CN101272761B - Uses of sporopollenin - Google Patents

Abstract

The invention provides the use of an exine shell of a naturally occurring spore, or a fragment thereof, as an antioxidant, for instance in a formulation containing an active substance. Also provided is a method for reducing rancidity, or other oxidative degradation, of a substance or composition, by encapsulating the substance or composition in, or chemically or physically binding it to, or mixing it with, an exine shell of a naturally occurring spore or a fragment thereof.

Description

The purposes of sporopollenin

Invention field

The present invention relates to natural spore shell as antioxidant with have a new purposes of the delivery vehicles of antioxidant properties.

Background of invention

Many active substances, for example medicine and nutritional supplementation property active substance and COF are exposed in the air or oxidized easily in the dissolved oxygen, for example under humidity or aqueous environment.As far as many materials, be exposed in the ultraviolet radiation that for example comes from natural light and can induce (promptly causing or acceleration) oxidizing process.Lipid for example oil is oxidized especially easily.

This susceptibility reduces active substance and any stability that comprises the composition of active substance.This can cause effect reduction and/or generation not to hope the side-product that produces.These side-products possibly for example destroy the taste (when for example fat or oily souring lose) of food, increase the toxicity of pharmaceutical preparation, damage cosmetic appearance, cause the operation problem of engine internal fuel, perhaps briefly in use damage its performance.

Can protect it to avoid for example oxygen and ultraviolet Effect of Environmental in the suitable delivery vehicles through being encapsulated into active substance.It often is complicated, time-consuming and expensive that yet preparation is mounted with the conveying whole body of active substance like this.For guaranteeing that the gained preparation meets quality control and supervision standard and uniform active material concentration is provided, need make the object of encapsulation big or small consistent with the shape ten minutes, this process possibly go wrong.If must greatly not damage the sized of those objects then the physical property of total formulation, then be difficult in the object of encapsulation and obtain sufficiently high active substance useful load.

Need guarantee that in addition any material that has encapsulated can use point moderately to discharge in expection.To do encapsulation enough well before use to protect this material also to be not easy.

But thereby the object of the invention provides the enhanced activity material overcomes or relax at least the problems referred to above to the stability of oxidation method for preparing.

Summary of the invention

According to first aspect of the present invention natural spore shell or its fragment purposes as antioxidant is provided.

" natural " is meant that spore originates from organism alive, and it can be prokaryote or eukaryote, also can be plant or animal.Spore (this term comprises pollen grain, also includes the for example endospore of antibacterial of body) for example can come from plant, perhaps comes from mushroom, algae or antibacterial or other microorganism sometimes.

The spore shell is the outside thin film around natural (naturalness) spore.The spore shell can be from spore separation; Maybe be for removing attached on the spore shell or other composition that is included in the spore in the spore shell for example cellulosic theca interna and lipid, protein and nucleic acid compositions, available organic solvent, alkali and acid are handled to come out exine from spore separation continuously.Also can use the enzyme facture to come out exine from spore separation.

Gained spore shell shape is the capsule of a basic hollow, and capsule typically comprises sporopollenin.Sporopollenin is a kind of known to that chemically and at physically extremely stable material (G.Shaw sees " chemical property of sporopollenin " in " sporopollenin " J.Brooks; M.Muir, P.Van Gijzel and G.Shaw (volume), academic press; London and New York; 1971,305-348), but sporopollenin still is an inertia and nontoxic.

The spore shell can obtain from spore through some known methods, and for example combined organic solution and strong acid and strong base carry out bulk processing (as refluxing) to spore.Way that method is suitable such as WO-2005/000280 patent (seeing the 10th page) and following example are said.Also can adopt other not too violent method, for example the method for enzyme processing (is seen S.Gubatz, M.Rittscher, A.Meuter, A.Nagler, R.Wiermann, Grana, Suppl.1 (1993) 12-17; K.Schultze Osthoff, R.Wiermann, J.PlantPhysiol., 131 (1987) 5-15; F.Ahlers, J.Lambert, R.Wiermann, Z.Naturforsch., 54c (1999) 492-495; C.Jungfermann, F.Ahlers, M.Grote, S.Gubatz, S.Steuemagel, I.Thom, G.Wetzels and R.Wiermann, J.Plant Physiol, 151 (1997) 513-519).

Perhaps, can use high pressure extruding in the natural hole of spore content from its epispore layer.These methods can be used to remove protein or carbohydrate roughly to be kept the spore shell of archesporium intact form.

For example for Herba Lycopodii (Lycopodium clavatum), gained spore shell can be made up of sporopollenin fully or basically, can have other material of fraction such as chitin, glucosan and/or mannan according to circumstances.Most of protein from archesporium will be removed.

Learn the spore shell useful as drug that comes from spore and the delivery vehicles of nutrient substance from the WO-2005/000280 patent.Active substance can be physically or chemically be incorporated into or be packaged in the spore shell.This document is mentioned the spore shell can be at the active substance that has encapsulated and physical barrier or make active substance avoid photodissociation for example is provided between the aerial oxygen.

Yet people find natural spore shell now amazedly and itself can be used as antioxidant with the protection material, particularly make lipid and lipoids material avoid oxidation.For example when in oil, blowing into oxygen bubble, oil just becomes sour owing to Oxidation fast.But in the time of in being contained in oil sealing on the spore shell that comes from spore, its oxidation just slowly many, this is shown in following example.

This antioxidant effect is not only owing to the spore shell provides physical barrier and is prevented that oxygen from getting into, even although---perfect condition is that both still contact or mixed with the spore shell---still can be observed this effect because material is in the outside of spore shell.In addition, of the WO-2005/000280 patent, known that the spore shell that comes from spore is local at least porous.Through the micropore of spore shell, can separate the time shift of epispore layer except that lipid, protein, nucleic acid and carbohydrate.Also can pass through during active substance infiltration spore shell from the hole.Oxygen around also can letting in the expection of these holes touches any material that is packaged in the spore shell, even and have been found that in fact oxygen can pass through these holes, still can stop the encapsulated substance oxidation.

Therefore it seems spore shell itself or its surface can be as antioxidant at least.So in the present invention, it is meant enhancing substance or the composition purposes to the inherent resistance of oxidation as antioxidant.Though this protection can take place with antiopxidant effect provided by the invention together, the present invention and not only comprising avoids the physical protection that contacts with oxygen.

According to the present invention, the spore shell can come from any suitable natural spore, comes from plant or animal.Here, term " plant " is construed to its broader sense, comprises for example lichen, fungus, algae, gymnosperm, angiosperm and pteridosperms plant.In addition, term " spore " not only is used for comprising the real spore of producing like pteridophyta, lichen and fungus etc., also comprises the for example endospore of antibacterial of the pollen grain that originates from the plant (seed plant) that has seed and organism.

Can obtain these spores from following suitable species, second hurdle is depicted as the diameter of its spore:

Bacillus subtilis (Bacillus subtilis) 1.2 μ m

Myosotis (Myosotis sylvatica) [Myosotis 2.4-5 μ m

(″forget-me-not″)]

Aspergillus niger (Aspergillus niger) 4 μ m

Penicillium (Penicillium) 3-5 μ m

Little chanterelle (Cantharellus minor) 4-6 μ m

Ganoderma (Ganomerma) 5-6.5 μ m

The edge of a field mushroom (Agrocybe) 10-14 μ m

Urtica dioica (Urtica dioica) 10-12 μ m

Black anthracene is spent mould (Periconia) 16-18 μ m

Attach coccus (Epicoccum) 20 μ m

Herba Lycopodii (Lycopodium clavatum) 25 μ m

Herba Lycopodii (Lycopodium clavatum) 40 μ m

Fir (Abies) 125 μ m

Short Fructus Cucurbitae moschatae (Cucurbitapapo) 200 μ m

Fructus Cucurbitae moschatae (Cuburbita) 250 μ m

The spore shell that the present invention uses can be in the WO2005/000280 patent, particularly type described in the 4th, 8 and 9 page and routine 1.Other spore that can extract the spore shell has open on the 8th page of publication of quoting of WO-2005/000280 patent.

According to the present invention, the spore shell can be used for strengthening the material that has added the spore shell or has used the oxidation stability of the composition (this composition comprises preparation) of spore shell, the oxidation rate that therefore can be used to slow down material or composition.

The spore shell can be used to protect material or composition to avoid UV-induced oxidation.Remind once more, this is meant that not only physical protection (i.e. shielding) avoids ultraviolet radiation.On the contrary, although find these spore shells to the screening ability of sunlight relatively a little less than, have been found that natural spore shell can reduce the tendency of material oxidation in ultraviolet radiation.(for example; In wave-length coverage approximate flat spectrum is arranged from the sporopollenin of the spore shell of Herba Lycopodii (Lycopodium clavatum) and Ambrosia trifida (Ambrosia trifida) during for 190-900nm; The absolute value of extinction coefficient is 1-2 * 105im-1, and concerning these two types of spore shells, does not have much differences.One spore shell is propagated about 45% light during for 450nm at wavelength.Wavelength similar on propagating (Zhengang Cui, Paul D.I.Fletcher, Grahame Mackenzie and Vincent Panel does not publish works for Stephen L.Atkin, Sylvain Barrier) between 190nm and the 900nm.)

According to the present invention, the spore shell is adapted at comprising in the preparation of active substance and is used as antioxidant.Active substance can be packaged in the spore shell or physically or chemically combine with the spore shell.Therefore the spore shell can be used as the delivery vehicles of material.Perhaps active substance and spore shell are present in the reagent with the simple physics mixture.

Because itself inherent avirulence, the spore shell that comes from spore be particularly suitable for various possibly contact human body or animal body or and by the reagent of human body or animal body feed in be used as delivery vehicles.It is preferred in the process of separating the epispore composition, removing the protein material that can cause allergic reaction.

Sporopollenin is the main component of most spore shells, is the human known natural organic substance that has resistance most.It can existence under the very harsh environment of pressure, temperature and pH value, and can be insoluble to most of organic solvents.This also makes sporopollenin be fit to very much be used as delivery vehicles.

The spore shell that comes from spore also has other potential advantages as delivery vehicles except its antioxidant activity, comprising:

The spore shell avoids very effective in the atmospheric action at the protection packaging material, and therefore the particularly effect of protected from light and/or oxygen can prevent too early degraded.

The physical protection that the spore shell provides can help to reduce material owing to the loss of for example evaporating, spreading or leaching causing.

No matter all very unified, be different from typical synthetic packaging body from its size of spore shell, shape and the surface nature of any organism preparation.

Yet the size of spore and change of shape are very big between the different plant species, and possible storage environment or the like is decided the preparation to obtain being fit to by place and mode, the active rate of release that needs of the character of active substance and the concentration that needs, intended use, before using.

Even very little spore shell also can be a large amount of relatively active substance encapsulation.Use other known encapsulation technology be difficult to accomplish the little encapsulating material of high activity material useful load, size and fully packaging protection combine.

The spore shell conveniently obtains, price is cheap usually, supply is arranged, and derives from nature, and these characteristics also make it to be well suited for as the mass transport carrier.

For example the 3rd and 4 page and said of more advantage such as WO-2005/000280 about the epispore purposes that comes from spore across the 5th and 6 page paragraph.

When the spore shell was used in the preparation that comprises active substance, preparation can be fit to and/or be applicable to and/or expect and carry by any way.For example; Active substance uses (for example medicine or nutritional supplementation property active substance as whole body; Foodstuff or any other expection clothes advance the active substance of living animal or plant) time, preparation can be fit to and/or be applicable to and/or be contemplated to via oral area, vein, pulmonary, nasal cavity, skin, subcutaneous, oral cavity, peritoneum or any other suitable transporting pattern.

Preparation can be fit to and/or be applicable to and/or expect active substance from the localized delivery to the top layer that the top layer can be lived top layer (no matter or plant or animal) or abiotic top layer in this case.The spore shell is not only as the physical barrier of protection packaging active substance; Its ability as antioxidant is remarkable especially in this case; This is after being discharged on the top layer because of active substance, will be exposed to outside the spore shell, and still can continue to obtain the benefit of oxidation protection to a certain degree.

In the present invention, " part " preparation can be fit to and/or be applicable to and/or be contemplated to and is applied topically to live body part for example skin or other epithelial cell, hair, fingernail or tooth, particularly skin.The live body top layer can be plant or animal, particularly animal.The animal top layer can be for the people's or is inhuman, particularly the people.

Use the preparation of spore shell to can be any suitable physical form.The spore shell can suspend in the liquid that is fit to (term " suspensions " comprises emulsion and other heterogeneous dispersity), perhaps exists with solid such as powder or tablet.Its form of preparation that is fit to localized delivery can be the physical form of washing liquid, butterfat, ointment, pasty state, gel, foam or other any known local application, for example comprise be used in as on the vehicles such as sponge, swab, brush, thin paper, skin patch, dressing or tooth fibre to make things convenient for the preparation of local application.Its form can be nasal mist or eye drop or [.

Topical formulations form or may be selected to be powder is for example when active substance is cosmetic product such as rouge, eye shadow or foundation cream, when perhaps expection is used to apply powder.Shown in following the 11 embodiment, all be encapsulated in liquid in the spore shell, the spore shell can absorb particularly lipid and obtain in fact dry and comfortable product of liquid extremely efficiently.Other active substance for example food supplement or food composition or medicine or active substance also can be made into Powdered.

Medicine that other is fit to and nutritional preparation form are open in the WO2005/000280 patent, for example at page 3 and 6-9 page or leaf.

Active substance can be any material that can tell in application site.For example can be selected from medicine or nutritional supplementation property active substance, food and food composition, food supplement, herbicide, insecticide and agent for controlling noxious insect pests, plant treatment agents such as growth regulator, antibacterial substance, cosmetic product (comprising fragrant atmosphere), toilet articles, disinfectant, cleaning agent and other abluent, binding agent, diagnostic reagent, dyestuff and ink, fuel, explosive, propellant and sensitive material.Generally speaking, the present invention can be used for stablizing any active substance, comprises the active substance of oligomer for example or polymer.

In one embodiment of the invention, active substance is the cosmetic material.The cosmetic material for example can be selected from cosmetic product (foundation cream for example; Powder; Rouge; Eye shadow; Eyeliner and lip liner; Lip pomade; Other dye agent and skin pigment); Skin nursing products (for example cleaning agent; Wetting agent; Emollient; Skin nourishing agent and freshener; Exfoliating Scrub cream and scrubbing cream); Fragrant atmosphere; Perfume products; Sunscreen and other ultraviolet screening agent; Self-tanning agent; Shine the back renovation agent; Age resister and anti-wrinkle agent; Skin whitener; The local anthelmintic of using; Depilatory; Hair growth promoter and manicure product such as nial polish or nail polish makeup removing liquid.Perfume products can comprise more than a kind of fragrance.

In another embodiment of the present invention, active substance can be used for toilet articles.Therefore optional from soap, cleaning agent and other surfactant; Deodorizer and antiperspirant; Lubricant; Fragrant atmosphere; Perfume products; Face powder and talcum powder; Hair care product is shampoo, hair conditioner and hair dye for example; And oral cavity and dental care products such as toothpaste, collutory and flavorants.

And in another embodiment of the present invention, active substance is used for household supplies.For example can be selected from disinfectant and other antibacterial, fragrant atmosphere, perfume products, air freshener, insecticide or other exterminator, insecticide, laundry articles for use (like detergent and maintaining agent), fabric-treating agent (comprising stain), abluent, ultra-violet protecting agent, paint and varnish.

In another embodiment of the present invention, active substance is medicine or nutritional supplementation property active substance, comprises material for animals.The pharmaceutically active substance that is fit to localized delivery is for example optional from the material that is used to handle skin or skin histology uncomfortable (like acne, psoriasis or eczema), wound or burn treating agent, anti-inflammatory agent, counter-stimulus, antimicrobial (comprising antifungal and antibacterial agent), vitamin, vasodilation, local effectively antibiotic and disinfectant.

Medicine or nutritional supplementation property active substance can be fit to and/or expect be used for treatment or prevention.

And in another embodiment of the present invention, active substance is a food, comprises food material.Food material can comprise for example food supplement (like vitamin and mineral, folic acid, Omega-3 oil or fiber), flavouring agent, fragrant atmosphere agent, go up the medium that toner, antiseptic, stabilizing agent, emulsifying agent perhaps change texture of food or persistence.

Active substance can be selected from medicine and nutritional supplementation property active substance, food and cosmetic material and washing material especially.

In one embodiment of the invention, active substance can expect and/or be applicable to and/or suitable localized delivery, preferably is not expection in this case and/or can uses the material of (particularly carrying through skin) by whole body.This material is fit to non-expection and/or is not suitable for and/or is not suitable for taking in particularly human absorption.

Active substance is suitably for the material except that essential oil in some cases, perhaps at least is expection and/or the essential oil that is not suitable for whole body use in vivo.

Active substance can be suitably for except that medicine (being at least the medicine of expection and/or suitable systemic administration) or the material the nutrient substance in some cases.

Active substance can be suitably for except that vitamin, mineral, essential oil, food flavouring agent and/or the material the nutraceutical in some cases.

Active substance can comprise volatile material, particularly fragrant atmosphere.Because helping to suppress any volatile component, the spore shell discharges before use, so the present invention is particularly suitable for comprising the preparation of this volatile material.This point is also non-must be expected, sincerely remember natural spore shell known be foraminous.But the spore shell can encapsulate volatile active and reduce it and evaporate in the air sometimes, shown in following routine 10.

Active substance can be lipid or is similar to the material of lipid (for example oil, fat or wax) and/or can be the amphiphilic cationic lipid material.It can be present in the second grade fluid carrier like liquid-carrier, and the carrier of particularly non-aqueous (or part is non-aqueous basically or at least) is more especially nonaqueous carrier, especially like oily lipid carrier.Therefore active substance can solution or the form of suspension exist, term " suspension " comprises emulsion and other heterogeneous dispersity.Two grade carriers for example can be water-in-oil emulsion or Water-In-Oil oil-in emulsion.

Active substance itself can be natural materials or comes from natural material, particularly plant material.

Active substance can be nonpolar in some cases.

Active substance can be to one or more external influence factors for example heat, light, oxygen or water sensitive.Particularly active substance can be prone to oxidated, especially by oxygen in the atmosphere or dissolved oxygen oxidation.Be more in particular under the external condition, it is subject to the oxidation (being photochemical oxidation) that ultraviolet causes.

The preparation that comprises active substance can be fit to and/or be applicable to and/or expect to be used for storing and/or to use and comprising the fluid environment of oxygen, for example in air or as comprise in the liquid such as water of dissolved oxygen.It can be fit to and/or be applicable to and/or expect to store and/or be used in and is exposed to particularly from the environment under the ultraviolet radiation of daylight.The present invention can protect this active substance to avoid oxidation especially effectively and therefore strengthen the overall stability of preparation in these cases.

The preparation that uses among the present invention can comprise more than a kind of active substance.For example two or more active substance can be encapsulated in the same spore shell simultaneously.As substituting or in addition, preparation prepared in accordance with the present invention can comprise two kinds or more kinds of colony that comprises the spore shell of active substance, each colony is all physically or chemically combine with the different activity material or encapsulating the different activity material.

Therefore, cosmetic formulations for example prepared in accordance with the present invention can comprise opacifier and anthelmintic, perhaps opacifier and wetting agent, perhaps foundation cream or other dye agent and opacifier.Therefore two or more active substances can benefit from the anti-oxidation protection that the spore shell provides.

This also can make two or more active substances can separately preserve before use, original position release together when expection is used then.This is especially valuable, if for example their objectionable interminglings perhaps produce bad interaction.

Preparation prepared in accordance with the present invention can be included in the product, for example can be selected from cosmetics; Toilet articles (like bath article, soap and personal care product); Hair care product; The manicure product; Dentistry article such as toothpaste, collutory and dental floss; Household products (interior or topical) is like surface cleaner, disinfectant, air freshener, anthelmintic and laundry and fabric treating articles for use; Paint, ink, dyestuff and other colouring product; Adhesive product; Medicine and nutritional supplementation property product; Food comprises food additive and food material; Agricultural and gardening product; Fuel; Explosive; Propellant and sensitive material.

This product can be fit to and/or be suitable for and/or expection is carried with any appropriate methodology, comprises for example topical application.

Particularly these commodity can be selected from cosmetic product (comprising skin nursing products), toilet articles, hair and manicure articles for use and dentistry article.

In another embodiment of the present invention, product is medicine or nutritional supplementation property product, and two kinds of products all comprise product for animals.

And in another embodiment, product is a food.

Preparation prepared in accordance with the present invention, active substance can chemically or physically combine with the spore shell or be packaged in the spore shell.Active substance is adapted at physically combining with the spore shell or is packaged in the spore shell.What be more suitable for is that active substance at least partly is packaged in the spore shell.

Material is said with bonded appropriate methodology of spore shell such as WO-2005/000280 patent chemically, for example in across the 4th and 5 page paragraph, 14-22 page or leaf and 24-32 page or leaf.Method can be included as the chemically derived of said spore shell, to promote itself and related material chemical bond.Chemical bond can comprise the chemical bond of covalent bond or other form, for example hydrogen bond, mercapto key, Van der Waals key or coordinate bond.

The physical bond of active substance and spore shell for example can comprise adsorbs material (as comprising that hydrophobic interacts or the aqueous favoring mutual effect) on the surface of spore shell (not pipe internal surface or outer surface).

The encapsulation of active substance is meant and is retained in this material in the chamber, in the central bore that chamber was present in the spore shell wall originally and/or the spore shell limits.

Active substance can be attached to the spore shell with surpassing a kind of aforesaid way; For example can be packaged in the spore shell, also can chemically combine, perhaps can the part of active substance be adsorbed on the spore outer surface of outer cover and another part is included in the spore shell with it.

The formulations prepared according to this invention, the diameter of shell spores (by scanning electron microscopy identified) for 1-300 Xie, suitable for 1-250 m or 3-50 m or 15-40 Xie.Grass pollen, spores from the outer wall and the other a diameter of about 20 spores Xie wall can be considered suitable.

Preferred spore particle size depends on the expection method of application of related activity material or preparation.For example, pulmonary delivery is relatively small particles (e.g., diameter of 10 m or less, or transporting the nasal cavity 8, or 5 m or less, or delivered to the lungs in less than 5 Xie) is preferred.Suitable for oral administration Xie particle size of less than 25.However, if the active substance is expected to transfer to the parenteral (e.g. certain nutrients such as probiotics), a suitable particle size of 40 m or more.Generally, the body for the intended use of the active substance, the particle size of 25 m or less is preferable, because the active material can easily pass into the bloodstream.

Preferred spore particle size depends on the expection method of application of related activity material or preparation.For example for the smaller microgranule of pulmonary delivery (for example diameter be 10 μ m or littler or in nasal cavity carry 8 or 5 μ m or littler or when being delivered to pulmonary for less than 5 μ m) for preferred.Being fit to oral particle size is less than 25 μ m.Yet if expection is arrived intestinal (for example some nutrient substance such as probiotic bacteria) to active species delivery, the particle size that is fit to is 40 μ m or bigger.Generally speaking, for the active substance that the expection whole body uses, particle size is 25 μ m or littler of preferred, gets into blood flow because active substance can pass through easily.

In some cases, for example, larger shell diameter of 30 spores or 40 m or greater, as likely to be pre-absorbed into the bloodstream, particularly suitable as a local delivery media.If yet the active substance of localized delivery need penetrate hair follicle, less spore shell-like 7 μ m or littler, perhaps 5 or 3 μ m or littler, perhaps be desirably 2 μ m or littler possibly be suitable like 1-2 μ m-.

Advantage than the megaspore shell is that it has higher active substance useful load, but also possibly damage preparation whole quality and/or outward appearance, and these carry very important to oral drawn game portion.Therefore, in this case, particularly for for example oral drugs or nutritional supplementation property material or food, the diameter of spore shell is suitably for 10 μ m or littler.In addition, when using bigger spore shell, compared to relevant a large amount of less spore shell, relevant active substance may be distributed in the total formulation more unevenly.Generally speaking, reach rational active substance useful load for asking, the minimum diameter of 4 μ m is preferred.Yet minimum diameter is 60 μ m the or more great talent is suitable in some cases.

In one embodiment of the invention, the spore shell can comprise all or part of cellulose theca interna from natural spore in addition.Spore can reach The above results as if only just handling together with organic solvent and alkali, and does not just reach above-mentioned result with organic solvent and acid processing together.This basic hydrolysis for example uses potassium hydroxide can guarantee that the protein component of spore removes, and lets the plain inwall of at least a portion fibril exist.

In one embodiment of the invention, the spore shell complete or intact substantially.In other words, the micropore or nano-pore on the top layer that is present in these spore shells naturally, the spore shell also provides successive outer wall to limit the internal chamber that active substance loads.Yet some part of spore shell possibility is broken off or is damaged; Therefore the present invention includes the fragment, particularly active substance that use the spore shell that comes from spore chemically or physically be incorporated into the situation of spore shell.Yet, the long-pending seriality of spore case surface with account for when its relevant species such as the spore shell when complete be suitable at least 50% or more, at least 75% or 80% or 90% is more suitable.Therefore as a rule, the present invention relates to the purposes of natural spore shell rather than the purposes of its fragment.

The spore shell can chemically change, and can be to change its attribute (for example dissolubility) or use the place and the change (for example making it to have more surface activity) done in response to its expection, perhaps makes things convenient for it attached on the active substance.The chemical modification that these are fit to and the method such as the WO-2005/000280 patent of roughly above-mentioned change are said, especially at the paragraph across page 4 and page 5 neutralize 14-22 page or leaf and 24-32 page or leaf.The outside of spore shell can be modified through for example making functional group adhere to (typically being chemically), like cation and anionic group (referring to WO-2005/000280 patent and G.Shaw, M.Sykes; R.W.Humble, G.Mackenzie, D.Marsdan & E.Phelivan; The reactive polymeric thing, 1988,2; 211-217), and/or make the spore shell to the enhanced functional group of the captivation on the surface of its intended use.

It is suitable to the described known technology of WO-2005/000280 patent to use, and active substance can adhere to or be packaged in the spore shell.Particularly can make the spore shell be full of active substance through immersing the spore shell in the active substance or in its solution or the suspension.Can help active substance to be full of the spore shell like the one or more enhancing permeating mediums of the said use of WO-2005/000280 patent.Can replace or use to reduce in addition or increase pressure (air pressure aspect) is infiltrated promoting.

The spore shell can load the active substance of any suitable quantity, looks expection operating position and deciding.Formulation example prepared in accordance with the present invention is as comprising active substance and spore shell weight ratio is 0.01: 1 to 35: 1 or 33: 1; For example from 0.01 to 20: 1 or from 0.1: 1 to 12: 1 or 8: 1 or 5: 1, perhaps from 0.5: 1 to 5: 1 or 1: 1 to 5: 1 or 8: 1 or the like.If active substance is contemplated to part encapsulation at least, getable useful load is decided according to the size of spore shell.

According to the present invention, preparation can comprise a part and not be encapsulated in the active substance in the spore enclosure chamber, and active substance is in the spore enclosure even this is, the spore shell still can provide antioxidant effect.Therefore can in this preparation, use higher relatively active material concentration, for example active substance and spore shell weight ratio surpass 5: 1 or 10: 1, even 20: 1 or 30: 1.As stated, maximum suitable useful load can be decided according to the size of spore shell.

In some cases, active substance and the spore shell weight ratio in preparation are the spore shell weight during the active substance solution or the suspension of active substance (or comprise abrim) and be enclosed in the ratio of weight that thick on the outer surface of spore shell reaches the film of 10 μ m or following active substance/solution/suspension in addition abrim.The maximum that on behalf of active substance and spore shell weight ratio, this situation can be fit to lets the antioxidant effect of spore shell reach reasonable level.

The spore shell can scribble the barrier layer and avoid atmospheric effect with further protection related activity material.This is for the conveying of volatile active matter and/or particularly useful to the material of oxygen sensitive.The coating (typically at room temperature) under preparation normal storage situation that is fit to is solid or semisolid, but can be in higher temperature (like the skin temperature) dissolving down of expection topical application.Lipid coatings is fit to use in these cases, for example comprises butter or other hard fat (like cupu oil or sclerosis palm-kernel oil), oil (like cod liver oil) and wax (like Brazil wax or Cera Flava).If particularly active substance is contemplated to localized delivery, coating can be when temperature is skin temperature or dissolved substances (for example cupu oil) during the skin temperature left and right sides, and active substance just can discharge to skin with the mode of topical application like this.Can disruptive material when other possible coating can be and uses with manual exerting pressure, for example frangible solid such as lacca, or when using (as partly), produce dissolving, break or the variation of others with the other materials of release of active agent.For example gelatin can be suitable coating material.

Other known coating excipient can be selected according to required carrying method and the where-used of expection (for example coating can be used for delaying, aiming at or control the release of active substance).Multiple natural or synthetic coating excipient comprises oligomer and polymer, can be used to protect the active substance in the preparation prepared in accordance with the present invention.The coated substance that comes from vegetable can be preferably.

Coating can be applied to the spore shell in a known way, as spraying, roll, screen or dipping.Coating needn't necessarily be enclosed on whole outer surfaces of spore shell continuously.

Second aspect of the present invention provides the purposes of natural spore shell or its fragment, and purpose is to remove the oxide that forms before from material or composition.In other words, natural spore shell or its fragment come to light might " removing " material or composition of oxidation to a certain extent, and remove at least a portion of this oxide, thereby strengthen effective stability of this material or composition.For example, material is lipid such as oil, and at least a portion can add spore or load this material with the spore shell and become sour with minimizing when having become sour in this material.

Therefore second aspect of the present invention comprises and alleviates material or composition becomes sour or the method for other oxidative degradation; This method comprises and being packaged in material or composition in natural spore shell or its fragment; Perhaps chemically or physically it is being combined with natural spore shell or its fragment, or mixing with natural spore shell or its fragment under some situation.

Therefore can following method carry out second aspect of the present invention: for example be packaged in natural spore shell to already oxidised active substance or the composition of part at least, perhaps chemically or physically combining with natural spore shell or its fragment.This material or composition when for example being transported to the where-used of expection, can be found to reduce before its degree of oxidation combines than with the spore shell when the spore shell separates subsequently.Degree of oxidation under these situation can come out in any suitable mode measurement, for example through assessing the level of oxidation reaction side-product (for example peroxide and/or acid) in active substance or the composition.For lipide actives matter, its degree of oxidation is typically identical with the level of becoming sour.

In an embodiment of second aspect of the present invention, all or part of cellulose theca interna that spore shell or its fragment comprise from natural spore is preferred.As stated, as spore only through organic solvent with alkali but not sour processing just can obtain.

According to second aspect of the present invention, the mean particle dia that the spore shell is fit to is 20-60 μ m or 20-50 μ m or 30-50 μ m, as about 40 μ m.The spore shell can be from the spore of Herba Lycopodii (Lycopodium clavatum).

The method that the third aspect of the invention provides the protection active substance to avoid oxidation, and/or enhanced activity material or comprise the stability of the composition of active substance, the method comprise with natural spore shell or its fragment and to prepare active substance.What be fit to is that this active substance is packaged in spore shell or its fragment, perhaps at chemistry or physically combine with spore shell or its fragment.

Fourth aspect of the present invention provides the method for preparing active substance, and this method comprises that (a) prepares or provide natural spore shell or its fragment; (b) be packaged in active substance in the shell, or chemically and physically active substance and spore shell or fragment combined, purpose is for the gained preparation antioxidant effect to be provided.

The 5th aspect of the present invention provides natural spore shell or its fragment purposes as the pharmaceutically active antioxidant.

The 6th aspect provides natural spore shell or its fragment production to flow to the purposes of human or animal body as the medicine of antioxidant.

The 7th aspect provides the human or animal patient's that treatment needs antioxidant Therapeutic Method, and the method comprises natural spore shell or its fragment of using effective treatment (comprising prevention) deal to the patient.

According to the 5th to the 7th aspect of the present invention, spore shell or its fragment can be used with another pharmaceutically active substance, for example Si Dating lipid lowering agents such as (statin).It can be used for treating any discomfort that causes or aggravate because of oxidative pressure, for example cardiovascular diseases.Can be used for treating any again owing to generating the discomfort that material that free radical and/or other oxidant for example come from absorption causes or aggravates in vivo; Therefore can be used for for example reducing inflammation and/or treatment cancer such as intestinal cancer.

Can resist high-intensity humidity, acid, alkali and heat because come from the spore shell of spore, so typically can be in orally-dissolvable or decomposition.Therefore it still is tasteless, can be used for covering the for example taste of medicine or nutritional supplement, food or food supplement of active substance.

Therefore, eight aspect of the present invention provides natural spore shell or its fragment purposes as the taste masking agent.Once more, this spore shell or fragment are suitable as the part of the preparation that comprises active substance to cover, and cover the taste of active substance at least in part.Said preparation can be fit to and/or be applicable to and/or be contemplated to oral, but or any order accept the carrying method of administered formulation patient perception taste.

In the whole description and claim of this description; Word " comprises (comprise) " and " comprising (contain) " and morphological change thereof are meant " including but not limited to " like " comprising (comprising) " and " comprising (comprises) ", and does not get rid of other part, additive, composition, integral body or step.

In the whole description and claim of this description, only if context has requirement in addition, otherwise odd number comprises plural number.Particularly use the place of indefinite article, only if context has requirement in addition, otherwise this description is interpreted as and possibly also possibly is plural number for odd number.

The preferred feature of each aspect of the present invention can be narrated with arbitrary others.

Further feature of the present invention becomes clear through following example.Generally speaking, the present invention can expand to the disclosed characteristic of this description any new feature or any new combination of (comprising any claim and accompanying drawing thereupon).Only if therefore incompatible with it, will be understood that can be applicable to said any others, embodiment or example in conjunction with certain particular aspects of the present invention, embodiment or the described characteristic of example, integral body, characteristic, chemical compound, chemical part or group.

In addition, only if statement is arranged in addition, any characteristic disclosed herein can replace for the characteristic selected that plays same or similar purpose.

Nonrestrictive example shows below the present invention will pass through.

Embodiment

Following description of test comes from the ability of the spore shell of spore as the Natural antioxidant; Particularly reduce the ability of the oxidation rate of oil.And this shows that they are suitable as the particularly delivery vehicles of lipid of oxysensible active substance, and before using, strengthens the stability of above-mentioned substance when using and after using.

The spore shell that uses extracts from the spore of Herba Lycopodii (Lycopodium clavatum L) (common Herba Lycopodii), can be available from for example Unikem, Post Apple Scientific, Fluka and TibrewalaInternational.The spore of 25 μ m and 40 μ m is all through overtesting, and the spore of 40 μ m comes from the subspecies or the heritability mutation of Herba Lycopodii.The former has netted outer surface and the latter it seems more smooth round.The spore outer casing thickness of believing both all is 1.5 μ m approximately.

Be described below spore shell isolating extraction procedures of other composition (particularly protein component) from spore: indicate the sample elder generation and the potassium hydroxide basic hydrolysis together of " AHS "; Back and phosphoric acid acid hydrolysis together, and the sample of indicating " BHS " only with potassium hydroxide basic hydrolysis together.Therefore the BHS sample comprises that not only the spore shell also comprises a part of cellulosic theca interna.

At first, undressed spore is suspended in the acetone and under agitation refluxed four hours.For this reason, 250 gram spores are dissolved in 750 milliliters of acetone, and in 2 liters of round-bottomed flasks that two two surperficial Liebig condensers (20 centimetres-4 centimetres) are installed, refluxed 4 hours.Filter the defat spore (DFS) of (porosity is 3 grades) gained then and spend the night at air drying.

Produce the epispore of basic hydrolysis (BHS), will defat spore (DHS) will be suspended in the aqueous potassium hydroxide of 6%w/v and under agitation reflux (condition as stated) 6 hours.After filtering (porosity is 3 grades), repeat this operation with fresh potassium hydroxide solution again.Filter (3 grades) suspension once more, and with hot water (3 times) and hot ethanol (2 times) flushing gained solid.Then reflux in ethanol (condition as stated) 2 hours, and filter (3 grades), spend the night at air drying.Finish-drying in 60 ℃ baking oven subsequently.

Produce the epispore of acidic hydrolysis (AHS), will the degrease spore be suspended in the orthophosphoric acid (750ml) of 85%v/v, (condition as stated) 7 days under agitation refluxes.Filter (porosity is 3) solid then, water (5 times, 250ml), acetone (5 times, 250ml), ethanol (1 time, 250ml), the 2M sodium hydroxid (1 time, 250ml), water (5 times, 250ml), acetone (1 time, 300ml) with ethanol (1 time, 300ml) wash.Then at 60 ℃ baking oven inner drying.

The all nonnitrogenous basically element of BHS and AHS product (through burning element analytic process and infrared spectrum measurement), this shows and has removed protein and nucleic acid, so the potential allergic component of primospore also removes.Can be observed BHS and the AHS product is the capsule of basic hollow through scanning electron microscope and confocal electron microscopy, do not had original inside sporoplasm.

Only if statement is arranged in addition, following steps are for to be loaded into oil in the spore shell.Elder generation is heated to oil between 40 ℃ to 60 ℃ and mixes several ethanol.Be added to corresponding spore shell in the gained suspension then and form homogeneous mixture.Placed vacuum (30hPa) 1-2 hour.

Example 1- With respect to ultraviolet stability (1)

This example is used the 25 μ m AHS epispores that loaded sun caul-fat, rapeseed oil or Oleum Glycines, and oil and epispore weight ratio are 1: 1.

Above-mentioned steps can be used to corresponding oil is loaded in the spore shell.On paper, launch each sample through ultraviolet radiation two hours then, the condition of ultraviolet radiation is: use each to be provided with four Philips of 30 bulbs ^TMCLEO type 15W Burdick lamp and employed light fixture is Philips ^TMOriginal HomeSolaria type, its parameter is: HB 171/A, 220-230 volt, 50 hertz, 75 watts

As reference standard, without the epispore sample process same treatment of loading.

After irradiation, confirm the peroxide value (PV) of each sample with titrimetry.For this reason, in chloroform (10ml), stir sample and make it dissolving, and add acetic acid (15ml) and saturated potassium iodide aqueous solution (1ml).Fill in flask and rocking this mixture one minute, at room temperature lucifuge was placed just in time five minutes again.Behind the distilled water diluting with 75ml,, and make indicator with starch solution with sodium thiosulfate solution (0.01N) titration.The peroxide value of measuring is to measure the method for measuring of contained active oxygen quantity in the sample; Its principle is that oxygen reduces fat and produced peroxide; After handling in the above described manner, just produce iodine molecule, can be discovered because of itself and starch reaction produce colourless sodium iodide.Therefore can use standardization program (IUPAC method 2.500) to confirm peroxide value (PV).

The peroxide value of lipid sample shows the degree of degradation of lipid to peroxide, therefore shows its degree of becoming sour.Peroxide value is high more, and lipid becomes sour more, and its oxidized degree is also just high more.

Shown in result such as the following table 1.

Table 1

Result in the table 1 shows and is encapsulated in the oxidation rate when significantly having reduced it in the spore shell and being exposed to ultraviolet to oils.This makes the spore shell be suitable for very much the carrier to oxygen and/or ultraviosensitive material, particularly lipid, so can protect these materials to avoid oxidation between the storage life before use.

Example 2- With respect to ultraviolet stability (2)

Prepare two identical samples, (0.5g) being added to 25 μ m AHS spore shells (0.125g) to blueweed oil (echium oil), to form oil and epispore weight ratio be 4: 1 homogeneous mixture.Different with routine 1, soak full oil in order not make the spore shell, mixture is not inserted in the vacuum; Therefore oil and spore shell are as the simple physics mixture, and most of oil is outside the spore shell.

Sample receives ultraviolet radiation, and its pre-irradiation and postradiation peroxide value all are determined, and is of example 1.In addition, ethereal blue Ji oil is as reference standard.

The result is as shown in table 2.

Table 2

Oil: epispore weight ratio	Be exposed in the ultraviolet (hour)	Peroxide value (meq/kg)
			1∶0	0	9.0
1∶0	0	8.5
			1∶0	2	110.1
1∶0	2	130.3
			4∶1	2	10.1
4∶1	2	12.5

In experimental error, these data show that the spore shell protects blueweed oil to avoid ultraviolet influence to a great extent.Because it is outer rather than within it packed that most of in this case oils possibly be enclosed in the spore shell, so this has explained that the spore shell has natural anti-oxidation character.

Example 3- The stability (1) of antagonism air oxidation

This experimental evaluation the spore shell avoid the protective nature of air oxidation.As around oxygen oleic acid is lost the standard of effect, oxidation induction time (OITs) is used Metrohm ^TM743 Rancimat appearance are measured, and the instrument version is 1.0SRI, and the air turnover rate is 20 liters/hour, and operative temperature is 50 ℃.According to AOCS air oxidation method (A.OM-AOCS Cd 12b-92), the Rancimat appearance is used to measure the particularly oxidation stability of edible oil & fat.

All materials-comprise oil, fat, fatty acid amino-compound and other derivative of fatty acid-all oxidation there is inherent resistance power to a certain degree.The degree of this natural anti-oxidation is by material itself and its contained any additives, with and in advance processing determined.Before the intrinsic resistance of material was overcome, its oxidation was carried out very slowly, and speed is accelerated rapidly afterwards.Oxidation induction time (OIT) is the time span before this acceleration begins.Become sour through it has been generally acknowledged that substances after this time restriction.

When using the Rancimat appearance, exsiccant air draught can pass through sample through filtering also, and sample is kept in the heating module that has preestablished temperature.The air that leaves sample and discharge is arranged into ionized water and is bubbled, and constantly measures the conductivity of deionized water through measuring transmitter again.Sample produces VOC when oxidation by air, these Organic substances comprise carboxylic acid, mainly are formic acid; These materials are present in the conductivity that causes initial deionized water in the air of discharge and produce respective change.From then on the pictorialization conductivity that produces in time and the variation that takes place can change to draw oxidation induction time (it is defined as the maximum change point of oxidation rate) automatically with reference to the second dervative maximum with respect to the conductivity of time through the Rancimat appearance.

Prepare three samples, two parts in each sample: fresh blueweed oil is mixed into fibre glass; Spore shell (obtaining like above description) is mixed into fibre glass; Be loaded into the blueweed oil of 40 μ m AHS spore shells.Oil and epispore weight ratio are 0.5: 1 under the back kind situation.Confocal ultramicroscope method shows that the 3rd sample medium oil is encapsulated in the spore shell.

For guaranteeing bigger contact surface, each sample is loose distribute under to its air blowing.Use Rancimat appearance assessment sample then as stated.The result is as shown in table 3.

Table 3

The data of table 3 show that the oil that is packaged with epispore is higher significantly to the resistance of the Oxidation of air, so stability is also higher significantly.This meaning protection effect comes from the spore shell.This protection is not the physical barrier that the spore shell gets into as oxygen probably, because the known spore shell that comes from spore is at least partly for foraminous.

Example 4- The stability (2) of antagonism air oxidation

Repeat example 3, but use the AHS spore shell of 25 μ m and the sample of the oil that encapsulates with the physical mixture replacement of blueweed oil and spore shell.The oil that physical mixture comprises and the weight ratio of epispore are 5: 1 (0.5g oil ratio 0.1g spore shell).

The result is illustrated in fig. 4 shown below.

Table 4

Find that once more blueweed oil can prevent that the time of oxidation by air from reaching at least 190 hours when superfluous blueweed oil (5: 1) and the mixing of spore shell.Because a large amount of in this case blueweeds oil is inevitable in the spore enclosure, this expression spore shell itself just can be used as antioxidant rather than to oxygen simple obstacle physically is provided.

When example 1 is contained in the spore shell (promptly be kept in the inner cavity chamber of epispore microcapsule and outer surface has minimum oil or do not have that oil-this observes through confocal microscopy and get) with example 3 explanation oil sealings, can be observed and oilyly receiving fine protection aspect the oxidation of avoiding ultraviolet induction and the air oxidation.When yet excessive oil exists, also find the oxidation that spore shell itself can be inhibited oil, as in this example and example 2, the outer oil mass of spore shell is very big, and therefore oil directly be exposed in air and the ultraviolet light on every side.

Example 5- For ultraviolet stability (3)

Use the above program to load the spore shell with blueweed oil or cod liver (cod liver) oil.In the both of these case, the weight ratio of oil and spore shell is 1: 1.Both tested the epispore of 25 μ m in the experiment, tested the epispore of 40 μ m again, and AHS (having only epispore) and BHS (epispore+inwall) had been made an experiment.

Saidly be deployed in each sample on the surface plate with ultraviolet radiation like example 1.As reference standard, the sample of encapsulation oil does not receive same treatment.

Example 1 is said for another example, is determined at the peroxide value of pre-irradiation and each sample of irradiation back.

The test result of variety classes spore shell like following table 5 to shown in the table 8.

Table 5-25 μ m AHS

Table 6-40 μ m AHS

Table 7-25 μ m BHS

Table 8-40 μ m BHS

These data acknowledgement oil sealings are loaded on can significantly reduce its oxidation rate in ultraviolet in the spore shell.

As if this result is remarkable especially concerning 40 μ m BHS, can protect two kinds of oil to avoid oxidation fully fully.In addition; As if the spore shell can " be cleared up " oils in this case; Even before ultraviolet radiation, just reduced its peroxide value: this shows this BHS no matter it stops that ability that oil avoids ultraviolet radiation how; Still has great antioxidant effect, in some cases even can eliminate becoming sour of producing before any.

Example 6-" cleaning " oil (1) that becomes sour

Repeat example 5, but use cod liver oil, 40 μ m spore shells (not only comprising AHS but also comprise BHS) and be 0.5: 1 with spore shell and weight of oil ratio are promptly used higher many oily useful loads.The result is as shown in table 9 below.

Table 9

Sample	Pre-irradiation peroxide value (meq/kg)	Irradiation back peroxide value (meq/kg)
			Pure cod liver oil	4.5	18
40 μ m AHS+ oil	10	13
			40 μ m BHS+ oil	0	0

This proves the ability that BHS (epispore+inwall) spore shell " cleaning " becomes sour once more, the peroxide value of (epispore+oil) sample even also lower than the peroxide value of the sample of original oil.

Example 7-" cleaning " oil (2) that becomes sour

Repeat example 6, but use peroxide value to be 20.5meq/kg, the blueweed oil that has promptly become and become sour.The result of pre-irradiation is as shown in table 10.

Table 10

Sample	Epispore: weight of oil ratio	Pre-irradiation PV (meq/kg)
			Ethereal blue Ji oil	0∶1	20.5
40 μ m AHS+ oil	1∶1	25.5
			40 μ m AHS+ oil	0.5∶1	26.5
40 μ m BHS+ oil	1∶1	3
			40 μ m BHS+ oil	0.5∶1	8.5

These data prove 40 μ m BHS (be epispore/inwall combination) " cleaning " the oily surprising ability of having become sour once more.The sample of oil originally in being packaged in the spore shell after its peroxide value significantly reduce.The spore shell proportion is high more, and its effect is good more.

The stability (3) of example 8-antagonism air oxidation

Repeat example 3, but use cod liver oil.

Having used 40 μ m epispores (not only comprising AHS but also comprise BHS) in these tests, is 1: 1,3: 1 and 5: 1 loading cod liver oil with oil and spore shell weight ratio.Each sample is inserted in two sample tube between the fiber glass packing.Capillary tube is passed to guarantee that oil can not flow down from the test tube bottom from corresponding stopper.Insert these test tubes between the heating module of Rancimat appearance then, air begins to flow.

The result is as shown in table 11 below.

Table 11

Sample	Oil: epispore is than (w/w)	Oxidation induction time (hour)
			Cod liver oil	1∶0	56
Oil: BHS	5∶1	59
			Oil: BHS	3∶1	＞120
Oil: BHS	1∶1	＞120
			Oil: AHS	5∶1	73
Oil: AHS	3∶1	＞120
			Oil: AHS	1∶1	＞120

The data of table 11 explain that once more the oil that is packaged in the epispore is stronger significantly for the resistance of air oxidation, and are therefore also much stable.

The useful load of oil is high more, and its protection effect is poor more.This possibly be since more oil in the outside of spore shell and/or just loosely getting in touch (the oily natural anti-oxidation character that has benefited from the spore shell of encapsulation also possibly have benefited from its certain physical protection for air) with epispore.

Example 9-spore shell is as the taste masking agent

Prepare the spore shell as stated., inserted both homogeneous mixtures in the vacuum 1.5 hours with cod liver oil (come from rich support company limited (The Boots Company PLC)) loading spore shell with oil and 2: 1 ratio of spore shell weight ratio.

The gained material is tasted through three people.Three people find the soft cunning of its quality, taste the taste and the quality that do not have oil.

This proof spore shell can be used as the taste masking agent in for example medicine and nutritional supplementation property product, food and food supplement.Much human thinks that for example the food supplement of Omega-3 oil has bad taste; Therefore prepare food supplement with the spore shell that comes from plant and can not only protect it to avoid oxidation, more can cover its taste and/or abnormal smells from the patient, particularly useful way when adding to it in food or the trophism supplementary of expection.

Example 10-protection volatile active matter

The evaporation rate of the volatile active matter of this experimental evaluation in the spore shell that comes from spore.

Prepare spore shell (AHS, diameter are 40 μ m) as stated, be mounted with butanols.Alcohols is not only volatile material, also is used in local topical preparation such as the cosmetic product usually and makes diluent.Through " passive contact ", promptly pure and mild spore shell mix under room temperature and the constant pressure and let fluid permeability in the spore shell to make it to soak into the spore shell.

Sample A comprises the pure butanols of 2ml as reference standard; Sample B comprises the 2ml butanols in the spore shell that is packaged in 1g.

Be layered on each sample in the culture dish, claim at a distance from five minutes that whenever weight is to measure the time that the encapsulation alcohols volatilizees and spent fully.All experiment is all carried out in triplicate.

Result of the test is as shown in table 12 below.The half-life that proposes under each situation is the time theoretic, that calculate, during the encapsulation alcohols of half amount vapor away.

Table 12

Sample	The volatilization time (minute)	Half-life (minute)
			A	200	61
B	300	115

Table 12 is explained and is packaged in volatile alcohols in the spore shell and can suppresses it through volatilization release in certain degree ground.Thereby protect the volatile active matter in the preparation prepared in accordance with the present invention for further slowing down volatilization loss, can the coating of protectiveness for example lipid coatings be coated on the spore shell.

Example 11-high activity material useful load

Stir the formation homogeneous mixture to oil and 25 μ m AHS spore shells, inserted in the vacuum (30kPa) 2 hours, let the spore shell soak full oil.The oil that uses is soybean oil, Oleum helianthi, blueweed oil and rapeseed oil, and ratio is every gram spore shell 3g oil, and cod liver oil is every gram spore shell 3.5g oil.

Even the result finds in these higher relatively useful loads, to have loaded oily spore shell and still shown as powder, confirm that these oily encapsulation are effective.Can further confirm through confocal microscopy this.This has proved that the spore shell that comes from spore is used as an advantage of the delivery vehicles of active substance.Explain that also the spore shell is suitable for doing in the powder formulation carrier, for example localized delivery cosmetic material, cleaning product or laundry product perhaps are used for the conveying of medicine or nutritional supplementation property active substance, food supplement or the like.

Useful load is an every gram spore shell 5g oil or during more than 5g oil, sample show more like pasty state, and expression very major part is oily in the spore enclosure.This preparation is suitable as butterfat or ointment, for example, perhaps can be applicable on certain based food.Useful load is an every gram spore shell 2g oil or when being less than 2g oil, the very thin and free-flow of children of powder, and touch suitably dry.

Claims (52)

1. the spore shell of natural spore or its fragment are as the purposes of antioxidant, and wherein said spore shell comprises sporopollenin.

2. purposes according to claim 1, wherein said natural spore is a pollen grain.

3. purposes according to claim 1, the endospore inwall that wherein said natural spore is microorganism.

4. according to the described purposes of claim 1,2 or 3, its objective is in order to protect material or composition to avoid the oxidation of air and/or ultraviolet induction.

5. purposes according to claim 1, its miospore shell or its fragment are used as antioxidant in comprising the preparation of active substance.

6. purposes according to claim 5, wherein active substance is packaged in spore shell or its fragment, perhaps chemically or is physically combining with spore shell or its fragment.

7. purposes according to claim 5, wherein active substance at least partly is packaged in the shell.

8. purposes according to claim 5, wherein active substance is used for the whole body use.

9. purposes according to claim 5, wherein preparation is used for the localized delivery of active substance.

10. purposes according to claim 5; Wherein active substance is selected from pharmaceutically active substance, food, agent for controlling noxious insect pests, plant treatment agents, cosmetic material, toilet articles, disinfectant, abluent, binding agent, diagnostic reagent, dyestuff and ink, fuel, explosive, propellant and sensitive material; Wherein said cosmetic material is selected from cosmetic product, and

Wherein said toilet articles is selected from soap; Deodorizer and antiperspirant; Lubricant; Face powder and talcum powder; Hair care product and oral cavity and dental care products.

11. purposes according to claim 5, wherein said active substance is selected from nutritional supplementation property active substance.

12. purposes according to claim 10, wherein said food comprises food material and food supplement.

13. purposes according to claim 10, wherein said agent for controlling noxious insect pests comprises insecticide.

14. purposes according to claim 10, wherein said plant treatment agents comprises growth regulator.

15. purposes according to claim 10, wherein said plant treatment agents comprises herbicide.

16. purposes according to claim 10, wherein said abluent comprises cleaning agent.

17. purposes according to claim 10, wherein said cosmetic product comprise renovation agent after skin nursing products, fragrant atmosphere, perfume products, sunscreen, self-tanning agent, the solarization, age resister, skin whitener, local with anthelmintic, depilatory, hair growth promoter and manicure product.

18. purposes according to claim 5, wherein active substance comprises volatile material.

19. purposes according to claim 5, wherein active substance is lipid or similar lipid matter.

20. purposes according to claim 5, wherein active substance is responsive to the external influence factors that one or more are selected from heat, light, oxygen G&W.

21. purposes according to claim 20, wherein active substance is prone to oxidated.

22. purposes according to claim 21, wherein active substance is subject to the ultraviolet induction oxidation.

23. purposes according to claim 5, wherein preparation is used for storing and/or being used in the fluid environment that comprises oxygen.

24. purposes according to claim 5, wherein preparation is used for storing and/or be used in and is exposed to the environment that maybe possibly be exposed to ultraviolet radiation.

25. purposes according to claim 5, wherein preparation comprises more than a kind of active substance.

26. purposes according to claim 25, wherein preparation comprises two kinds or the more kinds of spore shell of active substance or colony of its fragment of comprising, and each colony chemically or physically is being incorporated into or is encapsulating the different activity material.

27. purposes according to claim 5, wherein preparation is included in and is selected from the following products: cosmetic product; Toilet articles; Household supplies; The colouring articles for use; Adhesive product; Drug products; Food; Agricultural products; Fuel; Explosive; Propellant; And sensitive material,

Wherein said cosmetic product is selected from skin nursing products, and

Wherein said toilet articles is selected from soap, cleaning agent and surfactant; Deodorizer and antiperspirant; Lubricant; Face powder and talcum powder; Hair care product and oral cavity and dental care products, and

Wherein said household supplies are selected from disinfectant, air freshener, insecticide, laundry articles for use, fabric-treating agent, abluent and varnish.

28. purposes according to claim 5, wherein said preparation is included in and is selected from the nutritional supplementation property product.

29. purposes according to claim 27, wherein said colouring articles for use comprise paint, ink and dyestuff.

30. purposes according to claim 27, wherein said food comprises food additive.

31. purposes according to claim 27, wherein said food comprises food material.

32. purposes according to claim 27, wherein said agricultural products comprises gardening product.

33. purposes according to claim 1, the diameter of its miospore shell or its fragment are 1 to 300 μ m.

34. purposes according to claim 33, the diameter of its miospore shell or its fragment are 3 to 50 μ m.

35. purposes according to claim 1, the diameter of its miospore shell or its fragment are 10 μ m or littler.

36. purposes according to claim 1, its miospore shell or its fragment comprise all or part of cellulose inwall film of natural spore in addition.

37. purposes according to claim 5, wherein the weight ratio of active substance and spore shell or its fragment is that 0.01:1 is to 35:1 in the preparation.

38. according to the described purposes of claim 37, wherein the weight ratio of active substance and spore shell or its fragment is that 0.1:1 is to 5:1 in the preparation.

39. purposes according to claim 5, wherein the weight ratio of active substance and spore shell or its fragment is 5:1 or lower in the preparation.

40. purposes according to claim 5, its miospore shell or its fragment scribble the barrier layer.

41. according to the described purposes of claim 40, wherein the barrier layer comprises the lipid coatings material.

42. purposes according to claim 1, the outer surface of its miospore shell or its fragment is changed because of functional group adheres to, and functional group increase spore shell or its fragment are to the captivation on the surface of preparation intended use.

43. the spore shell of natural spore or the purposes of its fragment its objective is the oxide that forms before from material or composition, removing, wherein said spore shell comprises sporopollenin.

44. one kind is reduced becoming sour or the method for other oxidative degradation of material or composition; The method comprises and being packaged in material or composition in natural spore shell or its fragment; Perhaps chemically or physically combining with natural spore shell or its fragment; Or be mixed in natural spore shell or its fragment, wherein said spore shell comprises sporopollenin.

45. according to claim 43 or 44 described purposes or methods, wherein material or composition are lipid.

46. according to claim 43 or 44 described purposes or methods, its miospore shell or its fragment comprise all or part of cellulose inwall film of natural spore.

47. protect active substance to avoid oxidation and/or increase active substance or comprise the method for the ingredient stability of active substance for one kind; The method comprises the method for preparing active substance with the spore shell of natural spore or its fragment, and wherein said spore shell comprises sporopollenin.

48. a method for preparing active substance, the method comprise that (a) prepares or provide spore shell or its fragment of natural spore; (b) be packaged in active substance in spore shell or its fragment; Perhaps chemically or physically combining or be mixed in spore shell or its fragment with spore shell or its fragment; Its objective is provides gained preparation antioxidation, and wherein said spore shell comprises sporopollenin.

49. the spore shell of natural spore or its fragment are as the pharmaceutically active antioxidant, wherein said spore shell comprises sporopollenin.

50. the spore shell of natural spore or its fragment are used to human or animal body in production and carry the purposes on the medicament of antioxidant, wherein said spore shell comprises sporopollenin.

51. the spore shell of natural spore or its fragment are as the purposes of taste masking agent, wherein said spore shell comprises sporopollenin.

52. according to the described purposes of claim 51, its miospore shell or its fragment are used to comprise the part of the preparation of active substance, using described spore shell or its fragment is in order to cover, and part is covered the taste of active substance at least.