CN1704120A - Compound biological product conposition and preparation method thereof - Google Patents

Abstract

The object of the invention is to (1) firstly propose that effective joint of a special animalcule and a suffering body is realized by using body fluids (such as blood), secretion (such as latex), excrement (such as dejecta and stale) of suffering peoples or animals as animalcule resources for preparing a composite biologic preparation; (2) select and combine composite bacterins from selves which are suitable for a composite biologic preparation moden technic, compresses a desired time for preparing the composite biologic preparation, can be used by emergency sufferers in several hours; (3) propose a standpoint that human health begins from animals, plants and diet by perparing the composite biologic preparation as a moden preparation, an animal product and a plant product, make the pepoples be glad to accept the composite biologic preparation; by means of a macroscopical idea for a composite biologic preparation of the ancients without excluding a current biologic gene project. Thereby a composite biologic preparation composition capable of dealing with animalcule aberrance, increasing or adjusting immunity of peoples and animals all things considered, and a preparing method thereof, are provided to society, so as to further increase cure success rate and prevention success rate of diseases related to contagion and immunity.

Description

Compound biological product conposition and preparation method thereof

Technical field:

The present invention relates to biological product conposition and preparation technology thereof, belong to medical technical field.

Technical background:

Antibiotic discovery had once brought greatest hope to people, thought from then on to have welcome the New Times human and the disease fight by all Guaranteed people of all infectious disease.But good times don't last long, because symbiotic sensitive organism has been killed in antibiotic a large amount of uses, suppressed the intravital biological antagonist effect of micropopulation, makes fastbacteria be able to abnormality proliferation.This drug resistance can propagated between antibacterial, send out in worldwide again simultaneously, thereby the infection of multiple antibiotic resistant strain causes being reported in gradually of death to be increased.1992 the Center for Disease Control (CDC) data show that 13300 routine inpatients are arranged, be because to employed antibacterials drug resistance, bacterial infection can not get control and dead.

In addition, antibacterials can only optionally act on the particular attack target position of antibacterial, kill or suppress growth, the breeding of antibacterial.If pathogenic microorganism lacks above-mentioned target position, as virus, the endotoxin that antibacterial produced, extracellular toxin and thalline cell wall product etc., it is invalid adopting antibacterial drug therapy; Started and many inflammatory mediators of producing equally do not have a bit therapeutical effect with antibacterial drug therapy yet by materials such as endotoxins.Well imagine that it is irrelevant that severe infections but fails to save the not talkative and above-mentioned mechanism of its reason of patient's life through the responsive antibacterial drug therapy of excess dosage.Therefore, the overall immune ability that then needs biological product, needs to improve or regulate human body and animal.

The application on biological product of biological preparation and genetic engineering brings new bigger hope to people once more.But it is the most alarming with at present this very strong " science "---biological product of subjective will single, pure and pure, that lag behind, the people, come to control can according to varying environment fast changing, how drug-fast, the antibacterial of multiway cross or disease or the epidemic situation that virus is caused, probably be extremely difficult, remain the proof already kaput old road that antibiotic has been passed by with I'm afraid away.

The bright spot of prior art ... the compound recipe administration:

More and more accepted at present by people based on the mechanism of both synergetic immunity of antibacterial immunity.After laboratory animal was with lipopolysaccharide (LPS) vaccine immunization, the tolerance that viable bacteria is attacked had growth more than 4 times, then had more than 13 times during with the cholera toxin immunity to increase.As with the The combined immunity, its tolerance that viable bacteria is attacked then can reach more than 100 times.Peterson (1979) also has similar report, is 10 as list with its protection index of toxoid immunity, and single is 32 with vaccine immunization protection index.And both mix use, and its protection index is up to 1634, and is apparent, and above-mentioned result all is the result who has antibiotic and antitoxin two kinds of effects associating concurrently.(Wang Yishou, " medical bio goods " P172, in July, 1992 Zhejiang science tech publishing house)

U.S. Energy ' s Brookhaven National Laboratory has found the new method that the blocking-up human adenovirus infects in three researchs to the protein kinase of adenovirus, these results of study are published in the Biochemistry of calendar year 2001 10,11, December publication, and it will be used for design and development of new antiviral protease inhibitors.

The Brookhaven laboratory is found recently, and virus is the protein kinase of synthetic non-activity at first, has only behind the protein kinase and DNA combination of non-activity, and the active of protein kinase just can partly be activated.Mangel says that the DNA active mode of this protein kinase is former never to be found.The activated protein kinase hydrolysis of part goes out a cofactor, this cofactor and protein kinase combination, thus proteinase activity is just activated fully.The complex that is made of enzyme and cofactor has protein kinase activity completely, and it moves along viral DNA, the degraded scaffolding protein.

Based on above-mentioned discovery, Mangel proposes a kind of novel antiviral method, just acts on three different loci--active center, cofactor binding site and the DNA binding site of this protein kinase respectively with three kinds of different medicines.This " triadius type " antiviral method probably solves in the antiviral therapy problem of headache the most--the medicament-resistant mutation that virus is spontaneous.Mangel explains, because these three sites are complementary, a site produces the change that medicament-resistant mutation will cause other two site physiological functions, therefore is difficult to produce drug resistance.

Mangel thinks that the adenovirus protein kinases can be used for verifying this " triadius type " antiviral effectiveness.At present, the research group of Mangel has been developed two kinds of new drugs, reversible and the protein kinase activity center combination of a kind of energy, the then irreversible and protein kinase activity center combination of another kind, these medicines are very fast will be studied as antiviral drugs by U.S. sanitary academy (NIH).(selecting from the gene tide)

Above-mentioned is the bright spot of prior art, but stand in angle of the present invention think it compound degree not enough, it just carries out limited compound treatment to adenovirus artificially.Just as current tuberculosis drug combination, the bright spot and the direction of drug combination have just been provided, yet want by three, four kind of microbial variation that limited restriction point is dealt with to change all the time, probably the advocate knows most clearly that also that can not accomplish fully, just is higher than prior art.

The a large amount of biological product of record in medical science ancient books such as Chinese Compendium of Material Medica have as curing mainly in the medicine in Compendium of Material Medica the 3rd volume all kinds of diseases and ailments:

The typhoid fever calentura cures mainly in the medicine to be had: China ink, Catharsii molossi change ball, ancient Chinese prose money, afterbirth water, Kun crotch, menstruation clothing, dandruff, wash sufficient water, swash dirt, meal sieve, wormcast, Oletum Gallus domesticus Albus, Columba livia dung, Mus dung, horse dung, sheep dung, sheep urine, people's dung, Urina Hominis, Preparatum Glycyrrhizae on foot cloth, the anvil at the bottom of snow, LIANGSHANGCHEN, the still.

Pestilence cures mainly in the medicine to be had: ancient lavatory wood, patient's clothing, Dong Bitu, Oletum Trogopterori, male Vulpes dung, bullshit.

Cholera cures mainly in the medicine to be had: raise in the lavatory, family, lavatory curtain, wooden pail for urine plate, lose wooden comb, so dirt on the numb sole, roadside straw sandals, Calyx seu fructus physalis water, Loess liquid, Dong Bitu, reversal of the natural order of things dirt, anvil, cattle saliva, black cattle urine, cattle dung, bullshit, Urina Hominis, cock excrement in vain.

Dysentery cures mainly in the medicine to be had: hakuzen soil, Chibi soil, the rotten wood in city east, event clothing silks, horse dung ash, otter dung ash, cow dung juice, sheep dung juice.

Malaria cures mainly in the medicine to be had: black earth, swallow dung, cock dung, white bullshit, black cat dung, leopard cat dung ash, wild Vulpes excrement on Faeces Vespertilionis, Bombyx Batryticatus, event calendar, event sole, rice steamer band, dandruff, Urina Hominis, the burning people field.

Jaundice cures mainly in the medicine to be had: cow dung, Lac Bovis seu Bubali, porcupine dung, woman's menstruation clothing.

Though truly have its corresponding curative effect at that time and even present said medicine, but stand in the angle of " health " and so-called " science ", people give it up above-mentioned medicine already, think witch doctor, witch's medicine, these medicines seldom record in the Chinese medicine voluminous dictionary, rarelyr can climb up the such refined taste of Pharmacopoeia of People's Republic of China.Therefore, people even the professional gradually forgotten about these medicines, even have the people to think that is the product of people's ignorant at that time.

Relevant patent with feces: U.S. Microcarb, INC the publication number of China application be CN1168693A ' be used to produce the method for the antigenic enterobacteria with raising and comprise the vaccine of this kind antibacterial '; this invention relates to and is natural in vivo residing some condition of good simulation organism of intestinal creation and component; produce with traditional cultural method and compare the intestinal that antigenicity improves, its cross protection has strain widely or serotype at antibacterial of the same race.This patent has been pointed out the deficiency of traditional vaccine preparation method, illustrates simultaneously that antibacterial that natural intestinal environment is produced and vaccine are compared with the cultivation under the traditional experiment condition to have more wild nature, more be applicable to the antibacterial that has made a variation.The weak point of this invention is: 1. this patent is separated with intestinal bacteria, and selectively single variety is cultivated, thereby has limited the immunity spectrum of its vaccine; 2. it has simulated physical environment, the chemical environment of intestinal, and has ignored the symbiotic ecological environment of of paramount importance many bacterium in the intestinal.It increases than traditional cultural method antigenicity, it's a pity that it has only simulated the profile that natural intestinal is cultivated, and is also poor one step away apart from the marrow (comprehensive immunity) of catching the cultivation of nature intestinal.

The publication number of Jinan China three strain pharmaceutcal corporation, Ltds applications be the CNl273838A ' alimentation composition that contains dead probiotic bacteria symbiotic fermentation culture medium ', to be CN1186696A ' probiotic bacteria compare in the compound degree of intestinal and go forward to go a step further improving body specific immune power and the developing application of epidemic disease (bacterium) Seedling ' with United States Patent (USP) the publication number of Inst. of Epidemiology and Microbiology, Chinese Academy of Preventive Medicine (application, but it has just selected several probiotic bacterias to be used to improve immunity in known more than 400 kinds of intestinal, its way of giving up pathogenic bacterium with probiotic bacteria is equivalent to use from untrained big good person fully removes Catching the Spy, stop thief, see it is beneficial certainly from angle qualitatively, but their achievement was scarcely as being thief's people, the people who was spy's people or was subjected to special training, also the selection thinking with the preparation conventional vaccine runs in the opposite direction.

In a word, prior art can summarize following 2 points:

1, current vaccine development both at home and abroad is gone astray at the very start!

When people's discovery antibiotic had progressively lost its in the past ring of light, the whole world was again all at the various vaccines of research like a raging fire, but the thinking of existing regrettably vaccine development when still not jumping out the development antibiotic is not suitable for the development of epidemic situation.1. its reason is that the cycle of vaccine development is oversize, must need more than 1 year at least; 2. attenuation Seedling toxicity is big and the potential danger of reversion arranged.3. pursue the pure and pure, smart and smart of vaccine, make its achievement that finds out not catch up with the development of epidemic situation forever.Its main cause and antibiotic are identical, and the composition that is vaccine is too single and mutant microbial is had an opportunity to take advantage of.For example its vaccines such as SARS, acquired immune deficiency syndrome (AIDS) and flu reason of can not large tracts of land promoting and use also is this.

2, the men of old cures the disease with combination vaccine, and is clever more than the modern!

Far away from " Handbook of Prescriptions for Emergencies " (284～363 years Christian eras), " prescriptions worth thousand gold " (659 years Christian eras), Compendium of Material Medica (1596), closely prevent and treat the record of various infectiousness, immune disease to " Chinese medicine voluminous dictionary " all useful feces of the countless classics of TCM such as (1975).Wherein in the Compendium of Material Medica with the inapparent infectious disease of feces treatment other drug curative effect of kind of animal surplus 30.This is that gene, drug resistant gene or the epitopes gene of because the virus of most of infectious diseases of human body (or animal) (or pathogen etc.) all can be by means of plasmid, transposon, phage etc., by different approaches propagate or be transferred to the micropopulation of occurring in nature and reside in throughout the year about 1.5 kilogram weights of gross weight in people (or animal) body 400 surplus among kind of the intestinal bacteria, or be stored in the there or from form, embody with the form of expression with the form of gene.Enteric microorganism be in the past disease and PMI to the record of intestinal ecology influence, its vaccineization will be obtained and disease and the corresponding comprehensive combination vaccine of PMI in the past, this just why in the folklore ' drink half bowl of this liquid respectively in spring, autumn and can not fall ill the whole year ' reach and ward off the reason of pestilence in " Song Feng says epidemic disease " with the Preparatum Glycyrrhizae.This also be why people's dung (normal person's feces) big heat of row when being used to treat in the Compendium of Material Medica, typhoid fever pyretic toxicity (cilium all ceaselessly is transferred to the antibacterial in the respiratory tract or virus pharyngeally at any time in nose cilium and master, the bronchus, and is swallowed to esophagus with saliva.Therefore normal person's the formed biological product of feces have the curative effect of prevention and treatment respiratory tract infection), be not used to pestilence, cholera, dysentery, malaria, jaundice; And cow dung is used to treat the reason (cattle often contacts jaundice, cholera, dysentery cause of disease in the process of drinking river, food Caulis et Folium Oryzae, so " biological product " that the intestinal of cattle is made have the effect that prevents or treat jaundice, cholera, dysentery) of jaundice, cholera, dysentery.

Stand in microecology angle, stand in the angle of macroscopic view immunity, none is not compound biological for the medicine in the above-mentioned medical science ancient books, and at that time and even its definite curative effect all arranged now.Its weak point is: 1. its prototype directly is used as medicine and is made the patient be difficult to accept, so that modern no one is ready to use; 2. preparing compound biological, to consume the time oversize, the needs that have a year or several years; 3. preparing the raw material that compound biological selects for use is normal human or animal's feces, and whether whether this feces contains the content of wanting the extraordinary microorganism that the patient infected of medication, extraordinary microorganism enough still belongs to unknownly, and therefore, curative effect is uncertain sometimes.

Summary of the invention:

The objective of the invention is under the prerequisite of not repelling existing biological gene engineering, use ancients' compound biological macroscopic view thinking, 1. the body fluid (as blood), secretions (as milk), the Excreta (as feces, urine) that propose to be rich in ill human or animal cause of disease are the center, for preparing the microbe-derived of compound biological, finish extraordinary microorganism and dock with the effective of patient; 2. select, make up and be applicable to the compound biological modern technologies, compression preparation compound biological required time made critical patient can use the combination vaccine that comes from self in several hours; 3. by compound biological being made modern preparation, make animal product, made plant product, propose human health from animal pick up, from plant pick up, from the viewpoint that diet is picked up, make people's compound biological of taking like a shot; Thereby release a kind of microbial variation of can dealing with to society, compound biological product conposition of raising or mediator and animal immune ability and preparation method thereof systematically all sidedly,, with the treatment cure rate of further raising and infection and immune correlated disease and prevention success rate, and progressively reach the overall immune level that makes people and improve or be adjusted to and level off to the purpose of infantile state.

Compound biological product conposition of the present invention is characterized in that: it is not as prior art antibacterial or virus etc. to be separated laggard row to cultivate, and pursues pure and pure, smart and smart; It is with the micropopulation of occurring in nature and reside in the disease in the past of about 1.5 kilogram weights of gross weight in people (or animal) body throughout the year and PMI all place on record the sum of (variation) of influence reaches that the powerful gene bank of kind of intestinal bacteria is a platform surplus in the of 400 to intestinal microbial population, being received in the pathogenic microorganism that does not still stay the infectious disease of antigenic determinant vestige in this powerful gene bank simultaneously hatches on platform, again through means with whole complex microorganism vaccineization, the antigenic determinant that contains in complex microorganism is released, a kind of microbial variation of can dealing with is fast proposed, comprehensively, the compound biological product conposition of raising or mediator and animal immune ability systematically, it is the deactivation product by complex microorganism, pyrolysis product: combination vaccine, compound vaccine, the complex class toxin, the composite bacterial element, composite antibiotic, compound short-chain fatty acid is formed by combining, wherein, the pyrolysis product of complex microorganism: combination vaccine, compound vaccine, compound anatoxic biochemical component is including, but not limited to flagellin, toxoid albumen, peptide, lipopeptid, polysaccharide, the film lipopolysaccharide, oligosaccharide, one or more of pod membrane oligosaccharide;

The microbe-derived of compound biological of the present invention is:

The microbial enrichment ground such as the soil of natural and even collection, the waters, patient (or animal) contactant, the cause of disease pollutant, patient (or animal) secretions, Excreta, including, but not limited to: the strain that national microorganism fungus kind preservation administrative center is hidden, ancient lavatory wood, ancient Lignum catalpae ovatae, year is rotten for a long time wooden, dirt on the anvil, the refuse bin transudate, sewer water, excessive effluent, rainwater, dew, snow, spring water, well water, sea water, river, river, lake water, hakuzen soil, Montmorillonitum, red soil, loess, black earth, detritus soil, peat, post is soil down, the manure pit bed mud, the refuse bin bed mud, mud at the bottom of the sewer, black silt in a wall, wetland mud, GUWA, ancient brick, dirt on the fine strain of millet, cleaner dust-collection, waste and old books and periodicals, newspaper, old cattail leaf fan, cattail mat, the metal coin, bank note, patient's underwear, foot-binding cloth, shoe pad, various old footwear, door curtain, patient (or animal) focus secretions, patient's (or animal) blood, seminal fluid, milk, patient and normal person (or animal) body surface, tract secretions and Excreta such as saliva, sputum, pus, nasal mucus, menstrual blood, urine, feces etc.

Microbe-derived selection principle: 1. body fluid, secretions, the Excreta that is rich in cause of disease with ill human or animal is that middle mind-set environment spreads nearby that the person is preferably first selection principle; 2. with year for a long time, be rich in microorganism or peculiar microorganism is a priority principle; 3. with symbiosis between microorganism, antagonism phase principle of mutual.

The preparation method of compound biological can comprise: simple and easy fast preparation method, be suitable for modernization big production-scale inferior fast preparation method and natural post treatment method (autolysis method): simple and easy fast preparation method is finished by several procedures such as microbe-derived selection, deactivation, deodorize, simple refining, preparation packing; Be suitable for the inferior fast preparation method of modernization in the big production-scale preparation method and can be divided into container method and tunnel type continuous production method (can simulate intestinal in the tunnel and be equipped with the combined stuffing layer that can adhere to anaerobe) according to process equipment again, these two kinds of inferior fast preparation method all are to be finished by several procedures such as: microbe-derived selection, microorganism culturing, deactivation, refining, preparation packing; Be suitable for the natural post treatment method of modernization in the big production-scale preparation method and also can be divided into container autolysis method and tunnel type continuous production autolysis method (can simulate intestinal in the tunnel and be equipped with the combined stuffing layer that can adhere to anaerobe) according to process equipment, these two kinds of natural post treatment methods all are to be finished by several procedures such as: microbe-derived selection, microorganism culturing, digestion, cracking, liquefaction, deodorize, refining, preparation packing.

Wherein, 1, microbe-derived: microbe-derived selection can be according to above-mentioned seed selection principle, in particular;

At first check in the collected feces in the similar ill public lavatory, human or animal concentrated area of the infectious disease that will treat or prevent, whether have the pathogenic microorganism that carries this special type disease or have the extraordinary microorganism of carrying this pathogenic microorganism epitopes gene.If wherein all tool foots then can carry out next step operation;

If the extraordinary microorganism that does not wherein have required pathogenic microorganism and carry this pathogenic microorganism epitopes gene, then can from above-mentioned source of disease is microbe-derived, the form with inverted order upwards search one by one, if find to carry the pathogenic microorganism of this special type disease, or carry the carrier of the extraordinary bacterium of the source of disease microbial antigen determinant gene that causes a disease, then can carry out different processing: when carrying microbe carrier when enough such as blood according to the number that carries microbe carrier, milk, urine, soil, the waters then can be from blood, milk, urine, soil, directly extract in the waters, separate, this complex disease pathogenic microorganism of vaccineization; When carrying microbe carrier, then can add suitable carbon source, nitrogenous source, bile mixing, and the simulation intestinal environment enters the antibacterial culturing stage according to the habit of carrying microorganism after a little while as patient (or animal) focus secretions, patient's underwear;

All can not get in above-mentioned two kinds of methods under satisfied result's the prerequisite, can be by engineered means, by preparing the antibacterial that the pathogenic microorganism epitopes gene of this special type disease is carried in operations acquisitions such as genes of interest, vitro recombination, gene transfer, screening, and add suitable carbon source, nitrogenous source, bile according to the habit of carrying bacterium or pathogen and mix, and simulate other intestinal environment and enter the antibacterial culturing stage;

In order to prepare the effect of reaching maturity, wide spectrum antigen that have the effect of comprehensive stimulation immune response, that have the effect of comprehensive enhance immunity cytoactive further with comprehensive promotion host immune system, can be at the middle and late stage of above-mentioned cultivation, the growth that is culture reaches middle logarithmic (log) phase during latter stage, adds an amount of fresh healthy human or animal's feces or healthy completely human faecal mass compound bacteria in system.

For system being created as antagonism, complementation, the symbiotic system of improving of many kinds, can in above-mentioned source of disease is microbe-derived, select one or more, if selected bacterium source is a solid, then available water or washing water of rice dissociate out with composite bacterial, can be at the middle and late stage of above-mentioned cultivation, the growth that is culture reaches middle logarithmic (log) phase during latter stage, among the adding system.

In order to save nitrogenous source and carbon source, in order to give gene segment and the antigenic determinant segment that stays multiple microorganism in the system, after solidss such as the thalline of depleted sterilization after one or more production of antibiotics, mycelium are collected mixing, add in the above-mentioned antibacterial culturing system as carbon source, nitrogenous source by proper proportion.

2, microorganism culturing: the microorganism of microorganism culturing condition simulation is the intravital conditions of existence of host, more particularly the condition of anthropomorphic dummy or animal intestinal microenvironment: the ecological environment of promptly simulating cholic acid, nitrogenous source, carbon source, temperature, weary oxygen environment, multiple microbe symbiotic.

3, deactivation: when microorganism is former enough, or the growth of culture carries out deactivation when reaching late logarithmic (log) phase to stable phase, and ablation method comprises and kill deactivation or cracking deactivation, kills deactivation and comprises that the formalin of chemistry fixes the heat of physics, ultrasonic or radiation; The cracking deactivation comprises in ultrasonic fracture, oxidoreduction depolymerization, acid or the alkaline media controls hydrolysis, phage splitting, enzymatic hydrolysis; Thereby the antigenic determinant that contains in complex microorganism is released.

4, natural post processing: when microorganism is former enough, or the growth of culture reaches late logarithmic (log) phase to stable phase, and under anaerobism (or little oxygen) environment, the initial stage complex microorganism is further bred, and exhausts all carbon sources, nitrogenous source and other energy and makes its liquefaction; Mid-term, phage made complex microorganism cracking one by one, liquefaction; Cut into genetic fragment or antigenic determinant fragment by enzyme with the macromole of phage and complex microorganism latter stage, thereby the antigenic determinant that contains in complex microorganism is released.Its end product is including, but not limited to the composition and the small amount of impurities of biologically actives such as flagellin, toxoid albumen, peptide, lipopeptid, polysaccharide, film lipopolysaccharide, oligosaccharide, pod membrane oligosaccharide, bacteriocin, antibiotic, short-chain fatty acid.

5, refining: as refiningly can be divided into for three steps: the first gets biological product complex liquid crude product with products therefrom in above-mentioned 3,4 by centrifugal, vacuum deodorization, it two is that biological product complex liquid crude product gets biological product complex liquid elaboration through ultrafiltration desalination, the supervisor that redissolves again, and it three is that biological product complex liquid crude product gets each effective ingredient separating medium through electrophoresis or several procedures such as resin absorption, desorbing again.The method not only can reach the purpose of removing mechanical admixture, desalination, decolouring, and can make biological effective components classification, classification, even plurality of active ingredients in the complex liquid can be separated one by one; Wherein, the bioactive ingredients of refining gained is including, but not limited to flagellin, toxoid albumen, peptide, lipopeptid, polysaccharide, film lipopolysaccharide, oligosaccharide, pod membrane oligosaccharide, bacteriocin, antibiotic etc.

6, dock with people, animal and plant for the above-mentioned compound biological of health purpose and can derive following three kinds of forms:

(1), preparation:

Compound biological preparation of the present invention has three kinds, and first compositions is the deactivation product of complex microorganism, the preparation of pyrolysis product; Second kind is the active bacteria formulation that carries complex microorganism epitopes gene beneficial bacteria of intestinal tract (being the plant endogenesis predominant bacteria for plant); The third is the biological health fermented food that carries the complex microorganism epitopes gene.In the process of preparation, can also add and can further improve antigenic adjuvant according to the known prior art of professional, for example, but be not limited to, aluminum, water in oil emulsion, (ileum, colon targeting drug administration) microcapsule, or add other Chinese medicines or Western medicine is assisted a ruler in governing a country treatment.Wherein, first kind, second kind is applicable to people, animal, plant; The third is applicable to humans and animals.

1. compositions is the deactivation product of complex microorganism, the preparation of pyrolysis product: above-mentioned centrifugal, deodorize, refining gained biological product complex liquid, refined liquid or refined mixed liquid, can directly make intestinal, the non-intestinal drug delivery agent of various liquid, human or animal's biological health food; Also can be by after being made into the pressed powder that is beneficial to preservation including, but not limited to dry means such as lyophilization, cryogenic vacuum spray drying, spray dryinges, solid, liquid, the intestinal canal administration preparation of making according to different demands that prior art can reach, non-intestinal drug delivery agent again, the biological health food of people, animal edible.Wherein, the intestinal canal administration preparation, can be the various intestinal canal administration preparations that specialty goes up common dosage, can also be micro-administration, trace administration, and by the energy frequency spectrum zero-dose administration of medicine, in the application number of I, application on March 15th, 2005 is 200510006033.8 and 200510053389.7 ' can effectively promote the activated and magnetic water maker of biological existence quality ' on January 7th, 2005, use or in future use is used for the treatment of and prevents the former medicament of people, animal and plant and infection and immune diseases associated preparation in the homeopathic therapeutic method.

2. carry the active bacteria formulation of complex microorganism epitopes gene beneficial bacteria of intestinal tract: with the deactivation product of complex microorganism, antigenic determinant in the pyrolysis product with the method for professional known gene transfer, or in the Nutrient medium that is added with the deactivation product of complex microorganism, pyrolysis product one or more beneficial bacteria of intestinal tract of inoculation (for plant for plant endogenesis predominant bacteria), and, this beneficial bacteria of intestinal tract is converted into carries complex microorganism epitopes gene beneficial bacteria of intestinal tract in suitable fermentation condition bottom fermentation cultured method.Solid, liquid, intestinal canal administration preparation, non-intestinal drug delivery agent that this beneficial bacteria of intestinal tract can make that prior art can reach according to different demands; The milk that the human or animal eats, yoghourt, curdled milk, cheese, fermented milk, bifid yoghourt, the basic fermented product of suckling, ice cream, frumentum fermented product.Milk powder, baby food, pet food or tablet, liquid bacterial suspension, dried oral supplement, wet oral supplement, dried tube feed, wet tube feed biological health food and feedstuff.Wherein beneficial bacteria of intestinal tract including, but not limited to: bifidobacterium bifidum, bifidobacterium breve, bifidobacteria infantis, bifidobacterium longum, lactobacillus acidophilus, Lactobacillus bulgaricus, cheese lactobacillus, Deshi Lactobacillus, Lactobacillus plantarum, streptococcus thermophilus, enterococcus faecalis, enterococcus faecalis, have a liking for citric acid leukonid, bacillus cereus, hay bud pole bacterium and lichenoid form bud pole bacterium.

3. carry the biological health fermented food of complex microorganism epitopes gene: with the deactivation product of complex microorganism, antigenic determinant in the pyrolysis product with the method for professional known gene transfer, or in the Nutrient medium that is added with the deactivation product of complex microorganism, pyrolysis product inoculating starter, and, this leaven is converted into carries complex microorganism epitopes gene leaven in suitable fermentation condition bottom fermentation cultured method.This leaven can be made including, but not limited to biological health fermented food and fermented feeds such as beans, fermented bean curd, soy sauce, vinegar, yogurt, bean yoghourt, fruit juice and fruit fermented beverage, fermented vegetable beverage, edible fungi beverage, cheese, yellow wine, medicated beer by prior art according to different demands.The present invention on technology with prior art different except that leaven, be that mainly last procedure needs the operation of heat sterilization to change the ultrasonication sterilization in the present invention in former technology, to guarantee the effectiveness of corresponding antigens determinant.

(2), when above-mentioned three kinds of preparations are applicable to human body, also be applicable to animal.Animal:

1. compound biological is as comprehensive compound therapeutic and preventative vaccine, can be used for common animals treatment of diseases and the prevention (combination vaccine that is prepared into as the avian influenza poultry manure, preventive effect can not only be played, and also very effective therapeutical effect can be played for the poultry that has caught an illness.)；

2. compound biological (when selecting the animal wastes degradation product for use) is alternative almost follows the animal hormone and the antibiotics in all one's life, thereby can reduce feeding cost, reduction hormone and antibiotics greatly to zootoxin side effect and residual back toxic and side effects to human body;

3. compound biological (when selecting patient's feces for use) produces corresponding antibodies in animal body after giving the oral or injection of animal, and people can obtain immunity by edible animal product such as egg, milk etc.For example: the feces of hepatitis B patient makes cattle obtain immunity as feedstuff after the vaccine means are handled, and its antibody enters Lac Bovis seu Bubali by serum, and the people can obtain immunity when taking the Lac Bovis seu Bubali with hbv antibody.

(3) main component of human or animal's recipe is a plant, so the tool foot improves or regulate the disease-resistant R gene of compound parasite epitopes gene, composite plant, compound parasite exciton, the composite plant endogenous elicitor of plant immunization ability in the compound biological behind the human or animal's manure fermentation, vaccineization.Thereby help to start the disease-resistant gene of plant, make its activation and express, make its speed and intensity surpass original susceptible gene prior to susceptible gene activation or expression. so show as a disease-resistant property.

Therefore, when above-mentioned first kind, second kind preparation is applicable to human body, animal, also be applicable to plant.Plant:

1. compound biological can be used for frequently seen plants treatment of diseases and prevention as comprehensive compound therapeutic and preventative vaccine;

2. alternative chemical fertilizer and the pesticide of almost following plant all one's life of compound biological, thus chemical fertilizer and pesticide can be reduced greatly to the toxic and side effects of plant and residual back toxic and side effects to human body;

3. compound biological (when selecting patient's feces for use) can be directly used in pre-transgenic plant sexual cell (for the seed of skin depth by adding an amount of moistening promoter, also can take the method for laser boring and/or ultrasonic importing assist to soak) the bubble of invading handle, injured root system wound absorbs, and foliar spray imports by the blade face pore and/or the florescence spraying imports the plant that Plant Transformation is become carry pathogen antigen determinant gene by pollen tube channel, because seed, the root system wound, the continuous stimulation of florescence and blade face external source pathogen antigen determinant gene protein, the pathogen antigen determinant is expressed at the plant camber, the direct-edible human or animal of making of edible part obtains immunity in the plant, the non-edible part of plant can be used for human or animal's immunity with behind the antigenic determinant extraction separation.For example: the feces of hepatitis B patient makes Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross foretell dish, bean sprout, bean seedlings, Nicotiana tabacum L., Fructus Musae, Herba Medicaginis after the vaccine means are handled and produces immunne response, then the people food plant product such as Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross are foretold dish, bean sprout, bean seedlings, Nicotiana tabacum L., Fructus Musae, Herba Medicaginis etc. and are obtained immunity again.

Its positive role of compound biological of the present invention is to treat and to prevent existing at present and following when people, animal and the plant of taking place and infection and immune relevant, in plant and can stay the disease of disease antigen determinant gene vestige in humans and animals blood, milk, urine, feces and the focus Excreta, it is including, but not limited to following disease:

People: viral infectious: influenza, common cold, severe acute respiratory syndrome, measles, rubella, roseola infantum, erythema infectiosum, chickenpox and herpes zoster, epidemic encephalitis type B, lymphocytic choriomeningitis, central nervous system infection, central nervous system's chronic viral infection, dengue fever and dengue hemorrhagic fever, forest encephalitis, Economo's encephalitis, epidemic hemorrhagic fever, Xinjiang hemorrhagic fever, lassa fever, yellow fever, rabies, cancer, acquired immune deficiency syndrome (AIDS), Ai Bola, bovine spongiform encephalopathy, monkeypox, west Nile virus, condyloma acuminatum, verruca plana, genital herpes, Coxsackie virus infection, echovirus infects, viral hepatitis, herpes simplex, mumps, infectious monocytosis, cytomegalovirus infection, acute hemorrhagic conjunctivitis, foot and mouth disease, poliomyelitis, newtype enteroviru infects, and people's parvovirus like infects, viral diarrhea; Thin mattress sexually transmitted disease: diphtheria, hemolytic streptococcal infection, staphy lococcus infection, epidemic cerebrospinal meningitis, bacterial meningitis, pertussis, infection with legionella, tularemia, cholera, typhoid fever and paratyphoid fever, bacillary dysentery, coliform diarrhea, anaerobic infection, bacterial food poisoning, yersinia infects, campylobacter enteritis, spirillum infects, and aeromonas hydrophila infects, plesiomonas shigelloides diarrhoea, difficulty is distinguished clostridium colitis, infective endocarditis, brain abscess, urinary tract infection, anxious, chronic nephritis, pyelonephritis, the nephrotic syndrome, chronic renal failure, Salmonella typhimurium infection, other Salmonella infection, tetanus, anthrax, glanders (glanders), Bu Lusi bacillosis, the plague, leprosy, gonococcal infection (gonorrhea), Gartner bacterium property vaginitis, listeriosis, granuloma inguinale, lobar pneumonia, pulmonary abscess, tuberculosis, chancroid; Rickettsiosis: typhus fever, Q heat, scrub typhus; Fungal disease: deep mycosis, superficial mycosis, genital candidiasis, cryptococcal meningitis, aspergillosis, histoplasmosis, the slave blocks the bacterium disease; Chlamydia and mycoplasma infection: chlamydia infection, lymphogranuloma venereum, nongonococcai urethritis, mycoplasma infection; Spirochetosis: angle the Leptospiral disease, Ticks matchmaker spirochetosis (Lyme disease), refined department, relapsing fever, prunus mume (sieb.) sieb.et zucc. poison; Rheumatism, rheumatoid.

Animal: yellow scour of piglet, yellow and white dysentery of piglet, colibacillosis of piglet, the piglet coccidiosis, piglet pseudorabies and swine fever mixed infection, piglet diarrhea, early-weaned piglets diarrhoea, piglet clostridium enteritis, baby swine paratyphoid, bowel oedema disease, the sow obstipation, transmissible gastroenteritis, porcine contagious pleuropneumonia, foot and mouth disease, the porcine reproductive respiratory syndrome, acute swine flue, the porcine rotavirus disease, enterovirus infection, sow inappetence in puerperal, swine enzootic pneumonia, swine eperythrozoonosis, the sow infertility, the pig toxoplasmosis, postpartum paralysis of sow, porcine parvovirus, SVD, swine dysentery, swine fever, pig lung plague, the Intestinum caprae seu ovis toxemia, the sheep black disease, sheep struck, sheep clostridium property disease, the foot and mouth disease of cattle and sheep, the cattle and sheep brucellosis, the popular heat of cattle, lamb dysentery, the milch cow foot rot, newcastle disease, infectious bronchitis of chicken, fowl cholera, infectious bursal disease, chicken Marek's disease, duck viral hepatitis, gosling plague, the mucosal pattern fowlpox, aspergillus disease of chicken, the broiler chicks goat, the chicken listeriosis, the anemia leukemia, bird flu, viral arthritis, the mixed type fowlpox, infectious laryngotracheitis, the white scour of chicken, become the acute paratyphoid fever of chicken, staphylococcosis, the infective rhinitis, the chicken Mycoplasma infects, tuberculosis, coccidiosis, ascariasis, taeniasis, blackhead disease (caecum Histomoniasis), colibacillosis, the rabbit pestilence, Bacillus pasteurii disease, clostridieum welchii disease, staphylococcosis, colibacillosis, coccidiosis, mange and scab, the infectiousness stomatitis, rabbit variola, rabbit tuberculosis, rabbit Pneumocystis carinii disease, the rabbit listeriosis, the rabbit treponematosis, the Medulla Leporis seu Oryctolagi protozoacide, the pseudo-tuberculosis of rabbit, rabbit infectiousness vesicle stomatitis, rabbit hemorrhagic disease

Plant: fungal disease, bacteriosis, virus disease, MLO disease, insecticide disease

The invention has the advantages that: the present invention is under the prerequisite of not repelling existing biological gene engineering, with the micropopulation of occurring in nature and reside in the disease in the past of about 1.5 kilogram weights of gross weight in people (or animal) body throughout the year and PMI all place on record the sum of (variation) of influence reaches that the powerful gene bank of kind of intestinal bacteria is a platform surplus in the of 400 to intestinal microbial population, being received in the pathogenic microorganism that does not still stay the infectious disease of antigenic determinant vestige in this powerful gene bank simultaneously hatches on platform, again through means with whole complex microorganism vaccineization, a kind of microbial variation of can dealing with is fast proposed, comprehensively, systematically improve or the mediator, animal, compound biological product conposition of plant immunization ability and preparation method thereof, and propose human health first and pick up from animal, pick up from plant, the viewpoint of picking up from diet, with the prevention success rate of the human infectious disease of further raising and treatment cure rate, and reach the overall immune level that makes people step by step and improve or be adjusted to and level off to the purpose of infant immunization state.Wherein, simple and easy fast preparation method can be prepared required compound biological in 24 hours.

In order to further specify the present invention, but not limited provide following embodiment:

Embodiment 1, SARS (or acquired immune deficiency syndrome (AIDS)) combination vaccine formulation preparation method (container method)

Prescription:

Atypical pneumonia (or acquired immune deficiency syndrome (AIDS)) patient feces 2kg newly steams rice cooked rice 2kg

Carbamide 8g bile 16g

Preparation method:

4 flavor mix homogeneously in the side of getting place 30～37 ℃ of fermentations of round 24 hours,

Get the above-mentioned 24 hours about 4kg of fermented product normal public lavatory feces 4kg

The new rice 8kg carbamide 30g bile 60g that steams

Loess 4kg deepens well water 20kg

Under well-beaten condition, slowly add the loess that is ground into fine powder in the 20kg phreatic water, sedimentation, it is even to get five kinds of mixing of materials of supernatant 16kg and residue, place container, sealing, and stay a filtering type passage, under anaerobism (or little oxygen) environment, 25～37 ℃ of fermentations, cracking, liquefaction be standby after 24～72 hours;

This standby fermentation liquid can have two kinds of different post-processing approachs:

(1), above-mentioned fermentation liquid is filtered to take off the salt in the fermentation liquid at the following filter material of 2 μ m by bore dia, filter cake with distilled water diluting to original volume, place S-910BCA type continuous-flow and ultrasonic-wave cell breakage instrument, under the condition of frequency 15kHz, carry out ultrasonication.Ultrasonic deactivation liquid with the centrifugal 30min of 5000r/min, is got supernatant, and vacuum deodorization is the prepared biological product complex liquid stock solution that goes out of the inferior fast preparation method of container type;

(2), above-mentioned fermentation liquid is continued under anaerobism (or the little oxygen) environment, 28～37 ℃ of fermentations, cracking, liquefy standby after being 120～480 hours to total time; Fermentation liquid with the centrifugal 30min of 5000r/min, is got supernatant, and vacuum deodorization, is diluted to original volume with distilled water with filter cake at the ultrafiltration desalination, is the prepared biological product complex liquid stock solution that goes out of container type nature post treatment method;

This biological product complex liquid stock solution can further improve antigenic adjuvant according to the known prior art adding of professional and can make respectively:

1. can directly make intestinal, the non-intestinal drug delivery agent of various liquid, human or animal's biological health food is as the aerosol of oral formulations and the direct spray delivery of respiratory tract;

2. inoculation, one or more beneficial bacteria of intestinal tract of fermentation culture in the Nutrient medium that is added with biological product complex liquid stock solution are made the intestinal canal administration preparation, or the humans and animals biological health food;

3. after obtaining transgenic bacillus bifidus, lactobacillus with the method for the known gene transfer of professional, place high-quality milk co-fermentation to prepare the bifid yoghourt.

Embodiment 2, animal are used combination vaccine formulation preparation method (simple and easy express method):

Prescription:

Get the feces 400ml phreatic water 600ml of infected animal

Preparation method:

With above-mentioned patient's Excreta and/or patient's secretions and phreatic water mix homogeneously, filter with 20 mesh sieves, the mechanicalness impurity that filtering is big, filtrate places S-910BCA type continuous-flow and ultrasonic-wave cell breakage instrument, under the condition of frequency 15kHz, carries out ultrasonication.With ultrasonic deactivation liquid vacuum deodorization, be animal combination vaccine stock solution, this stock solution: can be directly used in the oral of animal after 1. can adding an amount of correctives packing.2. also can be spray-dried or lyophilization after add adjuvant and the acceptable solid preparation carrier of pharmacy is made solid orally ingestible.3. also this stock solution can be used for the fermentation of animal fermented feedstuff.

Embodiment 3, human or animal source composite immune reinforcing agent (tunnel type continuous production method)

This continuous production device image say the intestinal that duplicates in the human or animal, one end constantly, approximate constant speed ground adds the people or/and the material of the primary raising component of animal wastes and natural animal in system, one end constantly flows out through 25～42 ℃ of anaerobism (or little oxygen) environment and becomes thoroughly decomposed, fermentation, liquefaction is (when the simulation intestinal being housed can adhere to the combined stuffing layer of anaerobe time in the tunnel, after tunnel commencement of commercial operation a period of time, can in the combined stuffing layer of tunnel zones of different section, settle down the anaerobe that adapts to its environment, can improve the operational efficiency in tunnel whereby), the fermentation liquid after 24～72 hours is standby;

This standby fermentation liquid can have two kinds of different post-processing approachs:

(1), above-mentioned fermentation liquid is filtered to take off the salt in the fermentation liquid at the following filter material of 2 μ m by bore dia, filter cake with distilled water diluting to original volume, place S-910BCA type continuous-flow and ultrasonic-wave cell breakage instrument, under the condition of frequency 15kHz, carry out ultrasonication.Ultrasonic deactivation liquid with the centrifugal 30min of 5000r/min, is got supernatant, and vacuum deodorization is the prepared biological product complex liquid stock solution that goes out of the inferior fast preparation method of tunnel type; Or with the former powder of the spray-dired complex liquid of this complex liquid stock solution;

(2), continue in the tunnel under anaerobism (or the little oxygen) environment, 25～42 ℃ of fermentations, cracking, to liquefy to total time be standby after 120～480 hours; Fermentation liquid with the centrifugal 30min of 5000r/min, is got supernatant, and vacuum deodorization, is diluted to original volume with distilled water with filter cake at the ultrafiltration desalination, is the prepared biological product complex liquid stock solution that goes out of tunnel type nature post treatment method; Or with the former powder of the spray-dired complex liquid of this complex liquid stock solution;

This biological product complex liquid stock solution or former powder can be different according to its source, make embodiment 1 described three kinds of preparations under the known prior art condition of professional, and finish following four kinds of purposes:

1. the prepared composite immune reinforcing agent that goes out of compound biological (when selecting normal person's manure fermentation for use) is mainly used in immunocompetence crowd on the low side, application by this combination vaccine is expected to make people's immunocompetence to improve or is adjusted to and levels off to infantile state, resists ability various and infection and immune diseases related thereby improve human body.

2. compound biological (when selecting the animal wastes fermentation for use) is alternative almost follows the animal hormone and the antibiotics in all one's life, thereby can reduce feeding cost, reduction hormone and antibiotics greatly to zootoxin side effect and residual back toxic and side effects to human body;

3. compound biological (when elected personnel selection and/or animal wastes fermentation) is alternative almost follows the plant chemical fertilizer and the pesticide in all one's life, thereby can reduce after chemical fertilizer and the pesticide residues toxic and side effects to human body or animal greatly;

4. compound biological (when selecting patient's manure fermentation for use)

I, can be used for treating the disease that the patient suffers from by the patient is oral;

II, prevent the disease suffered from for the feces patient by the oral subhealth state person of can be used for of subhealth state person;

III, produce corresponding antibodies in animal body after giving the oral or injection of animal, people can obtain immunity by edible animal product such as egg, milk etc.For example: the feces of hepatitis B patient makes cattle obtain immunity as feedstuff after the vaccine means are handled, and its antibody enters Lac Bovis seu Bubali by serum, and the people can obtain immunity when taking the Lac Bovis seu Bubali with hbv antibody.

IV, can be directly used in pre-transgenic plant sexual cell (for the seed of skin depth by adding an amount of moistening promoter, also can take the method for laser boring and/or ultrasonic importing assist to soak) the bubble of invading handle, injured root system wound sucks, and foliar spray imports by the blade face pore and/or the florescence spraying imports the plant that Plant Transformation is become carry pathogen antigen determinant gene by pollen tube channel, because seed, the root system wound, the continuous stimulation of florescence and blade face external source pathogen antigen determinant gene protein can make the pathogen antigen determinant express at the plant camber.The direct-edible human or animal of making of edible part obtains immunity in the plant, and the non-edible part of plant can be used for human or animal's immunity with behind the antigenic determinant extraction separation.For example: the feces of hepatitis B patient makes Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross foretell dish, bean sprout, bean seedlings, Nicotiana tabacum L., Fructus Musae, Herba Medicaginis after the vaccine means are handled and produces immunne response, then the people food plant product such as Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross are foretold dish, bean sprout, bean seedlings, Nicotiana tabacum L., Fructus Musae, Herba Medicaginis etc. and are obtained immunity again.

Annotate: Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross are foretold dish, bean sprout, bean seedlings, Nicotiana tabacum L., Herba Medicaginis etc. and are selected for use the soilless culture effect can be better, this be because: 1. compound biological is saved in soilless culture; 2. the antigenic determinant of soilless culture compound biological and plant contact time are long; 3. soilless culture is convenient to handle root system and is made it to form wound, is convenient to epitopes gene and sucks from the injured root system wound of plant.

Embodiment 4, blood source composite immune reinforcing agent

Get ill people's (or animal) whole blood or blood plasma (or milk) 10～50ml

Under aseptic condition, handled 1～10 minute with ultrasonic cell disruption instrument, with the pathogen of contained all diseases in the blood (or milk), pathogen antigen, and blood plasma (or milk) in immune protein all smash, make in the pathogen, the epitopes gene in the pathogen antigen and the immunogene in the immune protein all discharge standbyly, this blood plasma of handling well (or milk) can be used for human or animal's treatment or prevention by following four kinds of modes:

1. get blood plasma that 1～10ml handles well and be recycled into and get in the blood patient body, be used for the treatment of the disease that the patient suffers from;

2. get the blood plasma that 1～10ml handles well and be expelled in subhealth state person's body, be used for the disease that subhealth state person prevents the blood supply patient to be suffered from;

3. get the blood plasma (or milk) that 10～50ml handles well and make 100～200mlW/O Emulsion, in intestinal, make the patient obtain immunity, be used for the treatment of the disease that the patient suffers from by the patient is oral;

4. get the blood plasma (or milk) that 10～50ml handles well and make 100～200mlW/O Emulsion, in intestinal, make subhealth state person obtain immunity, be used for the disease that subhealth state person prevents the blood supply patient to be suffered from by subhealth state person is oral.

Present embodiment is applicable to that those can stay the infectious disease and the immune disease of the pathogen of disease, pathogen antigen, immune protein vestige in blood plasma (or milk), as hepatitis B, acquired immune deficiency syndrome (AIDS), SARS, tuberculosis, cancer etc.

Claims (10)

1, a kind of compound biological product conposition is characterized in that: it is deactivation product, pyrolysis product by complex microorganism: combination vaccine, compound vaccine, complex class toxin, composite bacterial element, composite antibiotic, compound short-chain fatty acid are formed by combining; Wherein, the pyrolysis product of complex microorganism: combination vaccine, compound vaccine, compound anatoxic biochemical component are including, but not limited to one or more of: flagellin, toxoid albumen, peptide, lipopeptid, polysaccharide, film lipopolysaccharide, oligosaccharide, pod membrane oligosaccharide; Its positive role is treatment and prevention people, animal and plant and infection and immune diseases associated.

2, compound biological product conposition as claimed in claim 1, it is characterized in that: compound biological product conposition can treat and prevent existing at present, and it is following when people, animal and the plant of taking place and infection and immune relevant, in plant and can stay the disease of disease antigen determinant gene vestige in humans and animals blood, milk, urine, feces and the focus Excreta, it is including, but not limited to following disease:

People: viral infectious: influenza, common cold, severe acute respiratory syndrome, measles, rubella, roseola infantum, erythema infectiosum, chickenpox and herpes zoster, epidemic encephalitis type B, lymphocytic choriomeningitis, central nervous system infection, central nervous system's chronic viral infection, dengue fever and dengue hemorrhagic fever, forest encephalitis, Economo's encephalitis, epidemic hemorrhagic fever, Xinjiang hemorrhagic fever, lassa fever, yellow fever, rabies, cancer, acquired immune deficiency syndrome (AIDS), Ai Bola, bovine spongiform encephalopathy, monkeypox, west Nile virus, condyloma acuminatum, verruca plana, genital herpes, Coxsackie virus infection, echovirus infects, viral hepatitis, herpes simplex, mumps, infectious monocytosis, cytomegalovirus infection, acute hemorrhagic conjunctivitis, foot and mouth disease, poliomyelitis, newtype enteroviru infects, and people's parvovirus like infects, viral diarrhea; Thin mattress sexually transmitted disease: diphtheria, hemolytic streptococcal infection, staphy lococcus infection, epidemic cerebrospinal meningitis, bacterial meningitis, pertussis, infection with legionella, tularemia, cholera, typhoid fever and paratyphoid fever, bacillary dysentery, coliform diarrhea, anaerobic infection, bacterial food poisoning, yersinia infects, campylobacter enteritis, spirillum infects, and aeromonas hydrophila infects, plesiomonas shigelloides diarrhoea, difficulty is distinguished clostridium colitis, infective endocarditis, brain abscess, urinary tract infection, anxious, chronic nephritis, pyelonephritis, the nephrotic syndrome, chronic renal failure, Salmonella typhimurium infection, other Salmonella infection, tetanus, anthrax, glanders (glanders), Bu Lusi bacillosis, the plague, leprosy, gonococcal infection (gonorrhea), Gartner bacterium property vaginitis, listeriosis, granuloma inguinale, lobar pneumonia, pulmonary abscess, tuberculosis, chancroid; Rickettsiosis: typhus fever, Q heat, scrub typhus; Fungal disease: deep mycosis, superficial mycosis, genital candidiasis, cryptococcal meningitis, aspergillosis, histoplasmosis, the slave blocks the bacterium disease; Chlamydia and mycoplasma infection: chlamydia infection, lymphogranuloma venereum, nongonococcai urethritis, mycoplasma infection; Spirochetosis: angle the Leptospiral disease, Ticks matchmaker spirochetosis (Lyme disease), refined department, relapsing fever, prunus mume (sieb.) sieb.et zucc. poison; Rheumatism, rheumatoid;

Animal: yellow scour of piglet, yellow and white dysentery of piglet, colibacillosis of piglet, the piglet coccidiosis, piglet pseudorabies and swine fever mixed infection, piglet diarrhea, early-weaned piglets diarrhoea, piglet clostridium enteritis, baby swine paratyphoid, bowel oedema disease, the sow obstipation, transmissible gastroenteritis, porcine contagious pleuropneumonia, foot and mouth disease, the porcine reproductive respiratory syndrome, acute swine flue, the porcine rotavirus disease, enterovirus infection, sow inappetence in puerperal, swine enzootic pneumonia, swine eperythrozoonosis, the sow infertility, the pig toxoplasmosis, postpartum paralysis of sow, porcine parvovirus, SVD, swine dysentery, swine fever, pig lung plague, the Intestinum caprae seu ovis toxemia, the sheep black disease, sheep struck, sheep clostridium property disease, the foot and mouth disease of cattle and sheep, the cattle and sheep brucellosis, the popular heat of cattle, lamb dysentery, the milch cow foot rot, bovine spongiform encephalopathy, newcastle disease, infectious bronchitis of chicken, fowl cholera, infectious bursal disease, chicken Marek's disease, duck viral hepatitis, gosling plague, the mucosal pattern fowlpox, aspergillus disease of chicken, the broiler chicks goat, the chicken listeriosis, the anemia leukemia, bird flu, viral arthritis, the mixed type fowlpox, infectious laryngotracheitis, the white scour of chicken, become the acute paratyphoid fever of chicken, staphylococcosis, the infective rhinitis, the chicken Mycoplasma infects, tuberculosis, coccidiosis, ascariasis, taeniasis, blackhead disease (caecum Histomoniasis), colibacillosis, the rabbit pestilence, Bacillus pasteurii disease, clostridieum welchii disease, staphylococcosis, colibacillosis, coccidiosis, mange and scab, the infectiousness stomatitis, rabbit variola, rabbit tuberculosis, rabbit Pneumocystis carinii disease, the rabbit listeriosis, the rabbit treponematosis, the Medulla Leporis seu Oryctolagi protozoacide, the pseudo-tuberculosis of rabbit, rabbit infectiousness vesicle stomatitis, rabbit hemorrhagic disease;

Plant: fungal disease, bacteriosis, virus disease, MLO disease, insecticide disease

3, compound biological product conposition as claimed in claim 1, it is characterized in that: the preparation method of compound biological comprises: simple and easy fast preparation method, be suitable for modernization big production-scale inferior fast preparation method and natural post treatment method (autolysis method): wherein, simple and easy fast preparation method is finished by several procedures such as microbe-derived selection, deactivation, simple refining, preparation packing; Be suitable for the inferior fast preparation method of modernization in the big production-scale preparation method and can be divided into container method and tunnel type continuous production method (can simulate intestinal in the tunnel and be equipped with the combined stuffing layer that can adhere to anaerobe) according to process equipment again, these two kinds of inferior fast preparation method all are to be finished by several procedures such as: microbe-derived selection, microorganism culturing, deactivation, refining, preparation packing; Be suitable for the natural post treatment method of modernization in the big production-scale preparation method and also can be divided into container autolysis method and tunnel type continuous production autolysis method (can simulate intestinal in the tunnel and be equipped with the combined stuffing layer that can adhere to anaerobe) according to process equipment, these two kinds of natural post treatment methods all are to be finished by several procedures such as: microbe-derived selection, microorganism culturing, digestion, cracking, liquefaction, deodorize, refining, preparation packing.

4, the microbe-derived selection in the preparation method of compound biological as claimed in claim 3: it is characterized in that:

(1) source of microorganism is: microbial enrichment natural and even collection ground such as soil, the waters, patient (or animal) contactant, the cause of disease pollutant, patient (or animal) secretions, Excreta, including, but not limited to: the strain that national microorganism fungus kind preservation administrative center is hidden, ancient lavatory wood, ancient Lignum catalpae ovatae, year is rotten for a long time wooden, dirt on the anvil, the refuse bin transudate, sewer water, excessive effluent, rainwater, dew, snow, spring water, well water, sea water, river, river, lake water, hakuzen soil, Montmorillonitum, red soil, loess, black earth, detritus soil, peat, post is soil down, the manure pit bed mud, the refuse bin bed mud, mud at the bottom of the sewer, black silt in a wall, wetland mud, GUWA, ancient brick, dirt on the fine strain of millet, cleaner dust-collection, waste and old books and periodicals, newspaper, old cattail leaf fan, cattail mat, the metal coin, bank note, patient's underwear, foot-binding cloth, shoe pad, various old footwear, door curtain, patient (or animal) focus secretions, patient's (or animal) blood, seminal fluid, milk, patient and normal person (or animal) body surface, tract secretions and Excreta such as saliva, sputum, pus, nasal mucus, menstrual blood, urine, feces etc.;

(2) microbe-derived selection principle is: body fluid, secretions, the Excreta that is rich in cause of disease with ill human or animal is that middle mind-set environment spreads nearby that the person is preferably first selection principle; With year for a long time, be rich in microorganism or peculiar microorganism is a priority principle; With symbiosis between microorganism, antagonism phase principle of mutual.

5, the microbe-derived selection in the preparation method of compound biological as claimed in claim 4: in particular, it is characterized in that: (1) is at first checked in the collected feces in the similar ill public lavatory, human or animal concentrated area of the infectious disease that will treat or prevent, whether is had the pathogenic microorganism that carries this special type disease or have the extraordinary microorganism of carrying this pathogenic microorganism epitopes gene; If wherein all tool foots then can carry out next step operation; (2) if the extraordinary microorganism that does not wherein have required pathogenic microorganism and carry this pathogenic microorganism epitopes gene, then can from above-mentioned source of disease is microbe-derived, the form with inverted order upwards search one by one, if find to carry the pathogenic microorganism of this special type disease, or carry the carrier of the extraordinary bacterium of the source of disease microbial antigen determinant gene that causes a disease, then can carry out different processing: when carrying microbe carrier for a long time as blood according to the number that carries microbe carrier, milk, urine, soil, the waters then can be from blood, milk, urine, soil, directly extract in the waters, separate, this complex disease pathogenic microorganism of vaccineization; When carrying microbe carrier, then can add suitable carbon source, nitrogenous source, bile mixing, and the simulation intestinal environment enters the antibacterial culturing stage according to the habit of carrying microorganism after a little while as patient (or animal) focus secretions, patient's underwear; (3) all can not get under satisfied result's the prerequisite in above-mentioned two kinds of methods, can be by engineered means, by preparing the antibacterial that the pathogenic microorganism epitopes gene of this special type disease is carried in operations acquisitions such as genes of interest, vitro recombination, gene transfer, screening, and add suitable carbon source, nitrogenous source, bile according to the habit of carrying bacterium or pathogen and mix, and simulate other intestinal environment and enter the antibacterial culturing stage; (4) in order to prepare the effect of reaching maturity, wide spectrum antigen that have the effect of comprehensive stimulation immune response, that have the effect of comprehensive enhance immunity cytoactive further with comprehensive promotion host immune system, can be at the middle and late stage of above-mentioned cultivation, the growth that is culture reaches middle logarithmic (log) phase during latter stage, adds an amount of fresh healthy human or animal's feces or healthy completely human faecal mass compound bacteria in system; (5) for system being created as antagonism, complementation, the symbiotic system of improving of many kinds, can in above-mentioned source of disease is microbe-derived, select one or more, if selected bacterium source is a solid, then available water or washing water of rice dissociate out with composite bacterial, can be at the middle and late stage of above-mentioned cultivation, the growth that is culture reaches middle logarithmic (log) phase during latter stage, among the adding system; (6) in order to save nitrogenous source and carbon source, in order to give gene segment and the antigenic determinant segment that stays multiple microorganism in the system, after solidss such as the thalline of depleted sterilization after one or more production of antibiotics, mycelium are collected mixing, add in the above-mentioned antibacterial culturing system as carbon source, nitrogenous source by proper proportion.

6, the microorganism culturing in the preparation method of compound biological as claimed in claim 3, it is characterized in that: the microorganism of microorganism culturing condition simulation is the intravital conditions of existence of host, more particularly the condition of anthropomorphic dummy or animal intestinal microenvironment: the ecological environment of promptly simulating cholic acid, nitrogenous source, carbon source, temperature, weary oxygen environment, multiple microbe symbiotic.

7, deactivation in the preparation method of compound biological as claimed in claim 3 and natural post processing: it is characterized in that, deactivation: when microorganism former enough, or deactivation is carried out in the growth of culture when reaching late logarithmic (log) phase to stable phase, ablation method comprises and kills deactivation or cracking deactivation, kill deactivation comprise the chemistry formalin fix the heat of physics, ultrasonic or radiation; The cracking deactivation comprises in ultrasonic fracture, oxidoreduction depolymerization, acid or the alkaline media controls hydrolysis, phage splitting, enzymatic hydrolysis, thereby the antigenic determinant that contains in complex microorganism is released; The nature post processing: when microorganism is former enough, or the growth of culture reaches late logarithmic (log) phase to stable phase, and under anaerobism (or little oxygen) environment, the initial stage complex microorganism is further bred, and exhausts all carbon sources, nitrogenous source and other energy and makes its liquefaction; Mid-term, phage made complex microorganism cracking one by one, liquefaction; Cut into genetic fragment or antigenic determinant fragment by enzyme with the macromole of phage and complex microorganism latter stage, thereby the antigenic determinant that contains in complex microorganism is released; Its end product is including, but not limited to the composition and the small amount of impurities of biologically actives such as flagellin, toxoid albumen, peptide, lipopeptid, polysaccharide, film lipopolysaccharide, oligosaccharide, pod membrane oligosaccharide, bacteriocin, antibiotic, short-chain fatty acid.

8, making with extra care in the preparation method of compound biological as claimed in claim 3, it is characterized in that: refining can be divided into for three steps: the first gets biological product complex liquid crude product with products therefrom by centrifugal, vacuum deodorization, it two is that biological product complex liquid crude product gets biological product complex liquid elaboration through ultrafiltration desalination, the supervisor that redissolves again, and it three is that biological product complex liquid crude product gets each effective ingredient separating medium through electrophoresis or several procedures such as resin absorption, desorbing again.

9, the preparation in the preparation method of compound biological as claimed in claim 3 is characterized in that: compound biological preparation of the present invention has three kinds, and first compositions is the deactivation product of complex microorganism, the preparation of pyrolysis product; Second kind is the active bacteria formulation that carries complex microorganism epitopes gene beneficial bacteria of intestinal tract; The third is the biological health fermented food that carries the complex microorganism epitopes gene; In the process of preparation, can also add and can further improve antigenic adjuvant according to the known prior art of professional, for example, but be not limited to, aluminum, water in oil emulsion, (ileum, colon targeting drug administration) microcapsule, or add other Chinese medicines or Western medicine is assisted a ruler in governing a country treatment; Wherein, first kind, second kind is applicable to people, animal, plant; The third is applicable to humans and animals.

1. compositions is the deactivation product of complex microorganism, the preparation of pyrolysis product: above-mentioned centrifugal, deodorize gained biological product complex liquid, refined liquid or refined mixed liquid, can directly make intestinal, the non-intestinal drug delivery agent of various liquid, human or animal's biological health food; Also can be by after being made into the pressed powder that is beneficial to preservation including, but not limited to dry means such as lyophilization, cryogenic vacuum spray drying, spray dryinges, solid, liquid, the intestinal canal administration preparation of making according to different demands that prior art can reach, non-intestinal drug delivery agent again, the biological health food of people, animal edible; Wherein, the intestinal canal administration preparation, can be the various intestinal canal administration preparations that specialty goes up common dosage, can also be micro-administration, trace administration, and by the energy frequency spectrum zero-dose administration of medicine, in the application number of I, application on March 15th, 2005 is 200510006033.8 and 200510053389.7 ' can effectively promote the activated and magnetic water maker of biological existence quality ' on January 7th, 2005, use or in future use is used for the treatment of and prevents the former medicament of people, animal and plant and infection and immune diseases associated preparation in the homeopathic therapeutic method;

2. carry the active bacteria formulation of complex microorganism epitopes gene beneficial bacteria of intestinal tract: with the deactivation product of complex microorganism, antigenic determinant in the pyrolysis product with the method for professional known gene transfer, or in the Nutrient medium that is added with the deactivation product of complex microorganism, pyrolysis product one or more beneficial bacteria of intestinal tract of inoculation (for plant for plant endogenesis predominant bacteria), and, this beneficial bacteria of intestinal tract is converted into carries complex microorganism epitopes gene beneficial bacteria of intestinal tract in suitable fermentation condition bottom fermentation cultured method; Solid, liquid, intestinal canal administration preparation, non-intestinal drug delivery agent that this beneficial bacteria of intestinal tract can make that prior art can reach according to different demands; The milk that the human or animal eats, yoghourt, curdled milk, cheese, fermented milk, bifid yoghourt, the basic fermented product of suckling, ice cream, frumentum fermented product; Milk powder, baby food, pet food or tablet, liquid bacterial suspension, dried oral supplement, wet oral supplement, dried tube feed, wet tube feed biological health food and feedstuff; Wherein beneficial bacteria of intestinal tract including, but not limited to: bifidobacterium bifidum, bifidobacterium breve, bifidobacteria infantis, bifidobacterium longum, lactobacillus acidophilus, Lactobacillus bulgaricus, cheese lactobacillus, Deshi Lactobacillus, Lactobacillus plantarum, streptococcus thermophilus, enterococcus faecalis, enterococcus faecalis, have a liking for citric acid leukonid, bacillus cereus, hay bud pole bacterium and lichenoid form bud pole bacterium;

3. carry the biological health fermented food of complex microorganism epitopes gene: with the deactivation product of complex microorganism, antigenic determinant in the pyrolysis product with the method for professional known gene transfer, or in the Nutrient medium that is added with the deactivation product of complex microorganism, pyrolysis product inoculating starter, and, this leaven is converted into carries complex microorganism epitopes gene leaven in suitable fermentation condition bottom fermentation cultured method; This leaven can be made including, but not limited to biological health fermented food and fermented feeds such as beans, fermented bean curd, soy sauce, vinegar, yogurt, bean yoghourt, fruit juice and fruit fermented beverage, fermented vegetable beverage, edible fungi beverage, cheese, yellow wine, medicated beer by prior art according to different demands; The present invention on technology with prior art different except that leaven, be that mainly last procedure needs the operation of heat sterilization to change the ultrasonication sterilization in the present invention in former technology, to guarantee the effectiveness of corresponding antigens determinant.

10, as the preparation in the preparation method of claim 3,9 described compound biologicals, it is characterized in that: the compound biological preparation also is applicable to animal, plant when being applicable to human body:

(1) animal:

1. compound biological can be used for common animals treatment of diseases and prevention as comprehensive compound therapeutic and preventative vaccine;

2. compound biological (when selecting the animal wastes degradation product for use) is alternative almost follows the animal hormone and the antibiotics in all one's life, thereby can reduce feeding cost, reduction hormone and antibiotics greatly to zootoxin side effect and residual back toxic and side effects to human body;

3. compound biological (when selecting patient's feces for use) produces corresponding antibodies in animal body after giving the oral or injection of animal, and people can obtain immunity by edible animal product such as egg, milk etc.;

(2) plant:

1. compound biological can be used for frequently seen plants treatment of diseases and prevention as comprehensive compound therapeutic and preventative vaccine;

2. alternative chemical fertilizer and the pesticide of almost following plant all one's life of compound biological, thus chemical fertilizer and pesticide can be reduced greatly to the toxic and side effects of plant and residual back toxic and side effects to human body;

3. compound biological (when selecting patient's feces for use) can be directly used in pre-transgenic plant sexual cell (for the seed of skin depth by adding an amount of moistening promoter, also can take the method for laser boring and/or ultrasonic importing assist to soak) the bubble of invading handle, injured root system wound absorbs, and foliar spray imports by the blade face pore and/or the florescence spraying imports the plant that Plant Transformation is become carry pathogen antigen determinant gene by pollen tube channel, because seed, the root system wound, the continuous stimulation of florescence and blade face external source pathogen antigen determinant gene protein, the pathogen antigen determinant is expressed at the plant camber, the direct-edible human or animal of making of edible part obtains immunity in the plant, the non-edible part of plant can be used for human or animal's immunity with behind the antigenic determinant extraction separation; Institute's platymiscium is foretold dish, bean sprout, bean seedlings, Nicotiana tabacum L., Fructus Musae, Herba Medicaginis including, but not limited to Caulis et Folium Lactucae sativae, Herba Spinaciae, Brassica campestris L, Rhizoma Solani tuber osi, Hu Luobu, Fructus Lycopersici esculenti, Fructus Solani melongenae, Fructus Capsici, Fructus Cucumidis sativi, Fructus Melo, Herba Apii graveolentis, Plantula Brassicae chinensis, water spinach, small gross.