CN1898302A - Preparing active polymer extrudates - Google Patents

Abstract

Process for preparing active polymer extrudate comprising polymer matrix and guest matter, the process comprising contacting a polymer substrate and guest matter with a plasticising fluid under dense phase, sub critical or supercritical plasticising conditions of elevated temperature and/or pressure to plasticise the polymer substrate and incorporate guest matter and extruding polymer substrate incorporating guest matter under dense phase, sub critical or supercritical conditions via an extrusion orifice into a collection zone or a mould with simultaneous or subsequent release of pressure, whereby extrudate is obtained comprising a solid admixture of polymer matrix and guest matter in form conferred by the orifice or the mould; a novel extrudate; composition thereof and apparatus for the preparation thereof, and use thereof in fibre processing techniques, medical applications such as in delivery of drugs and other agents such as imaging and diagnostic agents, tissue engineering, and as medical devices or aids such as delivery devices or aids for drugs, imaging and diagnostic agents, as tissue engineering devices or aids such as sutures, and the like; as an anti-microbial for example having bacteria -static or -cidal activity; as a natural or synthetic barrier capable of immobilising e.g. naturally occurring or artificially introduced poisons or toxins by e.g. absorption, interaction or reaction; in agrochemical or crop protection applications; in the processing of thermally labile fibres for use in dying, textiles, electronics etc below the polymer Tg, Tm or viscosity; in incorporation of dyes and other thermally labile materials into polymers that cannot be formed by traditional processes e.g. melt extrusion and the like; or in incorporation of surfactants into fibres to control polymer properties.

Description

The preparation of active polymer extrudates

The present invention relates to by plasticized polymer and push through the method that nib prepares active polymer extrudates, novel extrudate, its composition, it is in the animal or human or purposes and its preparation facilities in relevant with the animal or human, cultivation or the non-culture.More particularly, the present invention relates to preparation and be combined with the method for guest materials (guest matter) as the active polymer extrudates of dyestuff, medicine, protein, metal or other molecule, described method comprises plasticized polymer and guest materials, and extrude by nib, active polymer extrudates is the solid mixture with guest materials, form is sheet material, film, tubing, right cylinder, ribbon, protofibril, fibrous, fiber, non-woven material etc., also relate to its composition, its preparation facilities; With its in fibre treatment technique, medical applications as purposes natural or synthetic blocking agent (barrier); purposes in agrochemistry or crop protection application; be lower than under polymer Tg, Tm or the viscosity; be used for dyeing, the purposes of the processing of the thermolability fiber of fabric, electronic material etc.; wherein introduce dyestuff and other thermolability guest materials in polymkeric substance, it can not form by traditional method.

Well-knownly be, supercutical fluid (SCF) mix can be used for inorganic materials and, recently biologically active substance is incorporated in the polymeric matrix, and latter's loss of activity not.For example, CO ₂-the plasticizing that causes be used to biodegradable polymer as poly-(DL-rac-Lactide) (PLA), polylactide-altogether-poly-glycollide (PLGA) and poly-(6-caprolactone) viscosity is reduced to and can be being sneaked into degree (Howdle etc. in the polymkeric substance near environmental stress as biological activity object under 35 ℃, 200 crust (bar), Chem.Commun.2001,190).The polymkeric substance that is combined with the active object of this life has been made into foam integral material and powder, and it is applicable to multiple medical applications, comprises organizational project, drug release etc.

In the drug release field, be well known that the biodegradable polymer fiber of preparation introducing biological active materials, this polymer fiber degraded is to discharge these materials.Fiber can be subcutaneous or muscle inject or embed, and the advantage that has is, single fiber can stay in position, relatively multiple particulate moves everywhere.The fiber releasable material with the advantage that conventional powder or particulate releasable material are compared is, can accurately locate to be used for the desired drug release or the fiber of transplanting.

The traditional method that guest materials is introduced in the polymer fiber comprises with the existing fiber of guest materials solution impregnation.But, owing to needing two treatment steps to cause efficient low.In addition, need to use solvent to flood and also cause residue handling problem, biological active materials inactivation etc.

Usually, polymer fiber forms by melt extruding, and thus with the polymer beads fusion, and generates fiber in the mode that melt is pushed through nib.Recently, developed and passed through supercritical CO ₂Soak into polymkeric substance and spin and extrude and form the method that fiber prepares polymer fiber, wherein carry out described method being lower than polymer melting temperature or being lower than under the temperature of Tg.But these methods are carried out under high relatively temperature usually, for some polymer/polymer type usually greater than 200 ℃.Therefore, this method can not be applicable to that use temperature unstable polymkeric substance or temperature sensitive inhibition biological active guest materials form fiber.

Particularly, there are two types of polymer fiber preparation methods that use SCF: continuous processing and interrupter method.The two depends on uses fluid or gas to soak into polymkeric substance under pressure, causes foaming, and comes the quencher system by relief pressure or elevated temperature subsequently.When extruded polymer gaseous mixture in continuous processing, foam; Perhaps in discontinuous technology, in relief pressure before extruding or immersion heating tank, cause foaming.The defective that these two kinds of fiber production methods exist is, will flood and the foaming condition combination, thus controlling fiber treatment process slightly.

We have found that now, handle by in one step, adopting SCF, and independent control SCF infiltration and fluid plasticising and polymer foaming condition, a kind of method that is prepared fiber by the polymer-extruded thing of introducing guest materials can be provided.Useful especially and it is shocking especially really, can be in conjunction with these technology in the method for one step, because need polymkeric substance to have enough force of cohesion to form fiber, normally by realizing, and need the polymkeric substance to have enough low viscosity to form contrast to introduce guest materials by means of more high molecular and more tacky material.But, we discover, method of the present invention can realize controlling of processing condition, as temperature and pressure, polymer performance such as molecular weight and limiting viscosity, apparatus characteristic such as extrusion die hole dimension, and SCF temperature and extrude back pressure (back-pressure) particularly can be introduced guest materials and formation fiber thus in one step.The special advantage of this method is, if desired, it can not use solvent to implement under moderate moisture, described temperature can make the activity of guest materials fully or mainly remain, and very low or the medium or very high-load guest materials of introducing as desired, and be dispersed among the extrudate with desired shape and size and desired performance such as porosity etc.

In broad aspect of the present invention, provide a kind of preparation to contain the method for the active polymer extrudates of polymeric matrix and guest materials thus, described method comprises: in high temperature and/or the close phase of highly compressed, under the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid with guest materials, with plasticized polymer matrix and introducing guest materials, and in close phase, under the subcritical or super critical condition, the polymeric matrix that to introduce guest materials by nib is extruded in collecting region or the mould tool, relief pressure simultaneously or subsequently, obtain extrudate with the shape of being given by nib or mould thus, described extrudate contains the solid mixture of mould polymeric matrix and guest materials.

According to the present invention, suitable polymers comprise shaping or at least one dimension continuous or adherent extrudate.According to the present invention, preferred extrudate comprises and is shaped as sheet material, film, tubing, right cylinder, bar, ribbon, protofibril, filament, fibrous, fiber, solid and hollow section, netted, fabric or nonwoven extrudate etc.Therefore, extrudate has been got rid of the particulate and the powder of non-shaping, and these particulates and powder are known in the field, and can obtain by polymkeric substance is blown to the low pressure collecting region from high pressure plasticising container.

Extrude (extruding or the extrusion) that mention herein refers to, by pushing the operating process that suitable material prepares bar, tubing, sheet material, film, cable coating and various solid and hollow section, in this case, by drift or suitable exerting pressure, for example use screw drive, under high pressure be pressed through the pore of spinning nozzle or nozzle, make polymer materials pass through die head.Can be extruded into collecting chamber or district, perhaps be extruded into and be used for the mould of profile extruded material subsequently, be also sometimes referred to as extrusion moulding.The extrudate of mentioning herein refers to thus obtained product, and it has the form or the shape of being given by die head when extruding by die head, the form or the shape of giving by the mould mould when perhaps entering mould and extruding, and it is also referred to as the molding extrudate.

The solid mixture of mentioning herein refers to, and introduces the polymeric matrix of guest materials, and form is the phase inclusion usually, the microparticle dispersion of homogeneous or non-homogeneous etc., or this arbitrarily desired form.For example, the polymeric matrix parcel that guest materials can coated form perhaps can be dispersed in the whole polymeric matrix.

Method of the present invention is particularly advantageous to be, opposite with expectation, and we can use the polymer manufacture extrudate, and described polymkeric substance helps to introduce guest materials, and it has the force of cohesion that is enough to form the moulding extrudate.These targets need different and common mutually exclusive polymer performance.Introducing guest materials needs low viscosity, and the relative high molecular that preparation moulding extrudate need be given force of cohesion.In the methods of the invention, the mixing of polymkeric substance and guest materials or combination and its are extruded, and carry out simultaneously or sequentially in one step, and this point obviously are different from most prior aries.The present invention is special, and advantage is, this method is adjustable, with the extrudate of preparation different shape (as different diameter, different porosities, different lengths), and the activity of maintenance guest materials, biological example activity etc.

Suitably; the polymeric matrix of being convenient to be incorporated into the desired shape in this method arbitrarily is provided; and provide the polymkeric substance that melt extrudes solid phase particle known in the field or particle or pellets basic usually, but solid block or monolith form can selectively be provided.Perhaps, can provide polymkeric substance, but not be easily like this, and advantage is less with fluid form.

Employed plasticizing fluid can be close arbitrarily phase, fluid such as subcritical, overcritical in the inventive method, preferably it is characterized in that its performance similar gas and liquid simultaneously.Especially, fluid density and dissolubility property and liquid phase seemingly, and its viscosity, surface tension are similar to gas with the diffuse fluid speed in any medium, produce the polymeric matrix infiltration as gas.Therefore, in the extrudate of this situation, the plasticizing fluid can make polymeric matrix help the extruding and be transformed into desired shape or structure of introducing, polymeric matrix of guest materials under plastic state.

Be well known that plasticizing fluid, particularly supercutical fluid can cause the remarkable reduction of many glass transition temperature of polymer (Tg) or melt temperature (Tm) or viscosity, this means that polymkeric substance can remain on liquid state under low relatively temperature.By reducing temperature or pressure or the two, reduced the plasticizing fluidic amount that absorbs by polymkeric substance, when Tg, Tm or viscosity begin to be elevated to Tg, the Tm of polymkeric substance wherein or point that viscosity is higher than plasticization temperature like this, at this temperature spot polymer form and structure owing to solidifying of polymkeric substance is fixed up.

Special advantage of the present invention is, can carry out described method under the additional solvent not existing basically.This is extremely important when guest materials has the situation of desired activity or performance, and its activity or performance can be by transformation mutually or solution and modification or destruction.Thus, special advantage of the present invention is that this method is applicable to and prepares the polymer-extruded thing of introducing the solvent sensitivity guest materials that it can have constant chemical form and/or physical aspect.

Can implement present method in any suitable manner, and preferably in such device, implement, described device comprises and is fit to temperature with boost in pressure and can comprise that the pressure chamber of the instrument that is used to mix each composition, this pressure chamber comprise that the nib that is used for by as defined above is extruded into each composition and can be below or above the collecting region that plastifies pressure or the instrument of mould.This device comprises the instrument that is used to introduce reactant and each component, and the while is the moulding pressure chamber as this area is known usually, to keep desired pressure in extrusion.The suitable nib of extruding comprises the die head with desired shape, size and length, and can comprise single or multiple nibs, to prepare single or multiple extrudates or composite extrusion.Collecting region can be open wide or sealing, for example collecting board, dish or chamber.The mould mould can be the mould any unlimited or sealing that is used to give shape arbitrarily.

The further advantage of the inventive method is, the present invention has realized that very high satisfactory degree ground removes residual monomer etc., and these materials may be present in the polymkeric substance and biological active materials that is provided.This point is useful especially for the toxicity purposes, and monomer etc. are discharged into not to be expected in human body or the animal body very much, and should avoid.

Yet desired in some cases is, is under the situation of solvent sensitivity at guest materials, has the additional solvent lower section or is implementing this method fully, for example promotes to disperse or extrudate form such as porosity are had specific influence.In this case, solvent can comprise any suitable solvent well known in the art, and can comprise that polymeric matrix and/or guest materials can be dissolved in or be not dissolved in solvent wherein.

Can introduce this method of enforcement in the required any appropriate fusion time in induced polymer plasticizing and guest materials, for example time range is 2 milliseconds～72 hours.Longer fusion time up to 72 hours magnitudes, for example 10 minutes～72 hours or 2 minutes～24 hours or 5 minutes～2 hours, go for stable or other insensitive matrixes or guest materials and be applicable to that expectation time expand is to introduce the situation of guest materials.Perhaps, the shorter fusion time of 2 milliseconds～10 the number of minutes magnitudes, preferred 20 milliseconds～5 minutes, more preferably 1 second～1 minute, for example 2～30 seconds or 2～15 seconds, go for unsettled or sensitive polymer matrix or guest materials, perhaps be applicable to the situation of guest materials dispersion where applicable heterogeneous.

Can be before using the plasticizing condition or among, with desired random order mixed stream, polymeric matrix and guest materials.Can implement this method like this, with polymkeric substance with before guest materials contacts, under the plasticizing condition, introduce the plasticizing fluid, fusion time can reach 5 hours in this case, perhaps, fluid can be introduced in the plasticizing condition gradually or fast, and with polymeric matrix and guest materials in a kind of or the two contact, as desired.

This method can comprise with its precursor monomer or oligopolymer form introduces polymeric matrix, and reaction in formation cure polymer, perhaps can comprise and introduce the polymeric matrix with desired chemical form.

This method can be implemented under mixing or unmixed situation, as defined above.

This method can be implemented under scope is any suitable temp of-200 ℃～500 ℃.Usually, be under 0 ℃～300 ℃ and standard plasticizing pressure, 7～1000 crust in temperature, will plastify fluid and be incorporated in the plastifying state.

The plasticizing condition optimization comprise desired temperature less than, be equal to or greater than fluid critical temperature (Tc), scope is preferably-200 ℃～200 ℃ at-200 ℃～500 ℃.

The selection part of plasticization temperature is according to plastifying fluid and will being determined by the character of plastifying polymeric matrix.What but the present invention was useful especially is, we have found that this method help to lower temperature range-200 ℃～200 ℃, more preferably-200 ℃～carry out under 140 ℃, more preferably-150 ℃～100 ℃.More preferably-100 ℃～100 ℃, more preferably-20 ℃～100 ℃, most preferably 3～75 ℃.For most fluids, temperature range is approximately 10～15 ℃, 15～25 ℃, 25～30 ℃, 30～35 ℃, 35～45 ℃ or 45～55 ℃, most preferably is approximately 28～33 ℃ of (CO ₂).Also can design other subrange, and also be within the scope of the present invention.The minimum temperature of preferred employing, its abundant reduction with polymer Tg, Tm or viscosity is consistent, to realize the introducing of plasticizing and guest materials.For enforcement at room temperature, method of the present invention may need to compensate by pressure boost.

In preferred implementation of the present invention, be less than or equal to 200 ℃ in temperature and for example be less than or equal to 140 ℃ and implement down these methods, and this method has been represented a kind of brand-new scheme in the SCF extruding technology field that is used for preparing the polymer fiber extrudate.Usually SCF extrudes under the high temperature that is higher than glass transition temperature of polymer (Tg), melt temperature (Tm) or high viscous state and implements, usually greater than 200 ℃.Reduce the temperature that polymkeric substance reaches fluidised form though known SCF technology is allowed, the requirement that forms the adhesion fiber is the polymkeric substance that needs higher molecular weight or viscosity higher, and implements to have become the general convention in this area under comparatively high temps.

Therefore, in preferred implementation of the present invention, provide a kind of preparation to contain the method for the active polymer extrudates of polymeric matrix and guest materials, described method comprises: in high temperature and/or the close phase of highly compressed, under the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid with guest materials, with plasticized polymer matrix and introducing guest materials, and in close phase, under the subcritical or super critical condition, the polymeric matrix that will be combined with guest materials by nib is extruded in collecting region or the mould, relief pressure simultaneously or subsequently, acquisition has the extrudate of the adhesion of the shape of being given by nib or mould thus, described extrudate contains the solid mixture of mould polymeric matrix and guest materials, it is characterized in that, be less than or equal to 200 ℃ and/or in temperature less than the Tg of polymeric matrix, under Tm or the non-viscous state, carry out described method.

Usually, can be under 7～1000 crust and 0 ℃～300 ℃ of the standard plasticization temperatures at pressure, will plastify in the fluid introducing plastifying state.Preferably, the plasticizing condition comprise desired pressure less than, be equal to or greater than the plasticizing fluid emergent pressure (Pc), greater than 1 the crust～1000 the crust, be preferably 2～800 crust, more preferably 2～400 crust, more preferably 5～75 crust, for example 15～73 crust or 75～380 crust for example 110～360 cling to.For most fluids, pressure range is approximately 30～40 crust, 40～50 crust, 50～60 crust, 60～75 crust or 75～125 crust or 125～380 crust, and for close phase, subcritical or supercritical CO ₂Most preferably be approximately 34～75 crust.Also can design other subrange, and also be within the scope of the present invention.

As known in the art, can select suitable plasticizing condition to realize desired plasticizing rate.Usually desired plasticizing rate will realize that viscosity or pseudo viscosity reduce, the extrudate that it can be introduced guest materials and polymeric matrix be extruded desired shape of formation and profile.Importantly, the reduction degree of viscosity or pseudo viscosity influences the form of extrudate, but this and other variable has complex interactions, and these variablees comprise the pressure drop in polymeric matrix molecular weight, mold hole dimension and length, the nib etc.

The measurement that absolute viscosity or viscosity reduce is neither directly, neither high precision, and therefore convenient by CONTROL PROCESS condition, matrix with extrude parameter and determine desired reduction.And polymeric matrix can be a solid form, and it is not a viscosity thus, and this method comprises and causes in the plasticizing form at first and give desired viscosity and reduce.Suitable range of viscosities is preferably 1～1,000,000 centipoise, and 500～500,000 centipoise more preferably, 1000～100,000 centipoise more preferably, and randomly determine by for example capillary rheometer.Can promote viscosity to reduce by the additional solvent of introducing as defined above.Selectively or additionally, can wait by blend, mixing, the stirring of polymeric matrix and promote viscosity to reduce.Blend can be to be undertaken by physics pumping or other replacement polymer matrix.Stirring can be by inflation or make mobile carrying out such as air-flow.Blend can be to use or not use the guest materials physical mixed to carry out among polymeric matrix, and carries out can or have guest materials before introducing guest materials the time.

Can use desired any polymeric matrix known in the field to implement method of the present invention, and to use molecular weight ranges suitably be 1～10, the polymkeric substance of 000kDa is implemented.Have in the existing practice that the SCF of the polymeric matrix of biological active materials handles in introducing, being well known that by lowering chamber pressure comes original position to remove SCF, to obtain monolith, perhaps come from the pressure chamber, to remove the biological activity mixture, with powder or the particulate polymers that obtains desired particle diameter by spraying under undercritical conditions.This method uses molecular weight to implement as the polymeric matrix of the 20kDa order of magnitude usually.We find amazedly now, by selecting the polymkeric substance of higher molecular weight, scope as defined above, and preferable range is 1～1000kDa, more preferably 1～500kDa, 1～250kDa more preferably, 1～200kDa more preferably, for example 1～50 or 50～200kDa, more preferably 1～150kDa, for example 1～30 or 30～150kDa, polymeric matrix is suitable for the introducing of guest materials and the formation of extrudate simultaneously.Yet the selection of molecular weight depends on the characteristic of polymeric matrix and the viscosity drop low condition that is adopted.The suitable polymers matrix is selected from force of cohesion between the molecule by force to the material fragmentation power of foot during overcoming extrusion.By this method, even under envrionment temperature and normal atmosphere, will suppress the extrudate of force of cohesion difference such as the formation of fine-fibered, and can prepare the high quality extrudate of desired size, as crin.Therefore, the polymkeric substance in above-mentioned lower molecular weight scope can be used, and the polymkeric substance in above-mentioned higher molecular weight range can be used with more weak force of cohesion with strong force of cohesion.

Therefore it can be seen that the molecular weight of polymeric matrix influences the form of extrudate.The further feature that influences the extrudate form comprises processing condition.The feature that the present invention is useful especially is, by selecting suitable substrate performance, processing condition etc., the extrudate that can obtain to have desired form.Back pressure that the processing condition that influence form comprise mold hole dimension and length, find time, plastify pressure, polymeric matrix is pressed against etc.

According to method of the present invention, the polymeric matrix that is used to handle can comprise one or more polymkeric substance, and can have identical or different phase, and identical or different performance for example forms identical or different porosity etc.Two or more polymkeric substance can be mixture of polymers or blend, perhaps can disperse.One or more can be porous, and one or more are for non-porous or have a different porosities.

In addition, guest materials can comprise single or multiple object individuality (entity).Multiple object individuality can comprise a kind of guest materials and the another kind of guest materials that is used for the type of identical or different set function, for example one or more medicines and one or more vehicle etc. that are used for the type of a certain set function.

Multiple polymers type and guest materials type can be introduced with mixture or discrete component.For example, two or more polymer types can contacts with plasticizing fluid as discrete component (discrete component), and coextrusion formation has the composite extrusion in two or more polymer layers or district.At least a polymkeric substance in these two or more polymeric constituents comprises guest materials.

For example, a kind of polymeric constituent can comprise guest materials, and second kind of polymeric constituent can not contain guest materials, and can be extruded into coating layer or wall (blanklayer) in the composite extrusion, for example is used to delay discharge or pulse release is used.Selectively, two or more polymeric constituents can comprise identical or different guest materials respectively, obtain to have a different performance in different zones or comprise or discharge two or more incompatible objects or discharge the matrix material of two or more antibody etc. with different releasing patterns (release profile).

According to extrudate of the present invention or composite extrusion, it can be arbitrary form as defined above, and be preferably tubing, right cylinder, fiber, sheet material or film or odd-shaped or hollow form, for example can be composite pipe or right cylinder hollow or that fill, with circular fiber or coated fibre, single or multiple fibril, or individual layer or sheet film or sheet material, wherein fibril can be the known fabric of textile field or cloth or spinning etc. again.

Can use any suitable nib shape and size to implement method of the present invention.The nib shape and size influence the shape of extrudate, for example sheet material as defined above, tubing, right cylinder, ribbon, fiber, protofibril, fibrous and fabric or nonwoven extrudate.The height of nib and width or size are selected according to the desired height of extrudate and width or diameter usually.Yet, it is 0.001～10 millimeter operation that method of the present invention is specially adapted to use the mold hole dimension scope, more preferably 0.001 millimeter～2 millimeters, and more preferably 0.005 millimeter～2 millimeters, more preferably 0.005 millimeter～1 millimeter, for example 0.01～2 millimeter or 0.05～1 millimeter.Known in the fieldly be, polymkeric substance can expand when extruding nib leaving, and can obtain larger sized extrudate, and this depends on pressure, porosity etc.But the more important thing is, we have found that the length of extruding nib is extremely important for method of the present invention.Specifically, we have found that relatively longer nib produces improved force of cohesion, and help to form more high stability, the extrudate of length more, and particularly at preparation fiberizing extrudate, also be like this when producing relatively large extrudate.Be not subjected to this theoretical the restriction, we believe, by relatively long nib, help polymkeric substance to arrange, promote that along extruding direction the polymkeric substance of extruding ruptures, obtains extended extrudate such as macrofiber vertically polymeric matrix.Therefore, nib length preferable range is 0.1 millimeter～1 meter, more preferably 0.2～200 millimeter, and for example 0.5～10 millimeter or 0.1 meter～1 meter.Usually nozzle is long more, and prepared fiber is long more.

Nib can be along continuous profile and size on its length or other yardstick.Suitable nib is, increases along size on its length, and preferably with respect to axially on first angle, increasing, and randomly with respect to axially on second angle, also increasing in the nib outlet.The angle that increases can be one or more sizes, for example for the sheet material extrudate, the angle that increases can be height or height and width, and for extrudates such as tubing, right cylinder, fibers, angle can be two kinds of sizes that form the conical profile nib.Preferably, the angle that the circular cone nib provides (with respect to axial angle) scope is for spending greater than 0 degree～89.9, and more preferably 45～80 spend, more preferably 50～65 degree, for example 60 degree.Nib can be one of a plurality of nibs, and it can be separately independently, and perhaps it can be to be adjacent to or to arrange coaxially or with one heart, to form a plurality of simple extrudates or to form aforementioned defined composite extrusion.Nib can extraly or be selected a ground and contain real core (solid core) etc., obtains the hollow extrudate thus, and for example ring mould hole can obtain tubing or right cylinder etc.

In one embodiment of the invention, this method is a kind of extruding-out process, and makes polymkeric substance-guest materials mixture leave to extrude nib, and mould also enters collecting chamber or the district that comprises one or more moulds or instrument.Mould or instrument can comprise one or more forming cavities, to receive extrudate, for example mould can comprise one or more less than the extrusion die bore dia, be suitable for extrudate is molded as the passage of fibers form.

Extrude the method for the present invention of implementing by extrusion pressure being applied to plasticizing polymerization thing-guest materials mixture with driving.Preferably apply the power of extruding by pressure difference (pressure difference between extruder chamber and the collecting chamber) or physical pressure spray boom for example known in the field or drift or screw rod.The power of extruding has partly determined the characteristic of the extrudate that obtained.Preferably, extruding power can be any appropriate power for preparing extrudate as defined above according to the present invention.It should be understood that use and implement that the effect of generation is that polymkeric substance is blown over nib, destroyed any force of cohesion, and can not obtain defined extrudate, and just obtain particulate or powder than the power that is suitable for the Li Genggao of extruding of the present invention.The present invention provides the extrudate of a kind of preparation moulding polymeric articles (described product comprises guest materials) form for the first time, and need not be reduced to the excessive temperature that needs to introduce the degree of guest materials and reach this polymkeric substance for Tg, Tm or the viscosity with the lower molecular weight polymkeric substance.

Can be by continuously or off and on extruded polymer and guest materials are implemented method of the present invention.Find time to wait in conjunction with the expectation form of extrudate and nib length and select.Atomizer length will influence the length and/or the form of product.Therefore, can help the form of extrudate so that, extrude and in nib, produce cooling effect by the stable enforcement of extruding.Perhaps, can adopt intermittently and extrude, for example the several seconds is extruded this method of enforcement at interval.

Can under any appropriate pressure as defined above, implement this method.Plasticizing pressure is extremely important for the viscosity that reduces polymeric matrix, and combines with pressure that polymeric matrix is extruded, influences the form and the characteristic of extrudate very significantly.Be used to extrude the method for relative low-molecular weight polymer matrix, with respect to the method that is used to extrude more tacky higher molecular weight polymer, lower to the dependency of pressure.Therefore, in the preferable range of the present invention's operation, the plasticizing pressure change is quite big.Therefore, implement method of the present invention greater than the plasticizing pressure of 120 crust in the preferred scope of using as defined above, and found significantly to reduce the viscosity of polymeric matrix.

When treatment with supercritical fluid, under critical or undercritical conditions, extrude aptly; Perhaps under close phase in Asia or other envrionment conditions, extrude.

Can be by implementing method of the present invention in the environment that is extruded into atmospheric pressure environment or rising " back pressure ".We find that this is the important factor of decision extrudate form.In fact, therefore can be by keeping elevated pressure, changing elevated pressure after nib or the mould or relief pressure is implemented this method by extruding.

The back pressure that is applied in the collecting region influences fibre shape strongly, is expressed into thus in the air under the normal atmosphere to form void-free extrudate, and is squeezed in the back pressure of any rare gas element of highly compressed such as nitrogen and forms the porous extrudate.Preferably, when the pressure in the pressure chamber low relatively (promptly less than 140 crust), must in collecting region, keep back pressure, make not curing too soon of polymkeric substance, stopped nozzles and inhibition fiber form.

Useful especially is that the present invention can control porosity by the back pressure that changes in the collecting chamber.Preferably, be squeezed in the collecting region under malleation, normal pressure or the negative pressure, described pressure can be greater than or less than plasticizing pressure, and preferable range is that 50～140 crust or scope are 1～50 crust.

Collecting region pressure can be greater than or less than the plasticizing pressure in the pressure chamber, and suitable scope be 50～140 the crust, be preferably 70～140 the crust, more preferably 80～125 crust for example 90 cling to, or scope is 1～50 crust, be preferably 1～30 crust, more preferably 5～15 crust, for example 10 crust.Usually the method for implementing under lower or atmosphere back pressure can obtain to have the thin extrudate that high polymer is arranged, and obtains to have the thick extrudate of arranging than the low degree polymkeric substance when implementing under higher back pressure.In addition, environmental stress or low back pressure help to prepare the extrudate with microvoid structure or non-porous structure, extrude simultaneously to help to prepare the extrudate with porous or big hollow structure under high back pressure.

Method of the present invention can be as known in the art intermittently or continuation method.Aptly, this method is an interrupter method, thus matrix is introduced in the pressure chamber, seals this chamber and keeps the plasticizing condition, finds time to extrude continuously or intermittently by the pressure chamber subsequently.Perhaps this method is a continuous processing, continuously matrix is delivered in the pressure chamber that remains under the desired plasticizing pressure content of this chamber of finding time continuously or intermittently all the time thus.

Can carry out method of the present invention in any suitable device, described device comprises pressure chamber as defined above and extrudes nib, constitutes plasticizing zone and extrudes the district.Carry out this method aptly in the extrusion device of any appropriate, described extrusion device for example comprises extruder barrel, and this extruder barrel has the rotary screw element that is assemblied in wherein and has the drivingmotor that drives the rotary screw element.This device can comprise loading hopper or other reservoir that is used for polymkeric substance is introduced extruder barrel.This device can comprise and is used for integration tool that guest materials and polymkeric substance are introduced together, perhaps can comprise the extra loading hopper or the reservoir that are used for guest materials is directly introduced extruder barrel.Extruder barrel can comprise heating tool, for example a plurality of material tube heaters that are set for this barrel of heating.This device comprises extraly and is used to connect the pressure entrance that plastifies fluid reservoir that described plasticizing fluid reservoir is used for will being pressurized to by pressurizing tool the fluid plasticizing of selected pressure.Pressure entrance comprises the instrument that is used for controlled rate metered amount being applied to extruder barrel.One or more pressure entrances can be configured in along on one or several position of this barrel, as desired, can dispose by pressure manifold known in the field if desired.

This device can comprise mixing tool as defined above, a plurality of blades etc. for example, and perhaps extrusion screw rod can provide suitable mixing.Device well known in the art comprises other nucleation step, and it can exist or not be present in and is used for device of the present invention, and does not preferably exist.The inventive system comprises and extrude nib, extrude nib and preferably include the die head or the nozzle of shape and size as defined above.Aptly, this device comprises the instrument that is used for controlling polymers, guest materials and plasticizing fluidic fluid rate.The instrument that is used to control flow rate is well known in the art, and comprises extrusion screw rod, reciprocating pump, volume pump etc.In addition, flow rate can be controlled by design polymkeric substance, guest materials and fluidic entry position.

This device can comprise the nib of extruding of one or more extrusion nozzle forms as defined above.If carry out this method in as the device of extruding nib, and use sticky polymers/when plasticizing fluid blend is carried out, because the pressure drop meeting that the friction in the nozzle causes causes length increase and width to reduce at the nozzle that comprises known length and width.Aptly, device of the present invention is determined with reference to quantity and the mold hole dimension of extruding nib.For example, use singlely when extruding nib, select diameter and length aptly, to obtain obvious pressure drop greater than desired minimum pressure drop.Pressure drop can be controlled by configuration extrusion die hole geometry well known in the art.By selecting the suitable nib of extruding, determine pressure drop thus, can be controlled in this device internal pressure control, and can keep plastifying pressure.Useful is to provide extra positive press tool, with the pressure loss in extruding nib during compensating continuously or intermittently extruding.In preferred implementation of the present invention, in order to form and desired pressure drop is provided in nib and, selects to extrude nib to the requirement of length in conjunction with being enough to obtain continuous extrudate.

Polymkeric substance can be selected from any known polymkeric substance that is applicable to set application.Suitable polymers is selected from amorphous arbitrarily (solid, semisolid or fluid such as liquid) or hypocrystalline or crystalline polymer.Be fit to import or to be incorporated into polymkeric substance in human body or animal body or the bioplasm in nontoxic mode, (Severian Dumitriu compiles can be selected from " Polymeric Biomaterials ", ISBN 0-8247-8969-5, MarcelDekker publishes, the USA New York, 1994) in disclosed synthetic biodegradable polymers, the non-biodegradable polymkeric substance of synthetic; And natural polymer.Preferred polymers is selected from homopolymer, block and random copolymers, blend polymer and can be straight chain, monomeric mixture (height) branching or crosslinked.

Polymkeric substance can include but not limited to only illustrate as an example and the following polymkeric substance that provides:

Polyester, the multipolymer, polycaprolactone that comprises multipolymer, lactic acid and the oxyacetic acid of poly(lactic acid), polyglycolic acid, lactic acid and oxyacetic acid and polyoxyethylene glycol is as poly-γ-Ji Neizhi and poly-epsilon-caprolactone, poly 3-hydroxy butyrate, Ju Dui diethyleno dioxide ketone (poly (p-dioxanone), poly-dioxane heptanone (polydioxepanone), poly-fumaric acid propylene glycol ester and poly-oxalic acid alkylene ester;

Poe comprises Heller at ACS Symposium Series 567,292-305, the polyvalent alcohol described in 1994/diketene acetal addition polymer;

Poly-acid anhydrides, comprise that Tamada and Langer are at Journal of Biomaterials Science-PolymerEdition, 3,315-353, in 1992 and Domb at the poly sebacic polyanhydride (PSA) described in Handbook of BiodegradablePolymers (A.J.Domb and R.M.Wiseman compile, and Harwood Academic Publishers publishes) the 8th chapter; Gather (carboxyl di carboxyl phenyloxy phenoxy group hexane) (PCPP); Gather [two (to the carboxyl phenoxy group) methane] (PCPM); The multipolymer of SA, CPP and CPM.

Polyamino acid;

Poly-false amino acid comprises that James and Kohn are at described in the 389th to 403 page of the Controlled Drug Delivery Challengesand Strategies (american chemical association, Washington D.C.) those;

Polyphosphonitrile comprises the derivative of poly-(dichloro) phosphonitrile, poly-(organic) phosphonitrile, and Schacht is at Biotecbnology and Bioengineering, 52,102-108, the polymkeric substance described in 1996;

Azobenzene polymer comprises that Lloyd is at International Journal of Pharmaceutics, 106,255-260, those described in 1994.

Vinyl polymer, comprise polyethylene, vinyl-vinyl acetate copolymer, polypropylene, polyvinyl chloride, polyvinyl acetate, the multipolymer of polyvinyl alcohol and vinyl alcohol and vinyl-acetic ester, polyacrylic acid, polymethyl acrylic acid, polyacrylamide, PMAm, polyacrylic ester, polyoxyethylene glycol, polydimethylsiloxane, urethane such as ester type urea (ester urethane) or epoxide, bismaleimides, methacrylic ester such as methyl methacrylate or glycidyl ester, polycarbonate such as Texacar PC (tri-methylene carbonate), two methylene trimethylene carbonic ethers (di-methylenetri-methylene carbonate), polystyrene and derivative;

Carbohydrate, polypeptide and protein comprise:

Sugar or carbohydrate and their derivative processed, starch, Mierocrystalline cellulose and derivative comprise ethyl cellulose, methylcellulose gum, Type 3U, Xylo-Mucine; Collagen; Gelatin; Dextran and derivative; Alginate; Chitin; And chitosan;

Polymkeric substance can comprise any additional polymer component with performance of raising or control action kou, described effect for example is to determine crosslinked degree and character, bending property, release performance or comprehensive mechanical performance, described crosslinked be in order to improve the perviousness of body inner fluid or the effective agent of pharmacy.

Guest materials can comprise that expectation is introduced in any material that is used for any desired application in the polymkeric substance.Suitable guest materials is selected from biological function or abiotic functional materials, includes, but are not limited to:

(1) (medicine) medicine and veterinary product;

(2) agrochemicals are as pest control medicament and plant growth control agent;

(3) humans and animals healthcare product;

(4) the humans and animals growth comprises and intends being used for the growth of bone, organ, tooth structure etc. or the product of repairing or moulding with product, structure product or cosmetic product;

(5) be used for the absorptivity Biofunctional materials of poison, toxin etc.;

(6) functional materials as any nutrient substance dependency biomaterial, is characterized in that duplicating, divides, regeneration, growth, propagation etc.;

(7) organic or inorganic material is used for dyeing, constitutes fabric, electronic material etc.;

(8) intelligence (SMART) material;

(9) in addition, guest materials can comprise the preparaton of stable or enhancement function material.

Preferably, as mentioned above, Biofunctional materials can be selected from any be adapted at comprising bioplasm or with the desired biological place of bioplasm bonded (biolocus) performance materials with function.Biofunctional materials can be bioactive, biologically inert, biocidal etc.Preferably; usually Biofunctional materials is fit to induce desired people, animal or the growth of bioplasm host structure thing, makes that they are strong, give them to replenish or their are strengthened, and perhaps can maybe can protect host structure thing etc. to exempt from these threats with waging a struggle for the threat of host structure thing or human or animal body.This material can be selected from any inorganic or organic materials that randomly is insoluble to supercutical fluid basically with any or both in its non-critical state and the supercritical state.

Preferably, guest materials is selected from Biofunctional materials, and described Biofunctional materials includes but not limited to: medical and veterinary product such as medicine and medical reagent are as developing or diagnostic reagent; Agrochemicals are as pest control medicament and plant-growth regulator; The humans and animals healthcare product; The humans and animals growth comprises and intends being used for the growth of bone, organ, tooth structure etc. or the product of repairing or moulding with product, infrastructure product or makeup; The absorptivity Biofunctional materials that is used for poison, toxin etc.; Functional materials as any nutrient substance dependency biomaterial, is characterized in that duplicating, divides, regeneration, growth, propagation etc.; Or comprise increased functionality component such as growth stimulant etc.; Or comprise organic or inorganic materials, be used for dyeing, constitute fabric, electronic material etc.

(1) medical and veterinary product, promptly medicine may be defined as any pharmaceutically active compounds of change physiology process to treat, to prevent, to cure, to alleviate or to diagnose the illness.

Medicine can be made up of inorganic or organic molecule, peptide, protein, enzyme, oligose, carbohydrate, nucleic acid etc.

Medicine can include but not limited to have the compound of the effect for the treatment of following disease:

Infect, as antiviral, antibacterials, antifungal drug, antiprotozoals, wormer, for example antibacterials include, but are not limited to penicillin such as penicillin G, cynnematin such as ceftazidime (ceftazidime), tetracyclines such as tsiklomitsin, aminoglycoside such as gentamicin, Macrolide such as erythromycin and following: clindamycin (clindamycin), paraxin (chloramphenicol), vancomycin (vancomycin), teicoplanin (teicoplanin), Coli-Mycin S, trimethoprim-sulfamethoxazole (co-trimoxazole) and trimethoprim (trimethoprim);

Cardiovascular system diseases is shunk medicine, diuretic(s), antiarrhythmic Agents, receptor, blocking drugs, calcium channel blocker, sympathomimetic drug, anti-coagulant, antiplatelet drug, fibrinolysis, fat-reducing medicament as strengthen muscle;

The gastrointestinal system medicine is as antacid, spasmolytic, healing medicine for ulcer, antidiarrheal, caccagogue, central nervous system soporific and anxiolytic;

Antipsychotic drug example hydrochloric acid chlorpromazine and " atypia " antipsychotic drug such as amisulpride (amisulpride), leoponex (clozapine), olanzapine (olanzapine), Quetiapine (quetiapine), risperidone (risperidone), Sertindole (sertindole), flupenthixol caprate (flupenthixoldecanoate), haloperidol caprate (haloperidol decanoate), Pipothiazine palmitate (pipothiazine palmitrate) and clopenthixol caprate (zuclopenthixol decanoate); Antidepressive, central nervous system stimulant, stomach desire inhibitor, the medicine that is used for treating nausea and vomiting, pain killer, antiepileptic drug, be used for Parkinsonian medicine, be used for the treatment of the medicine of substance depilatory;

Malignant disease and immunosuppressor are as cell toxicity medicament, immune response modifier, sexual hormoue and malignant disease antagonist;

The respiratory system medicament, as bronchodilator, corticosteroid, cromoglycate and associated treatment, antihistaminic agent, respiratory stimulant, lung surfactant, systemic snore mucous hyperemia is eliminated medicine;

Anti-tumor agents, as BCNU or 1,3-two (2-chloroethyl)-1-nitrosourea, Rubomycin C (daunorubicin), Zorubicin (doxorubicin), epirubicin (epirubicin), idarubicin (idarubicin), 4-demethoxylation Rubomycin C 3 ' Tuo amine (desamine)-3 '-(3-cyano group-4-morpholinyl)-Zorubicin, 4-demethoxylation Rubomycin C 3 ' Tuo amine-3 '-(2-methoxyl group-4-morpholinyl)-Zorubicin, etoposide (etoposide) and Vumon (teniposide);

Enzyme and hormone, as rnase, N,O-Diacetylmuramidase with list in " Novel TherapeuticProteins " (Klaus Dembowsky (editor), Peter Stadler (editor), Wiley-VCH VerlagGmbH, D-69469, Weinheim, Germany, 2001) in treatment with protein and enzyme; LHRH and LHRH analogue, Rat parathyroid hormone 1-34 and analogue;

Steroid (steroideals) is used for birth control and/or antineoplaston, for example medroxyprogesterone acetate or first ground hydroxyprogesterone acetate;

Flesh bone and joint disease medicine, as be used for rheumatism medicine, be used for the medicine of neuromuscular imbalance; With

Immunoassay product and vaccine.

Medical reagent can comprise fluorescence or radiation active agent arbitrarily as development or diagnostic reagent, it is provided to help to develop or diagnosis human body or animal body, for example be used for development or the diagnostic reagent built up at body tissue or organ, it makes this tissue or organ by imaging, with diagnose medical conditions such as cancer, lung imbalance, liver and kidney imbalance, intestines imbalance etc.Such reagent all is known in every field.

(2) agrochemistry and crop protection products may be defined as medicament, plant disease control agent, soil improvement agent of Pest Control arbitrarily or plant-growth etc.For example, the insect growth control agent comprises sterilant, miticide, rodenticide, invertebrate poison, slug-killer, vermicide (threadworms, anthelmintic), soil fumigant, insects repellant and insect attractive substance (as pheromone etc.), chemical warfare agents (chemical warfare agent) and biological control medicament (as microorganism, zoophagous animal and natural product).

Plant-growth regulator comprises weedkiller, weedicide, defoliating agent, siccative, shedding agent and control agent (set controller), the compound of taking root (rooting compound), sprout inhibitor, growth stimulant and retarding agent, liver moss control agent and plant gene are controlled thing or medicament as a result;

Plant disease control agent comprises mycocide, virucide, wood preservative and sterilant; And

Soil improvement agent comprises fertilizer, trace metal additive, bacteriological action control stimulant and soil consolidation agent.

(3) the humans and animals healthcare product may be defined as any of the above-mentioned substance of intending being used for the general health purpose, comprises VITAMIN, nutrient substance, steroide etc.

(4) humans and animals growth product, infrastructure product or cosmetic product

Preferably, humans and animals growth product as defined above, infrastructure product or makeup comprise the phosphatic rock derivatives class, for example, calcium hydroxylapatite (calcium hydroxyapatite) (playing bone or tooth component), silicon (working to organize the moulding component) and analogue, precursor or their functional deriv, biologically active substance such as collagen, bio-vitric and biological ceramics, with be suitable as implant and add meniscus, cartilage, tissue waits or is used for the component of suture line etc., preferably can promote collagen, the growth of other natural constituents of inoblast and these host structure things, moulding, strengthen or strengthen.

Organic or inorganic component as defined above can be selected from tricalcium phosphate or phosphatic rock derivatives class, for example, calcium hydroxylapatite (play bone or tooth component and promote biocompatibility), silicon (working to organize the moulding component) and analogue, precursor or their functional deriv, biologically active substance such as collagen, bio-vitric and biological ceramics, other mineral, hyaluronic acid ester (hyaluran), polyethylene oxide, CMC (carboxymethyl cellulose), protein, organic polymer etc., with be suitable as implant and add meniscus, cartilage, the component of tissue etc. preferably can promote collagen, the growth of other natural constituents of inoblast and these host structure things, moulding, strengthen or strengthen.

Increased functionality component as defined above can be selected from growth stimulant, biocompatible agent, VITAMIN, protein, glycoprotein, enzyme, nucleic acid, carbohydrate, mineral, nutrient substance, steroide, pottery etc., with the above-mentioned material of describing as medicine, present arbitrary form, for example microbiotic (antimicrobial drug), antipsychotic drug etc.Somatomedin particularly, for example Prostatropin, acid fibroblast growth factor, Urogastron, human growth factor, rhIGF-1, thrombocyte drive somatomedin (platelet drived growth factor), nerve growth factor, vascular endothelial growth factor, bone morphogenetic protein matter-2 and transforming growth factor.

(5) the absorptivity Biofunctional materials to poison, toxin etc. may be defined as arbitrarily and can or otherwise make natural existence or artificial poison or the immobilized any natural or synthetic product of toxin that imports by absorption, interaction, reaction.

(6) functional materials (as defined above) can be selected from ubcellular, cell or many cells material and aggregate and its mixture arbitrarily.Preferably, functional materials is selected from Mammals, plant and bacterial cell, comprises (ubcellular) cell organelle and its aggregate, comprises pancreas islet or liver spheroid etc., gemma, virus, bacterium etc.;

Non-cellular material, liposome for example, randomly as the carrier of material such as protein or enzyme, protein or enzyme liposome water (liposome water) when existing to the dense-phase fluid sensitivity.Cell material more preferably is selected from Mammals and plant protokaryon and eukaryotic cell and its mixture and aggregate, and most preferred mammalian cell is selected from inoblast, fibrocartilage cells (fibrochondrocyte), chondrocyte, bone formation cell such as sclerocyte and osteoclast, medullary cell, liver cell, heart cell (cardiomycyte), vascularization cell, neurocyte, sarcoplast, scavenger cell, microvascular endotheliocyte and its mixture and collagen.Biofunctional materials can natural formation or synthetic, for example pair cell carries out gene modification or variation in known manner, with in conjunction with, deletion or modified component.

Preferably, functional materials is selected from component or precursor, or derivatives thereof or the analogue of host structure thing, it is desired transplanting among the host structure thing or introducing, and preferably includes and be used for people, animal, plant or other live host structure the thing for example growth of bone, organ, tooth structure etc. or the material of reparation, isolation, protection, modification or moulding; To resist antagonist; Be used for the metabolism of poison, toxin, refuse etc., or be used for being used for biological rectification, biosynthesizing, biocatalysis etc. by the synthetic useful product of natural process.

Useful especially is, method of the present invention can be in a step apace preparation the extrudate of functional materials is housed, the extrudate of cell for example is housed, and last 24 or 48 hours formation supports and use the existing practice of cell breeding to form contrast.This is useful especially to patient's conveying at for example stem and progenitor cell.

Further useful is, we believe that this method can give to a certain degree germicidal action by the plasticizing fluid, and it selectively makes the material inactivation of non-preservation thus, for example is present in bacterium in the atmosphere etc.

(7) organic or inorganic material is used for dyeing, constitutes fabric, electronic material etc.

(8) intelligence (SMART) material, for example transmitter or probe, comprise and respond and maybe can discern the material of seeking detected matrix seeking detected matrix, for example in the environmental applications that is used for pollutent or other detection, perhaps in the technology controlling and process that is used for definite industrial fluids component is used; Perhaps comprise stimulating former or other influence to respond to change the material of performance, color change material for example, it responds to light or heat, and can be used among the fabric etc.Other intelligent material and their application also are known in the field.

(9) preparaton, it can exist with aforementioned defined guest materials, and can be selected from vehicle, carrier, upholder, tackiness agent, thinner, filler, snap-out release reagent, tackifier, stablizer, oxidation inhibitor, initiator, promotor, buffer reagent, stiffening agent etc.For example, carbohydrate such as glucose-derivative (N.F,USP MANNITOL or sorbyl alcohol) or inorganic salt such as zinc acetate can exist, to help to discharge and keep the activity of active guest materials, for example as buffer reagent.

Guest materials can be any desired form that is suitable for performed function, for example be solid form, semi-solid form such as thixotrope or gel form, semi-fluid form or fluid form such as lotion or liquid form, and can be can dissolve each other in or immiscible in, be dissolved in or be not dissolved in polymkeric substance and the plasticizing fluid among.Can regulate the form of guest materials easily, so that it presents optimum form with respect to processing and performed function.Preferably, the form of guest materials is a solid particulate, and grain diameter is selected according to desired should being used for.Preferably, it is identical or than its littler order of magnitude that particle diameter has a particle diameter with composition forms, and be any pore randomly, is preferably 10 ^-9M～10 ^-2M, for example nanometer, micron, millimeter or the decimetre order of magnitude.For example, the snap-out release that obtains with respect to using low relatively less extrudate, the prolongation of guest materials discharges, and can obtain by using relatively large extrudate.

Guest materials can be any desired significant quantity with respect to polymkeric substance.Usually volume value is 1 * 10 thus ^-12Wt% or 1 * 10 ^-9Wt%～99.9wt% is preferably 1 * 10 ^-12～1 * 10 ^-6Or 1 * 10 ^-6～1wt%, more preferably 1 * 10 ^-12～1 * 10 ^-9, 1 * 10 ^-9～1 * 10 ^-6Or 0.01 or 0.1～1wt%, perhaps greater than 0.5wt% or 1.0wt%～50wt%.In particularly preferred embodiments, a small amount of guest materials with respect to the 5g polymkeric substance introducing pik and the nanogram order of magnitude carries out this method.For example, represent with respect to the concentration of polymkeric substance that a small amount of scope can be 1 * 10 with guest materials ¹～1 * 10 ³Ng/mg, for example 5～150ng/mg.This is useful for most bioactive moleculess as enzyme or protein molecule, because their treatment concentration is very low.For example, the treatment consumption that obtains the needed somatomedin HGF of therapeutic response (pHGF) in the organizational project during the liver regeneration process in liver cell is 15ng/ml/ days.Consider survival and aftertreatment growth, can provide the breeding function material in the method with desired initial concentration.

For example, extrudate can comprise 80wt% hydroxyapatite, 10wt% cell, is lower than the somatomedin of 1wt% and greater than the antibiotic of 1wt%.

The plasticizing fluid is selected from carbonic acid gas, nitrous oxide, dithiocarbonic anhydride, aliphatic C _2-10Hydrocarbon (as ethane, propane, butane, pentane, hexane, ethene) and their halide derivative (for example tetrafluoro-methane or tetracol phenixin and three chloro-fluorocarbons (carbon monochloride trifluoride), trifluoromethane or trichloromethane), C _6-10Aromatics (as benzene, toluene and dimethylbenzene), C _1-3Alcohol (as methyl alcohol and ethanol), halogenation sulphur (as sulfur hexafluoride), ammonia, xenon, krypton etc.Usually, these fluids preferably can enter super critical condition under the pressure of 0-300 ℃ temperature and 7-1000 crust (preferred 12-800 crust).Be appreciated that fluidic selects to carry out according to its characteristic (for example, its diffusion property and as the characteristic of solvent).Preferably, fluid is as the solvent of all the other components of polymer composition (but be not as defined above guest materials).Fluidic is selected also to become according to the commercial production that can make polymkeric substance as defined above and is easy to critical condition and carries out.

Table 1

Fluid	Critical temperature/℃	Emergent pressure/crust
			Carbonic acid gas	31.1	?73.8
Ethane	32.4	?48.1

Ethene	9.3	?49.7
			Oxynitride	36.6	?71.4
Xenon	16.7	?57.6
			Trifluoromethane CHF 3	26.3	?48.0
Single fluoromethane	42	?55.3
			Tetrafluoroethane	55	?40.6
Sulfur hexafluoride	45.7	?37.1
			The chlorofluoromethane chlorotrifluoromethane	29 28.9	?38.2 ?38.7
Nitrogen	-147	?33.9
			Ammonia	132.5	?111.3
Hexanaphthene	280.3	?40.2
			Benzene	289.0	?48.3
Toluene	318.6	?40.6
			Trichlorofluoromethane	198.1	?43.5
Propane	96.7	?41.9
			Propylene	91.9	?45.6
Virahol	235.2	?47.0
			Right-dimethylbenzene	343.1	?34.7

Preferably, fluid comprises carbonic acid gas, and can be randomly mixes with as defined above other any fluids, perhaps mixes with the common solvent that is called " properties-correcting agent ".CO ₂Usually be used for medical applications by administration approval, and be chemically inert, do not stay resistates and can at random obtain.

The additional component that can introduce in the polymer-extruded thing of preparation, for example initiator, promotor, stiffening agent, stablizer, oxidation inhibitor, tackifier, filler etc. be directed among polymkeric substance or the vehicle.Can introduce mark and label etc. according to technique known, to follow the trail of or to detect the administration or the consumption of extrudate.

If wish tackifier are added in the polymer-extruded thing, then can be with before polymkeric substance combine, under the fluid that exists or do not exist as defined above by simply mix, spraying or other known coating step, with tackifier dipping or coating guest materials particle.Preferably, coat to combine and carry out, thereby obtain fabulous dressing with as defined above fluidic mixing.For example, tackifier are dissolved in as defined above the fluid, gained solution is contacted with the guest materials particle with as defined above polymkeric substance.Perhaps, in treating processes, tackifier are introduced, thereby it is attached on the guest materials particle in required mode.

Preferably, the filler total amount that comprises guest materials is preferably and is more preferably more than the 50 or 60 weight %, for example can reach 70 or 80 weight % by 0.1-99 weight % between 0.01-99.9 weight %.

Can with the suitable material of any its performance of suitable raising or mechanical characteristics it be handled before guest materials is introduced polymkeric substance or in the introducing process.Guest materials can be handled with various components, these components comprise the tackiness agent of the adhesive power that is fit to raising material and polymeric matrix, be used for being increased in the dispersion of whole matrix and the formation that prevents to lump, promote, be used for promoting in position the activator of any biological function effect etc. as the dispersive dispersion agent of suspension in whole plasticizing fluid.Preferably, available adhesive material (as silane etc.) is handled the Biofunctional materials that comprises hydroxylapatite, so that particle is easy to adhere to better with polymeric matrix.

Be not subjected to the constraint of this theory, think, tackifier adhere on the guest materials, thus expose or existing then may with polymer-bonded bond site.

Preferably, tackifier dissolve in as defined above the fluid, thereby the remaining tackifier that can will not adhere to guest materials or polymkeric substance by with fluid or expellant gas the polymer-extruded thing of product being extracted are removed.

Of the present invention further aspect, provide a kind of comprise as defined above polymeric matrix and the polymer-extruded thing of the solid mixture extrudate form of guest materials.Extrudate can be porous or atresia, and can have different shape and porosity, as defined above.The form that extrudate is suitable is sheet material, film, tubing, right cylinder, ribbon, protofibril, fibrous, fiber, fabric or nonwoven extrudate.Extrudate can have the size of any appropriate, and preferred diameter or height and/or width range are 0.001～10 millimeter, more preferably 0.001 millimeter～2 millimeters, more preferably 0.005 millimeter～2 millimeters, more preferably 0.005 millimeter～1 millimeter, for example 0.01～2 millimeter or 0.05～1 millimeter.Extrudate length can be greater than 0.01 millimeter, and do not have the effective upper limit, promptly can be preparation and collecting continuously in spool etc., obtains the extrudate of km length.Preferably, the extrudate length range is 0.01 millimeter～100 meters, is preferably 0.05 millimeter～2 meters, more preferably 0.1～50 millimeter.

Special feature of the present invention is, can utilize the character of density polymer and porosity and biodegradability, influence the release of guest materials valuably, guest materials for example is in human body or animal body or bioplasm or relative medicine etc. and/or in human body or animal body or bioplasm or relative structure graft, and it is being compatible aspect textural property of transplanted sites (locus of implantation).Therefore extrudate can be porous or atresia.

In addition, can select the extrudate porosity for obtaining desired physical strength and snappiness.Useful especially is, make polymkeric substance simulate the structure of porous humans and animals host structure, for example bone, meniscus and cartilage, tooth and weave construction strengthen its suitability as structure or release property graft thus, and improve its biocompatibility simultaneously.

The porous extrudate can be the porosity of closing cell or unlimited cell, and can comprise in the polymer arts known interconnection etc.

We find, reduce porosity and can gain in strength and snappiness, but porous extrudate intensity is lower and frangible.Porosity can be one or more orders of magnitude or multiple, and for giving desired mechanical property and/or desired guest materials release property all is suitable.Suitable hole is macrovoid well known in the art, mesoporosity or microporosity rank, scope is respectively＞50nm, 2～50nm and＜2nm.Suitable pore dimension depends on set application, for example is used to simulate porous host structure as defined above or is used for as defined above desired release performance.Porosity type and size can be controlled by technology known in the field, decompression rate for example, and for example fast decompression causes the formation of open pores, and decompression causes the formation of storage pore at a slow speed.

Guest materials can equably as desired or anisotropically be scattered in the whole extrudate.Guest materials can exist with crystallized form, as solid dispersion.Extrudate can comprise the combination of dissimilar guest materialss as defined above.

What the present invention was useful especially is that extrudate has superior quality aspect the homogeneity of the guest materials of form, porosity and introducing.

Of the present invention further aspect, a kind of composition that comprises polymer-extruded thing as defined above is provided, it obtains for extrudate and suitable carriers, tackiness agent, thinner etc. are mixed together, and perhaps it comprises for example one support etc. of one extrudate.Preferably, composition comprises that form is selected from the polymer-extruded thing of pottery, gel, paste, lotion, spray, solution, suspension or formed body, and (intrarespiratory) route of administration that is used in, upper epidermis (epicutaneous) outer by part, oral area, rectum, enteron aisle, subcutaneous, mucous membrane, intravenously, intramuscular or the respiratory tract is come administration; As structured material, comprise native metal, plastics, carbon or glass fiber mesh, gauze or excellent strongthener; In prescription, prescription is selected from and is used for bone or tooth inset or as bead, particle, filler or the tackiness agent of solid aggregates, perhaps as the monolith or the crown of plastic surgery or dental implant; The unsupported extrudate of polymeric matrix, as screened film, layer, cloth or sheet material, it is applicable to sealing or twines protected matrix or material; With its combination.

Preferably, composition comprises by moulding to form the extrudate of formed body, for example capsule bead, tablet, suppository, vaginal suppository, colloidal stroma, bolus (monolith bolus) etc., and it is the monolith of the powder of submicron to the decimetre magnitude for compact dimensions.

Of the present invention further aspect, a kind of device that is used to prepare polymer-extruded thing as defined above is provided, it comprises the pressure chamber that is fit to temperature and boost in pressure and can comprises the instrument that is used for the mixed content thing, and wherein the pressure chamber comprises the instrument that is used for by nib as defined above described content being extruded into second collecting region of lower pressure.This device comprises the instrument that is used to introduce reactant and component, and the while is the moulding pressure chamber as this area is known usually, to keep desired pressure in extrusion.The suitable nib of extruding comprises as defined above the die head with desired shape, size and length.

Preferably, pressure chamber is an autoclave, and it can comprise and be used for content is advanced to the instrument of extruding zone or district from the enter the mouth end or first cavity region or district through plasticizing and optional mixing region or district.Driving tool can comprise screw rod well known in the art or piston or suitable arbitrarily equivalent.

Of the present invention further aspect, provide as defined above extrudate or its composition or described method as the purposes of sustained release device, for example human or animal's medical product as defined above such as medicine or medical reagent are as developing or the e Foerderanlage of diagnostic reagent; In medicine or animal doctor use, for example as human or animal's health care or growth product, infrastructure product or cosmetic product, natural or artificial graft's thing, drug delivery or DNA e Foerderanlage, tissue engineering devices or supplementary unit such as suture line etc.; As antiseptic-germicide, for example has the antiseptic-germicide of antibacterial or fungicidal activity; As natural or synthetic barrier agent, its can be for example by absorbing, interact or reaction fixing poison or toxin that for example form naturally or artificial introducing; In agrochemistry or crop protection application; Be lower than under polymer Tg, Tm or the melt viscosity, be used for dyeing, the processing of the thermolability fiber of fabric, electronic material etc.; Introduce dyestuff and other thermolability material in polymkeric substance, described polymkeric substance can not for example melt extrude to wait and forms by traditional method; Or tensio-active agent is being introduced in the fiber, with the controlling polymers performance.

Preferably; composition as defined above is applicable to application as defined above; as the pharmacologically active product; be preferably medicine or veterinary product; human or animal's health care or growth product, infrastructure product or cosmetic product, agrochemistry or crop protective products; natural or synthetic barrier agent, the poison introduced that it can fixedly form naturally by absorption, interaction or reaction etc. or artificial or toxin etc.

Extrudate or composition are being incorporated in inside under the situation in desired site, can are waiting and carry out by arbitrarily desired mode such as injection, embedding, absorption.

Enter human or animal's host structure thing do or wet insert should use any known technology (for example being used for bone) to use to implant in plastic surgery and prosthesis, in dental applications or tooth reconstruct art as cement or crown implantation, perhaps as in the slowly-releasing implant implantation host structure thing.Polymkeric substance can be used for makeup/aesthetic applications or is used for medical use.Unique advantage is that the polymkeric substance as defined above that comprises Biofunctional materials can insert in the host structure thing in a known manner grows with promotion, thus inset and host structure thing formation one.

Release is as defined above used and is undertaken by composition is introduced desired location aptly.Not biodegradable polymer composition can wait and discharges guest materials by postponing water infiltration, the matrix diffusion by the finite rate of the hole in the polymeric matrix, and matrix excretes from human or animal body or remove in the surgery mode, perhaps optionally removes from any position.Biodegradable extrudate can make extrudate little by little be exposed to residing position along with degrading gradually during biological degradation and discharge.

Of the present invention further aspect, a kind of method that is used to prepare polymer-extruded thing is provided, be included in the close phase of high temperature and/or highly compressed, under the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid, with the plasticized polymer matrix, and in close phase, under the subcritical or super critical condition, by nib polymeric matrix is extruded in collecting region or the mould, relief pressure simultaneously or subsequently, obtain extrudate thus, described extrudate has the form of being given by nib or mould, it is characterized in that being less than or equal in temperature carrying out described method under 200 ℃.Preferably this polymeric matrix comprises the thermolability polymkeric substance.

Explain the present invention in non-limiting mode with reference to the following example and accompanying drawing now, wherein Fig. 1～3 have shown the image according to the fiber of the present invention's preparation.

Comparing embodiment-formation powder

To gather (D, L-lactic acid) (MW8,000) is added in the autoclave.Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, to guarantee by carbonic acid gas plasticizing polymerization thing.By short the angle nozzle arranged, content is discharged in second autoclave that is in normal atmosphere under the generation powdered product.

The embodiment of the invention

Embodiment 1

To gather (D, L-lactic acid) (MW107,000) is added in the autoclave.Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, to guarantee by carbonic acid gas plasticizing polymerization thing.By short the angle nozzle arranged, content is discharged in second autoclave that is in normal atmosphere under generation fibrous web-like solid product.This fibrous product is shown in Fig. 1.

Embodiment 2

To gather (D, L-lactic acid) (MW107,000) is added in the autoclave.Under specified temperature and pressure (about 35 ℃, 125 crust), in autoclave, inject enough carbonic acid gas, to guarantee by carbonic acid gas plasticizing polymerization thing.By short the angle nozzle arranged, content is discharged in have gas backpressure second autoclave of (about 90 crust), generate more porous single fibrous product.This fibrous product is shown in Fig. 2.

Embodiment 3

To gather (D, L-lactic acid) (MW107,000) is added in the autoclave.Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, to guarantee by carbonic acid gas plasticizing polymerization thing.By long the angle nozzle arranged, content is discharged in second autoclave that is in normal atmosphere under, generation is different from the fibrous web-like solid product of the form of embodiment 1.This fibrous product is shown in Fig. 3.

Embodiment 4

To gather (oxyacetic acid-be total to-D L-lactic acid) (MW158,000) is added in the autoclave.Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, to guarantee by carbonic acid gas plasticizing polymerization thing.By long the angle nozzle arranged, content is discharged in second autoclave that is under the normal atmosphere, generate single fibrous solid product.

Embodiment 5

To gather (D, L-lactic acid) (MW71,000) and rnase powder is added in the autoclave with specified ratio (weight ratio is about 20: 1).Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, guaranteeing by carbonic acid gas plasticizing polymerization thing, and with contents mixed together.By long the angle nozzle arranged, content is discharged in second autoclave that is in normal atmosphere under, generation fibrous web-like solid product, it contains rnase, and form is similar to embodiment 1.With respect to the rnase of handling, when discharging from this polymkeric substance, the biological activity of rnase is not subjected to the influence of carbon dioxide treatment.Standard activity described in the employing document chemically examines to determine ribonuclease activity.

Embodiment 6

To gather (D, L-lactic acid) (MW71,000) and N,O-Diacetylmuramidase powder is added in the autoclave with specified ratio (weight ratio is about 20: 1).Under specified temperature and pressure (about 35 ℃, 300 crust), in autoclave, inject enough carbonic acid gas, guaranteeing by carbonic acid gas plasticizing polymerization thing, and with contents mixed together.By long the angle nozzle arranged, content is discharged in second autoclave that is in normal atmosphere under, generation fibrous web-like solid product, it contains N,O-Diacetylmuramidase, and form is similar to embodiment 1.With respect to the N,O-Diacetylmuramidase of handling, when discharging from this polymkeric substance, the biological activity of N,O-Diacetylmuramidase is not subjected to the influence of carbon dioxide treatment.Standard activity described in the employing document chemically examines to determine lysozyme activity.

The diameter that the angle nozzle is arranged of employed weak point is less than 1mm among the embodiment, and length is less than 2mm, and spray angle is 8～20 °.The long diameter that the angle nozzle is arranged is less than 1mm, and length is 3～8mm, and spray angle is 50～75 °.

From aforementioned content other aspects of the present invention and advantage will be conspicuous.

Claims (30)

1, a kind of preparation contains the method for the active polymer extrudates of polymeric matrix and guest materials, described method comprises: in high temperature and/or the close phase of highly compressed, under the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid with guest materials, with plasticized polymer matrix and introducing guest materials, and in close phase, under the subcritical or super critical condition, the polymeric matrix that to introduce guest materials by nib is extruded in collecting region or the mould, relief pressure simultaneously or subsequently, obtain extrudate with the form of being given by nib or mould thus, described extrudate contains the solid mixture of polymeric matrix and guest materials.

2, according to the process of claim 1 wherein that the form of described extrudate is sheet material, film, tubing, right cylinder, bar, ribbon, protofibril, filament, fibrous, fiber, netted, fabric or nonwoven extrudate.

3, according to the method for claim 1 or 2, wherein said plasticizing fluid is selected from any close phase, subcritical or supercutical fluid.

4, according to each method in the claim 1～3, wherein said method is carried out under the situation that does not have additional solvent basically.

5, according to each method in the claim 1～3, wherein fusion time is 2 milliseconds～72 hours.

6, according to each method in the claim 1～5, wherein said method is carried out under-200 ℃～500 ℃ temperature.

7, a kind of preparation contains the method for the active polymer extrudates of polymeric matrix and guest materials, described method comprises: in high temperature and/or the close phase of highly compressed, under the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid with guest materials, with plasticized polymer matrix and introducing guest materials, and in close phase, under the subcritical or super critical condition, the polymeric matrix that to introduce guest materials by nib is extruded in collecting region or the mould, relief pressure simultaneously or subsequently, obtain extrudate thus with the form of giving by nib or mould, described extrudate contains the solid mixture of polymeric matrix and guest materials, it is characterized in that, be less than or equal to 200 ℃ and/or in temperature less than the Tg of polymeric matrix, under Tm or the non-viscous state, carry out described method.

8, according to each method in the claim 1～7, wherein plasticizing condition comprises that pressure is greater than 1 crust～1000 crust.

9, according to each method in the claim 1～8, wherein the viscosity of polymeric matrix is 1～1,000,000 centipoise, more preferably 500～500,000 centipoise, more preferably 1000～100,000 centipoise.

10, according to each method in the claim 1～9, wherein the molecular weight of polymeric matrix is 1～10, and 000kDa is preferably 1～250kDa.

11, according to each method in the claim 1～10, wherein polymeric matrix comprises one or more polymkeric substance, and described polymkeric substance can have identical or different phase, identical or different performance, for example forms identical or different porosity.

12,, wherein two or more type polymers are contacted with plasticizing fluid as discrete component, and coextrusion has the composite extrusion in two or more polymer layers or district with formation according to the method for claim 11.

13, according to each method in the claim 1～12, wherein said guest materials comprises single or multiple object individuality.

14, according to the method for claim 13, wherein multiple object individuality comprises a kind of guest materials that is used for the type of a certain set function, be used for the guest materials of the type of identical or different set function with another kind, for example one or more medicines and one or more vehicle.

15, according to each method in the claim 1～14, wherein mold hole dimension is 0.001～10 millimeter, is preferably 0.001～2 millimeter, and length is 0.1 millimeter～1 meter.

16, according to each method in the claim 1～15, wherein increase along mold hole dimension on the nib length direction, preferably with respect to axially on first angle, increasing, and axially on second angle, increasing with respect to the nib outlet randomly.

17, according to each method in the claim 1～16, wherein nib is one of a plurality of nibs, it can be separately independently or can be to be adjacent to or to arrange coaxially or with one heart, to form a plurality of simple extrudates or to form aforementioned defined composite extrusion, and can extraly or select a ground and contain real core etc., obtain the hollow extrudate thus, for example ring mould hole can obtain tubing or right cylinder.

18, according to each method in the claim 1～17, wherein continuously or off and on extruded polymer matrix and guest materials.

19, according to each method in the claim 1～18, wherein be expressed in the collecting region under malleation, normal pressure or the negative pressure, described pressure can be greater than or less than plasticizing pressure, and is preferably 50～140 crust or is 1～50 crust.

20, according to each method in the claim 1～19, wherein polymeric matrix is selected from amorphous arbitrarily, hypocrystalline or crystalline polymer, and suitable polymers is polyester, poly-(ortho ester), poly-acid anhydrides, poly-(amino acid), poly-(false amino acid), poly phosphazene, azobenzene polymer for example; Vinyl polymer, poly-(vinylformic acid), poly-(methacrylic acid), polyacrylamide, PMAm, polyacrylic ester, poly-(ethylene glycol), poly-(dimethyl siloxane), urethane, epoxide, bismaleimides, methacrylic ester such as methyl methacrylate or glycidyl methacrylate, polycarbonate, polystyrene and its derivative; Carbohydrate, polypeptide and protein; And multipolymer.

21, according to each method in the claim 1～20, wherein guest materials is selected from biological function or abiotic functional materials, includes, but are not limited to:

(1) (medicine) medicine and veterinary product;

(2) agrochemicals are as pest control medicament and plant growth control agent;

(3) humans and animals healthcare product;

(4) the humans and animals growth comprises and intends being used for the growth of bone, organ, tooth structure etc. or the product of repairing or moulding with product, infrastructure product or cosmetic product;

(5) be used for the absorptivity Biofunctional materials of poison, toxin etc.;

(6) functional materials as any nutrient substance dependency biomaterial, is characterized in that duplicating, divides, regeneration, growth, propagation etc.;

(7) organic or inorganic material is used for dyeing, constitutes fabric, electronic material etc.;

(8) intelligence (SMART) material;

(9) preparaton, its stable or enhancement function material.

22, according to each method in the claim 1～21, wherein guest materials content is 1 * 10 ^-12～1 * 10 ^-6Or 1 * 10 ^-6～1wt%, more preferably a small amount of, 1 * 10 ^-12～1 * 10 ^-9, 1 * 10 ^-9～1 * 10 ^-6, or 0.01 or 0.1～1wt%.

23, according to each method in the claim 1～22, wherein plastify fluid and be selected from close phase, subcritical or postcritical carbonic acid gas, nitrous oxide, dithiocarbonic anhydride, aliphatic C _2-10Hydrocarbon (as ethane, propane, butane, pentane, hexane, ethene) and their halide derivative (for example tetrafluoro-methane or tetracol phenixin and three chloro-fluorocarbons, trifluoromethane or trichloromethane), C _6-10Aromatics (as benzene, toluene and dimethylbenzene), C _1-3Alcohol (as methyl alcohol and ethanol), halogenation sulphur (as sulfur hexafluoride), ammonia, xenon, krypton etc.

24, each the polymer-extruded thing that comprises polymeric matrix and guest materials in the aforementioned claim 1～23, it is the solid mixture of extrudate form.

25, the composition that comprises the polymer-extruded thing of aforementioned claim 24, wherein extrudate and suitable carriers, tackiness agent, thinner, initiator, promotor, stiffening agent, stablizer, oxidation inhibitor, tackifier, filler etc. flock together, and perhaps contain for example single support etc. of one extrudate.

26, be used for using each method of aforementioned claim 1～23 to prepare the device of polymer-extruded thing, comprise the pressurized vessel that is fit to temperature and boost in pressure and can contains the instrument that is useful on the mixed content thing, wherein pressurized vessel comprises the instrument that is used for by nib as defined above content being extruded into second collection container of lower pressure.

27, the purposes of the product of aforementioned defined extrudate or its composition or described method is as sustained release device such as medicine delivering device; In medicine or animal doctor use, for example as human or animal's health care or growth product, infrastructure product or cosmetic product, natural or artificial implantation, drug delivery or DNA e Foerderanlage; As antiseptic-germicide, for example has the antiseptic-germicide of antibacterial or fungicidal activity; As natural or synthetic barrier agent, its can be for example by absorbing, interact or reaction fixing poison or toxin that for example form naturally or artificial introducing; In agrochemistry or crop protection application; Be lower than under polymer Tg, Tm or the melt viscosity, be used for dyeing, the processing of the thermolability fiber of fabric, electronic material etc.; Introduce dyestuff and other thermolability material in polymkeric substance, described polymkeric substance can not for example melt extrude to wait and forms by traditional method; Or tensio-active agent is being introduced in the fiber, with the controlling polymers performance.

28, the method for the polymer-extruded thing of preparation, be included under the close phase of high temperature and/or highly compressed, the subcritical or overcritical plasticizing condition, polymeric matrix is contacted with the plasticizing fluid, with the plasticized polymer matrix, and under close phase, subcritical or super critical condition, by nib polymeric matrix is extruded in collecting region or the mould, relief pressure simultaneously or subsequently, obtain extrudate thus, it is characterized in that being less than or equal to and carry out described method under 200 ℃ in temperature with the form of giving by nib or mould.

29, according to the method for claim 28, wherein polymeric matrix comprises the thermolability polymkeric substance, for example poly-(vinyl cyanide), and multipolymer.

30, method, extrudate, composition, device or purposes that exemplified or that set forth in foregoing in fact, specification sheets and the accompanying drawing.

Images