CN107261147A - A kind of composition of stable living body biological active material - Google Patents

Abstract

Present invention is disclosed a kind of stable composition and its preparation method for preserving bioactive materials, said composition includes at least one polysaccharide with least one non-oxidation resistant bioactivity, and the bioactive materials of at least one live body, with at least one pharmaceutically acceptable matrix components, there is the polysaccharide of bioactivity not have activity suppression or killing action to the bioactive materials for this, and the bioactive materials are scattered or are embedded in the glassy struc matrix of the polysaccharide for having bioactivity comprising this and/or the matrix components.Said composition can preferably stablize bioactive materials (activity), extend its storage time or period of validity.The invention further relates to the purposes of the polysaccharide with bioactivity.

Description

A kind of composition of stable living body biological active material

Technical field

The present invention relates to a kind of composition.Specifically, the present invention relates to a kind of stable group for preserving bioactive materials Compound, further relates to its preparation method.

Background technology

Biomaterial, such as protein, peptide, nucleic acid, bacterium, cell, antibody, enzyme, serum, vaccine, liposome and virus, It is typically unstable when being stored in medium.

US8,968,721 disclose a kind of dry glass state matrix of protection probiotics, and the matrix is (single by polysaccharide, carbohydrate Sugar, disaccharide, oligosaccharides) and polyalcohol (sugar alcohol) composition.

US9,072,310, US9,480,276 disclose a kind of dry glass state matrix for protecting probiotics, the matrix by Polysaccharide, carbohydrate (monosaccharide and disaccharide, oligosaccharides) and protein composition.

US9,504,275, US9,504,750, CN104244985A disclose a kind of the steady of drying of bioactive materials Surely change composition, it includes carbohydrate (polysaccharide, monose, oligosaccharides, disaccharide or sugar alcohol) and protein hydrolysate, further also include carboxylic acid (salt) component, and it is formed as tablet or other forms that bioactive materials provide enhanced stability.

CN101287449B discloses the method and composition that bioactive materials are preserved with powdery matrix of microparticles.This method Gases at high pressure are provided to preparation to spray and/or close to supercritical spray, then dry to form bag in adjusted air-flow The powdery particulate of stabilization containing bioactive materials.Said composition contain polyol (such as trehalose, sucrose, sorbose, Melezitose, glycerine, fructose, mannose, maltose, lactose, arabinose, xylose, ribose, rhamnose, palactose, grape Sugar, mannitol, xylitol, red algae alcohol, threitol, D-sorbite and melitriose), polymer (such as starch, starch derivatives, carboxylic Methyl starch, HES (HES), dextran, human serum albumin (HSA) and gelatin, to provide the life to particulate The protection of thing active material and structure), surfactant etc. can also include amino acid stabilizers additive (such as lysine, smart ammonia Acid, amion acetic acid, methionine, histidine etc.).

Bioactive materials have been played important stable protective effect by above-mentioned technology, the polysaccharide particularly wherein referred to, but Still have greatly improved space.

The content of the invention

It is an object of the invention to provide a kind of stable dry compositions for preserving bioactive materials and preparation method thereof.

Based on above-mentioned purpose, a person of good sense shows on unexpectedly in sheet, on the basis of original technology, former common (inactive ) polysaccharide is substituted for the polysaccharide with least one non-oxidation resistant bioactivity, other are basically unchanged, compared to former common (nothing (but can have inoxidizability, because then there is inoxidizability containing reduced sugar in molecular structure) of bioactivity) polysaccharide, can be more preferable The stable bioactive materials (activity) in ground, extend its storage time or period of validity.Wish not limited by the theory, have The polysaccharide of at least one non-oxidation resistant bioactivity, (inactive (but can have inoxidizability, because dividing compared to common Then there is inoxidizability containing reduced sugar in minor structure)) polysaccharide, there is higher affinity with bioactive materials, it is living to biology Property material primary structure, particularly secondary structure has preferably stable and protective effect, so as to have to it preferably stable And protective effect.

The present invention relates to a kind of stable composition for preserving bioactive materials, said composition includes (/ include) at least one Kind with it is at least one it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, remove free radical isoreactivity) biology The polysaccharide of activity, and at least one live body bioactive materials, and at least one pharmaceutically acceptable matrix components, the tool There is the polysaccharide of bioactivity not have activity suppression or killing action to the bioactive materials, the bioactive materials it is scattered or The glassy struc matrix for being embedded in the polysaccharide for having bioactivity comprising this and/or the matrix components (solid solution or is consolidated Body colloidal sol) in.

The invention further relates to a kind of purposes of the polysaccharide with bioactivity, the purposes has the polysaccharide of bioactivity for this For the stable composition for preserving the bioactive materials comprising live body, said composition includes that (/ include) is at least one to be had extremely It is few a kind of it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, remove free radical isoreactivity) bioactivity it is many Sugar, and at least one live body bioactive materials, and at least one pharmaceutically acceptable matrix components should have biological living Property polysaccharide do not have activity suppression or killing action to the bioactive materials, the bioactive materials are scattered or are embedded in bag The polysaccharide and/or the glassy struc matrix (i.e. solid solution or solid sol) of the matrix components that there is bioactivity containing this In.

When describing and advocating the present invention, following term will be used according to following definitions.It should be appreciated that making herein The purpose of term is just for the sake of description embodiment, it is no intended to limit.

In use, singulative " one ", " one kind ", " one " and " this " in this specification and appended claims Including its plural form, unless it is not such that context, which is clearly indicated,.Thus, for example, mentioning " protein " then includes single egg The combination of white matter or two or more protein；Mentioning " enzyme ", " bacterium " etc. then includes single or several types mixing Thing, etc..

Term " bioactive ingredients ", " bioactive materials " and " biomaterial " in the present invention is biological all referring to allowing In the molecular structure of the microorganism of activity or composition, its main or basis or basic composition or constituent comprising peptide chain or Protein chain or nucleic acid chains.Suitable for the present invention bioactive materials include but is not limited to active peptide, reactive protein, enzyme, swash Element, nucleic acid, antibody, vaccine, microorganism (such as yeast, fungi, bacterium (probiotics is other), virus, edaphon), lipid Body, serum and/or cell suspension.

Term " biological (medicine) composition " in the present invention refers to the biology in permission bioactive ingredients or reagent Prepared product (preparation) under active clearly effective form, and not comprising poisonous another of any subject being administered to composition Outer composition.

Term " stable (property) " in the present invention refers to that the bioactive materials in preparation or composition are basic after storage Upper its physical stability of reservation, chemical stability and/or bioactivity.Various analytical technologies for determining stability are abilities Domain is available, and visible, such as peptide and protein administration " (Peptide and Protein DrugDelivery), 247~ 301, Vincent Lee Ed., Marcel Dekker, Inc., New York, N.Y., Pubs. (1991) and Jones, A.Adv.Drug Delivery Rev.10：29~90 (1993)., can be in selected temperature for selected time span Stability is measured under degree and damp condition.The expected shelf life can be estimated with usage trend analysis, it is then just that material is real Border stores the time span.For example, for bacterium living, stability is defined as long in predetermined temperature, humidity and time The time that 1log CFU/g dry preparations are spent is lost under the conditions of degree.For influenza virus living, stability is defined as it and released Put 1logFFU/ml or 1logTCID₅₀Time used in/ml.

Wherein bioactive materials retain its physical stability and/or change substantially when " stabilization " preparation or composition are storages Learn the preparation or composition of stability and/or bioactivity.Said composition in the stable at least three month of (~25 DEG C) of room temperature and/or Stablize at least 1 year at about 2~8 DEG C preferably.Moreover, said composition in freezing (arrive, such as -70 DEG C) and after melting it is still stable compared with It is good.

For bacterium, " vigor " refers to the ability (CFU that bacterium colony is formed on the nutrient media for be suitable for bacterial growth Or CFU).For virus, vigor refers to the suitable host cell of infection and numerous in suitable host cell Grow, cause the ability that plaque is formed on the lawn (lawn) of host cell.

" glass strengthening agent ", " glass strengthening compound " and " glass formers " is used interchangeably herein, and referring to can be With the compound for forming amorphous or glassy struc ability during less than critical-temperature (glass transition temperature (Tg)).In glass In the formation of glass matter structure, biological substance can be embedded in glass structure.The combination of glass formers is also contemplated for single In composition.Method for obtaining glassy struc for the purpose of the present invention is typically solvent distillation and/or evaporation technique. Ideally, the compound for belonging to GRAS compounds is preferable over those compounds for being not belonging to GRAS.

" glass " or " glassy state " or " glass matrix " refer to liquid that fluid ability substantially reduces (i.e. solid solution or solid Colloidal sol), in other words, very highly viscous liquid, wherein range of viscosities is 10¹⁰To 10¹⁴Pascal second.It is considered The amorphous system of meta-stable, wherein molecule have oscillating movement but have rotation and the translational component of very slow (almost not measuring).Make For meta-stable system, it can stablize in a long time when being stored in the temperature far below glass transition temperature.Due to glass not In thermodynamic equilibrium state, it is stored in glass transition temperature and the glass close to glass transition temperature is relaxed to and balances and lose High viscosity.Produce like rubber or syrupy shape, working fluid often in chemistry with it is unstable in structure.Although glass can Obtained, but no matter obtained with any approach by many different approaches, it appears that the physically material as being in structure. The method of glass matrix for obtaining the present invention is typically solvent distillation and/or evaporation technique.

" glass transition temperature " is represented with symbol Tg, refer to composition from glass or class vitreousness be changed into syrupy shape or Like the temperature of the state of rubber.Usual Tg is by being somebody's turn to do using differential scanning calorimetry (DSC) determination and standard regulation scanning The temperature of change takes place as glass transition temperature in composition thermal capacity (Cp) during transformation.Tg definition length is often any , international regulations are there is no at present.Tg can be defined within beginning, midpoint or the end of conversion；We use for purposes of the invention The beginning of Cp changes on DSC and DER.Refer to entitled " with liquid and biopolymer formation glass " (" Formation of Glasses from Liquids andBiopolymers ") document, C.A.Angell：Science, 267,1924~1935 (Mar.31,1995) and entitled " the differential scanning calorimetry analysis of gamma transition " (" Differential Scanning CalorimetryAnalysis of Glasses Transitions ") document, Jan P.Wolanczyk：Cryo- Letters, 10,73~76 (1989).Detailed Mathematical treatment is shown in " gamma transition characteristic and window state " (" Nature of TheGlass Transition and the Glassy State "), Gibbs and DiMarzio：Journal ofChemical Physics, 28, NO.3,373~383 (March, 1958) these documents are incorporated herein by reference.

" pharmaceutically acceptable " matrix components (excipient, carrier, additive etc.) are that those can be reasonably administered to Mammalian subject is to provide the non-active ingredient used of effective dose.These excipient are China or United States drug management Office (SFDA or FDA) must indicate that preferable for " generally recognized as safe " (' Generally Regarded assafe ' (GRAS)).

" recommended storage temperature " is powder pharmaceutical composition storage for composition with the pot-life of said composition The interior temperature for keeping drug product stability to ensure its general releasing dosage.The temperature starts to be determined simultaneously by the manufacturer of composition By the government organs' approval (e.g., China or United States drug management board (SFDA or FDA)) for being responsible for approval composition sale.The temperature Change with each approved drug products, depending on the temperature sensitivity of active medicine in product and other materials.Recommend The change of storage temperature is about less than about 0 DEG C to 40 DEG C, but typically environment temperature, i.e., about 25 DEG C.Drug products are usually stored up There is recommended storage temperature or less than in recommended storage temperature.

If being that the pharmaceutical composition is reflected when preparing with combining in the bioactivity of preset time bioactive materials such as enzyme Within about 10% (within analytical error) of the bioactivity for determining method determination, then bioactive materials are in pharmaceutical composition " retaining its bioactivity ".For protein, such as antibody, with analytical technology such as size exclusion HPLC, FTIR, DSC, CD, ELISA The purity of acquisition is related to bioactivity.When living viral, composition virus titer a log starting It is believed that bioactivity is retained within potency.Analysis for determining Influenza virus titers is fluorescent foci analysis (Fluorescent Focus Assay)(FFA assay).Thus the potency of acquisition is analyzed with every milliliter of fluorescent foci unit (Fluorescent Focus Unit permilliliter) (FFU/ml) is represented.One FFU/ml is approximately equal to one per milli, Then bioactive materials in pharmaceutical composition " retaining its bioactivity " rise tissue culture infection (Tissue Culture InfectiousDose per ml)(TCID/ml)。

If for example caused in preset time chemical stability as noted above it is believed that bioactive materials still retain its life Thing activity, then bioactive materials " retain its chemical stability " in pharmaceutical composition.Or, chemical stability definable For for example, the biomaterial structure obtained using suitable analytical technology does not have significant change.Chemical stability can be by right The chemical change form of bioactive materials is detected and quantifies to evaluate.Chemical change can relate to size and change (such as egg White matter is wiped out), useful size exclusion chromatography, SDS-PAGE and/or matrix assisted laser desorption ionization/flight time mass spectrum Method (MALDI/TOF MS) is evaluated size and changed.Other kinds of chemical change includes the electricity such as evaluated with ion-exchange chromatography Lotus changes (e.g., the result of desamidation).

If for example to color and/or the visual inspection of the transparency, or with UV light scattering or passing through SEC Measurement display aggregation, precipitation and/or denaturation are not significantly increased, then bioactive materials " retain its thing in pharmaceutical composition Manage stability ".

In pharmacy meaning, bioactive materials " therapeutically effective amount " refer to the prevention or therapeutically effective amount to illness, Wherein " illness " is any disease that can be benefited from the treatment of bioactive materials.This includes chronic and acute illness or disease Disease, including those make mammal be susceptible to suffer from the pathological conditions of above-mentioned illness.

" treatment " refers to treatment processing and prevention or Prevention method.What those needed to treat include had an illness and it is pre- Anti- illness.

" unit dose " refers to the container of the composition comprising therapeutically effective amount of the present invention.

In the situation of drying agent composition, " water activity " or " Aw " refers to the availability of water, and represents system The energy state of reclaimed water.It is defined as the vapour pressure of the vapour pressure divided by pure water of water on sample at the same temperature.Pure distillation The water activity of water is just 1, i.e. Aw=1.0.

In the situation of storage stability, " relative humidity " or " RH " refers to water vapor in air at a given temperature Amount.Relative humidity, which is usually less than, makes the humidity needed for the saturation of the air, and is represented with the percentage of saturated humidity.

" drying " and its version refer to dehydration or anhydrous, i.e., substantially lack the physical state of liquid.Drying includes Such as spray drying, fluidized bed drying, lyophilized and vacuum drying.

" lyophilized " or freeze-drying refer to by snap frozen and in a cold or frozen state dehydration (sometimes referred to as distillation) come Prepare the composition of dried forms.Lyophilized betide causes at a temperature of sugar crystallizes.This process can be enough to maintain freezing to produce Occur under the vacuum of thing (in some embodiments, below about 2000mTORR).

" environment " room temperature or condition are the temperature or condition of any preset time in a given environment.Generally, ambient room temperature It is 22~25 DEG C, environment atmospheric pressure and ambient humidity are easily measured, and with the time in 1 year, weather and weather Condition, height above sea level etc. and become.

Embodiment

1st, the polysaccharide with bioactivity

The polysaccharide with bioactivity for the present invention generally makees glass strengthening agent (glass strengthening compound or glass shape Into agent) and stability protective agent, can be have it is one or more it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, Remove free radical isoreactivity) bioactivity/or pharmacological activity polysaccharide, such as there is anti-inflammatory selected from (including but is not limited to), resist Stress, radioresistance, adjust immune, antitumor, anti-infective (antibacterial, antibacterial is antiviral), promotion hematopoiesis, diuresis, antiulcer, drop Blood fat (or reduction cholesterol), hypoglycemic, hypotensive, antithrombotic, protection internal organs (such as liver/stomach), protection nerve, protection system genitale Unite, promote blood circulation, regulation nucleic acid or protein metabolism, promote DNA synthesis, promotion cell propagation and enhancing learning and memory etc. Effect or function the non-oxidation resistant bioactivity/of middle one or more or the polysaccharide of pharmacological activity, but it is preferred that the polysaccharide also With it is anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, remove free radical isoreactivity) activity.Tool for the present invention The polysaccharide for having bioactivity, which particularly preferably has, (partially or completely) identical bioactive functions or (portion with bioactive materials Divide or complete) identical medical usage (with bioactivity) polysaccharide, particularly preferably have has enhancing to bioactive materials (having bioactivity) polysaccharide that is its active function or having synergy between the two, has many of bioactivity compared to other There are sugar, above two the polysaccharide of bioactivity and bioactive materials to have higher affinity, to bioactive materials Primary structure and secondary structure have preferably stable and protective effect, have preferably stable and protective effect to it, particularly The latter.

For the polysaccharide with bioactivity of the preferred biological source of the polysaccharide with bioactivity of the present invention, such as plant Thing, macro fungi (such as edible fungus) class, algae, the polysaccharide with bioactivity of microorganism or animal origin, it is more preferably excellent The polysaccharide with bioactivity of the biological source of choosing entirety or part " integration of drinking and medicinal herbs ".

The preferably water miscible polysaccharide with bioactivity of the polysaccharide with bioactivity for the present invention.

Average weight-average molecular weight Mw for the polysaccharide with bioactivity of the present invention is usually 10,000 to 800,000 Dalton, preferred molecular weight is 40,000 to 300,000 dalton, more preferably molecular weight 40, and 000 to 200,000 dalton is special It is not the dalton of preferred molecular weight 60,000 to 200,000.

(solute is for its solution when the polysaccharide preferred concentration with bioactivity for the present invention is 2% (mass/volume) Water) viscosity less than 200mPas (it is preferred that less than 100mPas, more preferably, less than 50mPas, more preferably, being less than 30mPas. most preferably, less than 20mPas) the polysaccharide with bioactivity.

Degree of branching for the polysaccharide with bioactivity of the present invention is preferably 0.04~0.75 (it is preferred that being 0.05 ~0.5, be 0.1 more preferably~0.4).

For in addition to comprising (many) glycosyls (/ chain), may be used also in the polysaccharide molecule structure with bioactivity of the present invention Comprising peptidyl (/ chain), protein-based (/ chain), nucleic acid base (/ chain), lipid (lipoid) base (/ chain), included in preferred molecular structure The polysaccharide with bioactivity of peptidyl (/ chain) or protein-based (/ chain) or nucleic acid base (/ chain), the inventors discovered that this kind of many Sugar is stable, protect the with better function of bioactive materials.

The polysaccharide with bioactivity for the present invention can have been crossed molecular modification, performed the derivatization, As degraded, sulphation, sulfonylation, acetylation, alkylation, Phosphation, Sulfation, stearoylation, palmitoylation, diethyl Base is aminoethylated, carboxy methylation, carboxyethylation, iodate, nitridation etc., be conducive to improving its affinity with bioactive materials Property, strengthen the stable protective effect to bioactive materials.

The polysaccharide preferred embodiment with bioactivity for the present invention includes LBP-X, and (proteoglycan, increase is immune Ability, anti-oxidant and anti-aging, antitumor, neuroprotection, radioresistance, protection reproductive system etc.), (albumen is more for lentinan Sugar, it is anti-oxidant, antiviral, antitumor, regulation immunologic function and stimulate interferon formed), astragalus polyose (molecular weight 1~50,000, It is antiviral, antitumor, anti-aging, radioresistance, resisting stress, anti-oxidant), panaxan (molecular weight 5~160,000, anti-oxidant, enhancing Immunity, promotes hematopoiesis, hypoglycemic, antidiuresis, anti-aging, antithrombotic, antibacterial, anti-inflammatory is antitumor), BCG-polysaccharide it is (immune Regulation), Hemarisin (lipopolysaccharides, antitumor, immunological regulation), glossy-ganoderma-spore polysaccharide (adjustment vegetative nerve function, improve and micro- follow Ring, enhancing body immunity), the grifola polysaccharide cellular immune function of body (improve), Human Placental Lipo-glucosaminoglycan (lipopolysaccharides, strong machine Body is acted on the nonspecific immunity power of various bacteria and virus), it is Inokopolyose (improve immunity, antitumor, anticoagulation), (low Molecular weight, ＜ 10 ten thousand) algal polysaccharide (hypoglycemic anticoagulation, reducing blood lipid, antitumor and AntiHIV1 RT activity), polysaccharide from urtica fissa (anti-inflammatory, analgesia and Suppress hyperplasia of prostate), seam split (albumen) polysaccharide (antitumor), Cordyceps sinensis polysaccharide (tool it is anti-oxidant, improve immune function of human body, rise It is high leukocytic, hypoglycemic), (hypoglycemic, reducing blood lipid, antithrombotic is anti-oxidant, removes free radical, anti-aging, anti-spoke for GL-B Penetrate, it is antitumor, promote blood circulation, regulation is immune, adjusts Metabolism of nucleic acids and proteins, promote DNA synthesis, promote human navel blood LAK cells are bred), ganoderma spore polysaccharide (tool anti-oxidant, regulation immunity of organism), Hijiki polysaccharide (molecular weight, 4.2~9.5 ten thousand It is reducing blood lipid, hypoglycemic), lentinan (containing proteoglycan, have anti-oxidant, anticancer, hypoglycemic, blood fat, cholesterol), coriolan (- K) (containing proteoglycan, anti-oxidant, antitumor action, immunological enhancement and protection liver), corn silk polysaccharide (regulation blood Sugar, suppress tumour growth, regulation immunity of organism and anti-oxidant), silk cocoon polysaccharide (hypoglycemic), Fructus Schisandrae Polysaccharide (liver protection, anti-lack It is oxygen, antifatigue, strengthen immunity, anti-aging, anti-oxidant, antitumor), black nightshade polysaccharide (antitumor), black nightshade proteoglycan it is (anti-swollen Knurl), Chinese mugwort polysaccharide (regulation blood glucose, regulation immunity of organism and anti-oxidant), lily polysaccharide (exempt from by hypoglycemic, antibacterial, antitumor, regulation It is epidemic disease, antifatigue), Method of Polysaccharide in Radix Pinellia (antitumor), spirulina polysaccharide (antitumor, radioresistance, promote DNA synthesis and Immune-enhancing effect to make With), Chinese pine pollen polysaccharide (anti-oxidant, antitumor, strengthen immunity), Taraxacum Polysaccharides it is (antibacterial, anti-oxidant, immunological regulation, anti- Mutation, antifatigue, hormone control), epimedium brevicornum polysaccharide (immunological regulation), humulus grass polysaccharide (antibacterial), Gentiana Polysaccharides (anticoagulation, drop Blood fat, antitumor, immunological regulation), white chessman grass polysaccharide (hypoglycemic), Cells of Blue-green Algae exo polysaccharides (active anticancer), soluble polysaccharide (point Son amount 4000~10000) (anti-oxidant, strengthen immunity, hypoglycemic, anti-aging is antitumor), cactus polyoses (molecular weight 17.2 ten thousand, anti-aging, anti-inflammatory, anticancer and hypoglycemic), date polysaccharide (molecular weight 6.3 to 26.3 ten thousand, strengthen it is immune, anti-oxidant, Antitumor, anti-aging), Armillariella mellea (halimasch) polysaccharide (molecular weight, 7~13 ten thousand) (anti-oxidant, strengthen immunity, it is hypoglycemic, it is anti-ageing Always, anti-Alzheimer disease (AD), antitumor, anti-mutation), (water solubility) buckwheat polysaccharide (molecular weight 17.2 ten thousand) (immunological regulation, It is antitumor, antiviral and anti-infective), maize peel polysaccharide (molecular weight 10~18.6 ten thousand) (anti-oxidant, immunological regulation, antitumor), (weight average molecular weight 58.8 ten thousand, number equal 14.3 is ten thousand) (reducing blood lipid), black for corn pollen polysaccharide (suppression tumour), black fungus acidic polysaccharose Auricularia polysaccharide (molecular weight 150,000) (anticoagulant active, platelet aggregation-against and antithrombotic), (water solubility) nostoc (Nostoc commune) Polysaccharide (enhancing is immune, antibacterial, antitumor), root of herbaceous peony polysaccharide (molecular weight, 5.5 ten thousand proteoglycans) (antitumor, anti-oxidant), aloe 3.8 ten thousand) polysaccharide (molecular weight, (immunological regulation, antitumor, liver protecting, radioresistance, antiulcer, anti-oxidant, anti-aging and drop blood Sugar), Banlangen Polysaccharide (molecular weight, 0.25~2.6 ten thousand, anti-oxidant, immunological regulation, it is antiviral, sterilization and it is antibacterial), mulberries polysaccharide 7~10 ten thousand) (molecular weight, (anti-oxidant, regulation metabolism of blood glucose, immunological regulation), algal polysaccharides (6.8 ten thousand) are (immunological regulation, disease-resistant The effect of malicious, anti-oxidant, antitumor, complexing of metal ion), (water solubility) Chinese yam polysaccharide (molecular weight, 6.3~7.4 ten thousand) (exempt from by regulation It is epidemic disease, hypoglycemic, anti-oxidant, anti-aging, antitumor), (water solubility) zymosan (proteoglycan, oxidation resistance, growth promotion, Antiviral, Immune-enhancing effect, mitigate radiation injury, it is antitumor, absorption pathogen), rape pollen polysaccharide (proteoglycan, molecular weight, 80000 oxidation resistances (5~100,000 is most strong), Immune-enhancing effect, the protective effect of hepatic injury), coleseed polysaccharide (proteoglycan, resist It is oxidation, antitumor), Polysaccharide From Salvia Chinensis (regulation immune, anti-oxidant, antitumor), (regulation is immune, anti-oxidant, resists and swells for hedysarum polybotys saccharide Knurl), (water solubility) loquat leaf polyose (antioxidation, enhancing immune performance), (leaf roll) Siberian solomonseal rhizome polysaccharide (it is antitumor, anti-oxidant, Immunological regulation, antibacterial anti-inflammatory), tea polysaccharide (anti-oxidant, strengthen immunity, hypoglycemic, reducing blood lipid, radioresistance make, suppress leukaemia Cell is bred), Chinese hawthorn leaf polysaccharide (lowering blood pressure and blood fat, anti-inflammatory), squash polyoses (anti-oxidant, strengthen immunity, hypoglycemic), Laminarin (it is anti-oxidant, antitumor, improve renal failure, reduction blood fat, reduce blood pressure), Onion Polysaccharide (it is anti-oxidant, improve Immunity, reducing blood lipid), Scutellaria Barbata D. Don Polysaccharides (anti-oxidant, antitumor, regulation immune), pleurotus nebrodensis polysaccharide (it is anti-oxidant, antitumor, adjust Section is immune), Polysaccharide in Pleurotus eryngii (anti-oxidant, hypoglycemic, strengthen immune, antiviral, antitumor, reducing blood lipid), Pleurotus ferulae polysaccharide (resist Oxidation, anti-inflammatory, it is antitumor, improve immunity of organisms, radioresistance), garlic polysaccharide (anti-oxidant, antiviral, regulating blood lipoid, reduction Blood glucose, strengthen immunity, treatment vital myocarditis, improve hepatic injury), banana skin polysaccharide (it is anti-oxidant, antitumor, hypoglycemic, Antibacterial), maca polysaccharide (anti-oxidant, anti-aging, hypoglycemic, improve immunity, antiviral and anticancer), Sweet Potato Polysaccharide it is (anti-swollen Knurl, anti-oxidant, antibacterial, regulation are immune, hypoglycemic), watermelon peel polysaccharide (anti-oxidant, anti-aging, hypoglycemic), mao bamboon petiole polysaccharide (anti-oxidant, hypoglycemic), lithosperman (anti-oxidant, anti-aging, improve immunity, anti-inflammatory, suppress HPV, it is anti-prominent Become), cordate houttuynia polysaccharide (anti-oxidant, antitumor), dendrobium polysaccharide (anti-oxidant, antitumor, regulation immune and reduction blood glucose), balsam pear Polysaccharide (anti-oxidant, hypoglycemic, antitumor, antibacterial (such as significantly inhibiting staphylococcus aureus, Escherichia coli, aspergillus niger)), Hu Radish polysaccharide (anti-oxidant, hypoglycemic, anti-inflammatory), Russula polysaccharide (anti-oxidant, hypoglycemic, reducing blood lipid, antitumor, regulation are immune), rose Rare colored polysaccharide (anti-oxidant, antitumor, regulation is immune), ophiopogonpolysaccharide (it is anti-oxidant, resist myocardial ischemia, hypoglycemic, resist oxygen lack energy Power, promote immunologic function), blazei polysaccharide (anti-oxidant, antitumor action, it is hypoglycemic, improve diabetes, norcholesterol, improve dynamic Arteries and veins is hardened), (bar) sea grass polysaccharide (anti-oxidant, adjust immune, antibacterial, reducing blood lipid and antitumor), Stropharia rugoso-annulata polysaccharide (antioxygen Change, it is antibacterial), Bupleurum chinense polysaccharide (molecular weight 330,000, anti-oxidant, radioresistance, reducing blood lipid, enhancing immunologic function and antiviral, anti-swollen Knurl), Morchellaconica extracellular polysaccharide (anti-oxidant, antitumor, anti-aging, immunocompetence), fall certain herbaceous plants with big flowers polysaccharide (it is anti-oxidant, regulation It is immune, antitumor, antifatigue), Moringa polysaccharide (antiviral), Polysaccharides in Bamboo Leaves (it is anti-oxidant, adjust it is immune, antitumor, antifatigue, Hypoglycemic, antibacterial), (water solubility) Agrocybe chaxingu polysaccharide (anti-oxidant, regulation immune), (water solubility) mushroom polysaccharide (it is anti-oxidant, adjust It is immune, antitumor, improve human body metabolism, adjust vegetative nerve, norcholesterol, hypotensive and prevent and treat hepatitis, gastric ulcer, Duodenal ulcer), (water solubility) rabdosia lophanthide polysaccharide (anti-oxidant, antibacterial), (water solubility) cassia seeds polysaccharides (it is anti-oxidant, promote Growth of animal, enhancing immunologic function, raising intestinal beneficial bacterium quantity reduce the harmful microorganism quantity such as conditioned pathogen improvement intestines Road micro-ecological environment), (water solubility) bamboo shoots polysaccharide (anti-oxidant, regulation is immune, promote bifidobacterium growth), (water solubility) turnip Polysaccharide (molecular weight, 10,000, anti-oxidant, hypoglycemic) (water solubility) Saussurea Polysaccharide (anti-oxidant, antibacterial), (water solubility) Folium Panacis Quinquefolii Polysaccharide (anti-oxidant, immune, antitumor, the hypoglycemic, preventing cold of regulation and the infection of the upper respiratory tract, radioresistance), (water solubility) pupa Cordyceps sinensis polysaccharide (anti-oxidant, liver injury protection), (water solubility) stauntonvine polysaccharide (suppressing platelet aggregation, liver injury protection), (water Dissolubility) pachymaran (anti-oxidant, anti-aging, immune-enhancing activity, antiviral, antitumor, mitigate chemicotherapy side effect), (water Dissolubility) Glehnia Littoralis Polysaccharide (anti-oxidant, immunosuppressive activity), (water solubility) dictyophora fungus polysaccharide be (antioxidant, immunopotentiator, anti- Tumour, antibacterial (aspergillus, penicillium oxalicum, withered single bacillus, large intestine bar Tong and Staphylococcus aureus mattress)), (water solubility) Mongolian oak fern Polysaccharide (antibacterial, antibacterial), (water solubility) oyster polysaccharide (antitumor, hypotensive, protection hepatic injury, suppress proliferation of influenza virus), (water solubility) Codonopsis pilosula polysaccharide (anti-oxidant, anti-aging, immune enhancing, stimulation hematopoiesis, antitumor, enhancing memory capability, reduction blood Sugar, improve digestion power, protection NSC, resisting stress, antiinflammatory action), (water solubility) polysaccharide from Dunaliella salina it is (anticoagulation, disease-resistant Poison, antithrombotic, antitumor, strengthen immunity, regulation immunity, removing free radical, anti-aging, anticoagulation and antithrombotic, AntiHIV1 RT activity Virus, the disorder of elimination gastronintestinal system, antiallergy, enhancing liver function, reduction high fat of blood and hypertension, stabilizing blood sugar level, promotion Skin regeneration, skin moisture-keeping), (water solubility) Glehnia Littoralis Polysaccharide (immunosupress), (water solubility) elm fungus polysaccharides (antitumor), (water Dissolubility) pomelo peel hydrolyzed pectin polysaccharide (antibacterial), (water solubility) gastrodia elata polysaccharide (anti-oxidant, immunological regulation, hypotensive, combating vertigo Disease, antibacterial (such as Escherichia coli, mould, head mold mould and staphylococcus aureus, Bacterium enteritidis and bacillus subtilis Bacterium), (water solubility) cockroach polysaccharide (enhancing immune), (anti-oxidant, anti-aging, enhancing be immune, anti-swells for (water solubility) Ginkgo biloba polysaccharide Knurl), (water solubility) flammulina velutipes (improve immunity, liver protection, moisturizing, anti-infective, anti-oxidant, auxiliary improvement of memory and alleviation Physical fatigue), (water solubility) speciosus polysaccharide (anti-oxidant, antitumor and immunological regulation), oat polysaccharide (it is hypoglycemic, drop blood Fat, immunological regulation), peanut polysaccharide (immunological regulation, protection liver, hypotensive, anti-oxidant), newborn source casein polysaccharide (improve and burst Ulcer colitis), chondroitin sulfate proteoglycan (norcholesterol, anti-inflammatory, accelerating wound healing, enhancing human body constitution, disease-resistant It is bacterium, beauty, anti-ageing), Fructus Schisandrae Polysaccharide (anti-oxidant, anti-aging, immune enhancing, increasing leucocyte, antitumor, protect liver, analgesia, drop Fat fat-reducing, antiallergic action) (), (small molecule) proteoglycan decorin (regulation collage synthesis, the increasing of participation regulation cell Raw, migration), bacterioprotein polysaccharide (immunological regulation), QINBA selenium-mushroom extract selenoprotein polysaccharide (antitumor), mushroom protamine polysaccharide (protect liver), brown algae protein polysaccharide (anti-oxidant, promotion hematopoiesis and immunological regulation), abalone visceral protein polysaccharide are (anti-oxidant, anti-swollen Knurl, immunological regulation), U. pertusa polysaccharide (hypoglycemic, reducing blood lipid, anti-oxidant), U. pertusa proteoglycan (antiviral), Chinese yam polysaccharide (containing proteoglycan, anti-oxidant, anti-aging, enhancing are immune, antitumor, hypoglycemic), (such as ganoderma lucidum coagulates (higher fungus) agglutinin Collect cell, activated lymphocyte stimulates the division of lymphocyte；Immunological regulation and suppress tumour growth), ganoderma lucidum glycoprotein/sugar Peptide (enhancing immune, antitumor), mulberry leaf polysaccharide (anti-oxidant, hypoglycemic, anticoagulation), spirulina protein polysaccharide are (anti-mutagenesis, anti-swollen Knurl), newborn mushroom polysaccharide (immunological regulation, antitumor, antibacterial), Pasteur mushroom proteoglycan (hypoglycemic, immunological regulation), mankshood polysaccharide (neutral polysaccharide, Aci dic proteinpolysaccharide, immunological regulation, antitumor), hericium erinaceum polysaccharide (contain proteoglycan, antiulcer, anti-inflammatory are made With, antitumor action, liver protecting, increase immunity, anti-aging, improve body's hypoxia tolerance, increase heart blood export Amount, accelerate body blood circulation, reduction blood glucose, the effect of blood fat), kamuning GL-PP polysaccharide (antifertility), hydriopsis cumingii Polysaccharide (containing proteoglycan, anti-oxidant, immunological regulation, antitumor), Goods-Flow Plan (anti-oxidant, antitumor, protection hematopoiesis function, Enhancing is immune, promote hematopoiesis function), echinacea polysaccharide (antitumor), notoginseng polysaccharide (contain albumen/peptide polysaccharide, it is immunological regulation, anti-swollen Knurl), sposknikovan (anti-oxidant, antitumor), licorice polysaccharide (anti-oxidant, immunological regulation, antiviral, antitumor and bacteriostasis) With Radix Et Caulis Acanthopanacis Senticosi polysaccharide (anti-oxidant, immunological regulation, antitumor), semen litchi polysaccharide (hypoglycemic), Inonotus obliquus core polysaccharide (hypoglycemic), Sclerotium of Pleurotus tuber regium polysaccharide (hypoglycemic), and its mixture.

Consumption of the above-mentioned polysaccharide with bioactivity in above-mentioned composition is 0.5% (wt/wt) to 80% (wt/ ), wt preferably 1% (wt/wt) to 70% (wt/wt), more preferably 5% (wt/wt) to 50% (wt/wt), particularly preferably 5% (wt/wt) to 40% (wt/wt), the consumption is calculated based on above-mentioned composition overall weight.

2nd, the bioactive materials of live body

Bioactive materials for the live body of the present invention refer to bioactivity dead microorganism non-in other words or Micro-assembly robot, they be generally selected from and (include but is not limited to) microorganism (such as yeast, fungi, bacterium (probiotics is other), virus, Edaphon) or cell suspension, and their mixture.

It is thin that suitable cell example for the present invention is selected from (including but is not limited to) red blood cell, stem cell, T cell, COS Born of the same parents, NSO cells, Chinese hamster ovary celI, HT1080 cells, PER-C6 cells, bhk cell, Sf-9 cells, 293 or 293-EBNA cells, And their mixture.

For the present invention microorganism be selected from (including but is not limited to) yeast, fungi, bacterium (probiotic bacteria), virus, Edaphon, and their mixture.

(including but is not limited to) yeast, such as saccharomyces are selected from for the suitable microorganism of the present invention or probiotics example (Saccharomyces), Debaryomyces (Debaromyces), candida (Candida), pichia category (Pichia) and Torulopsis (Torulopsis), mould, such as aspergillus (Aspergillus), rhizopus (Rhizopus), Mucor (Mucor), Penicillium (Penicillium) and Torulopsis (Torulopsis), and bacterium, such as Bifidobacterium Belong to (Bifidobacterium), Clostridium (Clostridium), Fusobacterium (Fusobacterium), honeybee Coccus (Melissococcus), Propionibacterium (Propionibacterium), streptococcus (Streptococcus), Enterococcus spp (Enterococcus), lactococcus (Lactococcus), Cook Pseudomonas (Kocuriaw), staphylococcus (Staphylococcus), Peptostreptococcus (Peptostrepococcus), bacillus (Bacillus), piece coccus Belong to (Pediococcus), Micrococcus (Micrococcus), Leuconostoc (Leuconostoc), Wei Si Bordetella (Weissella), Aerococcus (Aerococcus), wine Coccus (Oenococcus) and lactobacillus (Lactobacillus)。

It is preferred that probiotics example be selected from (including but is not limited to) aspergillus niger (Aspergillus niger), aspergillus oryzae (A.oryzae), bacillus coagulans (Bacillus coagulans), slow bacillus (B.lentus), lichenoid form gemma It is bacillus (B.licheniformis), goldbeater's skin bacillus (B.mesentericus), bacillus pumilus (B.pumilus), withered Careless bacillus (B.subtilis), bafillus natto (B.natto), bacteroides amylophilus (Bacteroides Amylophilus), bacteroides capillosus (Bac.capillosus), the raw bacteroid of cud (Bac.ruminocola), pig bacteroid (Bac.suis), bifidobacterium adolescentis (Bifidobacterium adolescentis), animal bifidobacteria (B.animalis), bifidobacterium breve (B.breve), bifidobacterium bifidum (B.bifidum), bifidobacterium infantis (B.infantis), bifidobacterium lactis (B.lactis), bifidobacterium longum (B.longum), bifidobacterium pseudolongum (B.pseudolongum), bifidobacterium thermophilum (B.thermophilum), Candida pintolepesii, butyric acid fusiform bud Spore bacillus (Clostridium butyricum), butterfat enterococcus (Enterococcus cremoris), two butanone enterococcus (E.diacetylactis), VREF (E.faecium), middle enterococcus (E.intermedius), lactoenterococcus (E.lactis), E.muntdi, thermophilic enterococcus (E.thermophilus), bacillus coli (Escherichia Coli), Kluyveromyces fragilis (Kluyveromyces fragilis), lactobacillus acidophilus (Lactobacillus Acidophilus), digestion lactobacillus (L.alimentarius), food starch lactobacillus (L.amylovorus), Lactobacillus crispatus (L.crispatus), short and small lactobacillus (L.brevis), Lactobacillus casei (L.case 4), lactobacillus curvatus (L.curvatus), lactobacillus cellobiosas (L.cellobiosus), lactobacillus delbruockii subspecies bulgaricus (L.delbrueckii ss.bulgaricus), Lactobacillus farciminis (L.farciminis), lactobacillus fermenti (L.fermentum), Lactobacillus gasseri (L.gasseri), Lactobacillus helveticus (L.helveticus), lactobacillus lactis (L.lactis), Lactobacillus plantarum (L.plantarum), Yue Shi lactobacillus (L.johnsonii), lactobacillus reuteri (L.reuteri), Lactobacillus rhamnosus (L.rhamnosus), Lactobacillus saki (L.sakei), Lactobacillus salivarius (L.salivarius), mesenterium shape leukonid (Leuconostoc mesenteroides), beer (harmful) piece coccus (P.cereviseae (damnosus)), Pediococcus acidilactici (Pediococcus acidilactici), Pediococcus pentosaceus (P.pentosaceus) Roy Deng Shi Propionibacteriums (Propionibacterium freudenreichii), Xue Man Na Shi, are taken Propionibacterium (Prop.shermanii), Saccharomyces cerevisiae (Saccharomyces cereviseae), Staphylococcus carnosus (Staphylococcus carnosus), staphylococcus xylosus (Staph.xylosus), baby streptococcus (Streptococcus in fantarius), saliva chain coccus thermophilous subspecies (Strep.salivarius Ss.thermophilus), streptococcus thermophilus (Strep.Thermophilus) and streptococcus lactis (Strep.lactis).

Particularly preferred microorganism or probiotics example is selected from (including but is not limited to) streptococcus thermophilus, lactobacillus acidophilus (Lactobacillus acidophilus), lactobacillus bulgaricus (Lactobacillus bulgaricus), the newborn bar of cheese Bacterium (Lactobacillus casei), Lactobacillus rhamnosus (Lactobacillus rhamnosus), lactobacillus fermenti (Lactobacillus fermentum), Lactobacillus salivarius (Lactobacillus salivaroes), Lactobacillus brevis (Lactobacillus brevis), Lactobacillus plantarum (Lactobacillus plantarum), lactobacillus reuteri (Lactobacillus ruteri), Bacillus pasteurii (Bacillus pasteurii), streptococcus thermophilus (Streptococcus thermophilus), production spore bacillus (Bacillus sporogenes), bifidobacterium adolescentis (Bifidobacterium adolescentis), bifidobacterium infantis (Bifidobacterium infantis), long bifid Bacillus (Bifidobacterium longum), bifidobacterium thermophilum (Bifidobacterium thermophilus) or bifid Bifidobacterium (Bifidobacterium bifidum).Most preferred probiotics example is selected from (including but is not limited to) thermophilic chain Coccus is KB4, KB19 or KB25 bacterial strain.

A kind of any of the above-described microorganism (without virus) or probiotics are in above-mentioned composition per 1g contents about 100,000,000 to about 1000000000000 colony forming unit, the colony forming unit of preferably from about 500,000,000 to about 500,000,000,000, more preferably from about 1,000,000,000 to about 2000 Hundred million colony forming unit.

It may include for bioactive materials virus of the invention, the virus of Oncovirinae, including moloney (Moloney) murine leukemia malicious (MoMLV), murine stem cell virus (MSCV), and the like (be referred to as cancer virus in the present invention Virus)；Also those viruses for belonging to lentivirus subfamily, including human immunodeficiency virus (HIV) (such as HIV1 or HIV2), sick virus (the meadi visna of SIV (SIV), feline immunodeficiency virus (FIV), Mai Xiweisina Virus), equine infectious anaemia virus (EIAV), caraparu arthritis encephalitis virus (caraparu arthritis Encephalitis virus) (CAEV), and the like (present invention in be referred to as slow virus virus)；Also it is derived from foam The retrovirus of virus, including foamy virus (Spuma virus) (DE 4318387；WO 9607749；Virology (1995) 210,1,167-178；J.Virol. (1996) 70,1,217-22).HIV-1 include all main (M) hypotypes (including A-J), N and outlier (O) (Hu, D.J. etc., JAMA 1996,275：210-216；Zhu, T. etc., Nature 1998,5：391 (6667)：594-7；Simon, F. etc., Nat.Med.1998,4 (9)：1032-7).The example of SIV separation strains have SIVagm, SIVcpz, SIVmac, SIVmnd, SIVsnm and SIVsyk etc..The viral vector got by foamy virus (foamy virus) can For foreign gene to be imported into human body cell, it particularly can be used for being administered in gene therapy and recombinant vaccine etc..

The viral preferred foams of bioactive materials viral (foamy virus), influenza virus, parainfluenza for the present invention Virus, Respiratory Syncytial Virus(RSV), herpes simplex virus, cytomegalovirus, SARS virus, coronavirus family member, mankind's lung Scorching restrovirus and Epstein-Bar virus.

Potency scope of any virus in above-mentioned composition is about, such as from 10³TCID₅₀/ g to 10¹¹TCID₅₀/g。

Consumption of the above-mentioned bioactive materials in above-mentioned composition is minimal effective dose or 0.001% or less (wt/ Wt) to 80% (wt/wt), preferably minimal effective dose or 0.01% or less (wt/wt) is to 60% (wt/wt), more preferably Minimal effective dose or 0.05% or less (wt/wt) to 50% (wt/wt), particularly preferably minimal effective dose or 0.1% or more Few (wt/wt), to 40% (wt/wt), the consumption is calculated based on above-mentioned composition overall weight.

3rd, pharmaceutically acceptable matrix components

Pharmaceutically acceptable matrix components for the present invention generally make diluent, or skeleton agent, or glass formers (forming amorphous glass matter structure, the structure of glassy state or amorphous state), or carrier, they, which are generally selected from, (including but does not limit In) pharmaceutically acceptable monosaccharide and disaccharide, oligosaccharides (3~20 sugar), sugar alcohol, the polysaccharide of inactive, cyclodextrin, amino acid (and its salt), edible or medicinal peptide (selective hydrolysis albumen (matter), gelatin hydrolysate (preferably relative molecular mass 30000~ 40000), Polygeline (preferably mean molecule quantity (Mw) is 27500~39500), oxypolygelatin peptide, succinyl gelatin are (excellent Select number-average molecular weight：18000~26600)), polyaminoacid, polyvinylpyrrolidone (PVP), osamine (such as meglumine), at 25 DEG C of room temperature For the carboxylic acid of solid, carboxylate, acceptable inorganic salt, and their mixture.

Available for the present invention matrix components monose or (and) its sugar alcohol, including left-handed and/or dextrorotation monose and its sugar Alcohol, and its derivative, such as its methylated derivative, methylolated derivatives, hydroxyethylation derivative, hydroxypropylation derivative, (hydrogen (atom) in the hydroxyl i.e. in monosaccharide molecule structure is by methyl, hydroxyl for hydroxyl butylation or their mixed base dough derivative Derivative after methyl, ethoxy, hydroxypropyl, hydroxyl butyl, sulfate or their mixed group substitution), its preferred embodiment is selected from (including but is not limited to)：Triose and acetone glucose (such as D- glyceraldehyde, dihydroxyacetone (DHA), tetrose and ketotetrose (such as erythritol, red Moss ketose, threose), pentose and pentulose (such as D-ribose, ribitol, D-2- deoxyriboses, (L-) arabinose, arabinose Alcohol, D- xyloses, xylitol, lyxose, xylulose, ribulose), hexose (such as glucose, galactolipin, galactitol, mannitol, Mannose, inosite (inositol), rhamnose, altrose, allose, talose, gulose, idose), ketohexose (such as fructose, Sorbose or sorbierite, psicose, Tagatose, lyxose), heptose (such as D-mannoheptulose, mannoheptitol, D- red-spotted stonecrops Ketoheptose), other sugar are for example：Chalcose, Quinovose, cymarose, fucose, gluconolactone, the red moss of 2- ethoxys-D- Sugar, 3- methyl-glucose, 3- hydroxypropyls-L-arabinose, 4- hydroxyls butyl-galactolipin, and above-mentioned sugared mixture.

Matrix components disaccharide, oligosaccharides (3~20 sugar, including equal oligosaccharides and heterooligosaccharide) available for the present invention or (and) its sugar Alcohol, and their derivative, such as its methyl-derivatives, hydroxymethyl derivative, hydroxyethyl derivative, hydroxypropyl derivatives, hydroxyl fourth (hydrogen (atom) in hydroxyl i.e. in disaccharide, oligosaccharide molecular structure on sugar unit is by first for base or their mixed group derivative Derivative after base, methylol, ethoxy, hydroxypropyl, hydroxyl butyl, sulfate or their mixed group substitution) and its lactone, its Example is selected from (including but is not limited to)：Disaccharide (including α-diglucoside, β-diglucoside, α, β-diglucoside) (such as lactose or Lactitol, sucrose, cellobiose, melibiose, marine alga (two) sugar, isotrehalose, neotrehalose, Lactitol, maltose, malt Sugar alcohol, isomaltose, hydroxyl isomaltulose, isomaltoketose, lactulose, kojibiose, nigerose, rutinose, laminaribiose, dragon Courage disaccharides, sophorose, vicianose), trisaccharide (such as gossypose, melezitose, tetrose (such as stachyose, cellotetrose), pentasaccharides (such as hair Stamen spends sugar, maltopentaose, cellopentaose), (such as Fructus Hordei Germinatus oligose, cell-oligosaccharide, inulin, maltodextrin, Portugal gather for other oligosaccharides Sugar, FOS (FOS), galactooligosaccharide (GOS), manna oligosacchride (MOS), hydroxypropyl-cell-oligosaccharide, ethoxy-honey oligosaccharides, Hydroxypropyl-Fructus Hordei Germinatus oligose), gluconolactone, and their mixture.

It is preferred for the matrix components monose alcohol of the present invention, such as erythrite, D- threitols, L- threitol tetritol；D- The pentitols such as arabite, xylitol；D- iditols, galactitol (dulcitol), D- glucitols (sorbierite), mannitol Deng hexitol；Cyclitols such as inositol etc., and their mixture.

It is preferred for the matrix components dialditol of the present invention, such as maltitol, lactitol, isomalt (different wheat Bud ketose alcohol) etc., and their mixture.

It is preferred for example such as sucrose, trehalose, lactose, maltose, the isomaltose of the matrix components disaccharides of the present invention, And their mixture.

Being preferred for the example of the matrix components oligosaccharides of the present invention includes inulin, maltodextrin, glucan, FOS (FOS), galactooligosaccharide (GOS), manna oligosacchride (MOS), and their mixture.

Polysaccharide preferred molecular weight for the matrix components inactive of the present invention is less than 300,000, more preferably molecular weight Less than 200,000, particularly preferably molecular weight is less than 100,000, most preferably molecular weight 2000 to 30,000.

Its solution when polysaccharide preferred concentration for the matrix components inactive of the present invention is 2% (mass/volume) The viscosity of (solute is water) is less than 200mPas (it is preferred that less than 100mPas, more preferably, less than 50mPas, more preferably Ground, less than 20mPas less than 30mPas. most preferably) the polysaccharide with bioactivity.

Available for the polysaccharide of the matrix components inactive of the present invention, in addition to do not dissociate or non-ionic spread out in its water Biology, such as its methylated derivative, methylolated derivatives, hydroxyethylation derivative, hydroxypropylation derivative, hydroxyl butylation, (hydrogen in the hydroxyl i.e. in polysaccharide molecule structure on sugar unit is (former for sulfate or the derivative of their mixed base dough substitution Son) replaced by methyl, methylol, ethoxy, hydroxypropyl, hydroxyl butyl, sulfate or their mixed group after derivative) and (neutral or non-ionic) polysaccharide.

Polysaccharide example for the matrix components inactive of the present invention is selected from (including but is not limited to)：Glucan (Dextrates), (preferred molecular weight is 1200 for FOS, oligoisomaltose, reduced isomaltooligosaccharide, dextrin, glucan ~10000 glucan, more preferably molecular weight are 1200~2000 glucan, pulullan polysaccharide, bassora gum, xanthans, melon That glue, pectin, carrageenan, galactomannans, gellan gum (any derivative for including these compounds), Arabic tree Glue, locust bean gum, starch (preferably water soluble starch or starch piece), pregelatinized starch, modification or modified starch, carboxymethyl Cellulose and its sodium salt, hydroxyl second methylcellulose, hydroxyethyl cellulose (the following product of such as trade name：WP02、WP and QP09, WP and QP3, WP and QP40, WP and QP300), hydroxypropyl cellulose (the following product of such as trade name： Klucel JF, Klucel LF, Klucel EF), HPMC (the following product of such as trade name：Methocel K100Premium LVEP、Methocel F50Premium、Methocel E3Premium LV、Methocel E5Premium LV, Methocel E6Premium LV, Methocel E15Premium LV, Methocel E50Premium LV, low viscosity Level Metolose60SH, low viscosity level Metolose65SH, low viscosity level Metolose90SH), methylcellulose (such as trade name Following product：A15-LV), sodium alginate, alginic acid, and their mixture.

The particularly preferred mean molecule quantity of polysaccharide for the matrix components inactive of the present invention is 10000 to 70000 Dextran (the small molecule glucose polymer of generation after sucrose is fermented), HES (preferred its mean molecule quantity For 100000 to 200000, substitution value is 0.3 to 0.6, and most preferably its mean molecule quantity is 130000 ± 20000 (Weight-average moleculars Amount) substitution value is 0.4 ± 0.05), and their mixture.

The pharmaceutically acceptable cyclodextrin of matrix components available for the present invention including but not limited to (is selected from)：It is (water-soluble Or) pharmaceutically acceptable cyclodextrin (such as alpha-cyclodextrin, beta-schardinger dextrin, gamma-cyclodextrin) and its hydroxyl carbon atom number be C1~ C4 alkyl derivatives, monose or oligosaccharides radical derivative, methyl (such as single or double methyl) derivative, sulphur butyl (ether) derivative are (i.e. Hydrogen (atom) is C1~C4 alkyl, Dan Huo by hydroxyl carbon atom number in hydroxyl or hydroxyl in cyclodextrin molecular structure on sugar unit Derivative after oligosaccharides glycosyl, methyl, sulphur butyl substitution), water-soluble low molecule amount (is less than 20000, is more preferably less than 10000) (what is do not dissociated in water is neutral or non-ionic) cyclodextrin, its preferred embodiment, which is selected from, (including but not to be limited In)：Alpha-cyclodextrin, beta-schardinger dextrin, gamma-cyclodextrin, (one/or two/or three) methyl-(α -/or β -/or γ -) cyclodextrin (such as 2, 6 dimethyl-β-cyclodextrins；Trimethyl-β-cyclodextrin), (2-/or 3-) hydroxypropyl-(α -/or β -/or γ -) cyclodextrin (such as 2/ 3-HP- β-CD), (2-/or 3-) hydroxyl butyl-(α -/or β -/or γ -) cyclodextrin, (2-/or 3-) hydroxyethyl-(α -/or β -/ Or γ -) cyclodextrin, (2-/or 3-) hydroxyl cyclobutenyl (ether)-(α -/or β -/or γ -) cyclodextrin, (one/or two/or three) glucose Base-(α -/or β -/or γ -) cyclodextrin, (one/or two/or three) malt-base-(α -/or β -/or γ -) cyclodextrin, (one/or Two/or three) galactosyl-(α -/or β -/or γ -) cyclodextrin, (one/or two/or three) sorb glycosyl-(α -/or β -/or γ -) Cyclodextrin, (one/or two/or three) mannose group-(α -/or β -/or γ -) cyclodextrin (easily or be highly soluble in water), malt-base- It is (α -/or β -/or γ -) Beta-cyclodextrin-based-glucose, other monose (containing sugar alcohol) bases-(α -/or β -/or γ -) cyclodextrin, (many Sugar) side chain-((α -/or β -/or γ -)) cyclodextrin (such as glucosyl group-malt-base-(α -/or β -/or γ -) cyclodextrin, Portugal The glycosyl of grape two/or three-(α -/or β -/or γ -) cyclodextrin, the glycosyl of malt two/or three-(α -/or β -/or γ -) cyclodextrin), sulphur Butyl (ether)-(α -/or β -/or γ -) cyclodextrin and its salt such as sodium salt, sylvite, and its mixture.

Matrix components amino acid (and its pharmaceutical salts of salt, such as acid or basic amino acid) example available for the present invention Selected from (including but is not limited to)：(L and/or D-) cystine, (D-) tyrosine, aspartic acid and its salt such as pharmaceutically acceptable sodium salt, paddy ammonia Acid and its pharmaceutical salts such as sodium salt, (D-) tryptophan, (L and/or D-) threonine, (D-) leucine, (D-) phenylalanine, (D-) egg Propylhomoserin, (D-) isoleucine, (L and/or D-) histidine, (L and/or D-) serine, (D-) valine, (L and/or D-) third ammonia Acid, glycine, (L and/or D-) hydroxyproline, (L and/or D-) proline, (D-) lysine and its pharmaceutical salts, (D-) arginine And its pharmaceutical salts, (L and/or D-) glutamine, (D-) asparagine, amion acetic acid, methionine, and their mixing Thing.Its preferred embodiment such as, but not limited to this：D- methionine, D-phenylalanine, L-Histidine, Serine, Glu, ALANINE, L-threonine, glycine, L- hydroxyprolines, L-PROLINE, and their mixture；Most preferably：L- Soviet Unions ammonia Acid, ALANINE, glycine, L- hydroxyprolines, particularly L-PROLINE, ALANINE, glycine, and their mixing Thing.

Available for the matrix components edible or medicinal peptide of the present invention, including neutral peptide, acidity peptide and basic peptide and its medicine With salt, it, which is originated, is generally the degradation product (such as hydrolysis, glycolysis, enzymolysis) or its further isolate of edible or pharmaceutical protein Or artificial synthesized (replacement) thing of these degradation products or its isolate, including edible or medicinal dipeptides, edible or medicinal three (oligopeptides (4 peptides to 20 peptides, polypeptide (more than 20 peptides)), and acidity or the pharmaceutical salts of basic peptide, and theirs are mixed for peptide and above peptide Compound, above-mentioned edible or medicinal peptide generally select 2~50 peptides, it is generally preferable to and the peptide of edible 2~20, more preferably edible 2~ 10 peptides, the more preferably peptide of edible 2~6, the more preferably peptide of edible 2~3.Above-mentioned " degradation product of edible or pharmaceutical protein (or " protein hydrolysate ") " refer to that what edible or medical protein produced through acidolysis partially or completely or enzymolysis has average mark Son amount about 2kDa to about 50kDa protein hydrolysate, you can edible or medicinal hybrid peptide.It is preferred that " edible or pharmaceutical protein Depth degradation thing (or " depth hydrolysis' albumen ") " is that edible or pharmaceutical protein substrate are converted into mean molecule quantity about The edible or medicinal peptide of the molecular weight of 200 to about 2000 dalton.Protein hydrolysate has the ammonia roughly the same with intact proteins Base acid composition, and it is available from any amount of commercial source.Hypoallergenic protein hydrolysate is advantageously used for some use In the food of hypersensitization consumer such as baby and old man.

Above-mentioned matrix components edible dipeptides or tripeptides preferably comprise L and/or D-Thr, L and/or D-alanine, sweet Propylhomoserin, L and/or D- hydroxyprolines, L and/or D-PROLINE, L and/or D-Lys and its pharmaceutical salts, L and/or D-Arg And its dipeptides or tripeptides of pharmaceutical salts, such as by (L and/or D-) threonine, (L and/or D-) alanine, glycine, (L and/or D-) hydroxyproline, (L and/or D-) proline, (L and/or D-, preferably D-) lysine and its pharmaceutical salts, (L and/or D-, preferably D-) arginine and its pharmaceutical salts each other (including itself is such as glycylglycine) and/or with other amino acids formed dipeptides or tripeptides, Because should with preferable dissolubility or stability (such as correlation technique US5432160, DE3108079C2, EP0087751A1 and Discussed in EP0087750B1) and be more easy to absorb.More particularly, it is preferable that dipeptides example such as A-X, X-A, preferably tripeptides are real For example：X '-A-X, X '-X-A, A-X '-X, wherein, A is selected from any (natural) amino acid, preferred essential amino acid, especially Unstable or the low essential amino acid of water-soluble, such as glutamine, tyrosine, tryptophan, methionine, valine, Leucine, isoleucine, phenylalanine, X and X ' are selected from (L and/or D-) threonine, (L and/or D-) alanine, glycine, (L And/or D-) hydroxyproline, (L and/or D-) proline, (L and/or D-, preferably D-) lysine and its pharmaceutical salts, (L and/or D-, preferably D-) arginine and its pharmaceutical salts, preferably use ALANINE and glycine.Some dipeptides or tripeptides instantiation are such as： Glycylalanine, carnosine (alanyl-histidine, anti-oxidation peptide), methylcarnosine, whale carnosine or snake carnosine or anserine, dipeptides Sweetener, alitame element, the sweet peptide of lysine two, Aspartame, Gly-Leu (improvement palatability), Pro-Glu (improve agreeable to the taste Property), Val-Glu (improvement palatability), guanosine peptide, L-Glycylglycine (glycylglycine), glycylglutamine (Gly- ) and alanyl glutamine (power peptide, Ala-Gln), glycyl proline dipeptides, lysine glutamic acid dipeptides, gluathione Gln Peptide, alamethicin, glycyl-L-histidyl-L-lysine, and their mixture.

Above-mentioned matrix components edible peptide preferred embodiment including but not limited to (being selected from) derives from plant or animal or large-scale It is the protein hydrolysate (matter) of fungi or algae or microorganism, gelatin hydrolysate (preferably relative molecular mass 30000~40000), poly- bright Glue peptide (preferably mean molecule quantity (Mw) is 27500~39500), oxypolygelatin peptide, succinyl gelatin (preferably count equal molecule Amount：18000~26600), and their mixture.

Above-mentioned matrix components protein hydrolysate (matter) preferred embodiment including but not limited to (is selected from) beans (legume, such as flower Life, soybean, pea, Kidney bean (kidney bean), mung bean, red bean (red bean, rde bean), broad bean, cowpea, lens (Lens culinaris), black soya bean, Sword bean, pigeonpea, goa bean, chick-pea, white jade beans, kidney bean and French beans) seed-protein range of hydrolysed peptides, cereal (gramineous crop, Such as wheat, oat, corn, barley, rice, maize, broom corn millet, broomcorn millet, sorghum, black rice, buckwheat, myotonin) seed-protein water Solve peptide, amaranth seed protein range of hydrolysed peptides, sargassum protein range of hydrolysed peptides (such as sea-tangle), day lily protein range of hydrolysed peptides, potato class (potato class Crop stem tuber or rhizome, such as potato, sweet potato, konjaku, Chinese yam, cassava, jerusalem artichoke) protein range of hydrolysed peptides, fowl or poultry protein water Solve peptide (by its muscle, internal organ, blood, skin, bone, ovum, seminal fluid, milk etc. albumen (such as gelatin, albumin, lactalbumin, Casein, caseinate, immunoglobulin, collagen) through peptide prepared by enzymolysis, it is many that beef is made in such as de-fatted beef enzymolysis Peptide, fresh (pork liver) is refining to obtain liver peptide through enzymolysis, decolouring, deodorization, ultrafiltration, and hyperglobulinemia peptide is made through enzymolysis in (pig) blood；Its bone Or the collagen peptide that skin is obtained through the mode such as hydrolysis or enzymolysis；Bird's nest collagen hydrolysate peptide；Lactoprotein range of hydrolysed peptides；The white of an egg is hydrolyzed Peptide), aquatic animal protein range of hydrolysed peptides (as its meat albumen enzymolysis made from peptide, such as sardine meat protein range of hydrolysed peptides；Its bone or The collagen peptide that skin or squama are obtained through the mode such as hydrolysis or enzymolysis, such as fish, sea cucumber collagen hydrolysate peptide；Scallop protein is hydrolyzed Polypeptide), silk protein range of hydrolysed peptides, a variety of plant animal protein mixtures are through the obtained complex peptides of enzymolysis.

The particularly preferred example of above-mentioned matrix components edible peptide including but not limited to (is selected from)：Albumen calcium peptide is (referred to as CCP, is a kind of efficient accelerating agent of calcium absorption, a kind of calcic polypeptide that relative molecular mass is about 3000, color to yellowish toner , there is special flavour at end.(20% is completely dissolved) soluble in water), high F value oligopeptide (be obtained after animal and plant proteolysis The oligopeptides constituted with high side chain, low aromatic amino acid, using low phenylalanine oligopeptides as representative.F values refer to branched-chain amino acid (BCAA) with the molar ratio of aromatic amino acid (AAA).), mineral element binding peptide (such as CPP), seasoning peptide (biologically active peptide simulating, shelter, strengthen local flavor and improve the palatability of food, such as Umami flavor peptides (Lys- can be passed through Gly-Asp-Glu-Glu-Ser-Leu-Ala), short chain glutamate polypeptide (can effectively cover bitter taste), Curculin (thizoma curculiginis sweet tea eggs In vain, tart flavour can be covered and tart flavour is changed into sweet taste), (Miraculin, changes taste glycoprotein, can cover tart flavour and make for Mai Ruo Kelins Tart flavour is changed into sweet taste), thaumatin, mabinlin, monellin, mannatide.

The example of above-mentioned matrix components polyaminoacid including but not limited to (is selected from) polyalanine, poly arginine, gathers sweet ammonia Acid, polyglutamic acid are poly-, arginine-glutamic acid etc..

It is above-mentioned to be applied at 25 DEG C of the matrix components room temperature of the present invention include but is not limited to for carboxylic acid, the carboxylate of solid (being selected from) lactic acid and its salt, ascorbic acid and its salt, maleic acid and its salt, malonic acid and its salt, tartaric acid and its salt, malic acid And its salt, butanedioic acid and its salt, citric acid and its salt, gluconic acid and its salt, glutamic acid and its salt etc., the salt be as sodium, potassium, The water-soluble pharmaceutical salts of calcium, magnesium.

Consumption of the above-mentioned matrix components in above-mentioned composition is 0.5% (wt/wt) to 95% (wt/wt), preferably 1% (wt/wt), to 80% (wt/wt), more preferably 5% (wt/wt) to 60% (wt/wt), particularly preferably 5% (wt/wt) is extremely 50% (wt/wt), the consumption is calculated based on above-mentioned composition overall weight.

4th, other

The above-mentioned ratio of polysaccharide and above-mentioned matrix components in the composition with bioactivity is usually 20: 1 to 1: 50, Preferably 10: 1 to 1: 20, preferably 5: 1 to 1: 20, it is more preferably 1: 1 to 1: 20, is most preferably 1: 1 to 1: 10, it is above-mentioned Proportionate relationship is usually weight ratio or mol ratio.

The above-mentioned ratio of polysaccharide and above-mentioned bioactive materials in the composition with bioactivity is usually 2000: 1 It is more preferably 100: 1 to 1: 1 to 1: 20, preferably 500: 1 to 1: 10, preferably 200: 1 to 1: 5, is most preferably 50: 1 It is usually weight ratio or weight and potency ratio to 2: 1 aforementioned proportion relations.

Composition of the present invention, can also comprising surfactant, buffer, cosolvent, carrier, excipient and/or Other helper components such as stabilizer, as long as they are not adversely affected to the characteristic needed for composition, in the dosage that uses and dense Degree is nontoxic to recipient.Some examples are such as：Salt-forming counterion such as potassium and sodium；Antioxidant, such as methionine, N- acetyl Cysteine, or ascorbic acid；Chelating agent such as EDTA or EGTA.The scope for the amount that above-mentioned helper component exists in the composition 0.01 weight % is about to 20 weight %, depending on being actually needed.Such as, the concentration range of methionine present in composition It is about 1mM to 50mM or 10mM；The concentration range of glycerine present in composition is about 0.1 weight % to 5 weight %, or 1 weight %；The concentration range of EDTA present in composition is about 1mM to 10mM, or 5mM.

Buffer can be added in the composition of this method, for example, carried with the preparation to the present composition and the inventive method For properly stable pH.The typical buffer of the present invention includes, such as amino acid, potassium phosphate, sodium phosphate, sodium acetate, citric acid Sodium, histidine, amion acetic acid, sodium succinate, ammonium hydrogen carbonate and/or ammonium carbonate.Buffer can be adjusted to suitable acid and salt shape Formula e.g., from about arrives the scopes of pH 10 in pH 3, the pH stability of the scopes of pH 8 is about arrived in pH 4 to provide.For many compositions, It is preferably close to neutral pH such as pH 7.2.

Suspension or true solution or colloidal solution for preparing the present composition may include, such as contribute to composition into The dissolubility and one or more surfactants of stability divided.The concentration range of surfactant in the present composition The weight % of the weight % of about 0.001 weight %~5, or 0.01 weight %~1.Surfactant includes, such as nonionic detergent, Such as polyethylene glycol sorbitan monolaurate (Tween 20), Polysorbate 80 (Tween 80) and polyethylene glycol and polypropylene glycol block copolymer (Pluronic) etc..

The example of suitable nonionic surfactant is alkyl phenyl alkoxide, alcohol alkoxide, fatty amine alcoxyl Compound, polyglyceryl fatty acid ester, castor oil alkoxylates, aliphatic acid alkoxide, fatty acid amide alkoxide, fat The poly- diglycollic amide of fat acid, lanolin ethoxylate, fatty acid polyglycol diol ester, different tridecanol, fatty acid amide, methyl are fine Tie up element, fatty acid ester, silicone oil, alkylpolyglycosides, fatty acid glyceride, polyethylene glycol, polypropylene glycol, polyethylene/polypropylene glycol Block copolymer, polyethylene glycol alkyl ether, polypropylene glycol alkyl ether, polyethylene/polypropylene glycol ether block copolymers and they Mixture, polyacrylate and acrylic acid graft copolymer.Other nonionic surfactants are the skilled skill in this area in itself It is known to art personnel and having been described in the literature.Preferably material be polyethylene glycol, polypropylene glycol, polyethylene glycol/ Polyethylene glycol block copolymer, polyethylene glycol alkyl ether, polypropylene glycol alkyl ether, polyethylene/polypropylene glycol ether block copolymerization Thing and their mixture.More preferably surfactant includes the polymer of the mixture of polyoxyethylene and polyoxypropylene such as Pluronic F68 (are provided) by BASF.

The example of suitable ionic surface active agent is alkylaryl sulfonates, phenylbenzimidazole sulfonic acid salt, alkyl sulfate, alkyl Sulfonate, alkyl ether sulfate, alkyl aryl ether sulfate, alkyl polyglycol ether phosphate, poly- aryl phenyl ether phosphate, alkane Base sulfosuccinate, alkene sulfonate, alkane sulfonate, petroleum sulfonate, taurate, sarcosinate, fat Acid, alkyl naphthalene sulfonic acid, naphthalene sulfonic acids, lignosulphonic acid, sulfonated naphthalene and the condensation product or sulfonated naphthalene and formaldehyde of formaldehyde and the empty of phenol are closed Thing, and if appropriate, urea, lignin-sulfite waste liquid include their alkali metal, alkaline-earth metal, ammonium and amine salt, alkane Based phosphates, quaternary ammonium compound, amine oxide and glycine betaine and their mixture.Preferably material includes Pluronic F68 Or PluronicF188, Tween 20 (that is, Tween 20, is provided by Sigma) is more preferably.

Composition of the present invention typically " drying ", (remnants) moisture is generally less than about 10 weights in it % is measured, preferably the less than about residual moisture of weight 5% or less, preferably between the about weight of weight 3% to 0.1 %.It is " dry It is dry " refer to composition in suction particulate occasion and have moisture so that particulate in inhalation device can readily dispersed formation gas it is molten Glue.

Composition (solid solution or solid sol therein) of the present invention is typically solid without stationary state nature of glass knot Structure, stable protection bioactive materials are filled out for wrapping, and they can be block, graininess or powdered, their Ke Yi Jin mono- Walk It is made that tablet, capsule, granule, suppository, inhalant etc. be oral or external preparation, or injection preparation.

If appropriate, the preparation that composition and its Jin mono- Walk of the present invention are made, can be applied to such as mammal.This The bioactive materials invented in the composition that is related to may include, such as active peptide, reactive protein, enzyme, hormone, nucleic acid, antibody, Vaccine, microorganism (such as yeast, fungi, bacterium (probiotics is other), virus, edaphon), liposome, serum and/or Cell suspension.The material can such as pass through stomach as therapeutic agent, nutritional agents, vaccine, medicine, prophylactic, and/or analog Intestinal absorption, body surface coating, suction, and/or injection are applied to patient and provide benefit.

Bioactive materials can be applied to patient by body surface coating.For example, powdery particulate can be directly mixed in ointment, carrier In ointment, fluid under pressure, gaseous propellant, and/or bleeding agent, the skin of patient is coated on.Or, powdery particulate such as can be The preceding reconstruct in aqueous solvent is mixed with other compositions using preceding.

The bioactive materials of the present invention are inhalable to be applied.The dry powdery particulate that aerodynamic diameter is less than 10um can Being inhaled into lung is used for pulmonary administration.Optionally, aerodynamic diameter about 20um, or bigger powdery particulate intranasal can be applied With, or the upper respiratory tract is administered to, moved on to by inertia impact powdery particulate from air-flow on the mucous membrane of patient.Powdery particulate or It is reconfigurable into and the suspension or true solution or colloidal solution applied is sucked with aqueous mist.

The bioactive materials injectable of the present invention is applied.Powdery particulate can be used as general high voltage gas injection is directly applied Under the skin for using patient.More commonly, powdery particulate can be reconstructed with sterile aqueous buffer for passing through hollow syringe Needle injection.The injection can be, such as intramuscular, the suitable form of intravenous, subcutaneous, intrathecal, intraperitoneal.The powdery of the present invention Particulate be reconfigurable into be suitable for the bioactive materials concentration of dosage and processing requirement from less than about 0.1ng/ml to from less than about 1mg/ml is to about 500mg/ml, or from 5mg/ml to about 400mg/ml suspension or true solution or colloidal solution.The powder of reconstruct Shape particulate can be diluted again, such as be used to repeatedly be inoculated with, applied by IV injections etc..

The suitable dose (" therapeutically effective amount ") of bioactive materials can be depended on, such as illness to be treated, illness Seriousness and the course for the treatment of, bioactive materials apply be for prevent or therapeutic purposes, former treatment, the clinical disease of patient History and the reaction to bioactive materials, the type of the bioactive materials used, the judgment of attending doctor.Bioactivity material Material suitably can once or in a series of treatments be administered to patient, and be administered to patient any time from diagnosis.Biology is living Property material can be used as monotherapy apply or combined treatment described in the useful other drugs of illness or treatment apply.

Generally suggestion, the scope for the therapeutically effective amount that bioactive materials are applied is about one or many is applied in 0.0000l (such as in the situation of Attenuated Virus Vaccines living) arrives 50mg/kg weight in patients, is applied but regardless of one or many, For example, once-a-day administration, the usual scope of the protein used is about less than 0.01ng/kg to 20mg/kg, more preferable 0.1mg/ Kg to 15mg/kg.But, other dosage ranges can be used.The process of the treatment can easily be monitored by common technology.

The present invention also includes " Storage period " or the stable storing when the dry bioactive materials of increase are stored in rise temperature The method of property.Increased storage stability can recapture bioactivity by using accelerated aging test to determine.The inventive method The dry particles composition of generation can be stored in any suitable temperature.Said composition is stored in about 0 DEG C to about 80 DEG C preferably.Should Composition is stored in about 20 DEG C to about 60 DEG C more preferably.It is optimal that said composition is stored in room temperature.

5th, preparation method

The preparation method of composition of the present invention is usually not particularly limited.

The preparation method of composition of the present invention is generally included：

1), prepare comprising it is above-mentioned have it is at least one it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, antifatigue, clear Except free radical isoreactivity) the polysaccharide of bioactivity, the bioactive materials of live body, pharmaceutically acceptable matrix components and The suspension or true solution or colloidal solution of (aqueous) solvent, the above-mentioned polysaccharide with bioactivity is to above-mentioned bioactive materials Without activity suppression or killing action, above-mentioned polysaccharide and matrix components with bioactivity are dissolved in or are scattered in above-mentioned (aqueous) solvent formation true solution or colloidal solution；

2) (aqueous) solvent in suspension obtained above or true solution or colloidal solution, is removed.

The method that above-mentioned (aqueous) solvent is removed includes freezing, freeze-drying (in embodiment referred to as " lyophilized "), spray Mist seasoning (in embodiment referred to as " spray drying (I method) "), boulton process, natural wind dry method (freezing, freeze- Drying, spray-drying, vacuum-drying, or ambient air-drying) and their use in conjunction.It is above-mentioned (aqueous) solvent removal process can refer to following patent US8,968,721, US9,072,310, US9,480,276, US9,504, 275th, US9,504,750, disclosed in CN104244985A, CN101287449B, particularly patent CN101287449B (A) Method (in embodiment referred to as " spray drying (II method) ").

Specifically, particularly preferably preparing the method (" spray drying (II method) ") of composition of the present invention includes：

1), prepare comprising it is above-mentioned have it is at least one it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, antifatigue, clear Except free radical isoreactivity) the polysaccharide of bioactivity, the bioactive materials of live body, pharmaceutically acceptable matrix components and The suspension or true solution or colloidal solution of (aqueous) solvent, the above-mentioned polysaccharide with bioactivity is to above-mentioned bioactive materials Without activity suppression or killing action, above-mentioned polysaccharide and matrix components with bioactivity are dissolved in or are scattered in above-mentioned (aqueous) solvent formation true solution or colloidal solution；

2) mixture of above-mentioned suspension or true solution or colloidal solution and gases at high pressure or nearly supercritical liq, is made (it is preferred that above-mentioned gases at high pressure contain a pressure, the pressure limit is 250~15000psi)；

3) pressure of mixture, is reduced, so as to form the gaseous suspension of droplet；With

4), exchanged with dry gas with the gaseous suspension of droplet and droplet is dried powdering particulate.

Above-mentioned suspension or true solution or colloidal solution can be before the gaseous suspension (spraying) of droplet be formed with adding Calm the anger the gas mixing of body or nearly super critical condition.Gases at high pressure in the present invention can be, such as nitrogen, carbon dioxide, oxygen, Propane, nitrous oxide, helium, hydrogen and/or analog, pressure limit about for, 100 pounds (psi) to 15 per square inch, 000psi, or 1000psi.Closely overcritical to refer to, such as pressure limit is arrived in the critical pressure of fluid and/or about the 90% of temperature 110%.Wherein near supercritical fluid is carbon dioxide, and typical pressure is about 1200psi.It is near overcritical in the inventive method Fluid can be, such as carbon dioxide, sulfur hexafluoride, CFC, fluorocarbons, nitrous oxide, xenon, propane, pentane, second Alcohol, nitrogen, water, and/or analog.Gases at high pressure or nearly supercritical fluid with suspension or true solution or colloidal solution before mixing Temperature range often about 0 DEG C to 60 DEG C.Conditioning agent, such as methanol, ethanol, isopropanol or acetone can add gas or near overcritical In fluid, to influence the physical characteristic and/or influence suspension or true solution or colloidal solution of fluid to dry for the first time.

Gases at high pressure are contacted and can carried with suspension or true solution or colloidal solution in the mixture close to supercritical gas For such as certain solvation or emulsification effect.Control to the solvation or emulsification effect can be mixed by adjusting Thing temperature, the residence time in mixing chamber, suspension or true solution or colloidal solution and gases at high pressure or close to overcritical gas Relative scale, flow velocity, pressure, suspension or the true solution or colloidal solution composition of body, the solvent that it is possible to additionally incorporate etc. reach.

The mixture for forming gases at high pressure and/or nearly supercritical fluid and suspension or true solution or colloidal solution can be, Carried out if any in the nozzle, mixing chamber and/or capillary flow restrictor of T joints.Forming mixture needs to make suspension or true solution Or colloidal solution is flowed by mixing chamber with pressed gas or nearly supercritical fluid.The mixing chamber can have to be produced in flowing mixture Vortex or turbulent flow is given birth to increase the channel design of mixing efficiency.Mixture is by nozzle and from the spray outlet of capillary flow restrictor Hole sprays the suspension that droplet is formed in pressure (expansion) gas that can reduce mixture.The capillary flow restrictor can have less than mixing The internal diameter of room；The internal diameter is generally less than about 1000um, and scope is about 50um to 500um, or about 100um.

Various parameters are can adjust to change the mean size of droplet.The size of droplet can be by adjusting nearly supercritical fluid The pressure of pressure or gases at high pressure, regulation suspension or true solution or colloidal solution pressure, regulation suspension or true solution or glue The flow velocity of liquid solution, selects nozzle pipe internal diameter, adjusts the pressure in the temperature of dry gas, regulation particulate formation container, changes Become concentration of suspension or true solution or colloidal solution composition etc. to influence.For example, suspension or true solution or colloidal solution Can about 0.5ml/min to about 30ml/min be sent to mixing chamber with from 100um internal diameter nozzles hole spray；Speed is low to form smaller Droplet, speed forms larger droplet soon.In the methods of the invention, the mass median diameter scope of the droplet of formation is about arrived in 1um 200um is preferable.

After spraying forms droplet, first and second of drying makes droplet change into particulate.First drying is started with depressurizing With fluid-gas (suspension or true solution or colloidal solution-gases at high pressure or nearly supercritical gas) mixture expansion to be formed The gaseous state suspension of droplet.The evaporation solvent of the gas and expanded mix then can be with dry gas, and such as temperature range is about at 5 DEG C Exchanged to 90 DEG C of nitrogen.Drying may include second of drying, and wherein residual moisture is further subtracted after substantially first water removal It is few.Drying can in whirlwind vortex or by powdery particle suspension is formed in the ascending air of dry gas fluid bed come Carry out.For minimizing electrostatic accumulation and possible particulate caking, counter ion counterionsl gegenions can be added in hothouse or dry particles.Dry Gas can be recycled by being adjusted again in heat exchanger and/or drier or condenser.At the end of drying, pulvis Mean size (MMD) scope of particulate is about, 0.5um to 200um, or 1um to 150um, or 5um to 20um, and moisture is few In about 10 weight %, stored at least about 9 months at about 25 DEG C or keep steady at least about 2 years bioactive materials of about 4 DEG C of storages It is fixed.After treatment the cell of virus living in powdery particulate, the bacterium of work and work can retain former viability at least about half, or At least about 10%.

Particulate can be sent in hothouse with dry gas stream, separate, coat by size, collecting etc..Powdery particulate can lead to Cross and be collected being transferred them to dry gas stream in secondary drying chamber.Secondary drying chamber can be configured as whirlwind vortex chamber Make particulate that the time of contact of particulate and dry gas is contacted and extended with the warm surfaces of room.Can be according to size in the chamber particle Separation, such as passes through differential sedimentation.Particulate usable polymers are applied coated with formation protective coating.Particulate can be deposited to the room before recovery Gathered in the collection vessel of bottom.Total treatment effeciency is 50%, 70%, 80%, 90% or more bioactive materials thing Matter and/or activity are recyclable.

The powdery particulate of recovery is applied with particulate or the suspension or true solution or colloidal solution of reconstruct.In the process of the present invention The fine particles of preparation are reconfigurable into bioactive materials concentration and exceed the mixed of original processing suspension or true solution or colloidal solution Suspension or true solution or colloidal solution.For example, dry powdery particulate can originate into fluent material (suspension or true solution or Colloidal solution) 2~30 times of concentration reconstruct are without causing obvious loss of activity or albuminous degeneration；The reconstruct of 100mg/ml solution Time can be less than 5 minutes.Powdery particulate can by intramuscular, intraperitoneal, brain keel, subcutaneous, intra-articular, synovia, it is intrathecal, Orally, body surface, the intranasal and/or pulmonary route of suction are applied to mammal.

The method of the present invention can be carried out with following equipment.The equipment has several rooms can be in mixture from nozzle spray to particulate Accommodated before forming container and mixing suspension or true solution or colloidal solution and gas-pressurized or nearly supercritical fluid.There The particulate of formation can be dried and/or be sent in secondary drying chamber in dry gas stream, the room is configured to be further dried, Coating, by size screening, classification and/or collection particulate.In an example of equipment, such as the first Room, which is included, has biological live Property polysaccharide, bioactive materials, the suspension of matrix components or true solution or colloidal solution, second Room includes gases at high pressure And/or nearly supercritical fluid, mixing chamber is by the first pipeline and the progress liquid transmission of the first Room and passes through second pipe and second Room carries out liquid transmission, and capillary flow restrictor provides limited liquid transmission between mixing chamber and particulate formation container, mixed Suspension or true solution or colloidal solution mix and are sprayed onto particulate formation container with gas and/or nearly supercritical fluid in mixing chamber Dry gas stream flows to dry the thin mist of droplet formation when middle.The result is that the stable dry fine powder comprising bioactive materials The composition of particulate.

First indoor suspension or true solution or colloidal solution may include that such as polysaccharide with bioactivity, biology are living Property material, pharmaceutically acceptable matrix components and surfactant.

The gas and/or nearly supercritical fluid mixed in a device with suspension or true solution or colloidal solution can be, Such as nitrogen, carbon dioxide, oxygen, propane, carbon monoxide, fluorane (flaorahe), nitrous oxide, helium, hydrogen, sulfur hexafluoride, chlorine fluorine Hydrocarbon, fluorinated carbon compounds, nitrous oxide, xenon, propane, pentane, ethanol, nitrogen, and/or water.

Above-mentioned suspension or true solution or colloidal solution, and gases at high pressure and/or nearly supercritical fluid are repeated, this can be added to Mixture is formed in the nozzle of equipment to be sprayed onto in the particulate of equipment formation container.First flow control device, such as pump or valve, can The first pipeline between the first Room and mixing chamber is connected to control suspension or true solution or colloidal solution to enter mixing chamber Flow.Second of flow-control equipment, such as pump or valve, the second pipe that may be connected between second Room and mixing chamber is to control Gas and/or nearly supercritical fluid enter the flow of mixing chamber.From the first pipeline and/or second pipe to the import of the mixing chamber 90 degree are smaller than with mixing the angle between chamber axis.Capillary flow restrictor can be provided, such as the back pressure to flowing mixture and from Nozzle sprays the hole of mixture.Capillary flow restrictor can have, such as less than the internal diameter of mixing chamber；The internal diameter of capillary flow restrictor is usual Scope is about 50um to 1000um, 50um to 500um, or 100um.Nozzle may include, such as multiple capillary flow restrictors.Nozzle can There is the intersection of multiple feeding-passages and exceed a kind of gas and/or more than a kind of mixture of liquid feedstock to adjust.

Mixture, which sprays the fine droplets mist to be formed by nozzle, to be dried by dry gas.Particulate formation container can be made For secondary drying chamber, or carry out fluid with secondary drying chamber and contact, pass through contact drying gas and/or room in secondary drying chamber Surface, particulate can be transmitted and be dried.Dry gas can such as control the nitrogen of temperature and/or humidity.Dry gas (entering gas) may be at, and such as be less than the temperature of powdery particulate glass transition temperature.

Residual moisture may decrease to stable level in secondary drying chamber in particulate.Secondary drying chamber can be configured to whirlwind Protection coating material is sprayed onto the room on powdery particulate by vortex, the fluid bed of powdery particulate, the equipment separated by size, and/or Particulate collecting container.Dry gas can be by particulate formation container and/or secondary drying chamber after condenser or drier water removal It is recycled.It can pass through according to size separation particulate in a device, such as differential sedimentation, surface impacts or filtering, it is flat to produce Equal size (MMD) is about 1um to 150um scopes, or about 10um powdery particulate.It may include ion generator in equipment to neutralize Electrostatic charge.

Optimal technical scheme

1. a kind of stable composition for preserving bioactive materials, said composition includes at least one with least one non- The polysaccharide of oxidation resistant bioactivity, and at least one live body bioactive materials, and at least one is pharmaceutically acceptable Matrix components, the polysaccharide should with bioactivity does not have activity suppression or killing action, the biology to the bioactive materials Active material is scattered or is embedded in the polysaccharide for having bioactivity comprising this and/or the glassy struc matrix of the matrix components In；Or,

A kind of stable composition for preserving bioactive materials, said composition includes that (/ include) is at least one to be had at least It is a kind of it is non-it is anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, remove free radical isoreactivity) bioactivity polysaccharide, And the bioactive materials of at least one live body, and at least one pharmaceutically acceptable matrix components, there should be bioactivity Polysaccharide do not have activity suppression or killing action to the bioactive materials, the bioactive materials are scattered or be embedded in and include In the glassy struc matrix (i.e. solid solution or solid sol) of the polysaccharide with bioactivity and/or the matrix components.

2. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity has anti-inflammatory, resists and answer Sharp, radioresistance, regulation immune, antitumor, anti-infective (antibacterial, antibacterial is antiviral), promotion hematopoiesis, diuresis, antiulcer, drop blood Fat (or reduction cholesterol), hypoglycemic, hypotensive, antithrombotic, protection internal organs (such as liver/stomach), protection nerve, protection system genitale Unite, promote blood circulation, regulation nucleic acid or protein metabolism, promote DNA synthesis, promotion cell propagation and enhancing learning and memory etc. Effect or the non-oxidation resistant bioactivity/of middle one or more or the polysaccharide of pharmacological activity of function.

3. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is also with anti-oxidant (and to anti-oxidant related anti-aging, it is antifatigue, remove free radical isoreactivity) activity.

4. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity have with it is described What bioactive materials had (partially or completely) identical bioactive functions or (partially or completely) identical medical usage (has life Thing activity) polysaccharide.

5. the composition according to optimal technical scheme 1, lives wherein the polysaccharide of described bioactivity has to biology Property material have strengthening its active function or have the polysaccharide of synergy between the two.

6. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from biological source The polysaccharide with bioactivity.

7. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity be selected from plant, it is large-scale Fungi (such as edible fungus) class, algae, the polysaccharide with bioactivity of microorganism or animal origin.

8. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from, " medicine food is same The polysaccharide with bioactivity of the biological source in source ".

9. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from water miscible Polysaccharide with bioactivity.

10. the composition according to optimal technical scheme 1, wherein the average of the polysaccharide of described bioactivity is divided equally again Son amount Mw is 10,000 to 800,000 dalton.

11. the composition according to optimal technical scheme 1, wherein the average of the polysaccharide of described bioactivity is divided equally again Son amount Mw is 40,000 to 300,000 dalton.

12. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from concentration The viscosity of its solution (solute is water) is less than the 200mPas polysaccharide with bioactivity when 2% (mass/volume).

13. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from concentration The viscosity of its solution (solute is water) is less than the 100mPas polysaccharide with bioactivity when 2% (mass/volume).

14. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is selected from concentration The viscosity of its solution (solute is water) is less than the 50mPas polysaccharide with bioactivity when 2% (mass/volume).

15. the composition according to optimal technical scheme 1, wherein the degree of branching of the polysaccharide of described bioactivity is 0.04~0.75.

16. the composition according to optimal technical scheme 1, wherein the degree of branching of the polysaccharide of described bioactivity is 0.05~0.5.

17. the composition according to optimal technical scheme 1, wherein the polysaccharide molecule knot of the polysaccharide of described bioactivity Peptidyl (/ chain), protein-based (/ chain), nucleic acid base (/ chain), lipid (lipoid) base (/ chain) can be also included in structure.

18. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is more selected from matrimony vine Sugar, lentinan, astragalus polyose, panaxan, BCG-polysaccharide, Hemarisin, glossy-ganoderma-spore polysaccharide, grifola polysaccharide, Human plactnta Lipopolysaccharides, Inokopolyose, algal polysaccharide, polysaccharide from urtica fissa, seam split polysaccharide, Cordyceps sinensis polysaccharide, GL-B, ganoderma spore polysaccharide, sheep Dwell dish polysaccharide, lentinan, coriolan, corn silk polysaccharide, silk cocoon polysaccharide, Fructus Schisandrae Polysaccharide, black nightshade polysaccharide, Chinese mugwort polysaccharide, hundred Close polysaccharide, Method of Polysaccharide in Radix Pinellia, spirulina polysaccharide, Chinese pine pollen polysaccharide, Taraxacum Polysaccharides, epimedium brevicornum polysaccharide, humulus grass polysaccharide, rough gentian many Sugar, white chessman grass polysaccharide, Cells of Blue-green Algae exo polysaccharides, soluble polysaccharide, cactus polyoses, date polysaccharide, armillaria mellea polysaccharide, buckwheat are more Sugar, maize peel polysaccharide, corn pollen polysaccharide, Blackfungus polyhexose, nostoc polysaccharide, root of herbaceous peony polysaccharide, aloe polysaccharide, Radix Isatidis are more It is sugar, mulberries polysaccharide, algal polysaccharides, Chinese yam polysaccharide, zymosan, rape pollen polysaccharide, coleseed polysaccharide, Polysaccharide From Salvia Chinensis, red It is astragalus polysaccharides, loquat leaf polyose, Siberian solomonseal rhizome polysaccharide, tea polysaccharide, Chinese hawthorn leaf polysaccharide, laminarin, Onion Polysaccharide, Scutellaria Barbata D. Don Polysaccharides, white Clever mushroom polysaccharide, Polysaccharide in Pleurotus eryngii, Pleurotus ferulae polysaccharide, garlic polysaccharide, banana skin polysaccharide, maca polysaccharide, Sweet Potato Polysaccharide, watermelon peel are more Sugar, mao bamboon petiole polysaccharide, lithosperman, cordate houttuynia polysaccharide, dendrobium polysaccharide, bitter melon polysaccharide, carrot polysaccharide, Russula polysaccharide, rose Flower polysaccharide, ophiopogonpolysaccharide, blazei polysaccharide, sea grass polysaccharide, Stropharia rugoso-annulata polysaccharide, Bupleurum chinense polysaccharide, Morchellaconica extracellular polysaccharide, fall Certain herbaceous plants with big flowers polysaccharide, Moringa polysaccharide, Polysaccharides in Bamboo Leaves, Agrocybe chaxingu polysaccharide, mushroom polysaccharide, rabdosia lophanthide polysaccharide, cassia seeds polysaccharides, bamboo shoots polysaccharide, Turnip polysaccharide, Saussurea Polysaccharide, Folium Panacis Quinquefolii polysaccharide, Polysaccharides in Cultured Cordyceps militaris, stauntonvine polysaccharide, pachymaran, Glehnia Littoralis Polysaccharide, dictyophora phalloidea Polysaccharide, Mongolian oak fern polysaccharide, oyster polysaccharide, Codonopsis pilosula polysaccharide, polysaccharide from Dunaliella salina, Glehnia Littoralis Polysaccharide, elm fungus polysaccharides, pomelo peel hydrolyzed pectin are more Sugar, gastrodia elata polysaccharide, cockroach polysaccharide, Ginkgo biloba polysaccharide, flammulina velutipes, speciosus polysaccharide, oat polysaccharide, peanut polysaccharide, Ru Yuan Casein polysaccharide, chondroitin sulfate proteoglycan, Fructus Schisandrae Polysaccharide, proteoglycan decorin, bacterioprotein polysaccharide, Qin's bar selenium Mushroom extract selenoprotein polysaccharide, mushroom protamine polysaccharide, brown algae protein polysaccharide, abalone visceral protein polysaccharide, U. pertusa polysaccharide, Chinese yam Polysaccharide, agglutinin, ganoderma lucidum albumen/peptide sugar, mulberry leaf polysaccharide, newborn mushroom polysaccharide, Pasteur mushroom proteoglycan, mankshood polysaccharide, Hericium erinaceus Polysaccharide, kamuning GL-PP polysaccharide, hyriopsis cumingii polysaccharide, Goods-Flow Plan, echinacea polysaccharide, notoginseng polysaccharide, sposknikovan, radix glycyrrhizae Polysaccharide, Radix Et Caulis Acanthopanacis Senticosi polysaccharide, semen litchi polysaccharide, Inonotus obliquus core polysaccharide, Sclerotium of Pleurotus tuber regium polysaccharide, and its mixture.

19. the composition according to optimal technical scheme 1, wherein the polysaccharide of described bioactivity is in above-mentioned composition In consumption be 0.5% (wt/wt) to 80% (wt/wt), the consumption calculates based on above-mentioned composition overall weight.

20. the composition according to optimal technical scheme 1, wherein described bioactive materials are permission bioactivity Microorganism or composition.

21. the composition according to optimal technical scheme 1, wherein described bioactive materials are main or basis Or include peptide chain or protein chain or nucleic acid chains in the molecular structure of basic composition or constituent.

22. the composition according to optimal technical scheme 1, wherein described bioactive materials are selected from microorganism (such as Yeast, fungi, bacterium (probiotics is other), virus, edaphon) or cell suspension, and their mixture.

23. the composition according to optimal technical scheme 1, wherein described bioactive materials are in the composition Consumption be minimal effective dose or 0.001% or less (wt/wt) to 80% (wt/wt), the consumption is with composition entirety Calculated based on weight.

24. the composition according to optimal technical scheme 1, wherein described pharmaceutically acceptable matrix components are selected from Pharmaceutically acceptable monosaccharide and disaccharide, oligosaccharides (3~20 sugar), sugar alcohol, the polysaccharide of inactive, cyclodextrin, amino acid (and Its salt), be solid at edible or medicinal peptide, polyaminoacid, polyvinylpyrrolidone (PVP), osamine (such as meglumine), 25 DEG C of room temperature Carboxylic acid, carboxylate, acceptable inorganic salt, and their mixture.

25. the composition according to optimal technical scheme 1, wherein described pharmaceutically acceptable matrix components are selected from Protein hydrolysate (matter), gelatin hydrolysate, Polygeline, oxypolygelatin peptide, succinyl gelatin.

26. the composition according to optimal technical scheme 1, wherein the described polysaccharide and the base with bioactivity The ratio of matter component in the composition is 20: 1 to 1: 50.

27. the composition according to optimal technical scheme 1, wherein the described polysaccharide with bioactivity and the life The ratio of thing active material in the composition is 2000: 1 to 1: 20.

28. oral or external preparation has been made in the composition according to optimal technical scheme 1, said composition Jin mono- Walk, Or injection preparation.

Embodiment

The following example is only to provide explanation, rather than to proposing that the present invention of claim is limited.

Embodiment 1-1

Formula or proportioning (100)：5g root of herbaceous peonys polysaccharide (proteoglycan, molecular weight, 5.5 ten thousand) (antitumor, anti-oxidant), 1ml influenza viruses suspension (virus titer 10^8.8TCID₅₀/ ml), 15g inulin, 0.5g methionines, 0.2g Tween20 and appropriate Sterile (50mM) pH7.2 phosphoric acid (/ hydrogen) sylvite buffer, is made 100ml and is suspended (/ molten) liquid, spray drying (II method, explanation altogether：Adopt With nearly supercritical liq CO2).

Embodiment 1-2

The first active polysaccharide of sequence in embodiment 1-1 formulas removes protein chain in molecular structure or peptide chain by equivalent The root of herbaceous peony polysaccharide of holosaccharide is replaced, and it is constant that other (contain preparation method).

Embodiment 2-1

Formula is matched：1g breast source casein polysaccharide (improvement ulcerative colitis), 1ml bifidobacterium adolescentises suspension (5.2 ×10⁹CFU/ml), 5g pectin (molecular weight be less than 30,000), 0.5g methionines, 0.2g Tween80,0.2g EDTA-Na and suitable Sterile (50mM) pH7.2 phosphoric acid (/ hydrogen) the sylvite buffer of amount, is made 100ml and is suspended (/ molten) liquid, spray drying (II method, explanation altogether： Using nearly supercritical liq propane).

Embodiment 2-2

The first active polysaccharide of sequence in embodiment 2-1 formulas removes protein chain in molecular structure or peptide chain by equivalent The newborn source polysaccharide of holosaccharide is replaced, and it is constant that other (contain preparation method).

Embodiment 2-3

The active polysaccharide of sequence first place in embodiment 2-1 formulas nothing or deproteinized chain or peptide in the molecular structure of equivalent The Ginkgo biloba polysaccharide of the holosaccharide of chain is replaced, and it is constant that other (contain preparation method).

Embodiment 3-1

Formula is matched：10g bacterioproteins polysaccharide (immunological regulation), 0.5ml Lactobacillus caseis suspension (2.1 × 10⁹CFU/ Ml), 0.5g methionines, 0.2g Tween80,0.2g EDTA-Na, 1g ethoxys-honey oligosaccharides and appropriate sterile (50mM) PH7.2 phosphoric acid (/ hydrogen) sylvite buffer, is made 100ml and is suspended (/ molten) liquid, spray drying (II method) altogether.

Embodiment 3-2

The first active polysaccharide of sequence in embodiment 3-1 formulas removes protein chain in molecular structure or peptide chain by equivalent The bacterial polysaccharides of holosaccharide is replaced, and it is constant that other (contain preparation method).

Embodiment 3-3

The active polysaccharide of sequence first place in embodiment 3-1 formulas nothing or deproteinized chain or peptide in the molecular structure of equivalent The Cordyceps militaris polysaccharide (anti-oxidant, liver injury protection) of the holosaccharide of chain is replaced, and it is constant that other (contain preparation method).

Embodiment 4-1

Formula is matched：3g mushroom protamine polysaccharide (protect liver), 1ml stem cell suspensions (living cells 3.2 × 10⁸/ml)、15g Pulullan polysaccharide (molecular weight be less than 100,000), 0.5g methionines, 0.2g Tween80,0.2g EDTA-Na and appropriate sterile (50mM) pH7.2 phosphoric acid (/ hydrogen) sylvite buffer, is made 100ml and is suspended (/ molten) liquid, spray drying (II method) altogether.

Embodiment 4-2

The first active polysaccharide of sequence in embodiment 4-1 formulas removes protein chain in molecular structure or peptide chain by equivalent The smart polysaccharide of the mushroom of holosaccharide is replaced, and it is constant that other (contain preparation method).

Embodiment 4-3

The active polysaccharide of sequence first place in embodiment 4-1 formulas nothing or deproteinized chain or peptide in the molecular structure of equivalent The peanut polysaccharide of the holosaccharide of chain is (anti-oxidant) to be replaced, and it is constant that other (contain preparation method).

Embodiment 5-1

Formula is matched：5g spirulina proteins polysaccharide (anti-mutagenesis, antitumor), 10ml human red blood cells suspension (3 × 10⁸Hundred million Individual/ml), 8g HESs (mean molecule quantity be 130000 ± 20000 (weight average molecular weight), substitution value be 0.4 ± 0.05), 0.5g methionines, 0.2g Tween80,0.2g EDTA-Na and appropriate sterile water for injection, are made 100ml and are suspended (/ molten) altogether Liquid, spray drying (II method).

Embodiment 5-2

The first active polysaccharide of sequence in embodiment 5-1 formulas removes protein chain in molecular structure or peptide chain by equivalent The spirulina polysaccharide of holosaccharide is replaced, and it is constant that other (contain preparation method).

Embodiment 5-3

The active polysaccharide of sequence first place in embodiment 5-1 formulas nothing or deproteinized chain or peptide in the molecular structure of equivalent The gastrodia elata polysaccharide (anti-oxidant, immunological regulation, hypotensive, combating vertigo disease, antibacterial) of the holosaccharide of chain, replace, other are (containing system Method) it is constant.

Embodiment 6-1

Formula is matched：5g U. pertusas proteoglycan (antiviral, hypoglycemic, reducing blood lipid, anti-oxidant), 3ml moulds (category) Bacteria suspension (2.3 × 10⁹CFU/ml), 5g sodium alginates (molecular weight is less than 10,000), 10g glycine, 15g sucrose, 1g first sulphur ammonia Acid, 0.5g Tween80,0.3g EDTA-Na and appropriate sterile (50mM) pH7.2 citrate buffer agents, are made 200ml altogether Be suspended (/ molten) liquid, spray drying (II method).

Embodiment 6-2

The active polysaccharide of sequence first place in embodiment 6-1 formulas is (anti-oxidant, immune to adjust by hydriopsis cumingii deproteinized polysaccharide It is section, antitumor) equivalent replaces, other (contain preparation method) it is constant.

Embodiment 7-1

Formula is matched：1g lentinans (containing proteoglycan, have anti-oxidant, anticancer, hypoglycemic, blood fat, cholesterol), 5ml herpes simplex virus suspension (virus titer 10^7.8TCID₅₀/ ml), 20g hydroxyethyl cellulose (trade names：WP02)、0.5g Vit-C Na, 0.5g Pluronic F68,0.2g EDTA-Na and appropriate sterile (50mM) pH7.2 citrate buffer agents, 200ml is made altogether to be suspended (/ molten) liquid, spray drying (II method).

Embodiment 7-2

The active polysaccharide of sequence first place in embodiment 7-1 formulas is replaced by echinacea polysaccharide (antitumor) equivalent, and other are equal (containing preparation method) is constant.

Embodiment 8-1

Formula is matched：15g Chinese mugworts polysaccharide (adjust blood glucose, adjust immunity of organism and anti-oxidant), 5ml cytomegalovirus suspensions (virus titer 10^8.8TCID₅₀/ ml), 3g hydroxypropyl cellulose (trade names：Klucel JF), 10g sucrose, 4g trehaloses, 1g first Methyllanthionine, 0.3g Tween80,0.3g EDTA-Na and appropriate sterile (50mM) pH7.2 citrate buffer agents, are made altogether 200ml suspensions (/ molten) liquid, spray drying (II method).

Embodiment 8-2

The active polysaccharide of sequence first place in embodiment 8-1 formulas is replaced by sposknikovan (anti-oxidant, antitumor) equivalent, It is constant that other (contain preparation method).

Embodiment 9-1

Formula is matched：25g soluble polysaccharides (molecular weight 4000-1000) (anti-oxidant, strengthen immunity, it is hypoglycemic, it is anti-ageing Always, it is antitumor), 5ml aspergillus nigers suspension (5.1 × 10⁹CFU/ml), 5g glycine, 10g trehaloses, 2g methionines, 0.5g Tween80,0.3g EDTA-Na and appropriate sterile (50mM) pH7.2 citrate buffer agents, are made 500ml and are suspended (/ molten) altogether Liquid, spray drying (II method).

Embodiment 9-2

The active polysaccharide of sequence first place in embodiment 9-1 formulas is replaced by BCG-polysaccharide equivalent, and other are (containing system Method) it is constant.

Embodiment 10-1

Formula is matched：5g (water solubility) bamboo shoots polysaccharide (anti-oxidant, regulation is immune, promote bifidobacterium growth), 2ml two Discrimination Bifidobacterium (B.bifidum) suspension (4.8 × 10⁹CFU/ml), 5g gelatin hydrolysates (relative molecular mass 30000~ 40000), 25g sucrose, 10g trehaloses, 1.5g sodium thiosulfate, 0.5g Tween80,0.5g EDTA-Na and appropriate (50mM) pH7.2 citrate buffer agents, are made 500ml and are suspended (/ molten) liquid, spray drying (II method) altogether.

Embodiment 10-2

The first active polysaccharide of sequence in embodiment 10-1 formulas by equivalent (water solubility) polysaccharide from Dunaliella salina (anticoagulation, Antiviral, antithrombotic, antitumor, strengthen immunity, regulation immunity, removing free radical, anti-aging, anticoagulation and antithrombotic, Anti HIV-1 virus, eliminate gastronintestinal system disorder, antiallergy, enhancing liver function, reduce high fat of blood and hypertension, stabilizing blood sugar level, Promote skin regeneration, skin moisture-keeping) replace, it is constant that other (contain preparation method).

Embodiment 11-1

Formula is matched：3g (water solubility) zymosan (proteoglycan, it is anti-oxidant, growth promoting, antiviral, Immune-enhancing effect, subtract Light radiation injury, antitumor, absorption pathogen), 10ml thermophilus bacteria suspension (6.2 × 10⁹CFU/ml), 40g galactomannans Poly oligosaccharide, 2.5g Tween 80,0.5g EDTA-Na, 2g N-acetylcystein and appropriate sterile pH7.2 phosphoric acid (/ hydrogen) potassium Salt buffer agent, is made 500ml and is suspended (/ molten) liquid, spray drying (II method) altogether.

Embodiment 11-2

The active polysaccharide of sequence first place in embodiment 11-1 formulas is by watermelon peel polysaccharide (anti-oxidant, anti-aging, drop blood Sugar) equivalent replacement, it is constant that other (contain preparation method).

Embodiment 12 (- 1)

Formula is matched：5% (water solubility) pomelo peel polysaccharide (anti-oxidant), (adding 1ml per 100ml) pasteurellaceae brood cell's bar Bacteria suspension (5.3 × 10⁸CFU/ml), 5% trehalose, (75mM) pH7.2 phosphoric acid (/ hydrogen) sylvite buffer, 0.03%Tween 20th, 2mM methionines and appropriate sterile water for injection, are made 500ml and are suspended (/ molten) liquid, spray drying (II method) altogether.

Embodiment 13-1

Formula is matched：10g (water solubility) Ginkgo biloba polysaccharide (anti-oxidant, anti-aging, enhancing are immune, antitumor), 5ml intestines Mesentery shape leukonid (Leuconostoc mesenteroides) suspension (6.1 × 10⁹CFU/ml), 30g Polygelines are (flat Average molecular weight (Mw) be 27500~39500), 25g sucrose, 10g trehaloses, 1g sodium ascorbates, 0.5g Pluronic F68 With appropriate sterile (50mM) pH7.2 phosphoric acid (/ hydrogen) sylvite buffer, 500ml is made altogether and is suspended (/ molten) liquid, spray drying (II method).

Embodiment 13-2

The active polysaccharide of sequence first place in embodiment 13-1 formulas is by mao bamboon petiole polysaccharide (anti-oxidant, hypoglycemic) equivalent Instead of it is constant that other (contain preparation method).

Embodiment 14-1

Formula is matched：0.5g (water solubility) stauntonvines polysaccharide (suppressing platelet aggregation, liver injury protection), 10ml Epstein-Bar viral suspensions (virus titer 10^8.7TCID₅₀/ ml), 25g sucrose, 10g trehaloses, 0.2g Pluronic F68,1g methionine, 0.3g EDTA-Na, 10g arginine and appropriate sterile (50mM) pH7.2 citrate buffer agents, altogether 500ml is made to be suspended (/ molten) liquid, spray drying (II method).

Embodiment 14-2

The active polysaccharide of sequence first place in embodiment 14-1 formulas is by carrot polysaccharide (anti-oxidant, hypoglycemic, anti-inflammatory) etc. Amount is replaced, and it is constant that other (contain preparation method).

Embodiment 15-1

Formula or proportioning (100)：30g LBP-Xs (proteoglycan, increase immunocompetence, anti-oxidant and anti-aging, Antitumor, neuroprotection, radioresistance, protection reproductive system etc.), Debaryomyces (category) bacterium 5ml (about 2.9 × 10⁹CFU/ Ml), 150mg phenol, 100ml solution, sterile point is made in 172mg metacresols, 0.9g sodium chloride, appropriate sterile water for injection altogether Dress, every 1ml is freezed.

Embodiment 15-2

The active polysaccharide of sequence first place in embodiment 15-1 formulas removes protein chain or peptide chain in molecular structure by equivalent The LBP-X of holosaccharide replace, other (contain preparation method) it is constant.

Embodiment 15-3

(tool is anti-oxidant, drop by the mao bamboon petiole polysaccharide of equivalent for the active polysaccharide of sequence first place in embodiment 15-1 formulas Blood glucose activity) replace, it is constant that other (contain preparation method).

Embodiment 16-1

Formula or proportioning (100)：5g Pleurotus ferulaes polysaccharide (anti-oxidant, anti-inflammatory, antitumor, raising immunity of organisms, anti-spoke Penetrate), clostruidium 5ml (about 3 × 10⁹CFU/ml), 20g sucrose, 5g L-Histidines, the mono- aquations of 5g L-Histidines HCL 100ml solution is made in thing, 150mg phenol, 172mg metacresols, 1g Polysorbate 80s and appropriate sterile water for injection altogether, sterile Packing, every 1ml is freezed.

Embodiment 16-2

The active polysaccharide of sequence first place in embodiment 16-1 formulas is replaced by the oat polysaccharide of equivalent, and other are (containing system Method) it is constant.

Embodiment 17-1

Formula or proportioning (100)：(anti-oxidant, anti-aging, enhancing are immunized, stimulate and make 30g (water solubility) Codonopsis pilosula polysaccharide Blood, antitumor, enhancing memory capability, reduction blood glucose, raising digestion power, protection NSC, resisting stress, antiinflammatory action), 5ml (about 3 × 10⁹CFU/ml) staphylococcus, 150g mannitol, 5g sodium hydrogensulfites and appropriate sterile water for injection, are made altogether 500ml solution, aseptic subpackaged, every 5ml is freezed.

Embodiment 17-2

The active polysaccharide of sequence first place in embodiment 17-1 formulas by (water solubility) the cockroach polysaccharide of equivalent, (exempt from by enhancing Epidemic disease) replace, it is constant that other (contain preparation method).

Embodiment 18-1

Formula or proportioning (100)：(molecular weight 5-16 ten thousand, anti-oxidant, strengthen immunity promote to make 10g panaxans Blood, hypoglycemic, antidiuresis, anti-aging, antithrombotic, antibacterial, anti-inflammatory is antitumor), 5ml (about 3 × 10⁹CFU/ml) leukonid Belong to bacterium, 15g D-mannoheptuloses, 0.5g methionines and appropriate sterile water for injection, 200ml solution, sterile point are made altogether Dress, every 2ml (shading, shady place (being no more than 20 DEG C) are preserved), is freezed.

Embodiment 18-2

(tool is anti-oxidant, drop by the mao bamboon petiole polysaccharide of equivalent for the active polysaccharide of sequence first place in embodiment 18-1 formulas Blood glucose activity) replace, it is constant that other (contain preparation method).

Embodiment 19-1

Formula or proportioning (100)：(tool is anti-oxidant, improve immune function of human body, increasing leukocyte, drop for 1g Cordyceps sinensis polysaccharides Blood glucose), 5ml (about 3 × 10⁹CFU/ml) Wei Si Bordetella bacterium, 9g lactose, 13.5mg potassium dihydrogen phosphates (KH2PO4), 71mg phosphorus Sour disodium hydrogen (Na2HPO4), 0.5g sodium pyrosulfites and appropriate sterile water for injection, are made 50ml solution altogether, aseptic subpackaged, often Branch 0.5ml, is freezed.

Embodiment 19-2

(tool is anti-oxidant, drop by the mao bamboon petiole polysaccharide of equivalent for the active polysaccharide of sequence first place in embodiment 19-1 formulas Blood glucose activity) replace, it is constant that other (contain preparation method).

Embodiment 20-1

Formula or proportioning (100)：5g GL-Bs (hypoglycemic, reducing blood lipid, antithrombotic is anti-oxidant, removes free radical, Anti-aging, radioresistance is antitumor, promotes blood circulation, and regulation is immune, adjusts Metabolism of nucleic acids and proteins, promotes DNA synthesis, promotees Enter human navel blood LAK cells propagation), 5ml (about 3 × 10⁹CFU/ml) pluton belongs to bacterium, 15g trehaloses and appropriate sterile note Penetrate and use water, 200ml solution is made altogether, aseptic subpackaged, every 2ml is freezed.

Embodiment 20-2

The active polysaccharide of sequence first place in embodiment 20-1 formulas is replaced by the watermelon peel polysaccharide of equivalent, and other (contain Preparation method) it is constant.

Embodiment 21-1

Formula or proportioning (100)：0.1g coriolans (- K) (contain proteoglycan, it is anti-oxidant, antitumor action, immune Humidification and protection liver), 5ml (about 3 × 10⁹CFU/ml) Torulopsis bacterium, 5g Lactitols, 0.5g methionines, With appropriate sterile water for injection, 100ml solution is made altogether, aseptic subpackaged, every 1ml is freezed.

Embodiment 21-2

The active polysaccharide of sequence first place in embodiment 22-1 formulas removes protein chain or peptide chain in molecular structure by equivalent The coriolan of holosaccharide replace, other (contain preparation method) it is constant.

Embodiment 21-3

The first active polysaccharide of sequence in embodiment 21-1 formulas in the molecular structure of equivalent without or deproteinized chain or (water solubility) the turnip polysaccharide (molecular weight, 10,000, anti-oxidant, hypoglycemic) of the holosaccharide of peptide chain is replaced, and other (contain preparation method) no Become.

Embodiment 22-1

Formula or proportioning (100)：0.5g corn silk polysaccharides (regulation blood glucose, suppress tumour growth, regulation immunity of organism and It is anti-oxidant), 5ml (about 3 × 10⁹CFU/ml) Bacillus licheniformis, 10g hydroxyl isomaltuloses, 0.5g methionines, 0.2g Tween80,0.2g EDTA-Na and appropriate sterile (50mM) pH7.2 phosphoric acid (/ hydrogen) sylvite buffer, are made 100ml molten altogether Liquid, spray drying (either method disclosed in II method, i.e. CN101287449B/A refers to specification, similarly hereinafter), sterile point of powder Dress, is divided into 100.

Embodiment 22-2

The active polysaccharide of sequence first place in embodiment 22-1 formulas is replaced by BCG-polysaccharide equivalent, and other are (containing system Method) it is constant.

Embodiment 23-1

Formula or proportioning (100)：300mg Goods-Flow Plans (anti-oxidant, antitumor, protection hematopoiesis function, enhancing be immune, Promote hematopoiesis function), 5ml (about 3 × 10⁹CFU/ml) bacillus subtilis, 2g erythritols, 440mg sodium chloride, 19.5 μ g phosphorus Acid dihydride sodium, 130mg disodium hydrogen phosphates, 2.75mg Polysorbate 20s (20) with appropriate sterile water for injection, it is made altogether 50ml solution, aseptic subpackaged, every 0.5ml is freezed.

Embodiment 23-2

The active polysaccharide of sequence first place in embodiment 23-1 formulas is replaced by black nightshade polysaccharide equivalent, and other (contain preparation method) It is constant.

Embodiment 24-1

Formula or proportioning (100)：0.5g (leaf roll) Siberian solomonseal rhizome polysaccharide is (antitumor, anti-oxidant, immunological regulation, antibacterial anti- It is scorching), 5ml (about 3 × 10⁹CFU/ml) the poly- FOS of bacteroides amylophilus, 2g, 4g mannitol, 1g sucrose, 120mg trihydroxy methyls Aminomethane and appropriate sterile water for injection, are made 100ml solution altogether, aseptic subpackaged, every 1ml, freeze.

Embodiment 24-2

The active polysaccharide of sequence first place in embodiment 24-1 formulas is replaced by the white chessman grass polysaccharide of equivalent, and other (contain Preparation method) it is constant.

Embodiment 25-1

Formula or proportioning (100)：200mg Chinese yam polysaccharides (contain proteoglycan, anti-oxidant, anti-aging, enhancing are immune, anti- It is tumour, hypoglycemic), 5ml (about 3 × 10⁹CFU/ml) the raw bacteroid of cud, 1g Fructus Hordei Germinatus oligoses and appropriate sterile water for injection, altogether 50ml solution is made, aseptic subpackaged, every 0.5ml is freezed.

Embodiment 25-2

The active polysaccharide of sequence first place in embodiment 25-1 formulas is replaced by Saussurea Polysaccharide equivalent, and other (contain preparation method) It is constant.

Embodiment 26-1

Formula or proportioning (100)：3g (water solubility) Glehnia Littoralis Polysaccharide (immunosupress), 5ml (about 3 × 10⁹CFU/ml) Butterfat enterococcus, 10g glucans (mean molecule quantity 10,000), 1.8g biphosphate sodium-hydrates, the water of 5.5g disodium hydrogen phosphates seven Compound, 2.3g sodium chloride, 100mg Tween-80s and appropriate sterile water for injection, are made 500ml solution altogether, aseptic subpackaged, Every 5ml, is freezed.

Embodiment 26-2

(tool is anti-oxidant, drop by the mao bamboon petiole polysaccharide of equivalent for the active polysaccharide of sequence first place in embodiment 26-1 formulas Blood glucose activity) replace, it is constant that other (contain preparation method).

Embodiment 27-1

Formula or proportioning (100)：5g brown algae proteins polysaccharide (anti-oxidant, promote hematopoiesis and immunological regulation), 5ml (about 3 × 10⁹CFU/ml enterococcus, 15g FOSs (FOS) (molecular weight is less than 10,000) and appropriate sterile water for injection, are made altogether in the middle of) 500ml solution, aseptic subpackaged, every 5ml is freezed.

Embodiment 27-2

The active polysaccharide of sequence first place in embodiment 27-1 formulas removes protein chain or peptide chain in molecular structure by equivalent The algal polysaccharide of holosaccharide replace, other (contain preparation method) it is constant.

Embodiment 27-3

The first active polysaccharide of sequence in embodiment 27-1 formulas in the molecular structure of equivalent without or deproteinized chain or (raising immunity, liver protection, moisturizing, anti-infective, anti-oxidant, auxiliary improvement of memory ease up the flammulina velutipes of the holosaccharide of peptide chain Physical fatigue) replace, it is constant that other (contain preparation method).

Embodiment 28-1

Formula or proportioning (100)：1g abalone visceral proteins polysaccharide (anti-oxidant, antitumor, immunological regulation), 5ml (about 3 ×10⁹CFU/ml) bacillus coli, 6g malt-bases-(α -/or β -/or γ -) cyclodextrin and appropriate aseptic injection are used Water, is made 100ml solution altogether, aseptic subpackaged, every 1ml, freezes.

Embodiment 28-2

The active polysaccharide of sequence first place in embodiment 28-1 formulas removes protein chain or peptide chain in molecular structure by equivalent The abalone internal organ polysaccharide of holosaccharide replace, other (contain preparation method) it is constant.

Embodiment 28-3

The first active polysaccharide of sequence in embodiment 28-1 formulas in the molecular structure of equivalent without or deproteinized chain or The peanut polysaccharide (immunological regulation, protection liver, hypotensive, anti-oxidant) of the holosaccharide of peptide chain is replaced, and other (contain preparation method) no Become.

Embodiment 29-1

Formula or proportioning (100)：3g astragalus polyoses (molecular weight 1-5 ten thousand, antiviral, antitumor, anti-aging, radioresistance, It is resisting stress, anti-inflammatory, anti-oxidant), 5ml (about 3 × 10⁹CFU/ml) Kluyveromyces fragilis, 15g (2-/or 3-) hydroxypropyl- (α -/or β -/or γ -) cyclodextrin and appropriate sterile water for injection, are made 300ml solution, aseptic subpackaged, every 3ml freezes altogether It is dry.

Embodiment 29-2

Silk cocoon polysaccharide (hypoglycemic) replacement of the first active polysaccharide by equivalent of sorting in embodiment 29-1 formulas, other (contain preparation method) constant.

Embodiment 30-1

Formula or proportioning (100)：1.2g Inonotus obliquus core polysaccharide (hypoglycemic), 5ml (about 3 × 10⁹CFU/ml) bend Lactobacillus, 20g mannitol, 1.05g sodium acetate trihydrates, 0.9g methionines, 0.81g metacresols and appropriate aseptic injection are used Water, is made 300ml solution altogether, aseptic subpackaged, every 3ml, freezes.

Embodiment 30-2

The active polysaccharide of sequence first place in embodiment 30-1 formulas is replaced by the BCG-polysaccharide (immunological regulation) of equivalent, It is constant that other (contain preparation method).

Embodiment 31-1

Formula or proportioning (100)：5g hericium erinaceum polysaccharides (contain proteoglycan, antiulcer, antiinflammatory action, antitumor action, Liver protecting, increase immunity, anti-aging, raising body's hypoxia tolerance, increase heart blood output quantity, acceleration body blood Circulation, reduction blood glucose, the effect of blood fat), 5ml (about 3 × 10⁹CFU/ml) Pediococcus acidilactici, 20g alamethicins and appropriate sterile Water for injection, is made 300ml solution altogether, aseptic subpackaged, every 3ml, freezes.

Embodiment 31-2

Sorting oriental cherry polysaccharide (tool antioxidation activity) generation of the first active polysaccharide by equivalent in embodiment 31-1 formulas Replace, it is constant that other (contain preparation method).

Embodiment 32-1

Formula or proportioning (100)：2g (water solubility) elm fungus polysaccharides (antitumor), 5ml (about 3 × 10⁹CFU/ml sieve) is taken Her Deng Shi Propionibacteriums, 15g Dextran 40s and appropriate sterile water for injection, is made 200ml solution altogether, aseptic subpackaged, every 2ml, is freezed.

Embodiment 32-2

Human Placental Lipo-glucosaminoglycan (lipopolysaccharides, strong machine of the first active polysaccharide by equivalent that sort in embodiment 32-1 formulas Body is acted on the nonspecific immunity power of various bacteria and virus) replace, it is constant that other (contain preparation method).

Embodiment 33-1

Formula or proportioning (100)：1g (water solubility) buckwheats polysaccharide (molecular weight 17.2 ten thousand) is (immunological regulation, antitumor, anti- It is viral and anti-infective), 5ml (about 3 × 10⁹CFU/ml) Saccharomyces cerevisiae, 8g lactoproteins range of hydrolysed peptides (relative molecular mass 1000~ 5000) with appropriate sterile water for injection, 200ml solution is made altogether, aseptic subpackaged, every 2ml is freezed.

Embodiment 33-2

Polysaccharide from urtica fissa (anti-inflammatory, analgesia and suppression of the first active polysaccharide by equivalent of sorting in embodiment 33-1 formulas Hyperplasia of prostate) replace, it is constant that other (contain preparation method).

Embodiment 34-1

Formula or proportioning (100)：(proteoglycan, oxidation resistance is growth promoting, disease-resistant for 100mg (water solubility) zymosan Poison, Immune-enhancing effect, mitigate radiation injury, it is antitumor, absorption pathogen), 5ml (about 3 × 10⁹CFU/ml) Staphylococcus carnosus, 200mg glycine, 290mg AMSPs, 280mg ADSPs, 300mg metacresols, 4.1g mannitol and Appropriate sterile water for injection, is made 100ml solution altogether, and aseptic subpackaged, every 1ml is freezed.

Embodiment 34-2

(regulation is immune, antioxygen by the Polysaccharide From Salvia Chinensis of equivalent for the active polysaccharide of sequence first place in embodiment 34-1 formulas Change, it is antitumor) replace, other (contain preparation method) it is constant.

Embodiment 35-1

Formula or proportioning (100)：7g (water solubility) zymosan (proteoglycan, oxidation resistance, growth promoting, it is antiviral, Immune-enhancing effect, mitigation radiation injury, antitumor, absorption pathogen), 5ml (about 3 × 10⁹CFU/ml) streptococcus lactis, 5g high F values Oligopeptides and appropriate sterile water for injection, are made 200ml solution altogether, aseptic subpackaged, every 2ml, freeze.

Embodiment 35-2

Mulberries polysaccharide (anti-oxidant) replacement of the first active polysaccharide by equivalent of sorting in embodiment 35-1 formulas, other (contain preparation method) constant.

Embodiment 36-1

Formula or proportioning (100)：0.5g Inokopolyoses (improving immunity, antitumor, anticoagulation), 5ml (about 3 × 10⁹ Individual/ml) bhk cell suspension, 2g albumen calcium peptides (CCP) and appropriate sterile water for injection, 100ml solution is made altogether, it is aseptic subpackaged, Every 1ml, is freezed.

Embodiment 36-2

The first active polysaccharide of sequence in embodiment 36-1 formulas by equivalent Hemarisin (lipopolysaccharides, it is antitumor, Immunological regulation) replace, it is constant that other (contain preparation method).

Embodiment 37-1

Formula or proportioning (100 capsule)：100mg polysaccharide from urtica fissa (anti-inflammatory, analgesia and suppression hyperplasia of prostate), the 1ml mankind Metapneumovirus (virus titer 10^9.8TCID₅₀/ ml), 5g polyalanines (mean molecule quantity (Mw) be 10000~30000), 0.5g PEG (40) stearates and appropriate sterile water for injection, are made 200ml and are suspended (/ molten) liquid altogether, and spray drying (II method) is filled afterwards Enter capsule (100, equivalent).

Embodiment 37-2

The first active polysaccharide of sequence in embodiment 37-1 formulas by equivalent Scutellaria Barbata D. Don Polysaccharides (it is anti-oxidant, antitumor, Regulation is immune) replace, it is constant that other (contain preparation method).

Embodiment 38-1

Formula or proportioning (100)：1g mankshood polysaccharides (neutral polysaccharide, Aci dic proteinpolysaccharide, immunological regulation, antitumor), 1ml SIVs (SIV) (virus titer 10^9.8TCID₅₀/ ml), 10g glycine and appropriate sterile water for injection, altogether system Aseptic subpackaged into 300ml solution, every 3ml is freezed.

Embodiment 38-2

The first active polysaccharide of sequence in embodiment 38-1 formulas by equivalent watermelon peel polysaccharide (anti-oxidant, anti-aging, It is hypoglycemic) replace, it is constant that other (contain preparation method).

Embodiment 39-1

Formula or proportioning (100)：(anti-oxidant, regulation is immune, antitumor, improve human body for 1g (water solubility) mushroom polysaccharide Metabolism, adjust vegetative nerve, norcholesterol, hypotensive and prevent and treat hepatitis, gastric ulcer, duodenal ulcer), exhale 1ml Viral (the virus titer 10 of Mai Xiweisina diseases^9.8TCID₅₀/ ml), 5g poly arginines-glutamic acid (relative molecular mass 5000~ 10000), 50g sucrose, 20g trehaloses and appropriate sterile water for injection, are made 1000ml solution altogether, aseptic subpackaged, every 10ml, is freezed.

Embodiment 39-2

Banana skin polysaccharide (anti-oxidant) replacement of the first active polysaccharide by equivalent of sorting in embodiment 39-1 formulas, its It is constant that he (contains preparation method).

Embodiment 40-1

Formula or proportioning (100)：10mg (water solubility) cockroaches polysaccharide (enhancing is immune), 5ml (about 3 × 10⁹CFU/ml) Lactobacillus plantarum, 8g mannitol, 0.36g biphosphate sodium-hydrates, 1.1g sodium phosphate dibasic heptahydrates and appropriate sterile Water for injection, is made 100ml solution altogether, aseptic subpackaged, every 1ml, freezes.

Embodiment 40-2

The first active polysaccharide of sequence in embodiment 40-1 formulas by equivalent watermelon peel polysaccharide (anti-oxidant, anti-aging, It is hypoglycemic) replace, it is constant that other (contain preparation method).

Reference examples

Reference examples X-1 (X=1~40)

The first active polysaccharide of sequence in embodiment X-1 (X=1~40) formulas by equivalent the polysaccharide through heat and acid, The destruction of the non-oxidisers such as alkali makes it lose physiologically active substantially but retains its former inoxidizability (if yes) (i.e. secondary structure Destruction is larger, and primary structure is not destroyed or destruction (its mean molecule quantity reduce be substantially below 10%) on a small quantity substantially) polysaccharide generation Replace, it is constant that other (contain preparation method).

Reference examples X-2 (X=1~5)

The active polysaccharide of sequence first place in embodiment X-1 (X=1~5) formulas is replaced by the sodium alginate of equivalent, other (contain preparation method) constant.

Reference examples X-2 (X=6~7,12)

The active polysaccharide of sequence first place in embodiment X-1 (X=6~7,12) formulas is replaced by the ovalbumin of equivalent, It is constant that other (contain preparation method).

Reference examples X-2 (X=8~11)

The active polysaccharide of sequence first place in embodiment X-1 (X=8~11) formulas is replaced by the HES of equivalent, It is constant that other (contain preparation method).

Reference examples X-2 (X=13~16)

The active polysaccharide of sequence first place in embodiment X-1 (X=13~16) formulas is (heavy by the sucrose and trehalose of equivalent Measure ratio 5: 2) replace, it is constant that other (contain preparation method).

Reference examples X-2 (X=17~18)

The active polysaccharide of sequence first place in embodiment X-1 (X=17~18) formulas is replaced by the HES of equivalent, It is constant that other (contain preparation method).

Reference examples X-2 (X=19~21)

Mannitol and trehalose of the first active polysaccharide by equivalent that sorts in embodiment X-1 (X=19~21) formulas (weight is than 5: 2) are replaced, and it is constant that other (contain preparation method).

Reference examples X-2 (X=22~24)

The active polysaccharide of sequence first place in embodiment X-1 (X=22~24) formulas is replaced by the HES of equivalent, It is constant that other (contain preparation method).

Reference examples X-2 (X=25~27)

The active polysaccharide of sequence first place in embodiment X-1 (X=25~27) formulas (is divided equally again by the sodium alginate of equivalent Son amount 8-20 ten thousand) replace, it is constant that other (contain preparation method).

Reference examples X-2 (X=28~29)

Isomaltose of the first active polysaccharide by equivalent that sort in embodiment X-1 (X=28~29) formulas (isomalt) and trehalose (weight is than 5: 2) is replaced, other (contain preparation method) it is constant.

Reference examples X-2 (X=30~36)

The active polysaccharide of sequence first place in embodiment X-1 (X=30~36) formulas is replaced by the sodium alginate of equivalent, its It is constant that he (contains preparation method).

Reference examples X-2 (X=37~38)

(weight is equal by the gelatin (K＆K) of equivalent for the active polysaccharide of sequence first place in embodiment X-1 (X=37~38) formulas Molecular weight 10-30 ten thousand) replace, it is constant that other (contain preparation method).

Reference examples X-2 (X=39~40)

(weight is equal by the HES of equivalent for the active polysaccharide of sequence first place in embodiment X-1 (X=39~40) formulas Molecular weight 10-30 ten thousand) replace, it is constant that other (contain preparation method).

Test case composition stability test

Example and its reference examples be placed in simultaneously same enclosed environment (30~40 DEG C of temperature, relative humidity 70%~ 90%) in, (the content of the bioactive materials in reference examples X-2 (X=1~50) sample during this period after experience same time Or potency or activity should reduce by 20%~40% or more) take out, and the life in embodiment and its reference examples sample is determined at once The content or potency or vigor (property) of thing active material, and with placing the content or potency or vigor of the preceding bioactive materials (property) is contrasted, and calculates the reduction amount relative to the content or potency before placing.It the results are shown in Table 1.

Vitality test result before and after bioactive materials in table 1-1 samples are placed

Vitality test result before and after bioactive materials in table 1-2 samples are placed

Vitality test result before and after bioactive materials in table 1-3 samples are placed

Vitality test result before and after bioactive materials in table 1-4 samples are placed

Vitality test result before and after bioactive materials in table 1-5 samples are placed

	Embodiment 26-1	Embodiment 26-2	Reference examples 26-1	Reference examples 26-2
					Bacterial action (preceding)	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g
Bacterial action (rear)	4.3×107CFU/g	2.9×106CFU/g	5.6×104CFU/g	1.2×104CFU/g
						Embodiment 29-1	Embodiment 29-2	Reference examples 29-1	Reference examples 29-2
Bacterial action (preceding)	0.92×108CFU/g	0.92×108CFU/g	0.92×108CFU/g	0.92×108CFU/g
					Bacterial action (rear)	8.1×106CFU/g	5.4×105CFU/g	6.7×103CFU/g	2.3×103CFU/g
	Embodiment 30-1	Embodiment 30-2	Reference examples 30-1	Reference examples 30-2
					Bacterial action (preceding)	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g
Bacterial action (rear)	6.7×107CFU/g	2.2×106CFU/g	4.8×104CFU/g	8.3×103CFU/g
						Embodiment 31-1	Embodiment 31-2	Reference examples 31-1	Reference examples 31-2
Bacterial action (preceding)	8.7×107CFU/g	8.7×107CFU/g	8.7×107CFU/g	8.7×107CFU/g
					Bacterial action (rear)	7.7×106CFU/g	6.8×105CFU/g	5.7×103CFU/g	2.1×103CFU/g
	Embodiment 32-1	Embodiment 32-2	Reference examples 32-1	Reference examples 32-2
					Bacterial action (preceding)	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g	1.1×108CFU/g
Bacterial action (rear)	7.3×107CFU/g	5.2×106CFU/g	3.8×104CFU/g	1.3×104CFU/g
						Embodiment 33-1	Embodiment 33-2	Reference examples 33-1	Reference examples 33-2
Bacterial action (preceding)	1.2×108CFU/g	1.2×108CFU/g	1.2×108CFU/g	1.2×108CFU/g
					Bacterial action (rear)	5.2×107CFU/g	4.2×106CFU/g	6.3×104CFU/g	2.7×104CFU/g
	Embodiment 34-1	Embodiment 34-2	Reference examples 34-1	Reference examples 34-2
					Bacterial action (preceding)	8.5×107CFU/g	8.5×107CFU/g	8.5×107CFU/g	8.5×107CFU/g
Bacterial action (rear)	6.7×106CFU/g	5.5×105CFU/g	4.6×103CFU/g	1.6×103CFU/g
						Embodiment 35-1	Embodiment 35-2	Reference examples 35-1	Reference examples 35-2
Bacterial action (preceding)	9.1×107CFU/g	9.1×107CFU/g	9.1×107CFU/g	9.1×107CFU/g
					Bacterial action (rear)	8.8×106CFU/g	5.9×105CFU/g	4.2×103CFU/g	1.4×103CFU/g

Vitality test result before and after bioactive materials in table 1-6 samples are placed

Foregoing invention has been described in detail for illustrating and understanding, those skilled in the art are disclosed herein by reading Content can understand and know that the various changes in form and details can be carried out in the case where not departing from true scope of the present invention.For example, above-mentioned Composition or preparation, technology and equipment can be applied in combination with various.All documents of the application reference, patent, patent application, And/or alternative document is hereby incorporated by reference, as every a document, patent, patent application, and/or alternative document quilt It is individually incorporated to reference.

Claims (10)

1. a kind of stable composition for preserving bioactive materials, said composition includes at least one with least one non-antioxygen The polysaccharide of the bioactivity of change, and at least one live body bioactive materials, and at least one pharmaceutically acceptable matrix Component, the polysaccharide should with bioactivity does not have activity suppression or killing action, the bioactivity to the bioactive materials Material is scattered or is embedded in the glassy struc matrix of the polysaccharide for having bioactivity comprising this and/or the matrix components.

2. composition according to claim 1, wherein the polysaccharide of described bioactivity has anti-inflammatory, resisting stress, radioresistance, tune Section is immune, antitumor, anti-infective, promote hematopoiesis, diuresis, antiulcer, reducing blood lipid, hypoglycemic, hypotensive, antithrombotic, protection dirty Device, protection nerve, protection reproductive system, promote blood circulation, regulation nucleic acid or protein metabolism, promote DNA synthesis, promote it is thin Born of the same parents breed and enhancing learning and memory etc. the non-oxidation resistant bioactivity/of the middle one or more of effect or function or pharmacological activity Polysaccharide.

3. composition according to claim 1, wherein the polysaccharide of described bioactivity has and described bioactive materials There is the polysaccharide of identical bioactive functions or identical medical usage.

4. composition according to claim 1, wherein the polysaccharide of described bioactivity has has enhancing to bioactive materials Its active function or have the polysaccharide of synergy between the two.

5. composition according to claim 1, wherein the polysaccharide of described bioactivity is selected from LBP-X, lentinan, Huang Astragalus polysaccharides, panaxan, BCG-polysaccharide, Hemarisin, glossy-ganoderma-spore polysaccharide, grifola polysaccharide, Human Placental Lipo-glucosaminoglycan, the root of bidentate achyranthes are more Sugar, algal polysaccharide, polysaccharide from urtica fissa, seam split polysaccharide, Cordyceps sinensis polysaccharide, GL-B, ganoderma spore polysaccharide, Hijiki polysaccharide, mushroom Polysaccharide, coriolan, corn silk polysaccharide, silk cocoon polysaccharide, Fructus Schisandrae Polysaccharide, black nightshade polysaccharide, Chinese mugwort polysaccharide, lily polysaccharide, the tuber of pinellia are more Sugar, spirulina polysaccharide, Chinese pine pollen polysaccharide, Taraxacum Polysaccharides, epimedium brevicornum polysaccharide, humulus grass polysaccharide, Gentiana Polysaccharides, white chessman grass are more Sugar, Cells of Blue-green Algae exo polysaccharides, soluble polysaccharide, cactus polyoses, date polysaccharide, armillaria mellea polysaccharide, buckwheat polysaccharide, maize peel are more Sugar, corn pollen polysaccharide, Blackfungus polyhexose, nostoc polysaccharide, root of herbaceous peony polysaccharide, aloe polysaccharide, Banlangen Polysaccharide, mulberries polysaccharide, Algal polysaccharides, Chinese yam polysaccharide, zymosan, rape pollen polysaccharide, coleseed polysaccharide, Polysaccharide From Salvia Chinensis, hedysarum polybotys saccharide, loguat leaf Polysaccharide, Siberian solomonseal rhizome polysaccharide, tea polysaccharide, Chinese hawthorn leaf polysaccharide, laminarin, Onion Polysaccharide, Scutellaria Barbata D. Don Polysaccharides, pleurotus nebrodensis polysaccharide, apricot Bao Mushroom polysaccharide, Pleurotus ferulae polysaccharide, garlic polysaccharide, banana skin polysaccharide, maca polysaccharide, Sweet Potato Polysaccharide, watermelon peel polysaccharide, mao bamboon petiole are more Sugar, lithosperman, cordate houttuynia polysaccharide, dendrobium polysaccharide, bitter melon polysaccharide, carrot polysaccharide, Russula polysaccharide, rose polysaccharide, the tuber of dwarf lilyturf are more Sugar, blazei polysaccharide, sea grass polysaccharide, Stropharia rugoso-annulata polysaccharide, Bupleurum chinense polysaccharide, Morchellaconica extracellular polysaccharide, to fall certain herbaceous plants with big flowers polysaccharide, Moringa more Sugar, Polysaccharides in Bamboo Leaves, Agrocybe chaxingu polysaccharide, mushroom polysaccharide, rabdosia lophanthide polysaccharide, cassia seeds polysaccharides, bamboo shoots polysaccharide, turnip polysaccharide, saussurea involucrata Polysaccharide, Folium Panacis Quinquefolii polysaccharide, Polysaccharides in Cultured Cordyceps militaris, stauntonvine polysaccharide, pachymaran, Glehnia Littoralis Polysaccharide, dictyophora fungus polysaccharide, Mongolian oak fern are more Sugar, oyster polysaccharide, Codonopsis pilosula polysaccharide, polysaccharide from Dunaliella salina, Glehnia Littoralis Polysaccharide, elm fungus polysaccharides, pomelo peel hydrolyzed pectin polysaccharide, rhizoma Gastrodiae are more Sugar, cockroach polysaccharide, Ginkgo biloba polysaccharide, flammulina velutipes, speciosus polysaccharide, oat polysaccharide, peanut polysaccharide, newborn source casein are more Sugar, chondroitin sulfate proteoglycan, Fructus Schisandrae Polysaccharide, proteoglycan decorin, bacterioprotein polysaccharide, QINBA selenium-mushroom extract It is selenoprotein polysaccharide, mushroom protamine polysaccharide, brown algae protein polysaccharide, abalone visceral protein polysaccharide, U. pertusa polysaccharide, Chinese yam polysaccharide, solidifying Collect element, ganoderma lucidum albumen/peptide sugar, mulberry leaf polysaccharide, newborn mushroom polysaccharide, Pasteur mushroom proteoglycan, mankshood polysaccharide, hericium erinaceum polysaccharide, nine In fragrant GL-PP polysaccharide, hyriopsis cumingii polysaccharide, Goods-Flow Plan, echinacea polysaccharide, notoginseng polysaccharide, sposknikovan, licorice polysaccharide, thorn Slender acanthopanax polysaccharide, semen litchi polysaccharide, Inonotus obliquus core polysaccharide, Sclerotium of Pleurotus tuber regium polysaccharide, and its mixture.

6. composition according to claim 1, wherein the bioactive materials of described live body are selected from microorganism or cell suspension, And their mixture.

7. composition according to claim 1, wherein described pharmaceutically acceptable matrix components are selected from pharmaceutically acceptable Monosaccharide and disaccharide, oligosaccharides, sugar alcohol, the polysaccharide of inactive, cyclodextrin, amino acid and its salt, edible or medicinal peptide, poly- It is carboxylic acid, carboxylate, the acceptable inorganic salt of solid, and their mixture at amino acid, polyvinylpyrrolidone, osamine, 25 DEG C of room temperature.

8. a kind of preparation method of the stable composition for preserving bioactive materials, the preparation method includes：

1), prepare comprising with the polysaccharide of at least one non-oxidation resistant bioactivity, bioactive materials of live body, pharmaceutically The suspension or true solution or colloidal solution of acceptable matrix components and solvent, should have the polysaccharide of bioactivity to the biology Active material does not have activity suppression or killing action, and polysaccharide and matrix components that should be with bioactivity be dissolved in or be scattered in Solvent formation true solution or colloidal solution；

2) solvent in suspension obtained above or true solution or colloidal solution, is removed.

9. a kind of preparation method of the stable composition for preserving bioactive materials, the preparation method includes：

1), prepare comprising with the polysaccharide of at least one non-oxidation resistant bioactivity, bioactive materials of live body, pharmaceutically The suspension or true solution or colloidal solution of acceptable matrix components and solvent, should have the polysaccharide of bioactivity to the biology Active material does not have activity suppression or killing action, and polysaccharide and matrix components that should be with bioactivity be dissolved in or be scattered in Solvent formation true solution or colloidal solution；

2) mixture of above-mentioned suspension or true solution or colloidal solution and gases at high pressure or nearly supercritical liq, is made；

3) pressure of mixture, is reduced, the gaseous suspension of droplet is formed；With

4), exchanged with dry gas with the gaseous suspension of droplet and droplet is dried powdering particulate.

10. a kind of purposes of the polysaccharide with bioactivity, the purposes for this there is the polysaccharide of bioactivity to be used for stable preserve The composition of bioactive materials comprising live body, said composition bag at least one has at least one non-oxidation resistant biological living The polysaccharide of property, and at least one live body bioactive materials, and at least one pharmaceutically acceptable matrix components, this has The polysaccharide of bioactivity does not have activity suppression or killing action to the bioactive materials, and the bioactive materials are scattered or wrap In the glassy struc matrix for being embedded in the polysaccharide that there is bioactivity comprising this and/or the matrix components.