tool biological activity protein is used, be considered to useful once in a while. For example, United States Patent (USP) NO5932208 discloses some compositions, and in these compositions, muramyl peptide and some combination of cytokines are used, but the author does not have being used in combination of instruction and hCG.

Yet in the prior art, the combination of hCG variant and muramyl peptide is known mainly to be to do fertility or cancer vaccine. These vaccines contain the C terminal peptide of hCG β chain or hCG β chain only, and are not that whole dimer hCG is (referring to US Patent No 4313871,4256629,4310455,6146633,6143305,6096318,6039948,5891992,5817753,5698201,5106619,5006334,4855285,4791062,4767842 and 4762913). To hCG β chain or its peptide selectively preferably mainly for a kind of consideration, that is exactly will cause the glycoprotein hormones relevant with some such as LH with dimer or whole hCG immunity inoculation, the unexpected cross reaction of FSH and TSH produces the baleful consequences to the host subsequently. Up to now, the prior art reference that is used in combination about hCG dimer and muramyl peptide does not exist.

Opposite with the traditional concept that is dominant in the prior art, the inventor finds that surprisingly being used in combination of integral body or dimer hCG molecule and muramyl peptide can be worked in coordination with the anti-HIV of enhancing and active anticancer in vivo, and can not produce harmful effect to the host. Simultaneously, also surprisingly find, containing or do not containing the clinical effectiveness that the hCG for preparing in the O/w emulsion of muramyl peptide has identical dynamics.

Summary of the invention

Therefore, the purpose of this invention is to provide a kind of new composition, address other shortcoming in this area on this composition can overcome. The present invention has at first successfully reduced the application practice of water-soluble hormones in treatment virus disease and cancer of formulated. Consider that for these and other the present inventor finds to use hCG and muramyl peptide has better clinical effectiveness or reaction than using the non-modified form of the hCG that obtains on the present market. Consider that also HCG prepares in the O/w emulsion that contains or do not contain muramyl peptide. Other preparation is same suitable such as encapsulated liposome transporting pattern. Therefore, the present invention considers a kind of composition, and it comprises the new treatment form of dimer hCG.

Another object of the present invention refers to provide the method for preparing composition, and it also can overcome the defective of this area.

The present invention has considered that also some use the method for the preparation of a certain amount of hCG to the subject, these preparations treat clinically or pre-preventing virus infection in more effective, and these virus infectionses to be subjects suffered from maybe and will suffer from.

According to a further aspect in the invention, also provide some to be used for the treatment of the method for cancer among tested animal such as the people, the instant compositions of using doses for described subject, described dosage is effective for eliminating or preventing the growth of described cancer in described animal.

Some preferred use that the present inventor faces are some diseases such as AIDS, Kaposi sarcoma (comprising region and HIV correlation type), Huppert's disease, lymthoma, the cancer of melanoma and other form and leukemic treatment.

Do not imply any restriction, these pharmaceutical compositions can advantageously prepare by the solution form, and these solution can be used by parenteral form, and are especially subcutaneous, intramuscular, and the mode of intravenous or perfusion is used. Composition of the present invention is separately oral or when using with the form of galenica (galencica), effect equates, and all is favourable. Form with galenica can be protected these compositions as their capsules being changed into capsule form or spherula or liposome form, makes them can cross over the stomach barrier.

Implement best pattern of the present invention

The present invention is based on following discovery: although muramyl dipeptide (MDP) generally goes to induce immunity to vaccine antigen bunch as the composition of vaccine product, but in fact, these muramyl peptide compounds can act synergistically with hCG is active in vivo, rather than the activity of antagonism hCG. Although the above has mentioned the thing of this area instruction, muramyl peptide compounds and hCG are combined and used in HIV and infect and other life-threatening symptom, such as the treatment of cancer, are useful in prevention and the control.

The term that hereinafter uses " continues conveying device ", refers to some special devices, such as transdermal patch, and the pump of subcutaneous transplantation and pastille.

The term that hereinafter uses " slowly delivery formulations " refers to drug delivery form rather than lasting conveying device, comprises the hCG preparation relevant with the hCG preparation of not mentioning in this area.

Term " adjuvant " definition be to be incorporated in the antigen or and the material injected together of antigen. Adjuvant strengthens subsequently the immune response to antigen non-specificly. The application immunization therapy is that the low-level antigen of dosage obtains more lasting high-level body fluid or cell-mediated immunity than using equivalent water-based antigen by using still less with a main purpose of adjuvant. Common and the abiotic reagent of adjuvant (replacing lived microorganism) is used in combination for vaccine and prepares. Adjuvant also can improve the immune response of the cell that infects to the tumour cell of reduced immunogenicity or non-immunogenic and by intracellular organic matter effectively, and these intracellular organic matters exist in vivo, can not be by the enough preventions of the immune response of spontaneous induction institute.

Term " emulsifying agent " meaning of hereinafter using refers to the non-ionic surfactant compound of deriving from oxidation alkylene and/or hexahydroxylic alcohols and/or senior natural acid such as ester or ester-ether.

Term " Freund's complete adjuvant " (CFA) refers to the powerful immunostimulant of a kind of effect, and it has successfully used on experiment basis with many antigens. CFA comprises mineral oil, emulsifying agent/stabilizing agent such as sorbitan ester A, and lethal mycobacterium such as Much's bacillus. Water-based antigen/protein solution and these mixing compositions form water in oil emulsifying agent together. Yet CFA can cause very serious side effect, comprises pain, forms abscess and fever, can stop like this its use in human or live vaccine. Side effect mainly is by patient the reaction of mycobacterium composition among the CFA to be produced.

" incomplete Freunds adjuvant " is (IFA) except there not being the bacterium composition, and be similar with CFA. Although do not go through to use in the U.S., IFA has been used for the vaccine of some types in other countries. IFA successfully with in influenza and poliovirus vaccine and the some other animal vaccine comprises rabies in human body, canine distemper, and aftosa vaccine has used together. Experiment shows that the oil of using among the IFA and emulsifying agent can cause that all tumour appears in mouse, this means that a kind of alternative adjuvant of selection is the better selection for the people.

Muramyl dipeptide (MDP) expression be minimum unit in the mycobacterium cell membrane compound, can observe its tool adjuvanticity with CFA. Produced many artificial synthetic MDP analogs, they show scope wider adjuvant potential and side effect. Particularly useful when three kinds of analogs are made vaccine adjuvant, they are threonyl derivatives of MDP, the n-butyl derivative of MDP and the lipophilic derivative of muramyl-tripeptide (referring to United States Patent (USP) NO5709879). These compounds can stimulate body fluid and cell-mediated immunity effectively, and only show low-level toxicity. This muramyl peptide has a phosphatide tail, so so that the hydrophobic part of this molecule link to each other with the alicyclic ring border, muramyl peptide partly then with the aqueous environments combination. Therefore, MTP-PE itself can as a kind of emulsification reagent, be used for producing stable O/w emulsion.

Term " muramyl peptide " has a clear and definite meaning to those skilled in the art. It refers in particular to and contains one or more saccharide residues, is the compound that contains a saccharide residue at least, and this compound is normally a muramic acid residue, is replaced by at least one or a plurality of (normally 2 or a plurality of) amino acid residue. Muramyl peptide compounds is peptide glycan, and they can strengthen the antigenicity reaction of mammalian cell, and they are prototype or its analog or derivatives thereof of muramyl dipeptide (MDP).

Many previously disclosed muramyl peptide compounds play a role in treatment or prevention carrying out property leukaemia and septic shock, have the antibacterial activity of immunologic facilitation. Yet the muramyl peptide molecule is only effective in the immunocompetence host. Representational muramyl peptide is please referring to US Patent No 5506204 and 5534492, and is incorporated by reference in the lump here.

The prototype analog of multiple muramyl dipeptide all is known, and wherein some are suggested the treatment means as immunologic function or the recovery of immune nonspecific stimulation. These analogs and prototype MDP itself are generically and collectively referred to as " muramyl peptide ".

A first aspect of the present invention has provided the composition of a kind of muramyl peptide compounds and water-soluble biological activated protein such as hCG.

Need not to be confined to hCG, the other treatment agent is also paid attention to, and includes but not limited to insulin, hyperglycemic factor, calcitonin, atrial natriuretic peptide, secretin, cholecystokinin, thyrotropic hormone discharges thymopeptide-5, corticotropin, somatotropin releasing factor, enkephalins, oxytocins, vasopressin and luteinizing hormone-releasing hormone. These compositions also can be formulated into stroma ground substance in addition, it is selected from chitosan, phycocolloid, saturated polysaccharide glyceride (polyglycolysed glyceride), glycerine palm fibre oil-stearic acid methyl esters, the C12 of polyalcohol is to the polyunsaturated fatty acid ester of C22, glyceryl and polyethylene glycol mountain Yu acid methyl esters, PEO and ammonium glycyrrhizunate etc.

Adjuvant is selected from Monophosphoryl lipid A, fat A, keyhole limpet hemocyanin, the histidine label, alum, Freunds adjuvant, β-gal, palmitic acid, saponin(e, lipopolysaccharides, BCG cell wall skeleton, monomycolate trehalose, the dimycolate trehalose, fat X, isoprinosine, lithosperman (A, B or C), and muramyl dipeptide (MDP) fat cross-linking agent. These fat can be saturated and or unsaturated phosphatide or glycolipid. Preferred fat is selected from 1,2 two-myristoyl phosphatid ylcholine, DPPC, DMPG, cholesterol and their combination.

The example of the solid fat of suitable preparation instant compositions is by triglycerides natural, even number, that the chain length scope forms at the paniculate aliphatic acid of not having of C10-C18, or by natural origin, saturated, even number and do not have a triglyceride of the micro-crystallization that paniculate aliphatic acid forms, such as three certain herbaceous plants with big flowers acid glycerides, trilaurin, trimyristin, three palmityl glyceride and glycerine tristearate (tristearin). In a word, anyly when detecting in batch, can in room temperature (25 ℃), provide the lipid component of solid phase or the mixture of lipid component, be suitable as fat nuclear.

The preferred phosphatide that is used for making instant compositions has natural phosphatide, such as Fabaceous Lecithin, lecithin, phosphatidyl glycerol, phosphatidylinositols, phosphatidyl-ethanolamine, phosphatidic acid, sphingomyelins, diphosphatidylglycerol, phosphatidylserine, phosphatid ylcholine, cuorin etc., and synthetic phosphatide such as dimyristoyl phosphatidyl choline, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, DSPG, DPPC, Monophosphoryl lipid A, lecithin and the phosphatide of two phosphinylidyne fat A etc. and hydroxylating or part of hydroxyl.

Non-natural surfactant and detergent can randomly be incorporated in the composition of the present invention with some. Term used herein " surfactant " or " detergent " comprise the Energy spectrum of wide range, and they form protomere in the aqueous solution, comprise lipophilic and hydrophilic region. In a word, emulsifying agent comprises sorbitan ester, polyoxyethylene sorbitan list, two or three esters, polyoxyethylene fatty acid, polyoxyethylene fatty acid fat and their combination. The example of non-natural surfactant comprises, but be not limited to polysorbate (" Tween " or single oleic acid sorbitan ester), lauryl sodium sulfate (SDS), GREMAPHOR GS32 (" CREMOPHOR "), NP-40 and many other artificial synthetic molecules. In addition, some artificial synthetic surfactants, such as GERBU Adjuvant 100 (DDA), some linear polyoxypropylene-polyoxyethylene (POP-POE) block polymer (commercial can acquisition, its trade mark is PLUPONIC), it is reported the activity of adjuvant. Wherein, Pluronic L121, pluronic L62LF, pluronic L101, pluronic L64, PEG1000, extra-heavy Buddhist nun 1501, extra-heavy Buddhist nun 150R1, extra-heavy Buddhist nun 701, extra-heavy Buddhist nun 901, extra-heavy Buddhist nun 1301, Atmos300, Tween 20, Tween 40, and Tween 60, and Tween 80 and extra-heavy Buddhist nun 130R1 especially expect. Emulsifying agent also comprises sorbitan ester A or sorbitan ester 80 or Span80 (so-called single oleic acid mannide). These adjuvants can be used for different dosage. For example in instant compositions, when the preferable range of sorbitan ester A or sorbitan ester 80 or Span80 was between about 2-15% weight, the scope of Tween 80 was just in 0.2-0.4% weight. In a word, the gross weight that surfactant accounts for composition is less than 30%, preferably is less than 25%, more preferably is less than 10%, and most preferably is less than 5%.

The functional equivalent of MDP, include but not limited to muramyl dipeptide or tripeptides, such as N-acetyl-glucosamine base-N-acetyl-muramyl-L-alanyl-D-isoglutamine (GMDP), N-acetyl-GLUCOSAMINE base (β-1,4)-N-acetyl-muramyl-L-alanyl-D-isoglutamine, N-acetyl-glucosamine base-N-acetyl-muramyl-L-alanyl-D-Glu (GMDP-A), the muramyl dipeptide phosphatidyl-ethanolamine, MTP-PE, MTP-PE, GGP11637 (goes first-MDP), α (N-acetyl-muramyl-L-alanyl-D-isoglutamine), β, γ-two palmityls-sn-glycerine, α (N-acetyl-muramyl-D-alanyl-D-isoglutamine), β, γ-two palmityls-sn-glycerine, α (N-acetyl-muramyl-L-alanyl-D-isoglutamine-ALANINE), β, γ-two palmityls-sn-glycerine, α (N-acetyl-muramyl-D-alanyl-D-isoglutamine-ALANINE), β, γ-two palmityls-sn-glycerine, N-acetyl muramyl-L-alanyl-D-isoglutamine-ALANINE-2-(1,2-two palmityls-sn-glycerine-3-hydroxyl phosphorus acyloxy) acetamide, glucose amido muramyl peptide, murametide, murabutide, muradimetide, myramistin, Thr-MDP, N-acetyl muramyl-L-alpha-amido butyryl-D-isoglutamine, 6-O-stearoyl-N-acetyl muramyl-L-alpha-amido butyl-D-isoglutamine, N-acetyl muramyl-L-valyl-D-isoglutamine, N-acetyl muramyl-L-alanyl-D-isoglutamine, N-acetyl-demethyl muramyl-L-alanyl-D-isoglutamine, N-acetyl muramyl-L-alanyl-D-Gln butyl ester, N-acetyl muramyl-L-seryl-D-isoglutamine, N-butyl muramyl-L-alpha-amido butyl-D-isoglutamine, Thr-MDP, two (6-O-muramyl dipeptide) O-palmityl hydroxymalonic acid, MTP-PE, N-acetyl muramyl-L-alanyl-D-isoglutamine acyl-ALANINE-2-(1,2-two palmityls-sn-glycerine-3-(hydroxyl phosphorus acyloxy)) acetamide, N-acetyl muramyl-L-alanyl-D-Gln butyl ester, N-acetyl muramyl-L-alanyl-D-isoglutamine acyl-ALANINE-2-1,2-two palmityls-sn-glycerine-3-(hydroxyl phosphorus acyloxy) acetamide (MTP-PE), cholesterol-MDP, β-the butyl glycoside of N-acetyl muramyl-L-alanyl-D-isoglutamine, 2-acetylaminohydroxyphenylarsonic acid 4,1-(methoxycarbonyl group) ethyl of 6-two-O-acetyl-2-deoxidation-3-O-[(R)]-α-D-glucopyranose, (β-butyl MDP, MTPO-26, β-cholesterol-MDP), saponin(e (Taurosid I), N-acetyl removes first-muramyl-L-N-methyl propionyl-D-isoglutamine caprylamide, the UDP-N-acetylmuramyl pentapeptide, L4-MDP-ONB, L-alanyl-γ-D-glutamy-in-diaminopimelic acid, 1, the 6-muramyl dipeptide that dewaters, N-acetyl-glucosamine base-β-Isosorbide-5-Nitrae-Ｎ acetylmuramyl pentapeptide-pyrophosphoryl-undecaprenol, 3-O-[acetyl muramyl-D-isoglutamine acyl]-1,2-two palmityls-sn-glycerine, L-threonyl-MDP-GDP, the different threonyl-MDP-GDP of L-, trehalose 6, the 6-diester, muramyl dipeptide, B30 muramyl dipeptide and muramyl dipeptide-lysine.

Be appreciated that aminoacyl residue can be to be selected from alanyl, valyl base, leucyl-; isoleucyl-, α-ammonia butyl, Threonyl; methionyl, cysteinyl-, glutamyl; different glutamyl, glutaminyl, isoglutamine acyl group; aspartyl; phenylalanyl, tyrosyl-, tryptophanyl; lysyl-; ornithyl, arginyl-, histidyl-; the N acyl group; prolyl, hydroxyprolyl-, partly any of aminoacyl in seryl-and the glycyl.

Other muramyl peptide derivative comprises that those substitute the compound of the L alanyl residue in the muramyl peptidyl with L-threonyl residue. In addition, use the Isosorbide-5-Nitrae at glycosyl, it also is possible substituent adjuvant muramyl peptide being arranged on 6, and condition is they and the identical advantageous effects of preferred muramyl peptide tool mentioned above. Need not to be limited to the derivative of above-mentioned muramyl peptide, those are for example in US Patent No 4158052,4220637,4323559,4323560,4409209,4423038,4185089,4406889,4082735,4082736,4427659,4461761,4314998,4101536,4369178, disclosed derivative has equal use in the present invention in 5075287,5376369,5264431 and 5709879 (incorporated by reference in the lump at this).

The useful additive of in the composition other comprises N-hexamethylene acyl arginine, N-hexamethylene acyl tyrosine and the leucic mixture of N-hexamethylene acyl, the mixture of N-phenyl sulphonyl valine, N-phenyl sulphonyl leucine, N-phenyl sulphonyl phenylalanine, N-phenyl sulphonyl lysine and N-phenyl sulfuryl arginine, and the mixture of N-benzoyl valine, N-benzoyl leucine, N-benzophenone alanine, N-benzoyl lysine, N-benzoyl arginine and stabilizing agent such as 2-cyclohexyl sodium butyrate.

Need not to be limited to mentioned component, those skilled in the art is thinkable ovalbumin, cholera toxin; the amino acid of acidylate and salt thereof; contain the amino acid of at least a acidylate or the amino acids of its salt, a kind of Sulfonated amino acid and salt thereof, or any combination of these materials. This composition also comprises microsphere.

The polymer matrix that is used to form microsphere is well-known in the art. For example, comprise enzyme, hormone, semipermeable microsphere of vaccine and other biological products has been disclosed in US Patent No 5643605. Another US Patent No 5075109 discloses a kind of method, and this method is replied by using a kind of mixture Promote immunity, and this mixture is comprised of two groups of microspheres that contain bioactivator at least, and wherein the size of a group microsphere is between about 1-10 μ m. US Patent No 4293539 discloses the delivery formulations controlled of active component in the copolymer, and copolymer by the lactic acid of about 60-95% weight and approximately the glycolic of 40-4% weight derive and form. US Patent No 4919929 discloses the using of antigenic substance of the tangible structure of a kind of tool biocompatible matrix. US Patent No 4767628 discloses a kind of composition that polypeptide and polylactide are stablized in active acid that contains, and when this composition was placed the water-based physiological environment, it was basically with a kind of uniphase mode, with the speed release polypeptide of constant. US Patent No 4962091 discloses a kind of fine suspension of the water-soluble macromolecule polypeptide in polylactide matrix. US Patent No 4849228 and 4728721 discloses a kind of biodegradable HMW polymer, it is characterized in that the content of soluble, low molecular weight compounds less than 0.01mol/100g HMW polymer, the foundation of calculating is that this compound of hypothesis is monoacid. US Patent No 4902515 and 4719246 discloses polylactide composition, and it comprises poly-(R-lactide) section that links with poly-(S-lactide) section. US Patent No 4990336 discloses a kind of multistage sustained release system, and it comprises with the encapsulated anaphylactogen extract of microsphere form, but microsphere is a kind of encapsulated polymer of bioerosion, and it is so that irritated proper energy sustained release stage by stage. This system comprises first and the second portion of anaphylactogen extract, by injection, first is released in one way, in this mode, initial allergenicity (allergenicity) is minimized, produce a kind of and the viewed similar appropriate local reaction of the conventional anaphylactogen of using under normal circumstances low dosage, and second portion provides the anaphylactogen extract that dosage is higher basically, it can produce a kind of serious reaction in patient, if do not discharge the first of anaphylactogen extract. US Patent No 4897268 discloses the microcapsules induction system, and wherein in the biodegradable copolymer excipient that is made into by the different mol ratio rate, like this, will carry with constant rate of speed in the period of a prolongation by composition by encapsulated for composition. Therefore, it is known making and using the means of different of microsphere, can be used for easily the object of the invention.

Microsphere of the present invention also comprises liposome. The composition that is fit to the formation liposome is well-known at technical literature, and composition is also very abundant in this area. Preferred lipid composite is those compositions that can become phosphatide, such as phosphatid ylcholine (a kind of derivative of fatty acid, contain 12-20 carbon atom) (particularly 16-20 carbon atom), phosphatidylserine, phosphatidylinositols, phosphatidyl-ethanolamine, phosphatidyl glycerol and phosphatidic acid. These phosphatide cpds can use separately also can mix use. Especially advantageously adopt synthetic or natural DSPC (DSPC) or the mixture of phosphatid ylcholine, and the mixture of phosphatidylserine (PS) or phosphatidyl glycerol (PG). Advantageously, these liposomes form by containing above mentioned mixture of phospholipids, in this mixture, generally are that the DSPC of 7 times of volumes or phospholipid acid choline (PC) are to 1-10 times of volume, the preferably PS of 3 times of volumes. When the liposome that contains derivative of the present invention occurred with the form of individual layer lipid or multilayer lipid, it is the same good that its biologically active is proved to be. Preferably, the size of liposome particles is more than or equal to 0.1 μ m, for example, and between 1-10 μ m.

Compound of the present invention can as the modulator of non-specific antimicrobial resistance, be used for general and strengthen immune response and nospecific immunity.

Therefore, this shows for example in the symptom that immune response is descended, especially the symptom that descends of the symptom that descends of cell and humoral immune reaction and delayed-type allergy reaction is carried out curative therapy or supporting treatment (namely, with the further special or form support for the treatment of together) in, and further in the treatment of the symptom of the modulation that usually needs immune response.

It is particularly useful in the curative therapy of pathological state or supporting treatment, among pathological state and spontaneous immune deficiency or elderly patients or severe burn or the systemic infection patient institute to run into deficiency relevant.

Compound of the present invention further infects in virus infections such as propagated bleb and propagated varicella, HIV infects and the curative therapy of malignant tumour or supporting treatment in useful.

The hCG that slowly discharges can consider for RNA and dna virus. This includes, but are not limited to hepatitis viruse, herpesviral, influenza virus and Rift Valley fever virus.

The accurate quantity that produces the necessary active ingredient of given result should be according to specific compound, size, and the subject's that will treat age and situation and change, and this point all is clearly to any one those of ordinary skill of this area. These quantity can utilize the conventional method known to those of ordinary skills to be determined easily.

Adjuvant combination thing of the present invention and vaccine generally all are to use by injection. Yet, also can design easier medication, as oral. When composition of the present invention was used directly to clinical treatment and prevention, it had oral and the parenteral administration dual mode. Term " parenteral " comprises subcutaneous, intravenous, and outside the dura mater, gavage, intramuscular discharges pump or inculcates form. These compositions also can pass through in the joint by without stint, in the synovial membrane, and in the sheath, periosteum, in the tumour, around the tumour, in the scab, around the scab, the hypogloeeis contains clothes, and through skin, mode local or that suck is used. It also can be used as a kind of dressing and is used for wound or scab. Yet the particularly preferred administering mode of this composition is oral. When oral, composition of the present invention can use separately or and pharmaceutically suitable carrier in conjunction with making pharmaceutical formulation, such as capsule, pill, lozenges, tablet, grass sugar, little sachet, tea bag, particle, powder, coated tablet, sugar coated tablet, wafer paper, sugar, glue, the particle of hydrogel such as hydrophily moisture absorption polysaccharide, foam, suppository, inhalant, juice, shake, chewing gum, toothpaste, tooth powder, the powder of gargling, candy and emulsion.

Suitable pharmaceutical carrier comprises such as filler, bond, lubricant, disintegrant, promoter and wetting agent. Filler such as lactose, sucrose, sweet mellow wine, glucose, starch, D-sorbite, glycine, calcium phosphate and micro-crystallization fiber; Bond such as starch, casein, gelatin, Arabic gum, glucose, sucrose, D-sorbite, sweet mellow wine, tragcanth, hydroxy propyl cellulose, hydroxyl propoxyl group methylcellulose, carboxymethyl cellulose, 2-methyl-5-vinylpyridine/methyl acrylic acid/ethylacrylic acid resin copolymer, polyvinylpyrrolidone and mosanom, alginic acid glue; Lubricant such as stearic acid, fixed oil, dolomol, calcium stearate, monostearate polyoxyethylene, talcum powder, silica and polyethylene glycol; Disintegrant such as potato starch and the starch that contains surfactant etc.; Promoter such as magnesium sulfate; Wetting agent such as lauryl sodium sulfate.

Composition of the present invention also can be used with the form of liposome. As known in the art, liposome or artificial lipid bladder generally all are to be derived from phosphatide or other lipid material. They also contain muramyl peptide, and metabolizable oil also optionally adds emulsifying agent. Single or multiple lift hydration liquid crystal is dispersed in and forms liposome in the aqueous medium. The exemplary fabrication process of the Liposomal formulation that is comprised of the liposome that contains encapsulation composition of the present invention comprises: with solution hydration lipid material or liposome that will encapsulated material, dried lipid material or the dried Liposomal formulation of a plurality of parts are provided, then will carry out hydration with described a plurality of parts respectively by encapsulated described material solution with containing, and every part is combined together to form single Liposomal formulation, so just formed the Liposomal formulation that is formed by the liposome that contains described encapsulated materials. Any nontoxic physiologically acceptable metabolic lipid material all can be used to form liposome. The present composition of liposome form also comprises stabilizing agent except compound of the present invention, anticorrisive agent, excipient etc. Preferred lipid material is phosphatide and phosphatid ylcholine (lecithin), natural or artificial synthesize all passable. Prepare the method for liposome well-known in the art. For example, cochleate contains biological correlation molecule composition, namely negative electrical charge lipid composition with the bivalent cation composition. Cochleate has the shelf-life of prolongation, even if in drying regime. Picked-up cochleate is favourable.

For above-mentioned implication, the dosage that will use depends on character and the order of severity of disease to be treated, administering mode and the compound form of using. For a common subject, suitable dosage is the about 20000IU of 100IU-, applied once or separate administration. Every day one to three time or frequency still less, as three days once, weekly or 2 weeks once, or January is once, once can carry out easily repetitively administered per March even. In the situation that repeats to use, the appointment UD of compound per injection of the present invention is the about 10000IU of 100IU-, preferred approximately 1000-5000IU. If treatment if required, the dosage of applied once also can rise to about 20000IU. According to the description of product that hCG commodity preparation merchant provides, those skilled in the art can be easily be transformed into unit of weight with the IU unit of hCG, and vice versa.

Also available composition of the present invention in the irrelevant methods of many other and treatment indications. For example, in order to detect hCG or hCG antibody, composition can be used as mark or non-marked reagent is used for different immunoassays, biologicall test etc. Suitable mark comprises radio isotope, enzyme, fluorescence molecule, chemiluminescent labeling, zymolyte or co-factor, enzyme inhibitor, particle, dyestuff etc. The reagent of these marks can be used for many well-known mensuration, such as radioimmunoassay, and enzyme-linked immunoassay, such as ELISA, FIA etc.

The present invention also comprises and uses the general medicine in instant compositions and this area or the concept of compound to be used for different disease categories. In aforesaid compound, the member of following some classes and/or these classes is active ingredient, and they belong to: adrenocorticotro, adrenal gland matter skin inhibitor, aldosterone antagonist, amino acid, anobolite, androgen, anti-AIDS drugs, anthelminthic, anti-acne medicament, anti-adrenal function medicine, the antiallergic action thing, anti-amebic medicine, antiandrogen medicine, anti-anaemia, antianginal, Antiarthritic thing, antasthmatic, anti-atherogenic agent, antibacterial agent, anti-cholera agent, anticholelithogenic, anticholinergic, anticoagulant, anticoccidiosis medicine, antidiabetic, anti-diarrhea agents, antidiuretic, antidote, antiestrogenic, antifibrin-ferment, antifungal agent, the anti-glaucoma medicament, antihemophilic, antihemorrhagic, antihistaminic, antihyperlipidemic drug, antihyperlipoproteinemic, rescinnamine, hypotension agent, anti-infective, anti-local infection agent, anti-inflammatory agent, anti-keratinization medicament, Anti-Malarial, antimicrobial, antimitotic, the antimycotic medicine, antitumor agent, anti-neutrophil reduces agent, anti-parasitic medicine, the anastalsis agent, pneumocystosis medicine, antiproliferative, anti-hypertrophy of the prostate agent, antiprotozoal, the anti-agent of scratching where it itches, antipsoriatic, antirheumatic, the property agent of overflowing of schistosomicide, lipotropism, anti-secrete pharmaceutical, analgestic, anti-coagulants, antitussive, antiulcer agent, anti-urinary calculi agent, antivirotic; The appetite suppressant, treatment of benign prostate hyperplasia agent, bone resorption inhibitor, bronchodilator, carbonic anhydrase inhibitor, cardiac depressant, heart protective agent, cardiotonic, cardiovascular agents, cholagog, cholinergic drug, cholinergic agonist, CHE passivator, decoquinate; Diagnosis is used adjuvant, diuretics, ectoparasitcide, enzyme inhibitor, estrogen, fibrin, oxygen free radical scavenger; Glucocorticoid; Sexual gland stimulin, hair growth stimulus, styptic, hormone, hypocholesterolemia, hypoglycemic, hypolipemia, hypotensive, immunizing agent, immunomodulator, immunomodulator, immunostimulant, immunodepressant, impotence treatment additives, inhibitor, keratolytic, LHRH activator, the agent of liver disorder treatment, luteolysin, mucolysis, mydriatic, nose goes congested agent, neuromuscular blocking agents, non-hormone steroid derivatives, oxytocins, activator of plasminogen, platelet activating factor antagonist, platelet aggregation inhibitor, synergist, progesterone, prostaglandin, prostaglandin growth inhibitor, front thyroid-stimulating hormone, facies pulmonalis cordis, radioactive substance, instrumentality, the diastole thing, reallocation agent, the agent of mitigal mite, curing agent, selective adenosine A1 antagonist, steroids inhibitor, the inflammatory multiple sclerosis, synergist, thyroid hormone, thyroid imhibitor, thyromimetic, the one-sided curing agent of amyotrophia, paget's disease reagent, the UA medicament, uricosuric agent, vessel retraction flesh, vasodilator, vulneraia, Wound healing reagent and xanthine oxidase inhibitor etc.

Being used for those compounds of the present invention can the drug cocktail form carry. So-called cocktail is with top any compound of mentioning and compound of the present invention together. This mixture need to not mix at material, and medicine can be used separately, uses in order or uses simultaneously.

People are interested especially to also have cancer therapy drug except AIDS-treating medicine, cancer therapy drug can be used from administration with composition one of the present invention. Antineoplastic includes but not limited to following these medicines: the A Xuewei rhzomorph; Aclacinomycin; Acodazole Hydrochloride; AcrQnine; Adozelesin; Interleukin 2; Hemel; Ambomycin; The acetic acid Ametantrone; Aminoglutethimidium; SN-11841; The A Nashu azoles; Enramycin; Asparaginase; Asperlin; Azacitidine; Azetepa; Azotomycin; Batimastat; Benzodepa; He steps Bai Kaluo; Bisantrene hydrochloride; Bisnafide Dimesylate; Bizelesin; Bleomycin Sulphate; Boulez Kui sodium; Bropirimine; Busulfan; Act-C; Calusterone; Caracemide; Carbetimer; NSC-241240; Carmustine; The hydrochloric acid carminomycin; Carzelesin; Cedefingol; Chlorambucil; Cirolemycin; Cisplatin; The sharp guest of carat; Crisnatol Mesylate; Endoxan; Cytarabine; Dacarbazine; Dactinomycin D; The hydrochloric acid daunoblastin; Decitabine; Dexormaplatin; Dezaguanine; Dezaguanine Mesylate; Diaziquone; Taxotere; Adriamycin; Doxorubicin hydrochloride; Droloxifene; Droloxifene citrate; NSC-12198; Diazomycin; Edatrexate; Eflomithine Hydrochloride; Elsamitrucin; Enloplatin; Enpromate; Epipropidine; Epirubicin hydrochloride; Erbulozole; Esorubicin hydrochloride; Estramustine; Phosphorus Estramustine sodium; Etanidazole; Ethiodized oil I131; Etoposide; The phosphorus Etoposide; Etoprine; The salt acid system is bent azoles; Fazarabine; Suwei A amine; Fluorodeoxyuridine; Fludarabine phosphate; Fluorouracil; Flurocitabine; Fosquidone; The Fostriecin sodium salt; Gemcitabine; Gemcitabine hydrochloride; Gold Au198; The hydroxyl urea; Idarubicin hydrochloride; Ifosfamide; Ilmofosine; α-2a interferon; α-2b interferon; α-n1 interferon; α-n3 interferon; β-Ia interferon; γ-Ib interferon; Iproplatin; Irinotecan hydrochloride; Lanreotide acetate; Letrozole; Leuprorelin acetate; Liarozole Hydrochloride; The Lometrexol sodium salt; Lomustine; Losoxantrone hydrochloride; Masoprocol; Maytansine; The hydrochloric acid mechlorethamine; The acetic acid megestrol acetate; The melengestrol acetic acid esters; Melphalan; Menogaril; Mercaptopurine; Methotrexate (MTX); Methotrexate sodium; Metoprine; Meturedepa; Mitindomide; Mitocarcin; Mitocromin; NSC-69529; The Si Linma rhzomorph; Mitomycin; Mitosper; Mitotane; Mitoxantrone hydrochloride; Mycophenolic acid; Nocodazole; Nogalamycin; Ormaplatin; Oxisuran; Taxol; Pegaspargase; Peliomycin; Neptamustine; Peplomycin sulfate; Send phosphamide; Pipobroman; Piposulfan; The hydrochloric acid Piroxantrone; Mithramycin; Plomestane; Porfimer Sodium; Porphyromycin; Prednimustine; Procarbazine hydrochloride; Puromycin; Puromycin hydrochloride; Pyrazofurin; Riboprine; Rogletimide; Safmgol; Safingol Hydrochloride; Semustine; Simtrazene; Parfosate Sodium; Sparsomycin; Spirogermanium hydrochloride; Spiromustine; Spiroplatin; Streptonigrin; Streptozotocin; Strontium chloride Sr 89; Sulofenur; Talisomycin; The Japanese yew alcohols; Taxoid; Tecogalan Sodium; Tegafur; Teloxandrone hydrochloride; M-THPC; Teniposide; Teroxirone; Testolactone; Thiamiprine; Thioguanine; Thiotef; Thiazole furan quinoline; Tirapazamine; Topotecan hydrochloride; Toremifene Citrate; The acetic acid Methylestrenolone*; The phosphoric acid triciribine; Trimetrexate; Trimetrexate glucuronic acid fat; Music score of Chinese operas Rayleigh; Tubulozole hydrochloride; Uracil mustard; Uredepa; Vapreotide; Tie up fast Da Er; The sulfuric acid vinblastin where; Sulfuric acid vincristin sodium; Eldisine; Vindesine sulfate; The sulfuric acid vinepidine; The sulfuric acid vinglycinate; The sulfuric acid leurosine; Vinorelbine tartrate; The sulfuric acid vinrosidine; The sulfuric acid vinzolidine; Vorozole; Zeniplatin; Neoearcinostain and zorubicin hydrochloride.

Other anti-tumor compounds include :20-epi-1, 25 - dihydro-vitamin D3; 5 - Acetylene Uracil; abiraterone; Aclacinomycin; colorectal acyl fulvene; gland cyclopentanol; Addo To new; interleukin -2; ALL-TK antagonist; altretamine; ammonia Secretary Ting Mo; amidox; Amifostine; aminolevulinic acid; amrubicin; atrsacrine; anagrelide; Ana Shu yl; Andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-doralizing morphogenetic protein-1; antiandrogen; prostate cancer; antiestrogen; resistance Tumor substances; antisense oligonucleotides; glycine aphid habitat streptozotocin; programmed cell death gene transfer Preparations; Programmed cell death regulators; apurinic nucleic acid; ara-CDP-DL-PTBA; refined Threonine deaminase; asulacrine; doxorubicin carbon; Amos Ting; axinastatin 1; axinastatin 2; axinastatin 3; Azasetron; azatoxin; diazo tyrosine; baccatin III derivatives Biological; balanol; batimastat; BCR / ABL antagonist; benzochlorins; benzoylstaurosporine; β lactam derivatives; β-alethine; Yaa clarithromycin B; Betulinic acid; bFGH inhibitors; Bai Mai Carlo him; than cohort; bisaziridinylspermine; Dual Nai Fade; bistratene A; than fold to new; breflate; bromine horses Liming; Buddle titanium; Ding Thionine thioredoxin amine base; Hercules ointment; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carbamoylase - amino - triazole; carboxymethyl aminotriazole; CaRest M3; CARN 700; cartilaga derived inhibitors; Kazhe to new; casein kinase inhibition system (ICOS); Chestnut spermine; bactericidal peptide B; Cetrorelix; hydrogen chlorin; chloroquinoxaline sulfonamides; cicaprost; Shun porphyrin; cladribine; chlorine meters of analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogues; conagenin; crambescidin 816; crisnatol; Nostoc cyclic peptide 8; cyclic peptide Nostoc A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; Lytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; Right ifosfamide; dexrazoxane; dexverapamil; imine quinone; membrane Sea Sheath elements B; didox; dimethyl norepinephrine spermine (diethylnorspermine); dihydro-5 - azacytidine; Dihydro-paclitaxel 9 -; diamino oxalyl; diphenyl spiro Secretary Ting Mo; Docosanol; multi- Pull granisetron; Doxifluridine; Droloxifene; dronabinol; duocannycin SA; according cloth Selenium morpholino; according to exam Secretary Ting Mo; Yiddish Fuxin; edrecolomab; eflornithine; Elemene; Ethyl acetate for fluorine; epirubicin; epristeride; Estramustine analogues; estrogen agonist; female Hormone antagonists; According to his metronidazole; phosphate etoposide; Neumann Cassida; France flexor azole; Faza Pull Bin; Fenway A amine; filgrastim; fmasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; Formestane; phosphorus ene streptozotocin; Fotemustine; gadolinium taxaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitor; 21 - deoxy--21,21 - two flucytosine; Glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; Hypericum Su; Iban acid; idarubicin; Addo raloxifene; idramantone; Yimo Fu new; Iloilo Horse Division him; imidazoacridones; imiquimod; immunostimulatory peptides; insulin growth hormone - 1 receptor inhibitor; interferon agonists; interferon; interleukin; MIBG; iododoxorubicin; 4 - Potato Ning; irinotecan; iroplact; Irsogladine; isobengazole; isohomohalicondrin B; Iraq he granisetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; come filgrastim; sulfuric mushrooms and more Sugar; leptolstatin; letrozole; leukemia inhibitory factor; leukocyte interferon α; bright c Ruilin + estrogen + progesterone; leuprolide; levamisole; liarozole; linear multi-Amino Analogs; lipophilic two glycopeptides; lipophilic platinum compounds; lissoclinamide 7; contact platinum; earthworm Earthworm phospholipids; Lome song search; chlorine Nida Ming; Loxoprofen anthraquinone; lovastatin; loxoribine; Rene Prop topotecan; Texas porphyrin lutetium; lysofylline; lytic peptides; America tansin; made mannate neomycin A; marimastat; Masuo Luo phenol; maspin; matrix cracking inhibitors; matrix metalloproteinases Protease inhibitors; Miele HELIO; Maier Barron; meterelin; methionine enzyme; methoxychlor Cape amine; MIF inhibitors; mifepristone; Mitefuxin; mirimostin; mismatched double-stranded RNA; Mitoxantrone guanidine hydrazone; dibromo-dulcitol; mitomycin analogues; mitoxantrone naphthylamine; mitotoxin fibroblast growth factor-saporin; mitoxantrone; Mofaluoting; sargramostim; monoclonal antibody; Human chorionic gonadotropin; single phospholipase A very mycobacterial cell wall sk; mopidamol; multi- Resistance gene inhibitor; many tumor suppressor a basic therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyl Medina Lin; N-substituted benzamides; nafarelin; nagrestip; naloxone + PAN new cilostazol; napavin; naphterpin; nartograstim; Nida epoetin; Nanaimo doxorubicin; neridronic acid; neutral endopeptidase; Nilutamide; nisamycin; nitric oxide modulators; nitroxide anti- Oxidants; nitrullyn; O6-benzyl guanine; octreotide; okicenone; oligonucleotide; Ona mifepristone; ondansetron; Ondansetron; oracin; oral cytokine inducer; Austria Ma platinum; osaterone; oxaliplain; oxaunomycin; taxol analogues; paclitaxel derivatives Biological; palauamine; palmitoyl agile new; pamidronate; ginseng triol alkyne; panomifene; Vice micrococcin; Pago fold leptin; Peijia Pa enzyme; peldesine; much sodium pentosan, amyl system Streptozotocin; pentrozole; perflubron; faction phosphoramides; Perillyl alcohol; phenazinomycin; Phenylacetic acid; phosphatase inhibitors; picibanil; hydrochloric trichocarpa alkali; Pirarubicin; topiramate Cork Xin; placetin A; placetin B; plasminogen activator inhibitor; platinum complexes; platinum compounds Things; platinum three amino compound; parked non-US sodium; methyl mitomycin; propylbis - Acridone; ago Prostaglandin J2; proteasome inhibitors; protein A-based immune modulators; protein kinase C Inhibitors; protein kinase C inhibitor; smile algae; protein tyrosine phosphatase inhibitors; Purine nucleoside phosphorylase inhibitor; purine; pyrazoloacridine; pyridoxylated blood Myoglobin polyoxyethylene crosslinks; raf antagonists; raltitrexed; Rameau granisetron; ras farnesyl Ester transfer protein inhibitors; ras inhibitors; ras-GAP inhibitors; retelliptine demethylated; rhenium Re 186 etidronate; agile new; ribozyme; RII-dimensional methylamine; Luo Valley imine; rohitukine; Romo peptide; roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 analog Things; semustine; aging inhibitors a derivative; sense strand oligonucleotide; signal transduction inhibition Agent; signal transduction regulator; single-chain antigen-binding protein; Xizuo furans; Sobuzoxane; boron card Sodium; sodium phenylacetate; solverol; somatomedin binding protein; Suo Naming; Spa Fox acid; Spike ADM D; snails Secretary Ting Mo; splenopentin; sponge Su 1; squalene amine; stem cell suppression Preparation; stem cell division inhibitors; stipiamide; stromelysin inhibitors; sulfmosine; Super active vasoactive intestinal peptide antagonist; suradista; suramin; Swainsonine; synthesis Glycosaminoglycan; him Secretary Ting Mo; tamoxifen methiodide; taurocholic Secretary Ting Mo; him Zorro Ting; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; alternate Mo Porphine; temozolomide that bought; Table podophyllotoxin thiophene glycoside; tetrachlorodecaoxide; tetrazomine; thaliblastine; thalidomide; thiocoraline; thrombopoietin; Thrombopoietin mimetic; Zadaxin (tm) thymus 1; thymus erythropoietin receptor agonists; thymotrinan; TSH; ethyl First tin porphyrin (tin ethyl etiopurpurin); for La Zhaming; titanocene dichloride; topology Aitken; topsentin; removal Ruimi Fen; totipotent stem cells Factor; translation inhibitors; Vitamin A acid; triacetyl uridine; Qu Li Bin West; Acamprosate glucose Acid lipid; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitor; tyrosine Acid phosphorylation inhibitor; UBC inhibitors; Ubenimex; urogenital Dou Yansheng growth inhibition Factor; urokinase receptor antagonists; vapreotide; variolin B; vector system; erythrocytes group Due to therapy; velaresol; veramine; verdins; Witt porphine; vinorelbine; vinxaltine; vitaxin; volts chlorazol; zanoterone; fold Nepal platinum; benzylidene-dimensional C; net company he Martins esters. ...

Preparation does not contain hCG and the preparation that contains the bioactive water-solubility protein of having of other and peptide also is purpose of the present invention. Active water-solubility protein like this is a kind of growth hormone or a kind of somatotropin, human growth hormone (HGH) (HGH) for example, BGH (BGH or BST), pig growth hormone (PGH or PST) and their analog and derivative also have EGF (FGF) and its analog. Other admissible albumen has interleukins, interleukin-1 receptor, interleukin-1 receptor activator, chemotactic factor (CF) and interferon. For example, IFN-α, α-2a interferon, α-2b interferon, α-N1 interferon, α-N3 interferon, IFN-β, β-1 a1 interferon; β-1b interferon, γ-1a interferon, γ-1b interferon, omega interferon, the τ interferon, interleukin 1, interleukin-1 alpha, interleukin-1 ' beta ', interleukin 10, interleukin 11, interleukin 12, IL-15, interleukin 2, interleukin 3, interleukin 4, interleukin 5, interleukin 7, interleukin 8, MIP-1 α and β, RANTES etc. In addition, albumen also can be selected from haemocyte growth-stimulating factor and their precursor, hematopoietin (EPO) and analog thereof. Other albumen that needs on an equal basis has parathyroid hormone (PTH), selenoprotein P, Cystatin B and its liver thiol protease inhibitor analog, endotoxin neutralizing protein, lymphocyte migration inhibition factor (LIF), mast cell growth factor (MGF), megakaryocyte stimulating factor (MGDF), granulocyte macrophage colony stimulating factor (GM-CSF), genofibrate, α calcitonin, the β calcitonin, TNF (TNF), tumour is invaded inhibiting factor, TGF-β cytokines, AIDS and other retroviral trans-acting adjusting albumen (TAT ' s), protease inhibitors and BPC 157, lipopenicillinase hormone, and the analog of these albumen and variant. The protein that also can consider has; Insulin, hyperglycemic factor, gastrin, angiotensins, secretin, lactogen, thyroid-stimulating hormone, melanotropin, luteotropin (LH), follicle-stimulating hormone (FSH) (FSH), thyroid-stimulating hormone (TSH), TPO (TPO), luteotropin generates hormone, HMG, vasopressin, oxytocins, protirelin, corticotropin, SOD, urokinase and lysozyme. A cell factor that those skilled in the art will recognize other also is well-known, and in the composition that is applicable to too invent. Be not limited to above-named these biological activity proteins, other polypeptide also is the object of considering, G-CSF for example, M-CSF, LIF, INHA, inhibin B, activin A, activin B, NAP-1, MCP-1, MIP-1 α, MIP-1 β, MIP-2, SIS β, SIS δ, SIS ε, PF4, PBP, γ IP-10, MGSA, aFGF, bFGF, KGF, PDGF-A, PDGF-B, PD-ECGF, INS, IGF-I, IGF-II, NGF-β, GRO/MGSA, PF4, PBP/CTAP/ β. TG, IP-10, KC, 9E3, MCAF, ACT-2/PAT 744/G26, LD-78/PAT 464, RANTES, G26, I309, JE, TCA3, ICAM-1, ICAM-2, LFA-1, LFA-3, CD72, CTAPIII, ENA-78, GRO, I-309, PF-4 and LD-78.

Except top these albumen, other destination protein by the listed coded by said gene of table 1 also can be considered for composition of the present invention.

Table 1

Title	The sequence number of genetic fragment in Genebank	Length (starting point-terminal point) bp
			MmRad51; Cerevisiae dna is repaired albumen, and Rad51 and colibacillary RecA are homologous proteins	DT3473	855-1199
Interleukin-8 receptor	D17630	664-1022
			α-catenin	D25281	1276-1594
BST-1; Lymphocyte differentiation antigen CD38	D31788	674-1014
			Carcinogenic protein M	D31942	1017-1360
The CSA acceptor	L05630	841-1165
			Heparin-binding class EGF growth factor (diphtheria toxin acceptor)	L07264	258-673
The Fms EGFR-TK 3 of being correlated with; The Flt3/Flk2 part	U04807	46-418
			CD27; The special NGF receptor family of lymphocyte member	L24495	596-846
Basic fibroblast growth factor receptor (bFGF-R)	M28998	200-583
			Granulocyte colony stimulating factor receptor	M58288	251-529

Growth/differentiation 1 (GDF-1) (TGF-'beta ' family)	M62301	2267-2566
			δ-PKC; The alpha 2 delta-protein kinase c	M69042	1740-2011
GA is in conjunction with albumen β-2 chain	M74517	613-931
			CD 40L acceptor (TNF receptor family)	M83312	417-754
Fas1 acceptor (Fas antigen, Apo-1 antigen)	M83649	416-736
			Interleukin 12 (p40) β chain	M86671	652-963
Dimension endothelial tube growth factor (VEGF)	M95200	688-955
			Interleukin 11 (fat generates inhibiting factor)	U03421	196-475
Interleukin 15	U14332	605-1057
			LIMK; The LIM serine/threonine kinase	U15159	1376-1699
DAP-1; The dead sozin 1 of anti-cell	U83628	221-509
			CD 30L acceptor (lymphocyte activator antigens c D30, Ki-1 antigen)	U25416	135-435
The mast cell factor	U44725	79-417
			C-C chemokine receptors (CCL2) (MCP-1RA)	U56819	965-1262
LIF ELISA (LIF)	X06381	63-366
			Intercellular adhesion molecule 1	X52264	1053-1385
II class interleukin 1 receptor	X59769	882-1134
			The corticotropin releasing factor (CRF) acceptor	X72305	1411-1748
HGF (hepapoitein)	X72307	641-965
			Keratinocyte growth factor FGF-7	Z22703	63-325
Activin I receptoroid	Z31663	847-1130
			Transcription factor TFIID	D01034	291-556
Other anti-tumor compounds include :20-epi-1, 25 - dihydro-vitamin D3; 5 - Acetylene Uracil; abiraterone; Aclacinomycin; colorectal acyl fulvene; gland cyclopentanol; Addo To new; interleukin -2; ALL-TK antagonist; altretamine; ammonia Secretary Ting Mo; amidox; Amifostine; aminolevulinic acid; amrubicin; atrsacrine; anagrelide; Ana Shu yl; Andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-doralizing morphogenetic protein-1; antiandrogen; prostate cancer; antiestrogen; resistance Tumor substances; antisense oligonucleotides; glycine aphid habitat streptozotocin; programmed cell death gene transfer Preparations; Programmed cell death regulators; apurinic nucleic acid; ara-CDP-DL-PTBA; refined Threonine deaminase; asulacrine; doxorubicin carbon; Amos Ting; axinastatin 1; axinastatin 2; axinastatin 3; Azasetron; azatoxin; diazo tyrosine; baccatin III derivatives Biological; balanol; batimastat; BCR / ABL antagonist; benzochlorins; benzoylstaurosporine; β lactam derivatives; β-alethine; Yaa clarithromycin B; Betulinic acid; bFGH inhibitors; Bai Mai Carlo him; than cohort; bisaziridinylspermine; Dual Nai Fade; bistratene A; than fold to new; breflate; bromine horses Liming; Buddle titanium; Ding Thionine thioredoxin amine base; Hercules ointment; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carbamoylase - amino - triazole; carboxymethyl aminotriazole; CaRest M3; CARN 700; cartilaga derived inhibitors; Kazhe to new; casein kinase inhibition system (ICOS); Chestnut spermine; bactericidal peptide B; Cetrorelix; hydrogen chlorin; chloroquinoxaline sulfonamides; cicaprost; Shun porphyrin; cladribine; chlorine meters of analogues; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogues; conagenin; crambescidin 816; crisnatol; Nostoc cyclic peptide 8; cyclic peptide Nostoc A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; Lytic factor; cytostatin; dacliximab; decitabine; dehydrodidemnin B; deslorelin; Right ifosfamide; dexrazoxane; dexverapamil; imine quinone; membrane Sea Sheath elements B; didox; dimethyl norepinephrine spermine (diethylnorspermine); dihydro-5 - azacytidine; Dihydro-paclitaxel 9 -; diamino oxalyl; diphenyl spiro Secretary Ting Mo; Docosanol; multi- Pull granisetron; Doxifluridine; Droloxifene; dronabinol; duocannycin SA; according cloth Selenium morpholino; according to exam Secretary Ting Mo; Yiddish Fuxin; edrecolomab; eflornithine; Elemene; Ethyl acetate for fluorine; epirubicin; epristeride; Estramustine analogues; estrogen agonist; female Hormone antagonists; According to his metronidazole; phosphate etoposide; Neumann Cassida; France flexor azole; Faza Pull Bin; Fenway A amine; filgrastim; fmasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunorunicin hydrochloride; forfenimex; Formestane; phosphorus ene streptozotocin; Fotemustine; gadolinium taxaphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitor; 21 - deoxy--21,21 - two flucytosine; Glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; Hypericum Su; Iban acid; idarubicin; Addo raloxifene; idramantone; Yimo Fu new; Iloilo Horse Division him; imidazoacridones; imiquimod; immunostimulatory peptides; insulin growth hormone - 1 receptor inhibitor; interferon agonists; interferon; interleukin; MIBG; iododoxorubicin; 4 - Potato Ning; irinotecan; iroplact; Irsogladine; isobengazole; isohomohalicondrin B; Iraq he granisetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; come filgrastim; sulfuric mushrooms and more Sugar; leptolstatin; letrozole; leukemia inhibitory factor; leukocyte interferon α; bright c Ruilin + estrogen + progesterone; leuprolide; levamisole; liarozole; linear multi-Amino Analogs; lipophilic two glycopeptides; lipophilic platinum compounds; lissoclinamide 7; contact platinum; earthworm Earthworm phospholipids; Lome song search; chlorine Nida Ming; Loxoprofen anthraquinone; lovastatin; loxoribine; Rene Prop topotecan; Texas porphyrin lutetium; lysofylline; lytic peptides; America tansin; made mannate neomycin A; marimastat; Masuo Luo phenol; maspin; matrix cracking inhibitors; matrix metalloproteinases Protease inhibitors; Miele HELIO; Maier Barron; meterelin; methionine enzyme; methoxychlor Cape amine; MIF inhibitors; mifepristone; Mitefuxin; mirimostin; mismatched double-stranded RNA; Mitoxantrone guanidine hydrazone; dibromo-dulcitol; mitomycin analogues; mitoxantrone naphthylamine; mitotoxin fibroblast growth factor-saporin; mitoxantrone; Mofaluoting; sargramostim; monoclonal antibody; Human chorionic gonadotropin; single phospholipase A very mycobacterial cell wall sk; mopidamol; multi- Resistance gene inhibitor; many tumor suppressor a basic therapy; mustard anticancer agent; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyl Medina Lin; N-substituted benzamides; nafarelin; nagrestip; naloxone + PAN new cilostazol; napavin; naphterpin; nartograstim; Nida epoetin; Nanaimo doxorubicin; neridronic acid; neutral endopeptidase; Nilutamide; nisamycin; nitric oxide modulators; nitroxide anti- Oxidants; nitrullyn; O6-benzyl guanine; octreotide; okicenone; oligonucleotide; Ona mifepristone; ondansetron; Ondansetron; oracin; oral cytokine inducer; Austria Ma platinum; osaterone; oxaliplain; oxaunomycin; taxol analogues; paclitaxel derivatives Biological; palauamine; palmitoyl agile new; pamidronate; ginseng triol alkyne; panomifene; Vice micrococcin; Pago fold leptin; Peijia Pa enzyme; peldesine; much sodium pentosan, amyl system Streptozotocin; pentrozole; perflubron; faction phosphoramides; Perillyl alcohol; phenazinomycin; Phenylacetic acid; phosphatase inhibitors; picibanil; hydrochloric trichocarpa alkali; Pirarubicin; topiramate Cork Xin; placetin A; placetin B; plasminogen activator inhibitor; platinum complexes; platinum compounds Things; platinum three amino compound; parked non-US sodium; methyl mitomycin; propylbis - Acridone; ago Prostaglandin J2; proteasome inhibitors; protein A-based immune modulators; protein kinase C Inhibitors; protein kinase C inhibitor; smile algae; protein tyrosine phosphatase inhibitors; Purine nucleoside phosphorylase inhibitor; purine; pyrazoloacridine; pyridoxylated blood Myoglobin polyoxyethylene crosslinks; raf antagonists; raltitrexed; Rameau granisetron; ras farnesyl Ester transfer protein inhibitors; ras inhibitors; ras-GAP inhibitors; retelliptine demethylated; rhenium Re 186 etidronate; agile new; ribozyme; RII-dimensional methylamine; Luo Valley imine; rohitukine; Romo peptide; roquinimex; rubiginone B1; ruboxyl; safingol; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 analog Things; semustine; aging inhibitors a derivative; sense strand oligonucleotide; signal transduction inhibition Agent; signal transduction regulator; single-chain antigen-binding protein; Xizuo furans; Sobuzoxane; boron card Sodium; sodium phenylacetate; solverol; somatomedin binding protein; Suo Naming; Spa Fox acid; Spike ADM D; snails Secretary Ting Mo; splenopentin; sponge Su 1; squalene amine; stem cell suppression Preparation; stem cell division inhibitors; stipiamide; stromelysin inhibitors; sulfmosine; Super active vasoactive intestinal peptide antagonist; suradista; suramin; Swainsonine; synthesis Glycosaminoglycan; him Secretary Ting Mo; tamoxifen methiodide; taurocholic Secretary Ting Mo; him Zorro Ting; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; alternate Mo Porphine; temozolomide that bought; Table podophyllotoxin thiophene glycoside; tetrachlorodecaoxide; tetrazomine; thaliblastine; thalidomide; thiocoraline; thrombopoietin; Thrombopoietin mimetic; Zadaxin (tm) thymus 1; thymus erythropoietin receptor agonists; thymotrinan; TSH; ethyl First tin porphyrin (tin ethyl etiopurpurin); for La Zhaming; titanocene dichloride; topology Aitken; topsentin; removal Ruimi Fen; totipotent stem cells Factor; translation inhibitors; Vitamin A acid; triacetyl uridine; Qu Li Bin West; Acamprosate glucose Acid lipid; triptorelin; tropisetron; turosteride; tyrosine kinase inhibitor; tyrosine Acid phosphorylation inhibitor; UBC inhibitors; Ubenimex; urogenital Dou Yansheng growth inhibition Factor; urokinase receptor antagonists; vapreotide; variolin B; vector system; erythrocytes group Due to therapy; velaresol; veramine; verdins; Witt porphine; vinorelbine; vinxaltine; vitaxin; volts chlorazol; zanoterone; fold Nepal platinum; benzylidene-dimensional C; net company he Martins esters. ...	D14340	3714-4001
			ERCC5 excision repair protein; DNA repair proteins Complementary XP-G cells (XPG)	D16306	1336-1639
Bax; Bcl-2 heterologous dimerization partner and homologous Protein	L22472	172-534
			B7-2; T lymphocyte activation antigen CD86; CD28 Antigen ligand 2; B7-2 antigen; alternative Anti-CTLA4 receptor	L25606	570-967
NF-2; Merlin (moesin - Ezrin - root eggs White-like protein); shwannomin; neurofibromas The second category susceptible protein	L27105	2175-2400
			Pim-1 proto-oncogene	M13945	2713-2930
Egr-1 zinc finger regulatory protein	M20157	399-753
			PKC-α, α type protein kinase	M25811	1566-1924

CD44 antigen	M27129	789-1141
			T lymphocyte activation protein	M31042	285-606
Neuron - cadherin (N-cadherin)	M31131	1212-1409
			ATP-dependent DNA helicase II70kDa of Asia Base; thyroid Ku (p70/p80) autoantigen p70 Subunit (p70Ku)	M38700	274-632
G13, G-α-13 guanine nucleotide regulatory protein	M63660	2057-2377
			Transcription factor RelB	M83380	1456-1728
Microtubule bundle cell adhesion protein 1	M84487	984-1304
			ERCC3; DNA repair helicase; DNA-repair Complex protein complementary XP-B cells (XPBC)	S71186	1147-1444
ERCC3; DNA repair helicase; DNA-repair Complex protein complementary XP-B cells (XPBC)...	S76657	412-748
			ERCC3; DNA repair helicase; DNA-repair Complex protein complementary XP-B cells (XPBC)...	U53228	368-675
14-3-3 σ	U57311	374-640
			Prothymosin α	X56135	186-455
PAX-8 (paired box protein PAX8)	X57487	680-1011
			Camk IV; Ca2 / calmodulin-dependent protein kinase Enzyme IV (catalytic chain)	X58995	1269-1608
ATP-dependent DNA helicase II 80kDa in Asia Base; thyroid Ku (p70/p80) autoantigen p80 Subunit (p80Ku)	X66323	565-875
			Ret proto-oncogene (papillary thyroid carcinoma encoded protein White)	X67812	2359-2680
Nm23-M2; nucleoside diphosphate kinase B; transfer Restore protein; C-myc-related transcription factor	X68193	80-454
			MAPKK6; MAP kinase 6 (bispecific Sex) (MKK6)	X97052	375-711
MAPKK6; MAP kinase 6 (bispecific Sex) (MKK6)...	D17384	563-908
			MAPKK6; MAP kinase 6 (bispecific Sex) (MKK6)...	D28492	398-694
PSD-95/SAP90A	D50621
			Angiotensin converting enzyme (ACE) (clone ACE.5)	L04946	850-1113
Human lectin; complement lysis inhibitor, testosterone suppression Built prostate messenger 2, apolipoprotein J; sulfated Glycoprotein -2	L08235	515-744
			Adipocyte differentiation-related protein	L12721	404-709
Epidermal growth factor receptor kinase substrate EPS8	L21671	1562-1873
			Jak3 tyrosine kinase, Janus kinase 3	L33768	3123-3426

Desmosomes glue protein 2	L33779	1317-1691
			Stat6; transcription 6 signaling transcripts and activator; IL-4stat; STA6	L47650	2057-2411
Lymphocyte-specific protein tyrosine kinase LCK	M12056	1205-1488
			ERA-1 protein (ERA-1-993)	M22115	723-1062
ERA-1 protein (ERA-1-993)...	M26283	677-884
			ERA-1 protein (ERA-1-993)...	M32309	2153-2554
WT1; Wilms tumor protein inhibitors	M55512	1262-1563
			Tristetraproline	M57422	262-
Nucleobindin	M96823	80-357
			WT1; Wilms tumor protein inhibitors...	M97013	286-629
WT1; Wilms tumor protein inhibitors...	S69336	832-1089
			Transcriptional enhancer factor (TEF-1)	S74227	934-1233
Transcription factor NFAT1 isoforms, α	U02079	1601-1910
			DNA-binding protein SATB1	U05252	1101-1380
CCHB3; calcium channels (voltage-gated, dihydropyridine Sensitive L-type) (β-3-ylidene)	U20372	351-639
			P57kip2; cdk inhibitors kip2 (egg cell cycle White-dependent kinase inhibitor 1B), is p21CIP1Cdk inhibitor family members; candidate Tumor suppressor gene.	U20553	989-1272
SnoN; ski-related oncogene	U36203	671-1006
			Homeobox protein 7.1 (Hox7.1)	X14759	740-992
Neuronal cell surface protein F3	X14943	1033-1311
			Transcription factor GATA-3	X55123	858-1125
YB1DNA binding protein
			Dipeptidyl peptidase IV	X58384	61-294
Fli-lets-related oncogene	X59421	267-623
			RXR-β cis -11 - retinoic acid receptor	X66224	1225-1477
C3H cytochrome p450; Cyp1b1	X78445	295-593
			Ubiquitin conjugating enzyme, yeast Rad6 homologs, Mouse HR6B	X96859	51-392
Relaxin	Z27088	51-365
			LIM-1 transcription factor	Z27410	1673-1934
DNA topoisomerase I (Top I)	D10061	1051-1357
			DNA topoisomerase II (TopII)	D12513	520-870
GSTPi1; glutathione S-transferase, Pi1; ago Fat cell growth factor	D30687	62-369
			A glutathione S-transferase	J03958	54-311

Glutathione S-transferase Mul	J04696	13-263
			proto-oncogene c-Ab1	L10656	878-1145
A-Raf proto-oncogene	M13071	1042-1320
			c-Src oncogene	M17031	452-758
Cellular retinoic acid binding protein II (CRAB-II)	M35523	276-571
			Cyclin D2 (G1/S- specificity)	M83749	781-1074
Cyclin D3 (G1/S- specificity)	U43844	484-790
			5 - serotonin receptors (serotonin (Serotonin) by Figure 2 (SHT2))
Cyclin D1 (G1/S- specificity)	S78355	1858-2205
			Pur-α transcriptional activator, sequence-specific ssDNA Binding protein	U02098	1082-1309
Cdc2Sa; cdc2SM1; MPI1 (M phase induction phosphorus Acid enzyme 1)	U27323	606-986
			ERCC-1; DNA excision repair protein	X07414	189-484
c-rel protooncogene	X15842	1729-2064
			Inhibin α subunit	X69618	810-1117
Glutathione reductase	X76341	115-377
			Insulin-like growth factor binding protein -3 (IGFBP- 3)	X81581	474-719
Cyclin A (G2/M- specificity)	Z26580	701-1009
			preproglucagon	Z46845	172-531
NF-κB p65, NF-κ-B transcription factor p65 Asia Base, rel-related polypeptide	M61909	101-363
			PKC-θ; protein kinase Cθ type	D11091	658-957
Subunit of VLA-3α	D13867	288-589
			NADPH cytochrome p450 reductase	D17571	326-605
β tachykinin ago	D17584	273-523
			Kinase	D30743	1816-2159
Protein tyrosine phosphatase	D83966	1060-1426
			Jun-D; c-jun-related transcription factor	J05205	737-964
Integrin α7	L23423	2399-2713
			Gadd45; growth arrest and DNA damage-induced egg White	L28177	144-434
Bcl-xL apoptosis regulatory proteins (bcl-xLong); BcI-2 family members	L35049	641-906
			N-myc proto-oncogene protein	X03919	3262-3450
cAMP-dependent protein kinase type I-β chain adjustment	M20473	538-750
			IRF1, interferon regulatory factor 1	M21065	1-233
HSP86, heat shock 86kDa protein	M36830	255-551

LFA-1α; integrin αL; leukocytes stick Even glycoprotein LFA-1α chain antigen CD11A (P180)	M60778	1838-2050
			APC; adenomatous polyposis (Adenomatous polyposis coli) protein	M88127	4127-4476
Cdc2Sb; cdc2SM2, MPI2 (M phase induction phosphorus Acid enzyme 2)	S93521	1893-2200
			Phosphatidylinositol 3 - kinase catalytic subunit
RSP27, heat shock 27kDa protein 1	U03560	245-550
			Csk; c-Src-1 kinase and negative regulators	U05247	645-984
Fas1; Fas ligand antigen, mouse systemic lymphoid Proliferative disease gene (gld)	U06948	168-488
			MAPK; MAP kinase; p38	U10871	465-780
P19ink4; cdk4 and cdk6 inhibitor	U19597	228-516
			Elf1 Ets family transcription factors	U19617	1585-1902
CRAF1; TNF receptor (CD40 receptor) relevant factors Son; TRAF-related	U21050	1225-1466
			SPI3, serine protease inhibitor (serpin); And human proteinase inhibitor 6 similar (placental thrombin Inhibitor) serine protease inhibitors	U25844	915-1230
RIP cell death protein, Fas/Apo-1 (CD95) Interactive yuan (interactor), including death zone	U25995	1945-2223
			SLAP; src-like adapter protein, Eck receptor tyrosine Associated protein kinase	U29056	109-427
Atm; mouse ataxia telangiectasia	U43678	8989-9170
			EB1 APC-binding protein	U51196	607-834
TANK; I-TRAF; TRAF family members related Activator of NF-κB	U51907	135-437
			Caspase -11, ICH-3 cysteine Proteases, ICE upstream regulatory element	U59463	352-686
MIHI DNA mismatch repair protein, MutL fellow Matter	U59883	1037-1278
			Insulin-like growth factor-IA	X04480	183-406
Cell surface glycoprotein MAC-1α subunit	X07640	1892-2179
			N-ras oncogene; transforming G protein	X13664	548-857
L-myc proto-oncogene protein	X13945	5287-5590
			CD18 antigen β subunit (leukocyte adhesion LFA- 1) (CD3, p150, 95)	X14951	1366-1706
Oncogene C-Fgr	X52191	1305-1538
			Α4 integrin	X53176	2176-2449

PKC-β; protein kinase type CβII	X53532	1712-2089
			HSP60, heat shock 60kD protein I	X53584	1432-1691
Mitochondrial matrix protein
			c-CbI oncogene (Adaptor Protein)	X57111	858-
Cdc25 phosphatase; guanine nucleotide releasing protein	X59868	942-
			Ezrin; villin 2; NF-2 (merlin) Related filamentous / plasma membrane-associated protein	X60671	1571-1812
Cyclin B1 (G2 / M specificity)	X64713	1184-1447
			Integrin α6	X69902	-611
5 - hydroxytryptamine receptor 3 (serotoni)	X72395	1422-1711
			Homeobox protein HOXD-3	X73573	141-362
Cyclin E (G1 / S specific)	X75888	799-
			MAPKAPK-2; MAP kinase-activated protein -2 Kinase; MAPKAP kinase 2	X76850	719-987
Fra-2 (fos-related antigen 2)	X83971	617-844
			Cyclin A1 (G2 / M specificity)	X84311	656-916
DCC; axon growth cues (netrin) receptor; Immunoglobulin gene superfamily members, former tumor Candidate inhibiting protein	X85788	4193-4508
			MHR23A; Rad23 UV excision repair protein Homologue, xerodemia repair protein supplement	X92410	613-955
MHR23A; Rad23 UV excision repair protein Homologue, xerodemia repair protein supplement...	X92411	542-807
			MHR23A; Rad23 UV excision repair protein Homologue, xerodemia repair protein supplement...	Y00769	1990-2320
MmRad52; Yeast DNA repair protein Rad52 Homologous proteins	Z32767	159-417
			Cyclin G (G2 / M specificity)	Z37110	300-619
Prostaglandin E2 receptor subtype EP4	D13458	1146-1442
			Interleukin-5 receptor	D90205	1389-1739
Epidermal growth factor (EGF)	J00380	180-505
			Erythropoietin receptor	J04843	1193-1377
Insulin receptor	J05149	653-1011
			P53; tumor suppressor protein, DNA-binding protein	K01700	1125-1517
Cf2r, coagulation factor II (thrombin) receptor	L03529	762-1154
			PTPRG; protein tyrosine phosphatase γ	L09562	1248-1504
DNA-binding protein SMBP2	L10075	4790-5088
			Interleukin-10 receptor	L12120	1762-2110
Interleukin-2 receptor γ chain	L20048	1073-1313
				L24755	2402-2676

URO	L33406	1809-2136
			Thrombopoietin	L34169	652-954
transforming growth factor-β-	M13177	772-1075
			Granulocyte colony-stimulating factor (G-CSF)	M13926	86-377
Nerve interleukins	M14220	1110-1490
			Insulin-like growth factor-2 (somatomedin A)	M14951	46-328
interleukin-1 β	M15131	827-1225
			c-myb proto-oncogene protein	M16449	1212-1513
Tumor necrosis factor βTNF-β (lymphotoxin α)	M16819	461-805
			Interleukin-1 receptor	M20658	2050-2410
CSF-1, M-CSF, colony stimulating factor-1	X05010	1268-1657
			Interleukin-4 receptor (membrane-bound form)	M27959	2469-2705
IFN-γ receptor	M28233	1262-1550
			Interleukin -7 receptor	M29697	701-1104
γ interferon-inducible monokine	M34815	42-323
			Interleukin 10	M37897	175-456
NF-κB binding subunit (NF) (TFDB5)	M57999	3122-3417
			Tumor necrosis factor receptor 1; TNFR-1	M59378	1961-2376
Tumor necrosis factor receptor 1; TNFR-1...	M84607	474-803
			Tumor necrosis factor receptor 1; TNFR-1...	M84746	795-1086
INOS1; nitric oxide synthase (induced)	M87039	3178-3455
			Interferon α-β receptor	M89641	808-1120
Activating transcription factor 4 (mATF4)	M94087	416-769
			β2-RAR; retinoic acid receptor β2	S56660	589-896
Tie-2 proto-oncogene	S67051	1834-2179
			IGF-I-Rα; insulin-like growth factor I receptor α subunit	U00182	489-885
IGFR II; insulin-like growth factor receptor II, Cation dependent 6 - phosphate mannose - receptors, Granville Ear Farm's tumor cells to enhance the	U04710	707-1060
			Stat3; APRF; acute phase response factor	U06922	1575-1910
	U18542	1375-1630
			Endothelin b receptor (Ednrb)	U32329	379-695
Advance endothelin -3	U32330	703-1008
			Before the platelet-derived growth factor receptor	X04367	2336-2677
The CD4 receptor (T-cell activation antigen)	X04836	1652-1877
			The CD4 receptor (T-cell activation antigen)...	X07962	241-496
The CD4 receptor (T-cell activation antigen)...	X12531	25-359
			Thrombomodulin	X14432	1082-1365
Interleukin-6 (B cell differentiation factor)	X51975	1638-1898

Androgen receptor	X53779	2189-2491
			Bone morphogenetic protein 4 (BMP-4) (TGFβ family)	X56848	1275-1513
Transferrin receptor protein (p90, CD71)	X57349	654-1023
			Transforming growth factor β2	X57413	2227-2541
Glutamate receptors, ionization AMPAI	X57497	1290-1657
			TNF55; tumor necrosis factor-1 (55kd)	X57796	656-1022
Mdm2; pS3 regulatory protein	X58876	1364-
			Heat shock transcription factor I	X61753	203-570
CD40L; CD ligand	X65453	545-809
			c-Fms proto-oncogene (macrophage colony stimulating factor Sub-1 (CSF-1) receptor)	X68932	2399-2686
B-myb proto-oncogene; myb protein B	X70472	2109-2456
			Ear-2; v-erbA related oncogene	X76654	1065-1376
Tie-1 receptor tyrosine kinase	X80764	1425-1844
			Glutamate receptors, ionization NMDA2B (ε2)	D10651	506-786
Glutamate receptors, ionization NMDA2A (ε1)	D10217	3966-4209
			CD7 antigen	D10329	28-421
Transcription factor S-II (transcription elongation factor)	D00926	518-767
			Basic fibroblast growth factor (b-FGF)	D12482	290-620
Bone morphogenetic protein receptor	D16250	1454-1837
			Bone morphogenetic protein receptor...	D17292	833-1115
	D17407	734-1079
			Bone morphogenetic protein receptor...	D29678	552-882
TGT-β receptor type I	D25540	1407-1629
			Sports fibroin KIF3B	D26077	3519-3722
Sports prime family protein KIF1A	D29951	2553-2830
			Fibroblast growth factor 9	D38258	91-379
Neuronal death protein	D83698	627-805
			Syp; SR-PTP2; adapter protein tyrosine phosphatase Enzymes	D84372	1229-1543
Interferon regulatory factor 2 (IRF2)	J03168	718-976
			Laminin receptor 1	J02870	368-675
NF-IB proteins (transcription factors)	D90176	452-791
			Jun-B, c-jun-related transcription factor	J03236	514-740
Tissue plasminogen activator protein	J03520	622-1020
			Tissue plasminogen activator protein...	J03770	565-945
Tissue plasminogen activator protein...	J04113	825-1059
			Ets-2 transcription factor	J04103	917-1281
Ets-2 transcription factor...	J04115	951-1238

Ets-2 transcription factor...	J05609	581-855
			NGF)	K01759	642-901
Cdk4; cyclin-dependent kinase 4	L01640	230-616
			Acetylcholine receptor δ subunit	K02582	1400-1655
Acetylcholine receptor δ subunit...	L02526	1284-1583
			Acetylcholine receptor δ subunit...	L04662	960-1341
GABA-A transporter protein 3	L04663	1010-1320
			Vegfr1; vascular endothelial growth factor receptor 1/Fms Associated tyrosine kinase (Flt1)	L07297	1144-1541
Adrenergic receptor β1	L10084	404-772
			Eph3 (Nuk) receptor tyrosine kinase	L25890	2255-2491
MTJ1; mouse tumors DnaJ-like heat shock protein White	L16953	1059-1384
			Metalloproteinase-3 tissue inhibitor TIMP-3	L19622	274-592
Metalloproteinase-3 tissue inhibitor TIMP-3...	L24563	1027-1304
			Metalloproteinase-3 tissue inhibitor TIMP-3...	L13968	1052-1292
Interleukin transformation enzyme (TCE)	L28095	30-269
			Hepatoma transmembrane kinase ligand	L38847	927-1219
Voltage-gated Na channel	L36179	4179-4505
			Bcl-XL and Bcl-2, promotes cell death	L37296	1079-1375
Jnk stress-activated protein kinase (SAPK)	L35236	795-1032
			Epidermal keratin cytoskeleton (18)	M11686	473-773
nerve growth factor α (α-NGF)	M11434	294-494
			Epidermal keratin (a person)	M10937	326-683
Nicotinic acetylcholine receptor	M14537	1226-1568
			MDR1; P-glycoprotein multidrug resistance protein, outflow Pump	M14757	1500-1886
CD2 antigen	M18934	354-602
			Homeobox protein 1.1 (Hox-1.1)	M17192	466-723
Alkaline fetal myosin light chain	M19436	205-504
			Interleukin-4	M25892	77-310
Rb; pp105; retinoblastoma susceptibility phase Related protein (tumor suppressor genes, cell cycle regulation Protein)	M26391	2036-2296
			Rsk; ribosomal protein S6 kinase	M28489	1191-1436
Platelet-derived growth factor (A chain) (PDGF-A)	M29464	152-425
			Platelet-derived growth factor (A chain) (PDGF-A)...	M28698	194-500
Platelet-derived growth factor (A chain) (PDGF-A)...	M29475	2155-2404
			Interleukin -3 receptor	M29855	1975-2254

Interleukin -3 receptor...	M30642	309-577
			Interleukin -3 receptor...	M34381	774-999
Plasminogen activator inhibitor	M33960	1096-1344
			CD3 antigen, δ-peptide	M33158	73-361
Homeobox protein 2.5 (Hox2.5)	M34857	11-277
			HSP84, heat shock 84kDa protein	M36829	342-736
Mast cell protease (MMCP) -4	M55617	634-992
			Mast cell protease (MMCP) -4...	M61177	115-373
Mast cell protease (MMCP) -4...	M60651	981-1260
			P58/GTA; galactosyltransferase enzyme binding protein Kinase (cdc2-related protein kinase)	M58633	1022-1284
Serine protease inhibitor 2 (spi-2)	M64086	1499-1754
				M64429	1651-2036
Etk1 (Mek4; HEK), protein tyrosine kinase receptor Body HEK	M68513	2681-2915
			RAG-2; V (D) J recombination activating protein	M64796	671-944
Type IV collagenase	M84324	696-1040
			Interleukin-6 receptor β chain glycoprotein gp130	M83336	1423-1741
α cardiac myosin heavy chain	M76601	2094-2391
			Retinoic acid receptor RXR-γ	M84819	701-1082
Granulocyte-macrophage colony-stimulating factor receptor	M85078	904-1289
			GABA-A receptor α-1 subunit	M86566	1251-1606
Endothelial L-selectin ligand (GLYCAM1)	M93428	182-541
			Integrin subunit protein β7	M95633	2142-2423
DNase I	U00478	665-871
			Cortacin, protein tyrosine kinase substrate	U01384	426-653
Adenosine receptor A2M2	U05672	491-735
			DNA ligase 1	U04674	1678-2054
AIM adenosine receptor	U05671	302-673
			Non-muscle myosin light chain 3
Cathepsin H	U06119	325-694
			Stat1; transcription signal transduction and activator agents	U06924	1749-2104
P21/cip1/Waf1; cdk inhibitor protein	U09507	9-403
			Cdk7; M015; cyclin-dependent excitation Enzyme 7 (xenopus M015 cdk-activating kinase with Homologues)	U11822	454-824
P27kip1; G1 cyclin-Cdk protein	U10440	270-454

Kinase inhibitor, p21-related
			Gem; induced immediate early protein; Ras family Member	U10551	220-471
VRL; Von Hippel-Lindau tumor suppressor protein White	U12570	885-1111
			Cek5 ligand-receptor protein tyrosine kinase	U12983	1037-1287
Glutathione peroxidase (plasma membrane protein); selenium Protein	U13705	766-1046
			Integrin α5 (CD51)	U14135	2170-2516
Ski proto-oncogene	U14173	707-1037
			And HOXD3 similar Ablphilin I (abi-1)	U17698	351-585
BAG-1, with anti-apoptotic activity of bcl-2 Results Combined protein	U17162	17-334
			Conversion adapter protein Shc	U15784	1220-1451
Src homolog 2 (SR2) protein, SRB-
			MAPKK4; MAP kinase kinase 4, Jnk activation Kinase 1, (JNKK1, SEK1, MKK4)	U18310	1380-1749
Transcription factor LRG-21	U19118	618-966
			Interferon-inducible protein 1	U19119	1342-1636
A20 zinc finger protein, apoptosis inhibitors	U19463	1952-2293
			P18ink4; cdk4 and cdk6 inhibitor	U19596	16-284
I-κB (I-κB) βDv12; disheveled-2 Organization	U19799	419-778
			Polarity protein	U24160	1205-1578
And P45 NF-E2-related nuclear factor	U20532	1429-1759
			MSH2 DNA mismatch repair protein, Muts homologous Complex 2	U21011	2150-2490
GapIII, GTPase activating protein	U20238	328-644
			GapIII, GTPase activating protein...	U25685	1235-1524
GapIII, GTPase activating protein...	U27177	1973-2365
			PMS2 DNA mismatch repair protein, yeast PMS1 Homolog 2	U28724	749-1013
Limphotoxin receptor (TNFR family)	U29173	1415-1668
			BRCA1; breast / ovarian cancer susceptibility locus a product	U31625	5126-5430
Pml; murine leukemia-associated PML gene sources with Gene	U33626	1667-2064
			Transduction element β-2 subunit	U34960	515-834
I-κB (I-κB) βα chain	U36277	541-823
			TRAIL, TNF-related apoptosis-inducing ligand;	U37522	981-1288

Apo-2 ligand
			P130; retinoblastoma gene product-related Protein Rb2/p130 (cell cycle control agent)	U36799	970-1321
CACCC box binding protein BKLF	U36340	826-1065
			FAF1; Fas-binding protein factors, apoptosis stimulated Deactivators	U39643	423-681
Zinc finger transcription factor RU49	U41671	1229-1591
			GTBP; G / T mismatch binding protein; MSH6	U42190	1477-1769
βPLC, ​​phospholipase Cβ3	U43144	1933-2271
			Curl protein-3; Drosophila tissue protein gene with curl Homologue 3; dishevelled receptor	U43205	2037-2285
MAPKK3; MAP kinase kinase 3 (bispecific Sex) (MKK3, MEK3)	U43187	1436-1742
			Into myeloid cytokines, trypsin - chymotrypsin Related serine proteases	U43525	503-807
Kruppel-type zinc finger Zfp92	U47104	578-896
			TDAG51; and Fas (CD95) expression coupled TCR Signal	U44088	729-1042
Second POU domain binding factor I	U43788	610-884
			ALG-2; programmed cell death required for calcium-binding Protein	U49112	527-861
Unconventional myosin VI	U49739	3784-4021
			Transcription factor CTCF (11 zinc finger)	U51037	1625-1911
Transcription factor C1	U53925	3895-4227
			Madr1; mSmad1; anti dpp protein precursor (Mad) Murine homologue; TGF-β signaling proteins - 1 (bsp-1); candidate tumor suppressor gene	U58992	238-476
Bcl-W apoptosis regulator; Bcl-2 family members	U59746	153-368
				U60530	584-820
Cyclin C (G1-specific)	U62638	714-986
			Hox genes Mph-1 nuclear transcriptional repressor	U63386	1621-1884
Rad50; DNA repair proteins	U66887	1383-1707
			Fyn oncogene; Src family members	U70324	584-882
c-myc proto-oncogene protein	X01023	379-667
			c-Fos proto-oncogene; transcription factor AP-1 component fos Cellular oncogenes	V00727	482-734
Cathepsin L	X06086	267-588
			Glutamate receptor channel subunit γ	X04648	41-408
proto-oncogene c-Fes	X12616	2342-2598
			Cytotoxic cells protease 2 (B10)	X12822	439-686

Homeobox protein 3.1 (Hox3.1)	X07439	449-722
			Homeobox protein 3.1 (Hox3.1)...	X13721	1949-2284
Homeobox protein 3.1 (Hox3.1)...	X14897	920-1278
			Plasminogen activator inhibitor 2	X16490	674-978
oncogene c-ErbA; thyroid hormone receptor	X51983	400-675
			Vimentin (vimentin)	X51438	868-1096
HMG-14 non-histone chromosomal proteins	X53476	643-1017
			Macrophage inflammatory protein 2α (MIP2α)	X53798	14-352
Bone morphogenetic protein 7 (BMP-7) (osteogenic protein 1)	X56906	670-971
			Transcription factor SPIP (POU transcription factor region)	X56959	866-1128
Homeobox protein 8 (Hox8)	X59252	826-1132
			Fibroblast growth factor receptor 4	X59927	2446-2820
Fibroblast growth factor receptor 4...	X57277	425-651
			Fibroblast growth factor receptor 4...	X60831	689-993
Kinesin (kinesin) heavy chain	X61435	1898-2182
			Kinesin (kinesin) heavy chain...	X61800	904-1150
Kinesin (kinesin) heavy chain...	X62622	1236-1468
			Ets-related protein PEA3 ...	X63190	1702-2040
Ets-related protein PEA3 ...	X64361	1083-1351
			PAX-6 (paired box protein)	X63963	1081-1325
	X66032	874-1236
			Chop10; Gadd153 (growth arrest and DNA damage Injury induced protein) of the murine homologue	X67083	17-332
PD-1; possible cell death-inducing agent; Ig group Because superfamily member	X67914	1481-1734
			Inhibin βA subunit (TGFβ family)	X69619	1064-1304
Inhibin βA subunit (TGFβ family)...	X70842	1394-1721
			Inhibin βA subunit (TGFβ family)...	X70296	746-985
MRE-binding transcription factor	X71327	552-916
			Activator protein -1 140kDa subunit (replication factor C140kDa)	X72711	4137-4375
Activator protein -1 140kDa subunit (replication factor C140kDa)...	X72310	925-1305
			Activator protein -1 140kDa subunit (replication factor C140kDa)...	X72230	982-1314
Gelatinase B	X72795	599-954
			XPAC; disease xeroderma pigmentosum group A correcting protein	X74351	447-669
Integrin α (CD49b)	X75427	1595-1976
			Growth / differentiation factor 2 (GDF-2)	X77113	939-1329
Insulin-like growth factor binding protein 4 (IGFBP-4)

Insulin-like growth factor binding protein-1 (IGFBP-1)	X81579	27-256
			IGFBP-2; insulin-like growth factor binding protein 2, autocrine and / or paracrine growth promoters	X81580	449-817
IGFBP-2; insulin-like growth factor binding protein 2, autocrine and / or paracrine growth promoters...	X81583	461-824
			IGFBP-2; insulin-like growth factor binding protein 2, autocrine and / or paracrine growth promoters...	X81584	701-1039
A-myb proto-oncogene; myb-related protein A	X82327	1017-1334
			Membrane type matrix metalloproteinase	X83536	877-1101
Elk-1 ets-related oncogenes	X87257	1498-1680
			E2F5 transcription factor	X86925	426-728
Lbx-1 transcription factor	X90829	1000-1306
			P-selectin (glycoprotein ligand -1)	X91144	1095-1323
Transcription factor SEF2	X91753	755-1054
			Macrophage mannose receptor C	Z11974	807-1197
Macrophage mannose receptor C...	X95403	232-505
			Macrophage mannose receptor C...	X98055	14-298
Plaques associated protein; LIM zone protein; α actin Binding protein		-1812
			Met proto-oncogene	Y00671	3646-3933
c-Kit proto-oncogene (mast / stem cell growth factor Sub-receptor tyrosine kinase)	Y00864	2867-3181
			c-Kit proto-oncogene (mast / stem cell growth factor Sub-receptor tyrosine kinase)...	Y07960	723-973
c-Kit proto-oncogene (mast / stem cell growth factor Sub-receptor tyrosine kinase)...	X95346	180-516
			Substrate cleavage factor (Stromelysin) -3; matrix metalloproteinases Protease -11 (MMP-11)	Z12604	1463-1806
5 - hydroxytryptamine (serotonin) receptor 1eβ	Z14224	530-774
			5 - hydroxytryptamine (serotonin) receptor 1eβ...	Z15119	588-940
5 - hydroxytryptamine (serotonin) receptor 1eβ...	Z19521	1047-1324
			5 - hydroxytryptamine (serotonin) receptor 7	Z23107	460-817
c-Mp1; thrombopoietin receptor; mematopoietic growth factor receptor superfamily into Member	Z22649	1561-1772
			Catalytic subunit of DNA polymerase 6	Z21848	1256-1600
Follistatin	Z29532	764-1053
			Cyclin F (S/G2/M specificity)	Z47766	2431-2708
Ets-related protein Sap1A	Z26885	1267-1521
			Net; ets-related transcription factor	Z32815	1211-1595
Stat5a; breast Factor	Z48538	2269-2628
			Hck2 murine homologue; Mdk5 murine development Kinase; Eph receptor tyrosine kinase related	Z49086	1702-1930

D-factor / LIF receptor	D26177	2376-2775
			Epidermal keratin cytoskeleton (14)	M13806	108-469
R-ras protein, and is closely related to ras proto-oncogene	M21019	215-555
			Prolactin receptor PRLR2	M22959	1-328
Prolactin receptor PRLR2...	M30903	1307-1672
			Prolactin receptor PRLR2...	M35590	119-445
α-1 proteinase inhibitor 2, GABA-A transporter White 1	M75716	625-969
			Bone morphogenetic protein 8a (BMP-8a) (TGF-β family Family)	M97017	788-1139
Erythrocytes krupple like transcription factor	M97200	783-1171
			GATA-binding transcription factor (GATA-4)	M98339	81-379
Growth factor receptor	M98547	1701-2014
			Crk adapter protein; retinoid X receptor interacting protein White (RIP15)	U09419	1388-1682
Cek7 ligand-receptor protein tyrosine kinase	U14752	504-837
			C-C CKR-1; CCR-1; I-type C-C chemokines Acceptor; macrophage inflammatory protein-1α receptors; MIP-α-R; RANTES-R	U29678	168-495
Glucocorticoid receptor form A	X13358	1527-1816
			Anti-DPP protein precursor protein (mad homologues Smad1, transforming growth factor-β signaling protein)	X83106	464-728
Tyrosine kinase Hck	Y00487	1308-1563
			Photolyase / blue light receptor homolog	AB00077	1418-1737
Osp94 penetration stress protein; APG-1; hsp70 Related	D49482	1026-1266
			Glucose-regulated protein; 78kDa; Grp78	D78645	167-411
Glucose-regulated protein; 78kDa; Grp78...	D87747	584-867
			Glucose-regulated protein; 78kDa; Grp78...	M23384	325-653
Iht-3 oncogene; NOTCH family as the original; NOTCH4	M80456	1846-2145
			c-Akt oncogene; Rac-α; protein kinase B (PKB)	M94335	604-899
Bak apoptosis regulatory proteins; Bcl-2 family into Member	Y13231	1509-1786
			PS-2; Alzheimer's disease gene homolog	U57324	437-783
BRCA-2; breast cancer susceptibility locus 2 products	U65594	649-922
			DNA ligase III	U66058	2980-3205

DNA ligase III...	U67321	1040-1280
			DNA ligase III...	U75506	452-777
WBP6; pSK-SRPK1; WW domain binding protein 6; SP splicing factor serine kinase ...	U92456	482-774
			WBP6; pSK-SRPK1; WW domain binding protein 6; SP splicing factor serine kinase ...	U95826	408-688
Ung1; uracil-DNA glycosylase	X99018	444-729
			Rab-3b Ras-related protein	Y14019	232-562
Rab-3b Ras-related protein...	U28423	180-487
			Rab-3b Ras-related protein...	U34259	742-1060
ATP-binding cassette 8; ABC8; white flies CDC42 GTP-binding protein homologous protein	U34920	1011-1319
			G25k	U37720	1675-1982
ATP-binding cassette 8; ABC8; white flies CDC42 GTP-binding protein homologous protein...	U41751	1041-1296
			ATP-binding cassette 8; ABC8; white flies CDC42 GTP-binding protein homologous protein...	U51866	1237-1517
TSG101 tumor susceptibility protein ...	U52945	446-713
			TSG101 tumor susceptibility protein ...	U54705	251-507
FLIP-1, apoptosis inhibitory protein; class FLICE Inhibiting protein	U97076	1476-1811
			CamKII; Ca2 + / calmodulin-dependent protein kinase Enzyme II (β subunit)	X63615	1951-2219
Htk; Mdk2 mouse development kinases; Eph-related Receptor tyrosine kinase	Z49085	2032-2365
			Glial cell line derived neurotrophic factor	D49921	236-539
CD31 (platelet endothelial cell adhesion molecule-1)	L06039	1172-1494
			CD22 antigen	L16928	2314-2645
Gbx2	L39970	1122-1395
			CCPI serine protease gene (CTLA-1)	M12302	585-830
Cathepsin B	M14222	384-729
			Auxin receptor	M33324	1924-2240
CD28 (B71 receptor)	M34563	544-774
			Estrogen receptor	M38651	742-1013
Haplotype chemoattractant protein 3	S71251	201-491
			CD45-associated protein (CD45-ap, LSM-1)	U03856	620-898
Orphan receptor	U11688	1686-1943
			Cannabinoid receptor 1 (brain)	U17985	1091-1437
Malnutrition glycans 1	U43512	2267-2505
			G protein-coupled receptors	U46923	350-671
Urokinase-type plasminogen activator	X02389	1301-1538
			CTLA-4 (into the original immunoglobulin superfamily)	X05719	246-519

Myogenic factor 5	X56182	232-528
			UPAR1; urokinase-type plasminogen activator surface Receptor (CD87)	X62700	482-756
UPAR1; urokinase-type plasminogen activator surface Receptor (CD87)...	X69832	621-927
			UPAR1; urokinase-type plasminogen activator surface Receptor (CD87)...	X70298	34-311
Bone morphogenetic protein 2 (BMP-2) (TGF-β family Family)
			[K02588] P-1-450; dioxin-inducible cell Cytochrome P450 [K02588]	M10021	3729-4014
Bcl-2; B-cell lymphoma protein 2, apoptosis Inhibiting protein	M16506	2125-2367
			CD14 antigen	M34510	667-931
Somatostatin receptor 2	M81832	47-310
			Dopamine receptor 4	U19880	907-1191
Cannabinoid receptor 2 (macrophages, CB2)	U21681	910-1262
			Erf (Ets-related transcription factor)	U58533	1286-1613
5 - hydroxytryptamine (serotonin) receptor 1b	Z11597	1043-1355
			Tob antoproliferative factor, and p185erbB2 interaction	D78382	540-876
Glutathione S-transferase enzyme (microsomes)	J03752	185-428
			Glutathione S-transferase enzyme (microsomes)...	L20331	182-382
Glutathione S-transferase enzyme (microsomes)...	U05341	1061-1348
			AP endonuclease; depurinated / apyrimidinic nuclear Endonuclease (Apex); Mas proto-oncogene (G-protein White-coupled receptors)	U12273	1894-2150
AT motif binding factor ATBF1	D26046	9807-10112
			From testicular HMG box transcription factor (MusSox17)	D49474	427-662
Ikaros DNA-binding proteins	L03547	627-890
			Early B-cell factor (EBF)	L12147	750-1026
Engrailed protein (En-1) homolog	L12703	1323-1554
			Engrailed protein (En-2) homologues	L12705	1626-1895
Transcription factor A10	L21027	499-806
			Muscle nuclear factor (MNF)	L26507	1203-1456
Basic / leucine zipper transcription factor	L36435	872-1073
			Tail type homeobox 1 (Cdx1)	M37163	1040-1301
Butyrate response factor 1	M58566	768-22
			Brain-specific transcription factor NURR-1	S53744	1548-1754
Bm-3.2 POU transcription factor	S68377	877-1237
			Tail type homeobox 2 (Cdx2)	S74520	1085-1367

Cell cellular transcription factor NF-E2	U01036	1-241
			Gut-specific Kruppel-like factor (GKLF)	U20344	1558-1789
Gut-specific Kruppel-like factor (GKLF)...	U25096	898-1193
			Gut-specific Kruppel-like factor (GKLF)...	U36760	1080-1318
Split hand / foot gene	U41626	92-303
			Sim transcription factor	U42554	2828-3066
Glial cells lost gene homologues (mGCM1)	U59876	727-1080
			Sp4 zinc finger transcription factor	U62522	1704-1929
Heat shock transcription factor 2 (HSF2)	X61754	1445-1640
			RNA polymerase I terminator, TTF-1	X83974	3222-3433
Hepatocyte nuclear factor 3 / fork head protein homologues 8 (HFH-8)	L35949	913-1232
			SRX box containing gene 3 (Sox3)	X94125	212-443
Cot proto-oncogene	D13759	696-956
			HR21spA; involved in DNA double-strand break repair Protein; PW29; calcium-binding protein	D49429	103-434
MmLim15; RecA-like gene; DMC1 homologous Protein; meiosis-specific homologous recombinant protein	D64107	581-781
			Erp72 endoplasmic reticulum protein; protein disulfide isomerase Associated protein	J05186	1160-1470
HMG1 related VDJ recombination signal-binding protein	S50213	2263-2531
			Gli oncogene, the zinc finger transcription factor	S65038	104-505
Tiam-1 protein induced invasion; GDP-GTP exchange Body-related	U05245	4329-4628
			Sik; Src-related intestinal kinase	U16805	1246-1623
Lfc oncogene	U28495	853-1150
			Lfc oncogene...	U40930	1248-1561
Lfc oncogene...	U43900	576-811
			ShcC joints; Shc related; brain-specific	U46854	246-601
MmMrella derived endo / exonuclease	U58987	866-1204
			PCNA; proliferating cell nuclear antigen; continuous synthesis can Force factor	X53068	53-320
translin; recombination hotspot binding protein	X81464	205-431
			PA6 matrix protein; RAG1 gene activator	X96618	442-749
Sky oncogene (Tyro3; Rse; Dtk)	U18342	1927-2286
			H-ras oncogene; transporter G protein	Z50013	1307-1544
ERBB-2 receptor (c-neu; HER2 protein tyrosine Kinase)	L47239	16-266
			ERBB-3 receptor	L47240	4-243

Placental ribonuclease inhibitor (angiogenin)	U22516	512-766
			Myosin I	L00923	2578-2921
Ca2 +-binding protein: Cab45	U45977	597-1082
			Mouse Bird amino acid decarboxylase	M10624	865-1252

Example 1

The composition of the present invention, many of the art can be prepared by the method well known to persons Equipment. In short, the different hydrophilic lipophilic required by the application are as follows: 3 ~ 6 oil-in-water emulsifier (Such as sorbitan esters + squalene), 7 to 9 wetting agent; 8 to 13 oil-in-water emulsifier; 13 to 15 detergent; 15 to 18 solubilizer (eg aluminum stearate and magnesium stearate). These values Widely cited in the literature, as a special purpose emulsifier selection guide. They are designed For the non-ionic emulsifier. Similar systems have been developed for the anionic or cationic emulsion Agents, but their use as non-ionic emulsifier. Many non-ionic hydrophilic emulsifier Lipophilic balance number has been published. Containing about 0.5-55% oil, about 0.1 to 15% of an emulsifier, About 0.05 to 5% nonionic surfactant, about 0.00001% of the treatment agent and a A continuous aqueous phase of the water-in-oil emulsions best for this particular usage. Emulsifier compositions are A phospholipid compound or from phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, Phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, sphingomyelin, cardiolipin in a mixture of phospholipids. Examples of emulsifiers are sorbitan esters of a A. Surface active agents are usually selected from fatty acids, Polyethylene glycol fatty acid esters, polyethoxylated fatty acid esters, polyethoxylated fatty alcohol ethers, with 1 or more hydroxyl compounds of an alkylene oxide condensate. The surfactant can be days Natural biocompatible surface active agents such as lecithin or a pharmaceutically acceptable non-natural surfactant Of agents such as Tween-80. And lecithin related right natural ingredients such as EPICURON 120 (Lucas Meyer, Germany), which is about 70% of phosphatidyl choline, 12% phosphatidyl Ethanolamine and about 15 percent of a mixture of other phospholipids; OVOTHIN 160 (Lucas Meyer, Germany), which is containing about 60% of phosphatidyl choline, phosphatidyl ethanol 18% Amine and 12% of a mixture of other phospholipids; a purified phospholipid mixture LIPOID E-75 Or LIPOID E80 (lipoid, Germany), which is containing about 80% of phosphatidylcholine, 8% Phosphatidylethanolamine, 3.6% non-polar lipids and about 2% of a mixture of phospholipids sphingomyelin. Purified egg yolk lecithin, soybean lecithin or other purified phospholipid mixture can be used as such as Copies. Listed are representative phospholipids, but not limited to phospholipids, the person skilled in the art Other well-known members can also be used as phospholipids. Examples of other surfactants such as fatty acid Polyethylene glycol esters, they have different sources, such as beaver oil (EMULFOR), polyethoxylated fatty Acids, such as stearic acid (SIMULSOL M-53); NONIDET; polyethoxylated octyl phenol / Formaldehyde polymer (TYLOXAPOL); polyoxyethylene fatty alcohol ethers (BRIJ); polyoxyethylene non-benzene Ether (TRITON N);, and polyoxyethylene isooctyl phenyl ether (TRITON X) and so on. In some Embodiments, the emulsion may be formed and stabilized in one or more of the basic lack of surfactant Cases, these co-surfactant selected from a non-halogenated aliphatic C3-C6 alcohols, free fatty acids, Mono-or diglycerides, polyglycerol fatty acid ester or lysophosphatidylcholine. Alternatively, however, the group Compounds are also suitable and may be used by the person skilled in the art readily prepared, for example, with 5.0% PLURONIC, 10% squalene, 0.4% Tween-80, qs phosphate buffer (pH7.4) The composition of the ingredients into a test tube, mixed and stirred until a creamy emulsion. This kind Composition should be prepared before use, or frozen at 4 ℃. For example, the composition 2 containing 5.0% TETRONIC1501, 10% squalane, 0.4% Tween-80, qs phosphate buffer (PH7.4); then added to the composition to those of solid N-acetyl-muramyl-L-threonyl-D- Isoglutamine (Thr-MDP), thereby forming a concentration of 500μg/mL of the "concentrate." Then, this concentrated solution and 2 × antigen solution (hCG aqueous salt solution, 1mg/mL) formed by mixing The preparation of the present invention. HCG weight in the composition is preferably about 0.00001% More preferably from about 0.0001%, and most preferably is 0.001%. Moreover, pH should be The stability of hCG in a suitable range. The continuous phase of the composition is aqueous phase, which is attached salt, sugar, Antioxidants, preservatives, microbicides, buffers, wetting agent (osmoticant), frozen Protection agents and other pharmaceutically useful additives or solute. Typical preservatives include thimerosal Mercury, alcohol, methylparaben chloroprene, ethyl, propyl or butyl. Typical osmotic Adjusting agents include glycerol and mannitol, and glycerin is preferred. The preferred oxidizing agent is oil proposition α-tocopherol or α-tocopherol succinate. The aqueous phase may also include polyamines carboxylic acid antioxidant, Such as ethylenediaminetetraacetic acid or other pharmaceutically acceptable salt thereof. ...

The composition of the present invention, many of the art can be prepared by the method well known to persons Equipment. In short, the different hydrophilic lipophilic required by the application are as follows: 3 ~ 6 oil-in-water emulsifier (Such as sorbitan esters + squalene), 7 to 9 wetting agent; 8 to 13 oil-in-water emulsifier; 13 to 15 detergent; 15 to 18 solubilizer (eg aluminum stearate and magnesium stearate). These values Widely cited in the literature, as a special purpose emulsifier selection guide. They are designed For the non-ionic emulsifier. Similar systems have been developed for the anionic or cationic emulsion Agents, but their use as non-ionic emulsifier. Many non-ionic hydrophilic emulsifier Lipophilic balance number has been published. Containing about 0.5-55% oil, about 0.1 to 15% of an emulsifier, About 0.05 to 5% nonionic surfactant, about 0.00001% of the treatment agent and a A continuous aqueous phase of the water-in-oil emulsions best for this particular usage. Emulsifier compositions are A phospholipid compound or from phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, Phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, sphingomyelin, cardiolipin in a mixture of phospholipids. Examples of emulsifiers are sorbitan esters of a A. Surface active agents are usually selected from fatty acids, Polyethylene glycol fatty acid esters, polyethoxylated fatty acid esters, polyethoxylated fatty alcohol ethers, with 1 or more hydroxyl compounds of an alkylene oxide condensate. The surfactant can be days Natural biocompatible surface active agents such as lecithin or a pharmaceutically acceptable non-natural surfactant Of agents such as Tween-80. And lecithin related right natural ingredients such as EPICURON 120 (Lucas Meyer, Germany), which is about 70% of phosphatidyl choline, 12% phosphatidyl Ethanolamine and about 15 percent of a mixture of other phospholipids; OVOTHIN 160 (Lucas Meyer, Germany), which is containing about 60% of phosphatidyl choline, phosphatidyl ethanol 18% Amine and 12% of a mixture of other phospholipids; a purified phospholipid mixture LIPOID E-75 Or LIPOID E80 (lipoid, Germany), which is containing about 80% of phosphatidylcholine, 8% Phosphatidylethanolamine, 3.6% non-polar lipids and about 2% of a mixture of phospholipids sphingomyelin. Purified egg yolk lecithin, soybean lecithin or other purified phospholipid mixture can be used as such as Copies. Listed are representative phospholipids, but not limited to phospholipids, the person skilled in the art Other well-known members can also be used as phospholipids. Examples of other surfactants such as fatty acid Polyethylene glycol esters, they have different sources, such as beaver oil (EMULFOR), polyethoxylated fatty Acids, such as stearic acid (SIMULSOL M-53); NONIDET; polyethoxylated octyl phenol / Formaldehyde polymer (TYLOXAPOL); polyoxyethylene fatty alcohol ethers (BRIJ); polyoxyethylene non-benzene Ether (TRITON N);, and polyoxyethylene isooctyl phenyl ether (TRITON X) and so on. In some Embodiments, the emulsion may be formed and stabilized in one or more of the basic lack of surfactant Cases, these co-surfactant selected from a non-halogenated aliphatic C3-C6 alcohols, free fatty acids, Mono-or diglycerides, polyglycerol fatty acid ester or lysophosphatidylcholine. Alternatively, however, the group Compounds are also suitable and may be used by the person skilled in the art readily prepared, for example, with 5.0% PLURONIC, 10% squalene, 0.4% Tween-80, qs phosphate buffer (pH7.4) The composition of the ingredients into a test tube, mixed and stirred until a creamy emulsion. This kind Composition should be prepared before use, or frozen at 4 ℃. For example, the composition 2 containing 5.0% TETRONIC1501, 10% squalane, 0.4% Tween-80, qs phosphate buffer (PH7.4); then added to the composition to those of solid N-acetyl-muramyl-L-threonyl-D- Isoglutamine (Thr-MDP), thereby forming a concentration of 500μg/mL of the "concentrate." Then, this concentrated solution and 2 × antigen solution (hCG aqueous salt solution, 1mg/mL) formed by mixing The preparation of the present invention. HCG weight in the composition is preferably about 0.00001% More preferably from about 0.0001%, and most preferably is 0.001%. Moreover, pH should be The stability of hCG in a suitable range. The continuous phase of the composition is aqueous phase, which is attached salt, sugar, Antioxidants, preservatives, microbicides, buffers, wetting agent (osmoticant), frozen Protection agents and other pharmaceutically useful additives or solute. Typical preservatives include thimerosal Mercury, alcohol, methylparaben chloroprene, ethyl, propyl or butyl. Typical osmotic Adjusting agents include glycerol and mannitol, and glycerin is preferred. The preferred oxidizing agent is oil proposition α-tocopherol or α-tocopherol succinate. The aqueous phase may also include polyamines carboxylic acid antioxidant, Such as ethylenediaminetetraacetic acid or other pharmaceutically acceptable salt thereof. ...

Instant composition consists of two parts. The first part is N-acetyl-muramyl-L-threonyl - D-iso-glutamine (Thr-MDP), which is a constituent of mycobacterial cell wall derivatives. Second Part of the phosphate buffer solution, which comprises a final concentration of 5% squalane, 1.25% of the general flow Romania Nepal (Pluronic) and 0.2% Tween 80 (vehicle). For practical purposes, the required number of hCG and microscopic flow regime vehicle (Part II) mixed to obtain a homogeneous emulsion. Then add Into the MDP, simply shake it. MDP by changing the concentration of the mixture to determine the most Good clinical response concentration. According to manufacturer's instructions (Pierce chemical, Rockford, III), As an adjuvant control, mice can be injected into or mixed with alum, Freund's complete adjuvant (CFA) in Soluble hCG. ...

Those of ordinary skill in the art will recognize that such a mouse model that Equivalent experiments or processing in the human, domesticated animals or farm animals induce the same clinical Reaction. Through a number of well known to persons of ordinary skill in the art of conventional procedures, empirically Without undue experimentation can determine the clinical effects to produce the desired number of formulations and hCG Volume. Therefore, if such a mixture it is necessary to minimize side effects caused by the treatment, While also an effective reaction of ordinary skill in the art will identify this mixture Humans, domesticated animals and farm animals, the lowest level when administered to induce the desired Pro Bed effect. In normal use, many of the basic process according to any one of the injection which Species mixtures, subcutaneous or intramuscular injection is particularly preferred, the injection site can emulsion Remain stable form a few days or weeks. ...

Those of ordinary skill in the art will recognize that such a mouse model that Equivalent experiments or processing in the human, domesticated animals or farm animals induce the same clinical Reaction. Through a number of well known to persons of ordinary skill in the art of conventional procedures, empirically Without undue experimentation can determine the clinical effects to produce the desired number of formulations and hCG Volume. Therefore, if such a mixture it is necessary to minimize side effects caused by the treatment, While also an effective reaction of ordinary skill in the art will identify this mixture Humans, domesticated animals and farm animals, the lowest level when administered to induce the desired Pro Bed effect. In normal use, many of the basic process according to any one of the injection which Species mixtures, subcutaneous or intramuscular injection is particularly preferred, the injection site can emulsion Remain stable form a few days or weeks. ...

hCG aqueous suspension at room temperature, added to the oil phase, while homogenized with a homogenizer. When the oil and hCG ratio reached 5-6:3-5 suspension parts, stop adding the aqueous phase. Continue homogenized straight The size of the droplets of the aqueous phase to about 0.05-0.5μm. The oil phase comprises the following materials: 93.6% The macro 52; 6.0% sorbitan ester A or sorbitan esters 80 or Span80 (two Mannide mono-oleate (mannide monooleate)); 0.4% of Tween 80 (polyoxyethylene 20 Sorbitan monooleate). The composition of the liquid phase can be individually heated to the sterilization pot 110 ℃ or In a mixture is sterile filtered. Stability of the emulsion by the two factors: (1) emulsified Direct dripping water with a pipette, so that the droplet does not spread, intact; (2) at 37 ℃ Store four weeks will not form any aqueous phase. The emulsion thus prepared contained a final concentration of about 10% By weight of hCG, by intramuscular or subcutaneous injection, each dose is used in subjects 0.5mL. ...

hCG aqueous suspension at room temperature, added to the oil phase, while homogenized with a homogenizer. When the oil and hCG ratio reached 5-6:3-5 suspension parts, stop adding the aqueous phase. Continue homogenized straight The size of the droplets of the aqueous phase to about 0.05-0.5μm. The oil phase comprises the following materials: 93.6% The macro 52; 6.0% sorbitan ester A or sorbitan esters 80 or Span80 (two Mannide mono-oleate (mannide monooleate)); 0.4% of Tween 80 (polyoxyethylene 20 Sorbitan monooleate). The composition of the liquid phase can be individually heated to the sterilization pot 110 ℃ or In a mixture is sterile filtered. Stability of the emulsion by the two factors: (1) emulsified Direct dripping water with a pipette, so that the droplet does not spread, intact; (2) at 37 ℃ Store four weeks will not form any aqueous phase. The emulsion thus prepared contained a final concentration of about 10% By weight of hCG, by intramuscular or subcutaneous injection, each dose is used in subjects 0.5mL. ...

Without limited to the above embodiments, the hCG dimer-containing compositions of the invention can simultaneously Including two emulsifiers, thus providing better stability. In this composition, the main Emulsifiers selected from polyoxypropylene - polyoxyethylene block copolymers, glycerol monooleate, glycerol dioleyl Esters, sorbitan sesquioleate, Brij 93 polyoxyethylene glycol, sorbitan monooleate And mixtures thereof, and the second emulsifier is selected from polyoxyethylene fatty acid esters, general flow Ronnie F68, ethylene oxide, lecithin, and mixtures thereof. The composition of the oil fraction is glycerin Triester is selected from glyceryl three hexanoyl, trioctanoyl glycerol, glycerol and mixtures tripalmitoyl Thereof. Other suitable oils include vegetable and animal oils. Suitable vegetable oils include: olive oil, Safflower oil, sesame oil and soybean oil and animal oil suitable glycerides include those containing dynamic Oils. No.40 Preferred mineral oils include white oil, light oil, and Klearol naphtha carnations. Mixtures of these oils can also be used. ...

For the preparation of the primary emulsion containing mineral oil, about 1 - about 50% by volume, preferably about 2 - HCG about 40% by volume of an aqueous solution; about 8 - about 58% by volume, preferably about 14 - about 25% by volume Mineral oil;, and from about 2 - about 30% by volume, preferably about 5 - about 15% by volume of the main emulsifier Mixed together. HCG solution is preferably added slowly to the oil phase of rapid stirring, mixing, Such as with a magnetic stirrer, mixing about 15 to 60 minutes, preferably about 25-35 minutes. Mix well The primary emulsion and then higher shear emulsification, the pressure drop of about 1000-10000psi, Preferably about 1000-3000psi, and most preferably from about 1800-2000psi case to Second shear rate of about 100000-500000, preferably about 500000-1000000 into second Line cut, such as the application Microfluidization machine (microfluidizer). About Microfluidization machine More complete information in the United States Patent NO4533254 has been proposed. Microfluidization function provided Duration as short as a fraction of a second high shear rate, and not lead to proteins such as hCG becomes Sex. Primary suspension was then filtered, such as the use 5μm hydrophilic polyoxyethylene polyvinylidene difluoride Matter filter (Duropore, Millipore Corporation). HCG can before the emulsification solution Adding albumin, is added about 1-5g%, preferably about 2-3g%, thereby helping to stabilize Multiple emulsion size distribution. In mineral oil or the oil solidified hCG in the initial aqueous suspension suitable The liquid preparation of the present invention together more suspension should also yield primary floating liquid droplet diameter of less than 5 μm, preferably less than 3μm. ...

For the preparation of the primary emulsion containing mineral oil, about 1 - about 50% by volume, preferably about 2 - HCG about 40% by volume of an aqueous solution; about 8 - about 58% by volume, preferably about 14 - about 25% by volume Mineral oil;, and from about 2 - about 30% by volume, preferably about 5 - about 15% by volume of the main emulsifier Mixed together. HCG solution is preferably added slowly to the oil phase of rapid stirring, mixing, Such as with a magnetic stirrer, mixing about 15 to 60 minutes, preferably about 25-35 minutes. Mix well The primary emulsion and then higher shear emulsification, the pressure drop of about 1000-10000psi, Preferably about 1000-3000psi, and most preferably from about 1800-2000psi case to Second shear rate of about 100000-500000, preferably about 500000-1000000 into second Line cut, such as the application Microfluidization machine (microfluidizer). About Microfluidization machine More complete information in the United States Patent NO4533254 has been proposed. Microfluidization function provided Duration as short as a fraction of a second high shear rate, and not lead to proteins such as hCG becomes Sex. Primary suspension was then filtered, such as the use 5μm hydrophilic polyoxyethylene polyvinylidene difluoride Matter filter (Duropore, Millipore Corporation). HCG can before the emulsification solution Adding albumin, is added about 1-5g%, preferably about 2-3g%, thereby helping to stabilize Multiple emulsion size distribution. In mineral oil or the oil solidified hCG in the initial aqueous suspension suitable The liquid preparation of the present invention together more suspension should also yield primary floating liquid droplet diameter of less than 5 μm, preferably less than 3μm. ...

Preparation of the 50% v / v and 0.25% of the brine phase outer copolymer P123 oily-water-in-water Multiple emulsion. A water phase dispersed in the oil remaining 50% v / v from 72% salt solution, 18% Angle Squalene, 2% Span80 and L310 and a concentration of 32mg 0.5mg/0.5mL copolymer emulsion The TNP-HEA components. Latex emulsion containing 1mg/0.5mL hCG. This oil-in-water emulsion Liquid under the microscope is shown as the diameter of the particles of 1.0-20μm. This composition is also suitable for Other oil-in-water emulsifier is SF1328, Arlacel P135, DC3225C, DC5200, Abil EM-90 and Abil WE-09. The person skilled in the art realize that a number of other oil Water emulsifiers can replace the name of the components listed above.

Example 6

According to the basic method known in the art for preparing liposomes containing hCG (see, for example U.S. Patent NO6110492). You can apply the following ingredients: DLPC dilauroylphosphatidylcholine phosphatidylcholine Base, DMPC dimyristoyl phosphatidyl choline, DPPC dipalmitoyl phosphatidyl choline, DSPC Distearoyl phosphatidyl choline, DOPC dioleoyl phosphatidyl choline, DLnPc bis linoleic acid Phosphatidyl choline, DMPG dimyristoyl phosphatidylglycerol, CHOL cholesterol, LA fat A. In a typical preparation, multilamellar liposomes by the DMPC: DMPG: CHOL: LA in Mount A mixture molar ratio of 9:1:7.5:0.011 made. Lipid A as an adjuvant in which you are. In Pear Flask from the chloroform solution of the lipid mixture in a vacuum state, and about 40 ℃, rotary evaporation into Lord of the thin layer. In order to ensure the organic solvent completely removed, and at room temperature in the flask Desiccator overnight low vacuum (about 0.5mmHg column) dry. After drained by rotating small Heart wing make lipid in deionized sterile pyrogen-free water swelling. Use Virtis Unitop 800SL Freeze Mobile The resulting suspension was frozen at -55 ℃, then overnight at -20 ℃ Lyophilized day maintained at 0-10 ℃. Then the material, i.e. the presence of hCG, frozen Dry lipids were reconstituted with cystic, thereby to obtain multilamellar liposomes containing the hCG. Use Reconstituted to a suitable buffer is phosphate buffered saline (PBS) or Tris-glycine / NaCl buffer Fluid. The reconstituted liposome buffer phospholipid concentration is 10-200mM. With 0.15M NaCl solution at 10 ℃ liposomes with 27000xg washed three times, each time for 10 minutes, can not be removed Pack into liposome vesicles of hCG. In order to make a final phospholipid concentration of 10-200mM, will be Liposomes suspended in 0.15M NaCl solution or another suitable isotonic buffer. This In addition, elution step can be omitted, so that is not packed into liposomes or liposome package into the presence of hCG were Formulations. ...

According to the basic method known in the art for preparing liposomes containing hCG (see, for example U.S. Patent NO6110492). You can apply the following ingredients: DLPC dilauroylphosphatidylcholine phosphatidylcholine Base, DMPC dimyristoyl phosphatidyl choline, DPPC dipalmitoyl phosphatidyl choline, DSPC Distearoyl phosphatidyl choline, DOPC dioleoyl phosphatidyl choline, DLnPc bis linoleic acid Phosphatidyl choline, DMPG dimyristoyl phosphatidylglycerol, CHOL cholesterol, LA fat A. In a typical preparation, multilamellar liposomes by the DMPC: DMPG: CHOL: LA in Mount A mixture molar ratio of 9:1:7.5:0.011 made. Lipid A as an adjuvant in which you are. In Pear Flask from the chloroform solution of the lipid mixture in a vacuum state, and about 40 ℃, rotary evaporation into Lord of the thin layer. In order to ensure the organic solvent completely removed, and at room temperature in the flask Desiccator overnight low vacuum (about 0.5mmHg column) dry. After drained by rotating small Heart wing make lipid in deionized sterile pyrogen-free water swelling. Use Virtis Unitop 800SL Freeze Mobile The resulting suspension was frozen at -55 ℃, then overnight at -20 ℃ Lyophilized day maintained at 0-10 ℃. Then the material, i.e. the presence of hCG, frozen Dry lipids were reconstituted with cystic, thereby to obtain multilamellar liposomes containing the hCG. Use Reconstituted to a suitable buffer is phosphate buffered saline (PBS) or Tris-glycine / NaCl buffer Fluid. The reconstituted liposome buffer phospholipid concentration is 10-200mM. With 0.15M NaCl solution at 10 ℃ liposomes with 27000xg washed three times, each time for 10 minutes, can not be removed Pack into liposome vesicles of hCG. In order to make a final phospholipid concentration of 10-200mM, will be Liposomes suspended in 0.15M NaCl solution or another suitable isotonic buffer. This In addition, elution step can be omitted, so that is not packed into liposomes or liposome package into the presence of hCG were Formulations. ...

This embodiment may be coupled to the MDP on hCG. This process requires a thiol The first compound to quench the reaction. This reaction is 2 - (N-morpholino) ethanesulfonic acid (MES) (pH4.5-5.0) Carried out. Lyophilized from water MDP (10mg) resuspended in MES (0.5mL) (pH4.5-5.0), the And dissolved in MES (pH4.5-5.0) in EDC (0.5mg, or about 2mM) together, And reacted at room temperature for 15 minutes. Of 2 - mercaptoethanol (final concentration 20mM) to quench EDC, and separated by centrifugation. The reaction mixture was washed once with MES, and then resuspended In 0.5mL of MES (pH4.5-5.0) in. HCG dissolved in MES was added to the activated MDP, the molar ratio of about 2:1. Adding MES (0.5M, pH8.5), the pH of the reaction at 15 Slowly increased to 8.5 minutes, and reacted at room temperature for 2 hours. Join the MDP hCG Concentration of the terminal carboxyl group by the MDP to calculate quantitative analysis, and is expressed as mol / mg MDP. Added to a final concentration of 10mM hydroxylamine can quench the reaction. The method of quenching May be hydrolyzed MDP any unreacted active sites, leading to regeneration of the original carboxyl group. Other Quenching method involves adding 20-50mM of Tris, lysine, glycine, or ethanolamine. In addition to hCG, the other biological response modifiers such as IL2 to the skilled in the art are public Well known, can also be used for this purpose. By centrifugation, and the choice of elution buffer Separation can be achieved resuspended. ...

This embodiment may be coupled to the MDP on hCG. This process requires a thiol The first compound to quench the reaction. This reaction is 2 - (N-morpholino) ethanesulfonic acid (MES) (pH4.5-5.0) Carried out. Lyophilized from water MDP (10mg) resuspended in MES (0.5mL) (pH4.5-5.0), the And dissolved in MES (pH4.5-5.0) in EDC (0.5mg, or about 2mM) together, And reacted at room temperature for 15 minutes. Of 2 - mercaptoethanol (final concentration 20mM) to quench EDC, and separated by centrifugation. The reaction mixture was washed once with MES, and then resuspended In 0.5mL of MES (pH4.5-5.0) in. HCG dissolved in MES was added to the activated MDP, the molar ratio of about 2:1. Adding MES (0.5M, pH8.5), the pH of the reaction at 15 Slowly increased to 8.5 minutes, and reacted at room temperature for 2 hours. Join the MDP hCG Concentration of the terminal carboxyl group by the MDP to calculate quantitative analysis, and is expressed as mol / mg MDP. Added to a final concentration of 10mM hydroxylamine can quench the reaction. The method of quenching May be hydrolyzed MDP any unreacted active sites, leading to regeneration of the original carboxyl group. Other Quenching method involves adding 20-50mM of Tris, lysine, glycine, or ethanolamine. In addition to hCG, the other biological response modifiers such as IL2 to the skilled in the art are public Well known, can also be used for this purpose. By centrifugation, and the choice of elution buffer Separation can be achieved resuspended. ...

The composition of the present invention, the emulsion can also be used in the local administration, and can pierce the skin. A Typical composition for topical application comprising the following substances: 2% glycerol stearate, sorbitan oil Esters (sorbitan fat 481), 6% polyethoxylated fatty acids (fat sorbitan 989), 15% oleic acid decyl (dioctyl carbonate), 8% of branched paraffins (alkanes sixteen isomers), 1% of the micro- Crystalline wax, 1% of MDP, 4% glycerol, 0.7% of magnesium sulfate heptahydrate, 0.2% of sorbic acid Sodium salt, 1% of hCG, 0.1% diammonium hydrogen citrate, citric acid (adjusted to pH 4-5), plus Into deionized water to 100%.

Example 9

In the 30 days before the study began, according to Western blot proof of HIV infection of the blood Clear diagnosis, AIDS definition criteria, clinical symptoms and CD4 lymphocyte counts less than 300 fine Cells / μL, will be over 18 years of age for men and women are not pregnant elected. Clinical and basic Test parameters are used to evaluate performance. Clinical parameters including opportunistic infections changes changes in body weight Of gastrointestinal function changes, including stool consistency and frequency, the energy level changes, appetite Changes, changes in physical strength and endurance, and overall quality of life changes. Experimental parameters bag CD4 and CD8 lymphocytes, including changes in the number, selective hematology, blood chemistry and urine Analysis, and if it can be obtained, but also changes in viral load, which can be amplified by PCR To detect viral RNA. ...

The results show that, according to the spirit of the invention, by administering hCG preparations, HIV Positive patients in clinical improvement, reducing opportunistic infections, weight gain, gastrointestinal function has been Changes, including severe diarrhea decreased energy levels increase, increased appetite, increased libido, Improved physical strength and endurance, as well as an overall improvement in the quality of life. Experimental parameters are improved, Increase the number of CD4 and CD8 lymphocytes, hematology, blood chemistry and urinalysis parameters Have improved, in addition, by PCR detection of viral RNA, viral load drop found, and By TCID testing, found that infectious decline. HCG preparation administered, will produce some small Adverse reaction, only a small fever, chills, headache and muscle pain. ...

The results show that, according to the spirit of the invention, by administering hCG preparations, HIV Positive patients in clinical improvement, reducing opportunistic infections, weight gain, gastrointestinal function has been Changes, including severe diarrhea decreased energy levels increase, increased appetite, increased libido, Improved physical strength and endurance, as well as an overall improvement in the quality of life. Experimental parameters are improved, Increase the number of CD4 and CD8 lymphocytes, hematology, blood chemistry and urinalysis parameters Have improved, in addition, by PCR detection of viral RNA, viral load drop found, and By TCID testing, found that infectious decline. HCG preparation administered, will produce some small Adverse reaction, only a small fever, chills, headache and muscle pain. ...

Background with C3H (H2k / k, Harlan Sprague Dawley) female mice can be used for These studies. According to "Care and Use of Laboratory Animals Guide" (Guide for the care and use of laboratory animals) (DHHS, NIH) raising animals, and free to take food and water. HOPE2 tumor cell lines in vitro is maintained by continuous passage. In vitro by subcutaneous injection Shot 150000 Channel homologous C3H cells start tumors in mice. Cancer every two weeks through two Detecting the vertical direction species. Each treatment group and a control group did not receive treatment progress Are compared. Treatment in HOPE2 10 days after cell inoculation, then, most tumors are Palpable (about 50-75mm³). By injecting mice with soluble hCG initial treatment (By subcutaneous injection, total volume of 0.2mL), and hCG protein mixture or alum MDP Adjuvant. Before inoculation, hCG and MDP in Hanks' balanced salt solution were mixed for 60 seconds to Each mouse received the same amount and human hCG, i.e. in 0.2mL of 2000 or 5000IU hCG proteins. According to the manufacturer's instructions alum (Pierce Chemical Company) and hCG Mixed order can be accepted in 0.2mL per mouse in 5000IU equal hCG. In this Embodiment, after tumor cell inoculation 41 days only 5/8 or 4/8 for a single injection of soluble Of hCG (or respectively 2000IU 5000IU) mice shows detectable tumors. By comparison , All the alum injected with hCG in mice (8/8) showed active growth of the tumor. Furthermore, And the control (untreated) or Alum treatment groups compared with the hCG injection only at the MDP Management group was observed in tumor growth was significantly inhibited. While receiving a single injection of hCG alum In mice without tumor growth inhibition or tumor regression rate increases. ...

Accordingly, the present invention is characterized in that the dimer containing hCG and muramyl peptide pharmaceutical formulation. Further, the present invention can be characterized as a treatment composition comprises: (a) a therapeutically effective amount of Dimer bound to liposomes hCG; and (b) surrounding said liposomes containing oil-in-oil Water emulsion, relative to hCG and liposomes in the emulsion does not exist, the milk Sufficient to increase the number of fluid therapy. Furthermore, the present invention provides a method of treating required The subjects in their HIV infection, comprising administering to said subjects an effective amount of hCG, the hCG and the oil-in-water emulsion administered together, in respect of the said hCG Emulsion does not exist, the emulsion present in an amount sufficient to increase the clinical response. The present invention also Provides a method of treating cancer in subjects in need thereof, which comprises applying to said subjects With an effective amount of hCG, the hCG and the oil-in-water emulsion administered together, and with respect to The hCG is not present in the emulsion in the case of the emulsion in an amount sufficient to increase the clinical anti- Should. The present invention further provides a therapeutic composition comprising an oil-in-water Emulsion having a continuous aqueous phase and a discontinuous oil phase, and contains at least 0.01% Weight dimer hCG. The present invention also provides a method for the preparation of pharmaceutical preparations, the Said method including the supply and mixing of the aqueous suspension containing hCG and at least one oil component and at least An emulsifier, a sufficiently large number of them, so as to provide for the preparation of oil-in-water Emulsion. The present invention further provides a therapeutic composition comprising an oil-in-water Emulsion and at least one water-soluble natural or recombinant bioactive protein and optionally at least one Package wall acid peptide. The present invention also provides a kit for use in pharmaceutical compositions prepared in situ, The kit comprises: 1) a first vessel containing an emulsion, wherein said emulsion package Including: squalane or squalene, sorbitan esters and an aqueous solution, and 2) a second container Comprising a therapeutically effective amount of the dimer hCG, it exists in aqueous solution or in powder form deposits In which the concentration of components in each container is selected so that the two components in the container Combination will produce a preparation which contains said sorbitan ester in an amount of 1-30%, squalane Alkyl, or the amount of squalene 1-30%, the amount of muramyl peptides of 0.0001-30%, and the hCG An amount of 0.01-99%. ...

Accordingly, the present invention is characterized in that the dimer containing hCG and muramyl peptide pharmaceutical formulation. Further, the present invention can be characterized as a treatment composition comprises: (a) a therapeutically effective amount of Dimer bound to liposomes hCG; and (b) surrounding said liposomes containing oil-in-oil Water emulsion, relative to hCG and liposomes in the emulsion does not exist, the milk Sufficient to increase the number of fluid therapy. Furthermore, the present invention provides a method of treating required The subjects in their HIV infection, comprising administering to said subjects an effective amount of hCG, the hCG and the oil-in-water emulsion administered together, in respect of the said hCG Emulsion does not exist, the emulsion present in an amount sufficient to increase the clinical response. The present invention also Provides a method of treating cancer in subjects in need thereof, which comprises applying to said subjects With an effective amount of hCG, the hCG and the oil-in-water emulsion administered together, and with respect to The hCG is not present in the emulsion in the case of the emulsion in an amount sufficient to increase the clinical anti- Should. The present invention further provides a therapeutic composition comprising an oil-in-water Emulsion having a continuous aqueous phase and a discontinuous oil phase, and contains at least 0.01% Weight dimer hCG. The present invention also provides a method for the preparation of pharmaceutical preparations, the Said method including the supply and mixing of the aqueous suspension containing hCG and at least one oil component and at least An emulsifier, a sufficiently large number of them, so as to provide for the preparation of oil-in-water Emulsion. The present invention further provides a therapeutic composition comprising an oil-in-water Emulsion and at least one water-soluble natural or recombinant bioactive protein and optionally at least one Package wall acid peptide. The present invention also provides a kit for use in pharmaceutical compositions prepared in situ, The kit comprises: 1) a first vessel containing an emulsion, wherein said emulsion package Including: squalane or squalene, sorbitan esters and an aqueous solution, and 2) a second container Comprising a therapeutically effective amount of the dimer hCG, it exists in aqueous solution or in powder form deposits In which the concentration of components in each container is selected so that the two components in the container Combination will produce a preparation which contains said sorbitan ester in an amount of 1-30%, squalane Alkyl, or the amount of squalene 1-30%, the amount of muramyl peptides of 0.0001-30%, and the hCG An amount of 0.01-99%. ...

Claims (33)

1 comprising dimer hCG and muramyl peptide pharmaceutical formulation.

(2) as claimed in claim 1, wherein the composition further comprises an emulsifier.

3 according to claim 2, wherein the composition further comprises a surfactant Agent.

As claimed in claim 3, wherein the composition further comprises an oil.

5 according to claim 1, wherein the composition comprises at least 0.01% by weight of dimeric Body hCG.

6 A therapeutic composition comprising: (a) a therapeutically effective amount of a combination of liposomes Dimer hCG; and (b) surrounding said liposomes contain oil emulsion oil in water, as opposed to hCG and liposomes does not exist in the case of the emulsion, the emulsion present in an amount sufficient to increase Plus therapeutic response.

As claimed in claim 6, wherein the composition, wherein said oil is squalene.

As claimed in claim 6, wherein the composition, wherein said hCG containing at least 0.1% Volume of the oil.

(10) according to claim 6, wherein the composition, wherein said composition further comprises One of the other emulsifiers.

(10) according to claim 6, wherein the composition, wherein said composition further comprises One of the other emulsifiers....

(10) according to claim 6, wherein the composition, wherein said composition further comprises One of the other emulsifiers....

12 according to claim 11, wherein the composition, wherein said adjuvant is selected from N-acetyl- Glucosaminyl-N-acetyl - muramyl-L-alanyl-D-iso-glutamine (GMDP), N-acetylglucosamine Sugar amine (β-1, 4)-N-acetyl - muramyl-L-alanyl-D-iso-glutamine, N-acetyl glucosamine Amino-N-acetyl - muramyl-L-alanyl-D-glutamic acid (GMDP-A), muramyl dipeptide phospholipid Acyl ethanolamine, muramyl tripeptide phosphatidyl ethanolamine, muramyl tripeptide phosphatidyl ethanolamine, CGP11637 (demethyl-MDP), α (N-acetyl - muramyl-L-alanyl-D-iso-glutamine), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-D-alanyl-D-isoglutaminyl Amines), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-L-alanyl-D-isoglutaminyl Amide group-L-alanine), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-D-C Glycyl-D-iso-glutamine yl-L-alanine), β, γ-dipalmitoyl-sn-glycerol, N-acetylmuramic Wall acyl-L-alanyl-D-iso-glutamine yl-L-alanine -2 - (1,2 - dipalmitoyl-sn-glycero-3 - Hydroxyapatite acyloxy) acetamide, glucosaminyl muramyl peptides, murametide, murabutide, muradimetide, myramistin, N-acetyl-muramyl-L-threonyl-D-iso-glutamine, N-acetyl-muramyl-L-α-amino-butyl-D-iso-glutamine ,6-O-stearoyl-N-acetyl-muramyl Acyl-L-α-amino-iso-butyl-D-glutamine, N-acetyl-muramyl-L-valyl-D-isoglutaminyl Acrylamide, N-acetyl-muramyl-L-alanyl-D-iso-glutamine, N-acetyl - demethyl muramyl -L-alanyl-D-iso-glutamine, N-acetyl-muramyl-L-alanyl-D-glutamine butyl Ester, N-acetyl-muramyl-L-seryl-D-iso-glutamine, N-butyl-muramyl-L-α-amino- Iso-butyl-D-glutamine, N-acetyl-muramyl-L-threonyl-D-iso-glutamine, bis (6-O- Muramyl dipeptide) O-palmitoyl alcohol acid, muramyl tripeptide phosphatidyl ethanolamine, N-acetyl- Muramyl-L-alanyl-D-iso glutaminyl-L-alanine -2 - (1,2 - dipalmitoyl-sn-glycerol - 3 - (hydroxy-phosphoryloxy)) acetamide, N-acetyl-muramyl-L-alanyl-D-glutamine butyl ester, N-acetyl-muramyl-L-alanyl-D-iso glutaminyl-L-alanine -2-1,2 - dipalmitoyl-sn- Glycerol-3 - (hydroxy-phosphoryl) ethyl amide (MTP-PE), cholesterol group-MDP, N-acetyl-muramyl Acyl-L-alanyl-D-iso-glutamine butyl β-glucosidase 2 - acetamido-4, 6 - di-O-acetyl- - 2 - deoxy-3-O-[(R) -1 - (methoxycarbonyl) ethyl]-α-D-glucopyranose, (β-Butyl - MDP, MTPO-26, β-cholesteryl-MDP), saponin (Taurosid I), N-acetyl-demethyl Muramyl-LN-methyl-propionyl-D-iso-glutamine octanamide, UDP-N-acetyl-muramyl five Peptides, L4-MDP-ONB, L-alanyl-γ-D-glutamyl - in - diaminopimelic acid, 1,6 - de Water, muramyl dipeptide, N-acetyl glucosaminyl-β-1 ,4-N-acetyl muramyl pentapeptide - pyrophosphoric acid - Ten One terpene alcohol ,3-O-[acetyl-muramyl-D-iso-glutaminyl] -1,2 - dipalmitoyl-sn-glycerol, L- Threonyl-MDP-GDP, L-iso-threonyl-MDP-GDP, trehalose 6,6 - two esters, muramyl Dipeptide, B30 muramyl dipeptide and muramyl dipeptide - lysine. ...

12 according to claim 11, wherein the composition, wherein said adjuvant is selected from N-acetyl- Glucosaminyl-N-acetyl - muramyl-L-alanyl-D-iso-glutamine (GMDP), N-acetylglucosamine Sugar amine (β-1, 4)-N-acetyl - muramyl-L-alanyl-D-iso-glutamine, N-acetyl glucosamine Amino-N-acetyl - muramyl-L-alanyl-D-glutamic acid (GMDP-A), muramyl dipeptide phospholipid Acyl ethanolamine, muramyl tripeptide phosphatidyl ethanolamine, muramyl tripeptide phosphatidyl ethanolamine, CGP11637 (demethyl-MDP), α (N-acetyl - muramyl-L-alanyl-D-iso-glutamine), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-D-alanyl-D-isoglutaminyl Amines), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-L-alanyl-D-isoglutaminyl Amide group-L-alanine), β, γ-dipalmitoyl-sn-glycerol, α (N-acetyl - muramyl-D-C Glycyl-D-iso-glutamine yl-L-alanine), β, γ-dipalmitoyl-sn-glycerol, N-acetylmuramic Wall acyl-L-alanyl-D-iso-glutamine yl-L-alanine -2 - (1,2 - dipalmitoyl-sn-glycero-3 - Hydroxyapatite acyloxy) acetamide, glucosaminyl muramyl peptides, murametide, murabutide, muradimetide, myramistin, N-acetyl-muramyl-L-threonyl-D-iso-glutamine, N-acetyl-muramyl-L-α-amino-butyl-D-iso-glutamine ,6-O-stearoyl-N-acetyl-muramyl Acyl-L-α-amino-iso-butyl-D-glutamine, N-acetyl-muramyl-L-valyl-D-isoglutaminyl Acrylamide, N-acetyl-muramyl-L-alanyl-D-iso-glutamine, N-acetyl - demethyl muramyl -L-alanyl-D-iso-glutamine, N-acetyl-muramyl-L-alanyl-D-glutamine butyl Ester, N-acetyl-muramyl-L-seryl-D-iso-glutamine, N-butyl-muramyl-L-α-amino- Iso-butyl-D-glutamine, N-acetyl-muramyl-L-threonyl-D-iso-glutamine, bis (6-O- Muramyl dipeptide) O-palmitoyl alcohol acid, muramyl tripeptide phosphatidyl ethanolamine, N-acetyl- Muramyl-L-alanyl-D-iso glutaminyl-L-alanine -2 - (1,2 - dipalmitoyl-sn-glycerol - 3 - (hydroxy-phosphoryloxy)) acetamide, N-acetyl-muramyl-L-alanyl-D-glutamine butyl ester, N-acetyl-muramyl-L-alanyl-D-iso glutaminyl-L-alanine -2-1,2 - dipalmitoyl-sn- Glycerol-3 - (hydroxy-phosphoryl) ethyl amide (MTP-PE), cholesterol group-MDP, N-acetyl-muramyl Acyl-L-alanyl-D-iso-glutamine butyl β-glucosidase 2 - acetamido-4, 6 - di-O-acetyl- - 2 - deoxy-3-O-[(R) -1 - (methoxycarbonyl) ethyl]-α-D-glucopyranose, (β-Butyl - MDP, MTPO-26, β-cholesteryl-MDP), saponin (Taurosid I), N-acetyl-demethyl Muramyl-LN-methyl-propionyl-D-iso-glutamine octanamide, UDP-N-acetyl-muramyl five Peptides, L4-MDP-ONB, L-alanyl-γ-D-glutamyl - in - diaminopimelic acid, 1,6 - de Water, muramyl dipeptide, N-acetyl glucosaminyl-β-1 ,4-N-acetyl muramyl pentapeptide - pyrophosphoric acid - Ten One terpene alcohol ,3-O-[acetyl-muramyl-D-iso-glutaminyl] -1,2 - dipalmitoyl-sn-glycerol, L- Threonyl-MDP-GDP, L-iso-threonyl-MDP-GDP, trehalose 6,6 - two esters, muramyl Dipeptide, B30 muramyl dipeptide and muramyl dipeptide - lysine. ...

14 as claimed in claim 13, wherein said emulsion further comprises Effective amount of a muramyl peptide of subjects administered amount 1-500μg/kg weight.

15 as claimed in claim 13, wherein said liposome Results hCG and Together and able to offer.

16 A method for treating subjects in need thereof of cancer, comprising administering to said subjects Administering an effective amount of hCG, hCG, and the emulsion of oil in water with the application, and the relative In the absence of hCG in the case of the emulsion, the emulsion present in an amount sufficient to increase Pro Bed reactor.

16 A method for treating subjects in need thereof of cancer, comprising administering to said subjects Administering an effective amount of hCG, hCG, and the emulsion of oil in water with the application, and the relative In the absence of hCG in the case of the emulsion, the emulsion present in an amount sufficient to increase Pro Bed reactor....

16 A method for treating subjects in need thereof of cancer, comprising administering to said subjects Administering an effective amount of hCG, hCG, and the emulsion of oil in water with the application, and the relative In the absence of hCG in the case of the emulsion, the emulsion present in an amount sufficient to increase Pro Bed reactor....

19 as claimed in claim 16, wherein said hCG can be static Pulse, intraperitoneal, intrathecal, intramuscular, subcutaneous, intradermal, sublingual, oral, intranasal, intraocular Or topically. ...

19 as claimed in claim 16, wherein said hCG can be static Pulse, intraperitoneal, intrathecal, intramuscular, subcutaneous, intradermal, sublingual, oral, intranasal, intraocular Or topically. ...

21 according to claim 20, wherein the composition, further comprising a therapeutically effective amount of The muramyl peptides.

22 according to the composition of claim 20, wherein said oil phase comprises mineral oil, Squalene, peanut oil, vegetable oil or silicone oil.

23 according to the composition of claim 20, wherein said emulsion comprising surface Surfactant, said surfactant is selected from sorbitan esters, polyoxyethylene sorbitan mono-, di Or tri-esters, polyoxyethylene fatty acids, polyoxyethylene fatty acid ethers, and combinations of these materials.

A process according to claim 23, wherein the composition, wherein said surfactant package Include polysorbates ("Tween", or sorbitan monooleate), sodium dodecyl sulfate (SDS), Polyethoxylated castor oil ("CREMOPHOR"), NP-40, bromide dimethyl dioctadecyl Ammonium (DDA), linear polyoxypropylene polyoxyethylene (POP-POE) block polymers, parked Luo Shamrock 401, Pu stream Ronnie L62LF, general stream Ronnie L101, general stream Ronnie L64, PEG1000, 1501 Johnny special, special Johnny 150R1, especially Johnny 701, special Johnny 901, special Johnny 1301, Atmos 300, Tween 20, Tween 40, Tween 60, Tween 80, and special Johnny 130R1, Sorbitan esters A, sorbitan esters Span 80 and 80, or mannide monooleate. ...

A process according to claim 23, wherein the composition, wherein said surfactant package Include polysorbates ("Tween", or sorbitan monooleate), sodium dodecyl sulfate (SDS), Polyethoxylated castor oil ("CREMOPHOR"), NP-40, bromide dimethyl dioctadecyl Ammonium (DDA), linear polyoxypropylene polyoxyethylene (POP-POE) block polymers, parked Luo Shamrock 401, Pu stream Ronnie L62LF, general stream Ronnie L101, general stream Ronnie L64, PEG1000, 1501 Johnny special, special Johnny 150R1, especially Johnny 701, special Johnny 901, special Johnny 1301, Atmos 300, Tween 20, Tween 40, Tween 60, Tween 80, and special Johnny 130R1, Sorbitan esters A, sorbitan esters Span 80 and 80, or mannide monooleate. ...

26 A process for preparing a pharmaceutical preparation, said method comprising the supply and with a mixture of hCG And an aqueous suspension of at least one oil component and at least one emulsifier, in an amount sufficient to give the Said formulation provides oil in water emulsions.

27 according to the method of claim 26, further comprising a therapeutically effective amount of the The muramyl peptide added to the oil in water emulsion.

27 according to the method of claim 26, further comprising a therapeutically effective amount of the The muramyl peptide added to the oil in water emulsion....

29. According to claim 28, wherein the therapeutic composition, wherein said bioactive The protein is selected somatotropin, human growth hormone (HGH), bovine growth hormone (BGH or BST), Porcine somatotropin (PGH or PST), epidermal growth factor (FGF), α interferon, α-2a interference Su, α-2b interferon, α-N1 interferon, α-N3 interferon, β interferon, β-1 a1 interference Su; β-1b interferon, γ-1a interferon, γ-1b interferon, ω interferon, τ interferon, Interleukin-1, interleukin-1α, IL-1β, IL-10, white Interleukin-11, interleukin-12, interleukin-12, interleukin 15, white fine Cell interleukin-2, interleukin -3, interleukin-4, interleukin-5, interleukin -7, Interleukin-8, erythropoietin (EPO), parathyroid hormone (PTH), including Selenium protein P, cystatin B, endotoxin neutralizing protein, megakaryocyte Stimulating factor (MGDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), cytokines Sub synthesis inhibitory factor (CSIF), genofibrate, α calcitonin, β calcitonin, tumor necrosis Factor (TNF), lymphocyte migration inhibition factor (LIF), tumor invasion inhibiting factors, anti-make A regulatory protein (TAT's), protease inhibitors, BPC 157, lowering hormone, insulin, Glucagon, gastrin, angiotensin, secretin hormone, prolactin, thyroid-stimulating hormone, Melanocyte-stimulating hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), blood Small plate erythropoietin (TPO), luteinizing hormone generation, human menopausal gonadotropin, vascular Vasopressin, oxytocin, protirelin, adrenocorticotropic hormone, SOD, urokinase, dissolved Lysozyme, G-CSF, M-CSF, LIF, inhibin A, inhibin B, activin A, activation Su B, NAP-1, MCP-1, MIP-1α, MIP-1β, MIP-2, SISβ, SISδ, SIS ε, PF4, PBP, γIP-10, MGSA, aFGF, bFGF, KJF, PDGF-A, PDGF-B, PD-ECGF, INS, IGF-I, IGF-II, NGF-β, GRO / MGSA, PF4, PBP / CTAP / βTG, IP-10, KC, 9E3, MCP-1/MCAF, MCAF, ACT-2/PAT 744/G26, LD-78/PAT 464, RANTES, G26, I309, JE, TCA3, B7.1, B7.2, ICAM-1, ICAM-2, LFA-1, LFA-3, CD72, CTAPIII, ENA-78, GRO, I-309, PF-4, LD-78, eosinophil-derived neurotoxin (EDN), Antineoplastic urinary protein (ANUP), ribonuclease and angiostatin and their analogs and variants Body. ...

29. According to claim 28, wherein the therapeutic composition, wherein said bioactive The protein is selected somatotropin, human growth hormone (HGH), bovine growth hormone (BGH or BST), Porcine somatotropin (PGH or PST), epidermal growth factor (FGF), α interferon, α-2a interference Su, α-2b interferon, α-N1 interferon, α-N3 interferon, β interferon, β-1 a1 interference Su; β-1b interferon, γ-1a interferon, γ-1b interferon, ω interferon, τ interferon, Interleukin-1, interleukin-1α, IL-1β, IL-10, white Interleukin-11, interleukin-12, interleukin-12, interleukin 15, white fine Cell interleukin-2, interleukin -3, interleukin-4, interleukin-5, interleukin -7, Interleukin-8, erythropoietin (EPO), parathyroid hormone (PTH), including Selenium protein P, cystatin B, endotoxin neutralizing protein, megakaryocyte Stimulating factor (MGDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), cytokines Sub synthesis inhibitory factor (CSIF), genofibrate, α calcitonin, β calcitonin, tumor necrosis Factor (TNF), lymphocyte migration inhibition factor (LIF), tumor invasion inhibiting factors, anti-make A regulatory protein (TAT's), protease inhibitors, BPC 157, lowering hormone, insulin, Glucagon, gastrin, angiotensin, secretin hormone, prolactin, thyroid-stimulating hormone, Melanocyte-stimulating hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), blood Small plate erythropoietin (TPO), luteinizing hormone generation, human menopausal gonadotropin, vascular Vasopressin, oxytocin, protirelin, adrenocorticotropic hormone, SOD, urokinase, dissolved Lysozyme, G-CSF, M-CSF, LIF, inhibin A, inhibin B, activin A, activation Su B, NAP-1, MCP-1, MIP-1α, MIP-1β, MIP-2, SISβ, SISδ, SIS ε, PF4, PBP, γIP-10, MGSA, aFGF, bFGF, KJF, PDGF-A, PDGF-B, PD-ECGF, INS, IGF-I, IGF-II, NGF-β, GRO / MGSA, PF4, PBP / CTAP / βTG, IP-10, KC, 9E3, MCP-1/MCAF, MCAF, ACT-2/PAT 744/G26, LD-78/PAT 464, RANTES, G26, I309, JE, TCA3, B7.1, B7.2, ICAM-1, ICAM-2, LFA-1, LFA-3, CD72, CTAPIII, ENA-78, GRO, I-309, PF-4, LD-78, eosinophil-derived neurotoxin (EDN), Antineoplastic urinary protein (ANUP), ribonuclease and angiostatin and their analogs and variants Body. ...

31 A process for preparing a pharmaceutical composition field kit reagents described PACKER Comprising: 1) a first vessel containing an emulsion wherein the emulsion comprises: squalane or corner Squalene, sorbitan ester and an aqueous solution, and 2) a second container comprising a therapeutically effective The amount of dimer hCG, it is an aqueous solution or powder form, wherein each container Component concentration is selected so that the combination of two components of the container will produce a formulation It contains the amount of sorbitan ester is 1-30%, squalane or squalene in an amount of 1 - 30% of the muramyl peptide in an amount of 0.0001-30%, and hCG in an amount of 0.01-99%. ...

31 A process for preparing a pharmaceutical composition field kit reagents described PACKER Comprising: 1) a first vessel containing an emulsion wherein the emulsion comprises: squalane or corner Squalene, sorbitan ester and an aqueous solution, and 2) a second container comprising a therapeutically effective The amount of dimer hCG, it is an aqueous solution or powder form, wherein each container Component concentration is selected so that the combination of two components of the container will produce a formulation It contains the amount of sorbitan ester is 1-30%, squalane or squalene in an amount of 1 - 30% of the muramyl peptide in an amount of 0.0001-30%, and hCG in an amount of 0.01-99%. ...

33 to claim 31, wherein the kit further comprises a therapeutically effective amount of cells Acyl peptides wall, sealing it in a separate container.