CN1791385A - Homogeneous, thermoreversible alginate films transportation system - Google Patents

Abstract

The present invention is directed to a delivery system comprising a homogeneous, thermoreversible gel film, wherein the gel film comprises: (i) a film forming amount of low viscosity polymannan gum, e.g., low viscosity guar gum, and optionally at least one of a plasticizer, a second film former, a bulking agent, and a pH controlling agent; and (ii) an active substance. The present invention is also directed to a process for the manufacture thereof.

Description

Homogeneous, thermoreversible alginate films transportation system

Related application

The application requires to be registered in the rights and interests of 14 purpose U.S. Provisional Applications 60/462793 April in 2003.

Invention field

The present invention relates to comprise the delivery system of homogeneous, thermoreversible gel film, wherein said gel film comprises the reversible alginate water-soluble hot in nature of (i) film forming amount, and choose any one kind of them (ii) active substance in plasticizer, second film former, extender and the pH controlling agent at least.The invention still further relates to the preparation method of described delivery system.

Background of invention

In recent years, delivery system is used in the middle of refreshing tablets and the clean sheet etc. more and more, is used for throwing in mouth care active component etc.Present invention relates in general to comprise the delivery system of gel film, it can be used to hold and carries active substance very widely.

For example, WO 02/43657 discloses the purposes of the edible film compositions of no pulullan polysaccharide (pullulan), and described compositions comprises at least a film former, at least a extender filler, at least a plasticizer.These films can contain multiple material such as medicine, and can use for many mouth care, as the breath freshening sheet.Film former is described to any cellulose ether and (it is said and comprise: methylcellulose, ethyl cellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose; Carboxymethyl cellulose and its derivant); Modified starch (it is said and comprise: the corn and the potato starch of acid and enzyme hydrolysis); Natural gum (it is said and comprise arabic gum, guar gum, locust bean gum, carrageenin, Radix Acaciae senegalis (acacia), karaya, ghatti gum, Tragacanth, agar, tamrind gum, xanthan gum and their derivant); Edible polymer (it is said and comprise microcrystalline Cellulose, cellulose ether, xanthan gum and their derivant); Hydrocolloid powder (referring to comprise guar gum, locust bean gum, microcrystalline Cellulose, Caesalpinia spinosaKuntze and their derivant); Sargassum extract (it is said and comprise alginate, carrageenin and their derivant); With terrestrial plant extract (it is said and comprise Rhizoma amorphophalli (konjac), pectin, Arabic gala glue and their derivant).

WO 00/18365 openly is used for transmitting to the oral cavity film of the quick oral cavity corrosion of breathing deoderization agent, antibacterial and salivation stimulant.The film former that is used for making this invention film allegedly is selected from pulullan polysaccharide, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, hydroxy methocel, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, xanthan gum, Tragacanth, guar gum, Radix Acaciae senegalis, arabic gum (Arabic gum), polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl polymer, amylose, senior amylose, the senior amylose of hydroxypropylation, dextrin, pectin, chitin, chitosan, Gum levan, elsinan, collagen, gelatin, zein, glutelin, soy protein isolate, casein and their mixture.It is said that these films have overcome the problem that keeps quintessence oil to interact and be used for the high relatively oil content of some film of mouth care.

Summary of the invention

In first kind of embodiment, the present invention relates to comprise the delivery system of homogeneous, thermoreversible gel film, wherein gel film comprises: (i) the reversible alginate water-soluble hot in nature of film forming amount, and choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent; (ii) active substance.

In second kind of embodiment, the present invention relates to prepare the method for above-mentioned homogeneous gel film delivery system, described method comprise the steps: (i) in the equipment that enough shearing forces, temperature and retention time are provided to alginate, and choose any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heat, hydration, mixing, dissolving and the optional degassing, form the homogenizing melt composition, wherein temperature is equal to or higher than the solution temperature of compositions; The active substance that (ii) before or after forming melt composition, adds effective dose; (iii) contain the melt composition of active substance being equal to or less than under its gelation temperature cooling, form the gel film that contains active substance.

The accompanying drawing summary

Fig. 1 is the side view that fluid mixing apparatus is partly cut open, and described equipment is used for making first and second fluids that can be used for the inventive method to mix with steam.

Detailed Description Of The Invention

Derived and the alginates that come are unbranched straight chain chemical polymerization things by brown alga (Phaeophyceae sp.) etc., comprise beta-D-mannuronic acid (M) and α-L-guluronic acid (G) residue that (1-4) connects. Alginates are not random copolymers, but are comprised of the similar residue block that alternately occurs, for example MMMM, GGGG and GMGM, and they generally can be used to form alginic acid or alginates.

The alginates that can use in the present invention comprise the monovalent salt of alginic acid, such as mosanom and potassium alginate, and the esterified form of alginic acid, such as propylene glycol alginate. The definition of the used alginates of the present invention comprises the ester-formin that all are such. Other examples that can be used for alginates of the present invention comprise alginic acid magnesium and alginic acid 3-monoethanolamine. These class alginates all can use separately, also can be used in combination with other alginates of the present invention, described other alginates can comprise a small amount of other cations, as long as they do not cause adverse effect to the formation of gel or the uniformity of gel mould, will discuss in detail as following. Alginates can be from raw material fully, part clarified, or without clarification.

It has been generally acknowledged that in the presence of calcium ion some alginate produces the heat irreversible gel as sodium alginate.Make the present inventor be unexpectedly, discover that these alginate of the present invention can produce the homogeneous, thermoreversible gel film with remarkable film-strength.In addition, it has been generally acknowledged that some alginate, gelling can not take place as propylene glycol alginate.Make the present inventor be unexpectedly equally, discover that propylene glycol alginate can produce the homogeneous, thermoreversible gel film with remarkable film-strength.

Known alginate and the polyvalent cation (ion) that can touch are as calcium ion reaction and crosslinked.This crosslinked meeting causes adverse effect to the film formation and the thermal reversibility of alginate jelly film, specifically depends on used polyvalent cation; For example, magnesium ion can not cause adverse effect to the thermal reversibility of alginate jelly film.Therefore, the important point is can cause the content of these polyvalent cations of adverse effect to be lower than to a certain degree to the film formation and the thermal reversibility of alginate film in the alginate, in order to avoid the formation or the thermal reversibility of film in the alginate systems damaged.The consumption of this polyvalent cation (for example calcium ion) is not higher than 5.0 weight % usually, the more suitable 2.0 weight % that are less than, the more suitable 1.0 weight % (based on the dry weight of alginate in the gel film) that are less than, but the influence of concrete visual other components of consumption, alginate the types and sources, and the operating position of chelating agen etc. and changing.The chelating agen that can add capacity is at utmost to reduce the above-mentioned polyvalent cation that adverse effect is arranged, as the dissolubility (with the activity of remnants) of calcium.

Alginate use (for example can increase the amount of the film-strength of gel film) with the film forming amount in the present invention, and it is different from the low alginate of trace, the character that the latter can not reinforcing membrane.Therefore, for instance, in gel film of the present invention, the alginate of film forming amount are the amounts that can increase the film-strength of whole film.According to application, this film forming amount is at least 0.25 weight % (based on the xerogel film) usually, is preferably 0.5-90 weight %, more is preferably 0.5-50 weight %, more is preferably 0.25-25 weight % (based on the xerogel film).

Gel film of the present invention is the homogeneous, thermoreversible film.Here used " homogeneous membrane " is meant such film, and when detecting by an unaided eye, film is uniformly, does not contain block, crack, should dissolve and undissolved granule, does not have insoluble granule skewness etc." flake " (liquid and solid admixture) or " glueballs " (non-homogeneous gel structure) do not meet the definition of used " homogenizing " here.

Gel film of the present invention is the homogeneous, thermoreversible gel film.

Here used " hot reversible film " is meant such film, and it has fusion temperature.Here used fusion temperature is meant temperature or the temperature range when gel film is softening or mobile.

Here used phrase " gel film " is meant the thin film that is formed by the structuring alginate.The feature of gel-forming composition is a gelation temperature, and fused materials must be cooled to could form self supporting structure below this temperature.Randomly, melt substance can heat be cast, cooling then, and by dry further thickened solid (controlledly removing moisture), up to forming gel film by gel combination.The fusion temperature of heat-convertible gel film is higher than its gelation temperature.

Gel film of the present invention comprises a kind of active substance.Can be included in active substance in the gel film and be selected from oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, toner, cosmetic composition, agricultural active thing, sweeting agent, flavoring agent, aromatic or the food at least a.

Homogeneous, thermoreversible gel film of the present invention can be chosen wantonly and comprise at least a in plasticizer, second film former, extender and the pH controlling agent.The component and the addition thereof that add in the gel film can change according to the required characteristics of alginate delivery system.

The example of this plasticizer comprises polyhydric alcohol, as glycerol, Sorbitol, maltose alcohol, lactose, fructose, corn starch, polydextrose, solubilisation oils and poly alkylene glycol, as Polyethylene Glycol and propylene glycol.The elasticity required according to delivery system, this plasticizer dosage generally account at least 5 weight % of all components that comprises water in the dry film, and at least 10 weight % are preferably at least 20 weight %, more are preferably at least 30 weight %.Described delivery system can not contain any plasticizer.

The example that can be used for second film former of the present invention comprises at least a in starch, starch hydrolysate (hydrozylate), starch derivatives, cellulose gum, hydrocolloid, alkyl cellulose ether or the modification alkyl cellulose ether.The example of hydrocolloid comprises at least a in the following material: the κ carrageenin; Kappa-2 carrageenan; The ι carrageenin; Mannan glue such as locust bean gum or guar gum comprise the low viscosity guar gum; Dextran; Pulullan polysaccharide; Gellan gum (gellan) (comprising high acyl group and low acyl group gellan gum); Pectin and they are without the form of fully modification and their combination.Here used kappa-2 carrageenan had 3: (3: 6AG-2S) with 3: (3: 6AG) mol ratio of content is 25-50% to the 6-Anhydrogalactose. to the anhydrous galactose of 6--2-sulfuric ester, the ι carrageenin had 3: 6AG-2S and 3: the mol ratio of 6AG content is 80-100%, the κ carrageenin had 3: 6AG-2S and 3: the mol ratio of 6AG content is less than kappa-2 carrageenan.For example, from the κ carrageenin of the prominent Eucheuma muricatum (Gmel.) Web.Van Bos. (Eucheuma cottonii) of κ carrageenin Sargassum commonly used source ear had 3: 6AG-2S and 3: the mol ratio of 6AG content is approximately less than 10%; From the ι carrageenin of ι carrageenin Sargassum source Eucheuma spinosum commonly used (Eucheuma spinosum) had 3: 6AG-2S and 3: the mol ratio of 6AG content is approximately greater than 85%.Kappa-2 carrageenan can derive from for example China fir algae (Gigartina skottsbergii).κ carrageenin, kappa-2 carrageenan and ι carrageenin differ from one another on 26S Proteasome Structure and Function.If desired with ι, κ or kappa-2 carrageenan as second film former, account in the 0.10M sodium chloride solution of solution gross weight 1.5% at the carrageenin of decrease in molecular weight, the viscosity of this carrageenin under 75 ℃ is 19cps or littler, and is more suitable less than 10cps.This viscosimetric analysis can use Brookfield LVF (Brookfield Engineering Laboratories, Inc.) viscometer carries out, and adopts the #1 spindle, rotating speed is 60rpm, changes 6 circle backs and measures viscosity.An example that can be used for alkyl cellulose ether of the present invention is a hydroxyethyl-cellulose.The example that can be used for modification alkyl cellulose ether of the present invention comprises hydroxypropyl cellulose and hydroxypropyl emthylcellulose.Should be noted that some second film former,, may comprise the cation that gelling properties and film-strength to carrageenin and/or alginate have positive influences and negative effect as carrageenin.This useful cation comprises potassium ion, magnesium ion and ammonium ion.These cationes can be present in the middle of the carrageenin, also can add from other organic or inorganic sources.These useful cationic content can account for below 20% of alginate dry weight in the gel film (comprising water).This content can change according to the component in the system and required fusing and seal temperature.

Other cationes can take place disadvantageous crosslinkedly with alginate as calcium (top once mentioned), aluminum and chromium ion, and/or the stability of carrageenin are had adverse effect, should make its content keep minimum, as be lower than 5% of the middle alginate dry weight of xerogel film (comprising water), and be lower than 2%, be lower than 1%.

Alginate can be the unique film former in the gel film.If gel film of the present invention comprises second film former, then the content of alginate can account at least 10 weight % of film former total amount in the xerogel film, at least 40 weight %, at least 60 weight %, or at least 80 weight %.

The example of extender comprises microcrystalline Cellulose, Microcrystalline Starch, modification and unmodified starch, starch derivatives, inulin, starch hydrolysate (hydrozylate), sugar, corn syrup and polydextrose.Used term " modified starch " comprises some starch like this in this description and claim, as hydroxypropyl starch, sour thinned starch etc.The example that can be used for modified starch of the present invention comprises Pure Cote ^TMB760, B790, B793, B795, M250 and M180, Pure-Dent ^TMB890 and Pure-Set ^TMB965 (all available from GrainProcessing Corporation, Muscantine, Iowa), and C AraTex ^TM75701 (available from Cerestar, Inc.).The example of starch hydrolysate (hydrozylate) comprises maltodextrin, also claims dextrin.Unmodified starch, as potato starch, when with the scope of the invention in hydrocolloid when being used in combination, also can increase film-strength.Usually, modified starch is that starch is handled the product that obtains, for example acid treated starches, enzyme treated starch, Oxytarch, crosslinked starch and other starch derivatives.Modified starch is preferably such derivant, and promptly side chain carries out modification with hydrophilic or hydrophobic group, forms the more complicated structure that has strong interaction between the side chain.

The consumption of extender accounts for the 0-20 weight % of dry film weight usually among the present invention, but if need, according to the purposes of delivery system, also available more amount for example is at least 20% of dry film, more is preferably at least 30%.Notice that starch, starch derivatives and starch hydrolysate can have multi-functional.That is to say that except being used as extender, they also can be used as second film former.If as the extender and second film former, their consumption accounts at least 10 weight % of xerogel film weight usually, is preferably at least 20 weight % like this.

The example that is used for pH controlling agent of the present invention comprises alkali such as hydroxide, carbonate, citrate and phosphate.The pH controlling agent can be used to improve the stability of gel film.Comprise the compositions of second film former for some, the pH controlling agent can be selected as useful cationic source, as potassium or ammonium.The consumption of pH controlling agent accounts for the 0-4 weight % of xerogel film, more is preferably 0-2 weight %.

Discover that the disruptive force of xerogel film of the present invention (for example containing 80% solid at least) is (for example) 250g, 1000g at least at least, at least 2500g, 4000g, 5000g at least at least, at least 6000g, available Texture Analyzer TA-108S Mini Film Test Rig measures.In addition, measurement shows, the disruptive force of desciccator diaphragm of the present invention surpasses 7000 and 8000g.

Discover that the solids content of film of the present invention accounts at least 50%, at least 60%, at least 70%, at least 80%, at least 90% of all components in the gel film.Be appreciated that and still have in the xerogel film nearly that 15%, 10%, 5% water is combined on the solid consumingly.

Gel film of the present invention also can comprise coloring agent and flavoring agent, as sugar, corn syrup, fructose, sucrose etc., and no matter whether have other components, as plasticizer, extender, second film former etc.A kind of embodiment of gel film of the present invention comprises alginate of the present invention, flavoring agent and water, forms high solids regimes, and for example solids content surpasses 50%, 60%, 65%, 75%, 80%, 85%, 90%.

Film of the present invention can comprise non-thermal reversibility natural gum.But for homogeneity and the thermal reversibility to gel film of the present invention not causes adverse effect, the content of this non-thermal reversibility film should be less than 50 weight % of alginate weight, should be less than 40 weight %, the more suitable 30 weight % that are less than.The example of this non-thermal reversibility natural gum comprises crosslinked and partial cross-linked natural gum, solidifies (for example crosslinked) pectin or alginate as calcium.If there is not bivalent cation, active alginate of calcium and pectin, and their refining poor slightly forms of degree can be considered as thermal reversibility glue.

Usually with such prepared, this process using can provide the equipment of sufficiently high shearing force, temperature (being higher than gelation temperature) and sufficiently long retention time to film of the present invention, and to obtain the homogenizing melt composition, the cooling back forms gel.This normally in equipment by compositions is heated, hydration, mixing, solubilising and the optional degassing finish.The example of this equipment has Ross blender, Stephan datatron, extruding machine, common jet boiler and fluid mixing apparatus shown in Figure 1.Ross blender, Stephan datatron and common jet boiler are easy to buy.Before cooling, fused mass can be sent at least one in pump, blender or the deaerator, as extruding machine.Notice that as another aspect of the present invention, fused mass needn't reach homogenizing at step (i).That is, when using other equipment such as blender, pump and/or exhaust chamber, melt composition can sent into blender, before or after at least one, obtain the homogenizing fused mass, in pump or the exhaust chamber as long as fused mass reaches homogenizing before gelling.The fused mass of extruding can be sent into film forming or former (for example spread-coating case), be beneficial to evenly cast successive film, perhaps send the fused mass of extruding to mould, so that directly form the extrusion material of film or shaping from the fused mass conveying equipment.Must be noted that, before the gel structure that flows in qualification/form begins, keep the state of fused mass.Can adopt adiabatic and preheating (in order to keep suitable temperature) delivery hose, guarantee that fused mass can flow, begin to carry out up to required gel film forming process.Can force (passing through pressure) fused mass by delivery hose above-mentioned with other processing methods (as preheating discharging/piston-like head (discharge/plunger-likehead), as in the Ross processing system, seeing).Other adiabatic measures also can help to keep the temperature of fused mass, as cover teflon sheet in melt surface immediately after removing mixing apparatus.Notice that as another aspect of the present invention, fused mass needn't reach complete homogenizing at step (i).That is, when using other equipment such as blender, pump and/or deaerator, melt composition can sent into blender, before or after at least one, obtain the homogenizing fused mass, in pump or the exhaust chamber as long as fused mass reaches homogenizing before gelling.

Here used " fluid mixing apparatus " is meant the equipment among Fig. 1.Figure 1 shows that fluid mixing apparatus 10.Fluid mixing apparatus 10 is used for mixed vapour 2 and first fluid or serosity 4 and second fluid or serosity 6, produces fused mass or mixed slurry 8.

Fluid mixing apparatus 10 comprises first Room 20, is furnished with in the chamber to allow first import 22 of steam 2 inlet chambers 20, and steam 2 is discharged the end 24 of the nozzle of chambers 20, is placed in nozzle valve or cadre 26 on the nozzle-end 24.Actuator 30 links to each other with first Room 20, in order to egress rate or the outlet pressure of control first fluid (steam) 2 at nozzle-end 24.Actuator 30 can be the type that Fisher Controls U.S.A. produces.

Fluid mixing apparatus 10 also comprises second mixing chamber 40, and it links to each other with first Room 20 at the nozzle-end 24 of first Room 20.Second Room 40 comprises to be allowed first fluid 4 enter second import 42 of second Room 40 and allows second fluid 6 enter the triple feed inlet 44 of second Room 40. Import 42 and 44 is positioned at the downstream of first import 22.As shown in Figure 1, second import 42 and triple feed inlet 44 are positioned at same plane, face each other each other diametrically, preferably for the central shaft Y of mixing apparatus 10 (promptly differing 180 °) fully relatively.Second Room 40 has constituted cylindrical circular generally mixing chamber 52, and it then constitutes the flow channel that extends along the shaft length direction of mixing chamber 52, from the inlet end 54 of mixing chamber 52, till the port of export 56 of chamber 52.Actuator 30 can make the nozzle valve 26 on the inlet end 54 move between sealing station and enable possition, to control the flow rate that steam 2 enters mixing chamber 52.

The nozzle end 24 of first Room 20 imports steam 2 inlet end 54 of mixing chamber 52.Second import 42 and triple feed inlet 44 radially import mixing chamber 52 with the first fluid 4 and second fluid 6 respectively.Steam 2, first fluid 4 and second fluid 6 mix in mixing chamber 52, form fused mass or mixture 8, come out from mixing chamber 52 then.Next, fused mass 8 can form molded article or form film, for example mixture 8 is cast on the drum cooler, perhaps allows mixture 8 pass through extruding machine.

Fluid mixing apparatus 10 is fit to preparation and is used for film forming mixture, particularly is used for preparing the edible film of edible delivery system.Generally inconsistent membrane component is placed in the different fluid air inlets, in the mixing chamber 52 of fluid mixing apparatus, these non-interfering components are run into together on the vapor injection interface immediately.Though Fig. 1 shows steam, first and second fluidic three imports, also can provide one or more imports again, use for one or more other fluids.The chamber 20,40 and the miscellaneous part of fluid mixing apparatus 10 should be by the high-class stainless steel manufacturings.

Also available gel film changes the stripping character of dosage form.For example, can add the component that can produce solid dosage forms in the gel film of the present invention, this dosage form have promptly release, intestinal is released or the ability of slow release." promptly release ", the definition of " slow release " and " intestinal is released " can find in American Pharmacopeia, draw at this to be reference.

Describe the present invention in more detail below by embodiment, but should be appreciated that the present invention is not subject to these embodiment.Except as otherwise noted, all part, percent, ratio etc. are all with regard to weight.

Embodiment

Except as otherwise noted, following processes is to be used for preparing and to measure material among the embodiment 1-3 and film.Stephan UMC5 datatron is the laboratory mixing apparatus, can be to carrying out suitable high speed shear mixing, heating and the degassing by the preparation of casting film in laboratory.Suitable batch processing scale is 1500g.

The aqueous dispersion for preparing starch like this: any salt/buffer agent and pH regulator agent are dissolved in the deionized water, add starch and/or maltodextrin (M100), mix, up to they dissolution.Pure Cote ^B760 starch can be available from Grain Processing Corporation, Muscatine, Iowa.Preparation hydrocolloid mixture in the StephanUMC5 datatron: the premixing plasticizer adds the dry hydrocolloid of premixing until evenly in batches, and each back that adds was with the speed stir about of 200rpm 30 seconds.Make plasticizer with Sorbitol Special and glycerol.Sorbitol Special is the aqueous solution of Sorbitol and sorbitan, and solids content is 76%, and by SPI Polyols, (New Castle DE) produces Inc..

In anhydrous hydrocolloid mixture, add starch dispersions, stirred 5 minutes with the speed of 300rpm.Mechanical agitation speed is increased to 2100rpm, under agitation mixture heated is arrived 85-95 ℃.After reaching target temperature, stirred the mixture 30 minutes, under continuous stirring, sample remained under the vacuum (50-60 crust) then 45 minutes.

After the retention time under vacuum and the target temperature finishes, sample is poured into through in 1 quart of Mason glass jar of wide-mouth of preheating.Record temperature and pH.Viscosity with the hot sample of Brookfield LVF viscometer determining.

Take out the fraction sample, cold preservation is spent the night, and (Gardco, Pompano Beach FL) measure gel/melt property and solids content to use Atago E series hand-held refractometer then.The gel of one fritter through cold preservation is placed on the wire stent, and support is fixed in the test tube, makes gel piece not reach test tube wall, measures the fusion temperature of gel thus.Cover test tube with aluminium foil, open an aperture on the aluminium foil, so that measure the temperature of gel with the digital temperature probe.Test tube is immersed in the heating bath, gel piece is in below about 100 ℃ hot bath surface.Be higher than 90 ℃ sample for fusion temperature, adopt silicone oil bath.Become wet when gel sample looks, when deliquescing also can be stirred, write down fusion temperature (writing down temperature range).Sample is fusing in a single day, and test tube is transferred in second beaker that cold running water (15 ℃) is housed.In the refrigerative process of sample, measure temperature with temperature probe, and the sample for reference surface, see whether sample begins gelling.Gelation temperature is that sample is no longer mobile when cooling, the temperature when popping one's head in the indenture that stabs out to fill up.

Next, hot sample is cast on 177mm * 177mm * 5mm metallic plate, is sprayed with PAM (lecithin) on the metallic plate in advance, to make things convenient for the moving film material with the scraper plate that has the 3mm broad gap.Cover the metallic plate of coating gel, in case the moisture loss in the cast membrane, and want cold preservation (being lower than 8 ℃) half an hour at least, film is taken off test then.Do not need cold preservation in the film forming process.Dry coating plate in 40 ℃ of blast furnaces, preparation desciccator diaphragm bar.Film reaches average solids content and is about 60% 40 ℃ of dryings 2 hours.If film, then generally obtains 80% or above solids content 40 ℃ of dried overnight.(about 20 ℃) working sample character except as otherwise noted, generally at room temperature.The percent solids of dry film is determined by the cast membrane of its solid preparation and the weight difference of dry film.Measure the disruptive force (BF) of cast membrane bar and dry film bar with Texture Analyzer TA-108S Mini Film Test Rig.

Except as otherwise noted, Maltrin M100 is available from Grain Processing Corporation, and PureCote B760 is available from Grain Processing Corporation, and Sorbitol Special is available from SPIPolyols, and glycerol is available from VWR (EP/USP level).

Embodiment 1

Table I has been listed composition and the character with the gel film of the mixture preparation of the low viscosity guar gum Edicol ULV 50 of sodium alginate and Indian Gum Industries Ltd. production.Protanal ^LFR5/60, Protanal ^LF20/40 and Protanal ^SF120 RB is available from FMC Corp. (Philadelphia, sodium alginate PA).

Table I

	Embodiment 1-1	Embodiment 1-2	Embodiment 1-3
				Component (g)
Water	836.3	836.3	836.3
				LFR5/60	40.5	0	0
LF20/40	0	40.5	0
				SF120 RB	0	0	30
Guar gum ULV 50	49.5	49.5	45
				Starch B760	220.8	220.8	220.8
M100	0	0	15.0
				Sorbitol SP	264.4	264.4	264.4
Glycerol	88.2	88.2	88.2
				Gross weight (g)	1500.0	1500.0	1500.0
Temperature (℃ *)	90	94	93
				Viscosity (mPas*)	31650	＞50000	＞50000
Gelation temperature, ℃	50	RT	RT
				Fusion temperature, ℃	70-71	95*	87*
pH	5.6	5.5	5.6
				Cast membrane
Solids content (estimation)	40％	40％	40％
				BF(g)	＜40	102	110
Dry film (2 hours, 40 ℃)
				Solids content (estimation)	60％	64％	67％
BF(g)	617	1250	1126
				Dry film (16 hours, 40 ℃)
Solids content (estimation)	80％	80％	94％
				Average film thickness (mm)	0.53	0.89	0.51
BF(g)	4780	7701	10850
				* fused mass the casting before temperature and viscosity

The molecular weight that increases sodium alginate is favourable to the structure of whole film, can improve film strength (embodiment 1-1,1-2 and 1-3).The listed fusion temperature of last table obtains by oil bath heating gel film.After being heated, they take place softening, can stir.During cooling, under the temperature more than the room temperature, just form gel.

Embodiment 2

Adopting two kinds of potassium alginate: KAHG is from the potassium salt of the alginic acid of Thallus Laminariae (Thallus Eckloniae) (Laminaria hyperborean) extraction, contains more guluronic acid (G) unit; KAHM is from the potassium salt of the alginic acid of Lessonia nigrescens extraction, contains more mannuronic acid (M) unit.Utilize 1% aqueous solution when measuring for 25 ℃, the viscosity of KAHG and KAHM is respectively 5cps and 12cps.

Help causing the process that κ carrageenin and/or kappa-2 carrageenan and alginate form homogenizing casting and cured film structure with the bonded potassium cationic of alginic acid root.The κ carrageenin is the clarified extract that obtains through alkali treatment from Kappaphycus alaverei (ear dash forward kylin algae (Eucheuma cottonii)).Bivalent cation content in all hydrocolloids that use is all lower, as shown in Table II.

Table II: cationic content in the hydrocolloid

Experiment	KAHG	KAHM	κCgn
				Viscosity
Mg％	0.07	0.12	0.09
				Ca％	0	0	0.06
K％	15.73	16.01	2.60
				Na％	0.63	0.59	5.45

Table III has been listed with potassium alginate and other film former, the composition and the characteristic of the film that the mixture of the low viscosity guar gum Edicol ULV 50 that produces as κ carrageenin and Indian Gum Industries forms.

The film that Table III prepares with low viscosity guar gum, potassium alginate and carrageenin

	Embodiment 2-1	Embodiment 2-2	Embodiment 2-3	Embodiment 2-4	Embodiment 2-5	Embodiment 2-6
							Component (g)
Water	836.3	836.3	836.3	836.3	836.3	836.3
							KAHG	60	60	40.5	10.5	0	0
KAHM	0	0	0	0	60.0	10.5
							κCgn	30.0	30.0	0	30.0	30.0	30.0
Guar gum	0	0	49.5	49.5	0	49.5
							Starch B760	220.8	220.8	220.8	220.8	220.8	220.8
Sorbitol SP	264.4	264.4	264.4	264.4	264.4	264.4
							Glycerol	88.2	88.2	88.2	88.2	88.2	88.2
Gross weight (g)	1500.0	1500.0	1500.0	1500.0	1500.0	1500.0
							Temperature (℃ *)	90	90	88	90	93	92
Viscosity (mPas*)	26500	28650	24800	28250	42650	31250
							Gelation temperature, ℃	42	41	50-51	53	39	55
Fusion temperature, ℃	60-65	62-67	60-61	70-74	60-63	65-69
							PH	7.6	7.2	6.3	5.6	7.4	5.9
Cast membrane
							Solids content (estimation)	40％	40％	40％	40％	38％	41％
BF(g)	＜40	＜40	＜40	188	＜40	185
							Dry film (2 hours, 40 ℃)
Solids content (estimation)	66％	62％	63％	64％	62％	66％
							BF(g)	370	248	445	1811	502	1265
Dry film (16 hours, 40 ℃)
							Solids content (estimation)	81％	79％	85％	80％	77％	80％
Average film thickness (mm)	0.83	0.76	0.56	0.60	0.56	0.59
							BF(g)	3826	4253	4144	7960	6918	8301
* fused mass the casting before temperature and viscosity

The result shows that no matter contain more mannuronic acid root or more guluronic acid root, perhaps the two is all more, after potassium alginate and κ carrageenin and the guar gum combination, can form favourable interaction.Further change the weight ratio of the alginate and second film former, change process conditions, can be used to be cast into highly filled (＞80%) fused mass equally, be shaped and refrigerative gel film, also can further process.

Embodiment 3

Table IV has been listed composition and the character with the gel film of propylene glycol alginate and the preparation of κ carrageenin.Protanal ^Ester BV4830 is a propylene glycol alginate, can available from FMC Corp. (Philadelphia, PA).HEC is a hydroxyethyl-cellulose.The κ carrageenin is as described in the top embodiment 2.

Table IV

Compositions based on the propylene glycol alginate mixture

	Embodiment 3-1	Embodiment 3-2	Embodiment 3-3
				Component (g)
Water	840.3	836.3	840.3
				BV4830	91.2	49.5	66.0
HEC	1.9
				κCgn	24	40.5	54.0
Potassium citrate	2.9
				Starch B760	207.8	220.8	207.8
Sorbitol SP	264.4	264.4	248.8
				Glycerol	88.2	88.2	83
Temperature (℃ *)	91	87	89
				Viscosity (mPa-s*)	24800	6550	12500
pH	4.2	3.8	3.9
				Gelation temperature, ℃	59	42-43	43-44
Fusion temperature, ℃	72-75	54-63	62-64
				Cast membrane
Solids content (estimation)	45％	38％	36％
				BF(g)	136	89	113
Dry film (16 hours, 40 ℃)
				Solids content (estimation)	87％	79.8	86.6
Average film thickness (mm)	0.72	0.68	0.79
				BF(g)	8838	5244	7638
* fused mass the casting before temperature and viscosity

Table V has been reported the composition and the film character of the film for preparing with propylene glycol alginate and potassium alginate with kappa-2 carrageenan.Kappa-2 carrageenan is from China fir algae (Gigartina skottsbergii) and Sarcothaliacrispata, is mainly monoploid (gametocyte) the plant mixture clarified extract that processing obtains through alkali.It also comprises about 10-20% (being equivalent to total amount) from the λ of diploid (tetrasporaphite) plant-and θ-carrageenin.

Table V

Alginate film with the kappa-2 carrageenan preparation

	Embodiment 3-4	Embodiment 3-5
			Component (g)
Water	834.7	834.7
			κ-2 Cgn	40.5	54.0
KAHG	31.5	36
			BV4830	18.0	36.0
M-100	227.3	227.3
			Sorbitol SP	272.2	272.2
Glycerol	90.8	90.8
			Temperature (℃ *)	87	84
Viscosity (mPas*)	4250	1050
			Solids content	40	37
Fusion temperature, ℃	77-78	74-79
			Gelation temperature, ℃	54	52
PH	4.8	5.5
			Cast membrane (estimation contains 40% solid)
BF(g)	142	168
			Dry film (estimation contains 80% solid, and 16 hours, 40 ℃)
Average film thickness (mm)	0.67	0.48
			BF(g)	3409	4004
* fused mass the casting before temperature and viscosity

In embodiment 3-4, potassium ion is provided by potassium alginate.Can form at carrageenin under the temperature of gel film structure, potassium ion can promote the double-stranded formation of carrageenin.In embodiment 3-5, intensity increase and the reason of processing viscosity degradation to be the content of propylene glycol alginate higher.

Table VI has been listed by hanging down compositions and the gel film that viscosity guar gum Edicol ULV 50 and propylene glycol alginate and other hydrocolloids form.Protanal ^Ester BV4830 and Protanal ^Ester SLF3 is a propylene glycol alginate, can be respectively available from FMC Corp. (Philadelphia, PA) and Kibum.The molecular weight of SLF-3 is less than BV-4830.HEC is a hydroxyethyl-cellulose.

Table VI

Film with propylene glycol alginate and guar gum preparation

	Embodiment 3-6	Embodiment 3-7	Embodiment 3-8	Embodiment 3-9
					Component (g)
Water	840.3	840.3	840.3	836.3
					BV4830	0	0	91.2	12.0
SLF-3	114	85.5	0	0
					HEC	2.4	1.8	1.9	0
κCgn	0	0	24	40.5
					Guar gum ULV 50	0	30	0	37.5
Starch B760	207.8	207.8	207.8	220.8
					M-100	0	0	0	0
Sodium citrate	3.6	2.7	0	0
					Potassium citrate	0	0	2.9	0
KCl	0	0	2.4	0
					Sorbitol SP	248.8	248.8	248.8	264.4
Glycerol	83	83.0	83.0	88.2
					Temperature (℃ *)	91	87	90	90
Viscosity (mPas*)	3250	16500	25000	23100
					Gelation temperature, ℃	34-35	34-38	43-46	46
Fusion temperature, ℃	58-60	62-64	56-62	60-68
					pH	4.4	4.5	4.3	4.6
Cast membrane
					Solids content (estimation)	39％	41％	45％	41.5％
BF(g)	＜40	＜40	231	147
					Dry film (2 hours, 40 ℃)
Solids content (estimation)	74％	65％	55％	60％
					BF(g)	1877	355	842	592
Dry film (16 hours, 40 ℃)
					Solids content (estimation)	85％	77％	78％	80％
Average film thickness (mm)	0.67	0.60	0.75	0.62
					BF(g)	4677	3317	9599	7214
* fused mass the casting before temperature and viscosity

Embodiment 4

Following examples have illustrated the film with fluid mixing apparatus preparation shown in Figure 3.In these embodiments, part A and part B respectively at room temperature from storage capsule separately as two strands independently logistics 4,6 pump into two different inlets 42,44, they are admitted to the fluid mixing apparatus 10 that injects steam from these two inlets.Independently join on the vapor interface of logistics 4,6 in the mixed zone 52 of fluid mixing apparatus 10 for two strands.Part A and part B solution separately pump into fluid mixing apparatus 10 easily and mix with steam 2.Steam 2 enters the mixed zone with the pressure of 120psi.Gained fused mass or mixed slurry 8 flow out from the outlet 56 of fluid mixing apparatus 10.Mixture 8 is poured on the smooth surface, pull into homogeneous membrane 9 downwards.

For measuring the viscosity of mixture 8,, pour in the jar from exporting the sample of the about 500ml mixture 8 of 56 collections.95 ℃ of temperature, pH and viscosity of measuring this sample.With Brookfield LVF viscometer determining viscosity.Adopt the combination of proper speed and spindle, but read off like this.Reading on the scale is converted to dynamic viscosity (cP)

For measuring film-strength and solids content, collect fused mass 8 from exporting 56, the scraper plate that is set at 3mm with the gap is cast on the corrosion resistant plate.Collect initial film 9 or " fresh film ".Several parts of fresh films 9 are put into 40 ℃ of draft furnaces, make fresh film 9 dryings.Measure the disruptive force of cast membrane bar and desciccator diaphragm bar with Texture Analyzer TA-108S Mini Film Test Rig.Measure the initial weight of fresh film and the final weight of desciccator diaphragm, determine percent solids by their difference.

For measuring gelation temperature, collect a part of fused mass 8 from the outlet 56 of mixing apparatus 10, put into test tube, it is empty that test tube has half.Glass-stem thermometer is inserted fused mass 8.Allow material 8 cool off at ambient temperature.Every cooling is once taken out thermometer from material 8.A slight temporary transient indenture is arranged on the surface of observing material 8, write down this temperature.Thermometer is inserted material 8 again, allow material further cool off.Every cooling was once just taken out thermometer, and then inserted, and formed permanent indenture on material 8, and promptly indenture can not be filled again.Temperature when record forms permanent indenture.The gelation temperature of being reported is the scope between two temperature that write down.

Table VII

The mixture that comprises PGA

Embodiment number	4-1	4-2	4-3	4-4	4-5
						Part A (%)
Component (gms)
						Carrageenin B κ-2	2.7	3.2	3.2	4.0	0.0
Carrageenin A κ	0.0	0.0	0.0	0.0	4.0
						PGA	3.3	3.9	3.9	4.9	4.9
Glycerol	22.4	26.5	26.5	33.5	33.5
Part B (%)
						KOH	0.0	0.0	0.1	0.0	0.0
K2CO3	0.0	0.0	0.0	0.3	0.3
						Starch	13.9	16.4	16.4	20.7	20.7
Water	57.8	50.0	49.9	36.6	36.6
The mixing chamber temperature (℃)	108	107	108	107	108
						Outlet temperature (℃)	102	102	102	101	102
Viscosity cP (95 ℃)	5500	4650	2200	12400	9400
						pH	4.1	4.2	8.7	6.3	6.8
The % solid	42	50	50	65	65
						Gelation temperature (℃)	35-40	Do not survey	Do not survey	58-66	63-71
Wet film intensity (gram)	60	117	3874	337	822
						Dry film intensity (gram)	2408	3069	4335	4561	4795

Table VII shows that film former can be a hydrocolloid, as the combination of carrageenin and PGA.In addition, can add the character that salt changes film, as intensity, gelation temperature and pH.

Following Table VIII and IX have further described component described in the foregoing description.

Table VIII

Description to component

Title	Trade name	Supplier	Describe
				Propylene glycol alginate (PGA)	Protanal BV 4830	FMC BioPolymer
Glycerol		Callahan Chemical	99.70％
				Starch	Pure-Cote B790	Grain Processing Corporation

Following table IX has described the used various carrageenin of present embodiment.

Table I X

Description to carrageenin

Labelling	The carrageenin type	Describe	Supplier
				Carrageenin A	κ	Through the clarification κ carrageenin extract that alkali treatment obtains, bivalence content is low from Kappaphycus alverezii (ear dash forward Eucheuma muricatum (Gmel.) Web.Van Bos.)	FMC Corp.
Carrageenin B	κ-2	Be mainly the low bivalence extract of monoploid (gametocyte) the plant mixture clarification that processing obtains through alkali from China fir algae and Sarcothalia crispata, this extract often is called " kappa-2 carrageenan ".Also comprise λ and the θ carrageenin of about 10-20% (total amount) from diploid (tetrasporaphite) plant.Be defined as κ carrageenin and ι carrageenin in 1.0-3.0: the natural statistic copolymer that 1 ratio forms, compare by the mixture that same ratio mixes with ι carrageenin natural polymer with independent κ, it has visibly different function.	FMC Corp.

Embodiment 5

Transport membrane of the present invention prepares in order to the below method: alginate and κ carrageenin dry blending are formed gum mixture.KAHG and NAHG are respectively from the potassium salt and the sodium salt of the alginic acid of Laminaria hyperborean extraction, have higher guluronic acid (G) unit horizontal.KAHM is the alginic acid potassium salt that extracts from Lessonia nigrescens, has higher mannuronic acid (M) unit horizontal.In 1% aqueous solution, when measuring for 25 ℃, 1% solution viscosity of KAHG and KAHM is respectively 5cP and 12cP.(Grain Processing Corporation, Muscatine is Iowa) with the gum mixture dry blending for maltodextrin Maltrin M 100.In 1.2 liters of rustless steel beakers, quantitatively add deionized water and glycerol.Under fully stirring, dry pre-composition is added in the entry, be heated to 90 ℃ then, and in 90-95 ℃ of scope, kept 15 minutes, so that fully hydration of natural gum.After replenishing the water that loses because of evaporation, add and carry composition, stir 2 minutes to disperse.The conveying composition that is used to test has: (1) natural and artificial strawberry flavor (Dragoco, 0.1%), (2) titanium dioxide, (3) caffeine.Pour hot solution into container fast.With the solution cool to room temperature that casts in the culture dish, form film, dried overnight in 45 ℃ of blast furnaces then is to reach constant weight.With the sample cooling, cold preservation then (being lower than 8 ℃) is spent the night, and (Gardco, Pompano Beach FL) measure gel/melt property and solids content to reuse Atago E series hand-held refractometer.The gel of one fritter through cold preservation is placed on the wire stent, and support is fixed in the test tube, makes gel piece not reach test tube wall, measures the fusion temperature of gel thus.Cover test tube with aluminium foil, open an aperture on the aluminium foil, so that measure the temperature of gel with the digital temperature probe.Test tube is immersed in the heating bath, gel piece is in below about 100 ℃ hot bath surface.Be higher than 90 ℃ sample for fusion temperature, adopt silicone oil bath.Become wet when gel sample looks, when deliquescing also can be stirred, write down fusion temperature (writing down temperature range).Sample is fusing in a single day, and test tube is transferred in second beaker that cold running water (15 ℃) is housed.In the refrigerative process of sample, measure temperature with temperature probe, and the sample for reference surface, see whether sample begins gelling.Gelation temperature is that sample can't flow in refrigerative process again, the temperature in the time of the indenture that stabs out with probe can not being filled out.Measure the disruptive force (BF) and the penetrating value of cast membrane bar and dry film bar with TextureAnalyzer TA-108S Mini Film Test Rig.Disruptive force just can calculate hardness divided by penetrating value.

Table X I

The alginate delivery system

Component (g)
							NAHG	1.65	0.00	1.65	0.00	0.00	0.00
KAHG	0.00	1.65	0.00	1.65	1.65	0.00
							KAHM	0.00	0.00	0.00	0.00	0.00	1.65
κCgn	1.25	1.25	1.25	1.25	1.25	1.25
							Maltodextrin	7.00	7.00	7.00	7.00	10.00	10.00
Water	80.00	80.00	80.00	80.00	80.00	80.00
							Glycerol	6.70	6.70	6.70	6.70	6.70	6.70
Spice	3.30	3.30	0.00	0.00	0.00	0.00
							TiO 2	0.00	0.00	3.30	3.30	0.00	0.00
Caffeine	0.00	0.00	0.00	0.00	0.30	0.30
							Cast membrane
Solids content	～22％	～22％	～22％	～22％	～22％	～22％
							BF(g)	190	2075	197	1562	1986	1686
Penetrate (cm)	0.4	0.3	0.4	0.3	0.4	0.3
							Hardness	476	6916	492	5036	4966	5620
Dry film
							BF(g)	8775	14549	8926	7551	11600	9453
Penetrate cm	1.3	1.1	1.7	1.2	1.3	1.1

Though describe the present invention in detail, it will be apparent to those skilled in the art that and under the prerequisite that does not deviate from purport of the present invention and scope, can make various changes and modifications in conjunction with the specific embodiment.

Claims

(according to the modification of the 19th of treaty)

12. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 2500g at least.

13. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 4000g at least.

14. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 5000g at least.

15. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 6000g at least.

16. prepare the method for the described homogeneous gel film of claim 1-15 delivery system, it comprises the steps:

(i) in the equipment that enough shearing forces, temperature and retention time are provided to described alginate, and heating of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent, hydration, mixing, dissolving and the optional degassing, form the homogenizing melt composition, wherein said temperature is equal to or higher than the solution temperature of described compositions;

The active substance that (ii) before or after forming melt composition, adds effective dose;

(iii) cooling contain described active substance described melt composition to being equal to or less than its gelation temperature, form the described gel film that contains described active substance.

17. method as claimed in claim 16, it is characterized in that described active substance is at least a in oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, cosmetic composition, agricultural active composition, coloring agent, sweeting agent, flavoring agent, spice or the food.

18. method as claimed in claim 16 is characterized in that, described equipment is the Ross blender, extruding machine, Stephan datatron, jet boiler or fluid mixing apparatus.

19. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 250g at least.

20. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 1000g at least.

21. delivery system as claimed in claim 1, described system also comprises flavoring agent, and solids content is at least 50%.

22. delivery system as claimed in claim 1, it is characterized in that, described second film former is a kind of carrageenin, when in the 0.10 mole nacl aqueous solution that contains based on 1.5% described carrageenin of all components weight of described solution, measuring, described carrageenin 75 ℃ viscosity less than 10 cp.

23. delivery system as claimed in claim 1 is characterized in that, described gel film is plasticizer-containing not.

24. delivery system as claimed in claim 1, it is made up of described water-soluble reversible alginate hot in nature, extender, active substance and water.

25. the described delivery system of claim 24 is characterized in that described extender is a corn syrup.

Claims (22)

1. the delivery system that comprises the gel film of homogeneous, thermoreversible, wherein said gel film comprises: (i) the reversible alginate water-soluble hot in nature of film forming amount, and choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent; (ii) active substance.

2. delivery system as claimed in claim 1, it is characterized in that described active substance is at least a in oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, cosmetic composition, agricultural active composition, vitamin, mineral, coloring agent, sweeting agent, flavoring agent, spice or the food.

3. delivery system as claimed in claim 1 is characterized in that the content of described alginate accounts at least 0.25% of gel film dry weight.

4. delivery system as claimed in claim 1 is characterized in that the content of described alginate accounts for the 0.25%-25% of gel film dry weight.

5. delivery system as claimed in claim 1 is characterized in that, the content of described alginate accounts at least 10% of film former gross dry weight in the gel film.

6. delivery system as claimed in claim 1 is characterized in that, the content of described alginate accounts at least 40% of film former gross dry weight in the gel film.

7. delivery system as claimed in claim 1 is characterized in that, the content of described alginate accounts at least 60% of film former gross dry weight in the gel film.

8. delivery system as claimed in claim 1 is characterized in that, the content of described alginate accounts at least 80% of film former gross dry weight in the gel film.

9. delivery system as claimed in claim 1 is characterized in that, described alginate are the unique film former in the gel film.

10. delivery system as claimed in claim 1, it is characterized in that described second film former is selected from starch, starch derivatives, starch hydrolysate, cellulose gum, κ carrageenin, ι carrageenin, mannan glue, dextran, pulullan polysaccharide, gellan gum, pectin, alkyl cellulose ether and modification alkyl cellulose ether.

11. delivery system as claimed in claim 1, it is characterized in that, described plasticizer is selected from glycerol, Sorbitol, maltose alcohol, lactose, solubilisation oils and the poly alkylene glycol a kind of at least, and described second film former is selected from starch, starch derivatives, starch hydrolysate, cellulose gum, κ carrageenin, ι carrageenin, mannan glue, dextran, pulullan polysaccharide, gellan gum, pectin, alkyl cellulose ether and the modification alkyl cellulose ether a kind of at least; Described extender is selected from a kind of in microcrystalline Cellulose, Microcrystalline Starch, starch, starch derivatives, inulin and the starch hydrolysate at least.

12. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 2500g at least.

13. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 4000g at least.

14. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 5000g at least.

15. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 6000g at least.

16. prepare the method for the described homogeneous gel film of claim 1-15 delivery system, it comprises the steps:

(i) in the equipment that enough shearing forces, temperature and retention time are provided to described alginate, and heating of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent, hydration, mixing, dissolving and the optional degassing, form the homogenizing melt composition, wherein said temperature is equal to or higher than the solution temperature of described compositions;

The active substance that (ii) before or after forming melt composition, adds effective dose;

(iii) cooling contain described active substance described melt composition to being equal to or less than its gelation temperature, form the described gel film that contains described active substance.

17. method as claimed in claim 16, it is characterized in that described active substance is at least a in oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, cosmetic composition, agricultural active composition, coloring agent, sweeting agent, flavoring agent, spice or the food.

18. method as claimed in claim 16 is characterized in that, described equipment is the Ross blender, extruding machine, Stephan datatron, jet boiler or fluid mixing apparatus.

19. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 250g at least.

20. delivery system as claimed in claim 1 is characterized in that, it has the disruptive force intensity of 1000g at least.

21. delivery system as claimed in claim 1, described system also comprises flavoring agent, and solids content is at least 50%.

22. delivery system as claimed in claim 1, it is characterized in that, described second film former is a kind of carrageenin, when in the 0.10 mole nacl aqueous solution that contains based on 1.5% described carrageenin of all components weight of described solution, measuring, described carrageenin 75 ℃ viscosity less than 10cp.

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