CN1791382A - Process for making gel films - Google Patents
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- CN1791382A CN1791382A CN 200480013903 CN200480013903A CN1791382A CN 1791382 A CN1791382 A CN 1791382A CN 200480013903 CN200480013903 CN 200480013903 CN 200480013903 A CN200480013903 A CN 200480013903A CN 1791382 A CN1791382 A CN 1791382A
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Abstract
The present invention is directed to a process for making homogeneous, thermoreversible gel films comprising the steps of: (i) heating, hydrating, mixing, solubilizing, and, optionally, de-aerating a high solids, low moisture film forming composition in an apparatus providing sufficient shear, temperature and residence time to form a homogeneous molten composition, wherein the temperature is at or above the solubilizing temperature of said composition; (ii) feeding the molten composition into at least one of a mixer, pump or devolatilizer; and (iii) cooling the homogeneous molten composition at or below its gelling temperature to form said gel films. The present invention is also directed to various products made from such films, such as the gel films themselves, soft capsules, solid dosage forms and delivery systems.
Description
Related application
The application requires to be registered in the U.S. Provisional Application 60/462785 on April 14th, 2003; 60/462721; 60/462758; 60/462617; 60/462793; 60/462783; 60/462792; 60/462794 rights and interests.
Technical field
The present invention relates to prepare homogenizing, hot reversible gel film method, this method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form the melt composition of homogenizing, wherein temperature is equal to or higher than the solution temperature of described compositions; (ii) with in melt composition input mixer, pump or the exhaust chamber at least one; The melt composition of described homogenizing is cooled to is equal to or less than its gelation temperature, form described gel film.The invention still further relates to the various products of making by this film, as gel film itself, soft capsule, solid dosage forms and delivery system.
Background technology
Known, some for example contain that the low-moisture film-forming composition of high solid of hydrocolloid can form full-bodied solution, and this solution is difficult to obtain hydrated film.The invention provides a kind of method for preparing high solid, low moisture film by such high viscosity solution.
In addition, many people once attempted preparing soft capsule with solids content height, film that moisture is few as hydrocolloid.But the effort of these preparation soft capsules has all run into the problems referred to above.That is to say that hydrocolloid is known to form high-viscous solution, this solution is difficult to abundant hydration formation film in conventional soft capsule preparation method.Therefore, the inventive method is considered with this film preparation soft capsule.
Summary of the invention
As first kind of embodiment, relate to homogenizing, the hot reversible gel film method of preparation, this method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form the melt composition of homogenizing, wherein temperature is equal to or higher than the solution temperature of described compositions; (ii) with in melt composition input mixer, pump or the exhaust chamber at least one; The melt composition of described homogenizing is cooled to is equal to or less than its gelation temperature, form described gel film.
As second kind of embodiment, the present invention relates to homogenizing, hot reversible gel film by method for preparing.
As the third embodiment, the present invention relates to make the method for soft capsule, described method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form the melt composition of homogenizing, wherein temperature is equal to or higher than the solution temperature of described melt composition; (ii) with in melt composition input mixer, pump or the exhaust chamber at least one; The melt composition of described homogenizing is cooled to is equal to or less than its gelation temperature, form homogenizing, hot reversible film; (iv) gel film is made soft capsule thus.
As the 4th kind of embodiment, the present invention relates to the soft capsule that adopts said method to make.
As the 5th kind of embodiment, the present invention relates to make the method for the solid dosage forms of the packing material of being sealed by reversible gel film homogenizing, hot, described method comprises the steps: that (i) prepares reversible gel film homogenizing, hot according to the method described above; (ii) packing material is encapsulated in this gel film.The invention still further relates to the solid dosage forms of making by this method.
As the 6th kind of embodiment, the present invention relates to make the method for the gel film delivery system that comprises homogenizing active substance and homogenizing, hot reversible gel film, described method comprises the steps: that (i) prepares melt composition as stated above; The active substance that (ii) before or after forming this melt composition, adds effective dose; The melt composition that (iii) will contain active substance is cooled to and is equal to or less than its gelation temperature, forms the gel film that comprises active substance.The invention still further relates to the delivery system that adopts this method to make.
As the 7th kind of embodiment, the present invention relates to make method homogenizing, hot reversible gel film, this method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form the melt composition of homogenizing, wherein temperature is equal to or higher than the solution temperature of described compositions; The melt composition of described homogenizing is cooled to is equal to or less than its gelation temperature, form described gel film.The invention still further relates to the dosage form, solid dosage forms and the delivery system that adopt this method to make.
Description of drawings
Fig. 1 implements the sketch map that the present invention prepares the method for film and soft capsule together with Stephan processor and extruding machine.Extruding machine is chosen wantonly in the figure, and the Stephan processor can be substituted as the Ross blender.In addition, though this figure relates to " LV guar gum " (low viscosity guar gum), the invention is not restricted to this.
Fig. 2 implements the sketch map that the present invention prepares the method for film and soft capsule with fluid mixing apparatus shown in Figure 3 and extruding machine.Extruding machine is chosen wantonly among this figure.
Fig. 3 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 Fig. 2 method to mix with steam.
Fig. 4 is the another kind of form of Fig. 2 sketch map, shows that film comes out from extruding machine, is just entering capsule envelope equipment.
The specific embodiment
First kind of embodiment of the present invention relates to preparation method homogenizing, hot reversible gel film, this method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form melt composition, wherein temperature is equal to or higher than the solution temperature of described melt composition; (ii) with in melt composition input mixer, pump or the exhaust chamber at least one; Described melt composition is cooled to is equal to or less than its gelation temperature, form described gel film.
The inventive method provides to be had as reversible gel film highly filled relatively homogenizing, hot.
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 homogenizing, hot reversible gel film.They can be cast, and have extensive use as cast membrane, perhaps are used for further processing.
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 hydrocolloid.The gel-forming composition feature is to have gelation temperature, and fused gel combination 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 the reversible gel film of heat is higher than its gelation temperature.
Temperature when used here " solution temperature " refers to that compositions becomes even.Dissolving refers to that all soluble components dissolve fully in the melt composition, the insoluble material homodisperse of separating.
Component in the film-forming system can form high solid low moisture gel film in the time of can being heating and hydration, and can form any component in film-forming composition homogenizing, hot reversible gel film.For example, such compositions can comprise hot reversible hydrocolloid.
The hot reversible hydrocolloid that is used for forming hot reversible gel film among the present invention comprises polysaccharide, and for example, carrageenin comprises ι carrageenin, κ carrageenin, kappa-2 carrageenan; Xanthan gum; Polymanna glue (polymannan) (as Portugal's polymanna glue and gala polymanna glue) is as locust bean gum, Rhizoma amorphophalli, Caesalpinia spinosaKuntze (tara) glue, cassia gum, guar gum (as the low viscosity guar gum); Alginate comprise monovalent salt such as the potassium and the sodium salt of propylene glycol alginate and alginic acid; Pulullan polysaccharide (pullulan); Gellan gum (gellan) (comprising high acyl group and low acyl group gellan gum); Dextran; Pectin and their combination.Carrageenin can modification, and the degree of modification is low fully, perhaps non-modified.Here used, the 3:6-Anhydrogalactose. of kappa-2 carrageenan-2-sulfuric ester (3:6AG-2S) is 25-50% with the mol ratio of 3:6-Anhydrogalactose. (3:6AG) content, the mol ratio of the 3:6AG-2S of ι carrageenin and 3:6AG content is 80-100%, and the mol ratio of the 3:6AG-2S of κ carrageenin and 3:6AG content is less than kappa-2 carrageenan.For example, from the mol ratio of the 3:6AG2-S of the κ carrageenin of Eucheuma cottonii (the ear Eucheuma muricatum (Gmel.) Web.Van Bos. that dashes forward, known usually Sargassum source) and 3:6AG content as the κ carrageenin less than about 10%; From the mol ratio of the 3:6AG2-S of the ι carrageenin of Spinosum (usually known Sargassum source) and 3:6AG content as the ι carrageenin greater than about 85%.The mol ratio that this means κ (3:6-AG) repetitive that kappa-2 carrageenan comprises and ι (3:6-AG-2-S) repetitive was preferably 1.5 to 3.0: 1 (better depending on required application) at 1.0 to 3.0: 1.The mol ratio that keeps 3:6AG-2S and 3:6AG content in these carrageenin, and irrelevant with the content of its modification degree and precursor (as μ and ν repetitive).
The homogenizing of the inventive method preparation, hot reversible gel film can be according to required purposes, optionally comprises at least a in plasticizer, second film former, extender and the pH controlling agent.
The example of this plasticizer comprises polyhydric alcohol, as glycerol, Sorbitol, maltose alcohol, lactose, corn starch, fructose, polydextrose, dissolved oil and poly alkylene glycol, as Polyethylene Glycol and propylene glycol.For example, the higher gel film of elasticity if desired for example is used for preparing the film of soft capsule, this plasticizer dosage generally accounts at least 5 weight % of all components that comprises water in the dry film, at least 10 weight % are preferably at least 20 weight %, more are preferably at least 30 weight %.Use for other, for example the elasticity to film requires lower hard capsule, and the content of plasticizer can account for the 0-20 weight % of all components weight in the dry film.Gel film of the present invention also can not contain any plasticizer.If desired, when using ι carrageenin, κ carrageenin or kappa-2 carrageenan as hydrocolloid, such carrageenin, with the composition total weight is benchmark, in containing 0.10 mole nacl solution of 1.5% these carrageenin, 75 ℃ viscosity for being less than or equal to 19cp, better less than 10cp.This viscosity test adopts Brookfield LVF, and (Brookfield EngineeringLaboratories, Inc) viscometer adopt the #1 spindle, and rotating speed is 60rpm, change 6 circle backs and measure viscosity.
The example that can be used for second film former of the present invention comprises in starch, starch derivatives, starch hydrolysate (hydrozylate), cellulose gum, hydrocolloid, alkyl cellulose ether or the modification alkyl cellulose ether at least a.The example of hydrocolloid is those that list above.Other comprise non-agglomerative carrageenin such as λ carrageenin.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.Main film former can be a film former unique in the gel film.When gel film of the present invention contains second film former, main film forming dosage can be in the gel film film former gross weight at least 10%, at least 40%, at least 60%, or at least 80%.
The example of extender comprises microcrystalline Cellulose, Microcrystalline Starch, modification and unmodified starch, starch derivatives, inulin, starch hydrolysate, 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 Grain ProcessingCorporation, Muscatine, 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 carried out the product that chemical treatment 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 application, 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 solubilizing agent and second film former, their consumption accounts at least 10 weight % of gel film weight usually, is preferably at least 20 weight % like this.
The example that is used for pH controlling agent of the present invention be can choose wantonly and alkali such as hydroxide, carbonate, citrate and phosphate comprised.The pH controlling agent can be selected as useful cationic source, as potassium.To some compositions, the pH controlling agent can be used to improve the stability of gel film.The consumption of pH controlling agent accounts for 0-4%, more is preferably 0-2%.
Discover that the disruptive force of the film formed xerogel film of gel of the present invention is (for example) 1000g at least, 2500g at least, 4000g at least, 5000g at least, 6000g at least, available Texture AnalyzerTA-108S Mini Film Test Rig measures.In some situation, adopt the wet film of the inventive method preparation to produce low disruptive force intensity (as 250-320g), but can produce strong dry film with above-mentioned disruptive force intensity.
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 gel film nearly that 15%, 10%, 5% water is combined on the solid of gel film consumingly.
The thickness of desciccator diaphragm that is used for soft capsule is usually between 0.5-3.0mm, and is more suitable between 0.8 1 1.2mm.
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 natural gum film should be less than 50 weight % of hot reversible film former 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 or partial cross-linked natural gum, solidifies (for example crosslinked) pectin and/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 natural gum.
Usually with such prepared, this process using can provide the equipment of sufficiently high shearing force, temperature (being higher than gelation temperature) and the sufficiently long time of staying to gel film of the present invention, and to obtain the melt composition of homogenizing, the cooling back forms gel.By to compositions heating, hydration, mixing, dissolving and the optional degassing, this can finish in this equipment.This equipment includes but not limited to Ross blender, Stephan datatron, common jet boiler, extruding machine and fluid mixing apparatus shown in Figure 3.Ross blender, Stephan datatron, extruding machine and common high compressed steam pot are easy to buy.Before cooling, fused mass can be sent at least one in pump, blender or the exhaust chamber.The example that can finish the equipment of any one in these functions is an extruding machine.The fused mass of extruding can be sent into film forming or former (for example spread-coating case, as be used in the capsule forming machine), be beneficial to evenly cast continuous film, perhaps send extrusion melt to mould, so that from the fused mass conveying equipment, directly form film.Must be noted that, limit to flow/before gel structure begins to form, 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, become on the film spot at casting roll or other up to required gel film forming process, as beginning to carry out on extruding machine (restricted mobile, film-forming apparatus) or the mould.Can force (passing through pressure) fused mass by delivery hose above-mentioned with other processing methods (as preheating discharging/piston-like head (discharge/plunger-like head), 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.In addition, fused mass charging (casting) case that feed hose can be packed into and be arranged in the thermal control on the capsule machine, directly pack in the case, choose wantonly material feeding box is transformed, surround/cover the first half, to help in the process that continues formation capsule film, keep temperature, the minimizing moisture loss of fused mass in the material feeding box and guarantee evenly (at the center) material feeding in case.Should be appreciated that and to keep melt temperature with additive method, to form the capsule film.This includes but not limited to by mould/hole fused mass is extruded into film, it can directly be sent into film and form capsular equipment, perhaps be kept under the temperature that to keep suitable membrane stage (to form capsule) when needs, perhaps be dried to desired moisture content, solids content and structure level, utilize up to needs.This desciccator diaphragm has the character (can introduce water by any method) that absorbs moisture in its whole gel film matrix again, can be as required, and for example rehydrated in preparation soft capsule or other solid dosage formss.In film, introduce moisture,, so just film can be sent into capsule machine, the preparation soft capsule up to reaching desired moisture content and intensity/structural property.
When using Stephan datatron or common jet steam pot, use the conventional method of hydrocolloid as follows.To uniform temperature, component is dissolved being higher than under its gelation temperature the component of film-forming composition input Stephan datatron and heating (stirring simultaneously).Then, described materials processing is become gel film or as fused mass.With suitable device this material is further processed, formed its last form.
Here used " fluid mixing apparatus " is meant the equipment among Fig. 3.Figure 3 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.
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.
After making melt composition, remain on and be equal to or higher than solution temperature, then fused mass is directly sent in pump, blender or the exhaust chamber at least one.Then, fused mass is cooled to the gelation temperature of compositions or is lower than this temperature, form gel film.
Preferably, under atmospheric pressure solution temperature is higher than the boiling point of the melt composition of homogenizing, can be higher than under the atmospheric pressure heat, hydration, mixing and dissolving.
Preferable methods comprises directly sends melt composition into blender, outgases at the gelation temperature that is cooled to melt composition or before being lower than this temperature, decompression and pumping.
A kind ofly comprise that equipment at least a in pump, blender and the exhaust chamber is extruding machine.Extruding machine is to be used for removing volatile matter before cooling, thus the preferred equipment of concentration, smelting composition solid.
The extruding machine that uses among the present invention comprises monotubular or bitubular extruding machine, and inlet device is arranged, and can transmit complete hydration or partially hydrated compositions, and does not have temperature to descend during transmitting.Composition material reaches its target solids content, and after temperature was kept above its gelation temperature, the fused mass of formation can be according to use noted earlier.
Another aspect of the present invention notices that fused mass needn't reach homogenizing in step (i).That is, melt composition blender can be sent into, before or after at least one, the fused mass of homogenizing can be obtained in pump or the exhaust chamber, as long as fused mass reaches homogenizing before gelling.
Have as 2500g dry film intensity at least because gel film of the present invention shows, so their are fit to various application.For example, such gel film can be used to prepare soft capsule.Therefore, as second kind of embodiment, the present invention relates to make the method for soft capsule, this method comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form melt composition, wherein temperature is equal to or higher than the solution temperature of described fused mass; (ii) melt composition is imported extruding machine, form high solid, low moisture, homogenizing, hot reversible gel film; (iii) prepare soft capsule by described gel film.Gel film and its component, and the equipment and the extruding machine that use are all as described above.
The method that the present invention makes soft capsule is used any conventional packaging apparatus after being included in and making above-mentioned gel film, as, conventional rotating mould equipment or concave surface stamping die.For example, in case make fused mass of the present invention, it is cast on the drum, cooling is sent into rotation then and is sealed between the mould, to film reheat, filling, sealing and cutting.Be described in more detail in 98/42294 pair of this conventional method of WO.Perhaps, be better than the advantage of conventional soft capsule method, use above-mentioned High shear device that fused mass is being cooled as the present invention, when sending into the conventional packaging apparatus of filling, sealing and cut then, fully hydration, extrusion molding, be applied on the drum.Adopt this continuous method can eliminate to being used to prepare the step of capsular complete gelation and refrigerative film reheat.
Other of gel film of the present invention are used also to relate to and are comprised the preparation method of being sealed the solid dosage forms of packing material by reversible gel film homogenizing of the present invention, hot.One type of described solid dosage forms is hard capsule.Here used hard capsule is meant those solid dosage formss that (for example) medical industry is commonly used.On medical industry, form two half-shells earlier, the packing material that is generally powder type is put in the shell, the two halves shell is incorporated into together, form hard capsule.Preparing the step that the method for this hard capsule is usually directed to is, pin or bar are immersed melt composition of the present invention, forms gel film around pin, and the desiccant gel film takes off them then from pin.These processes are industrial hard capsule preparation methoies of knowing.The packing material of hard capsule can be any packing material that is usually used in this dosage form.Usually, packing material can be a liquid, can be solid also, as powder.Packing material can be ingredient, agricultural composition, nutritional labeling, composition for animals, food, cosmetics, flavoring agent etc.
The also available known technology of solid dosage forms is sealed powder, tablet, capsule sheet, microcapsule or capsule.For example, seal sealingly secure/anti-damage ability that hard capsule can strengthen product with gel film of the present invention.
Also available gel film changes the stripping character of dosage form.For example, can add the component that can form special solid dosage forms in the gel film of the present invention, the ability that this dosage form has release immediately, sustained release, intestinal release or delays to discharge." release immediately ", " delaying to discharge " and the definition of " intestinal release " can be found in American Pharmacopeia, draw at this to be reference.
In addition, gel film of the present invention can be used for preparing the method for the gel film delivery system that comprises homogenizing active substance and homogenizing, hot reversible gel film, and this method comprises the steps: (i) preparation melt composition; The active substance that (ii) adds effective dose therein; (iii) cooling contain active substance melt composition to its gelation temperature or be lower than this gelation temperature, form the described gel film that contains active substance.Active substance comprises at least a oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, toner, sweeting agent, flavoring agent, aromatic, food.
Method homogenizing, hot reversible gel film that the present invention makes also comprise the steps: (i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heat, hydration, mixing, dissolving and the optional degassing, form the melt composition of homogenizing, wherein temperature is equal to or higher than the solution temperature of described compositions; (ii) the melt composition with homogenizing is cooled to its gelation temperature or is lower than this gelation temperature, forms described gel film.This method can be used to prepare dosage form recited above, solid dosage forms and delivery system.The equipment that is particularly suitable for this method is the Ross blender, when preparing soft or hard capsule, can be used for directly providing gel film to the capsule manufacturing equipment, if desired, offers the roller that uses in the back.All materials described herein all can be used for this method.
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
Following examples explanation prepares gel film of the present invention with fluid mixing apparatus shown in Figure 3.In this embodiment, part A and part B respectively at room temperature from storage capsule separately as two strands independently logistics 4,6 enter two different inlets 42,44, logistics can be expelled to the fluid mixing apparatus 10 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, pulls 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 blast 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.Half of test tube is empty.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 of two temperature of record.The component of listing in the table will further define at table 5 and table 6 below.
Table 1
The mixture that contains carrageenin
| The embodiment numbering | 1A | 1B | 1C | 1D | 1E |
| Part A (%) | |||||
| Carrageenin D | 0.0 | 0.0 | 0.0 | 0.0 | 8.9 |
| Carrageenin C | 7.0 | 8.4 | 8.9 | 0.0 | 0.0 |
| Carrageenin B | 0.0 | 0.0 | 0.0 | 8.9 | 0.0 |
| Glycerol | 26.5 | 31.8 | 33.5 | 33.5 | 33.5 |
| Part B (%) | |||||
| Starch | 16.4 | 19.7 | 20.7 | 20.7 | 20.7 |
| Water | 50.0 | 40.0 | 36.9 | 36.9 | 36.9 |
| The mixing chamber temperature (℃) | 107 | 107 | 108 | 108 | 108 |
| Outlet temperature (℃) | 101 | 102 | 102 | 102 | 102 |
| Viscosity, cP (95 ℃) | 7300 | 5200 | 48000 | 50000 | 12400 |
| pH | 7.3 | Undetermined | 8 | 6.4 | 6.7 |
| The % solid | 53 | 54 | 65 | 61 | 53 |
| Gelation temperature (℃) | 46-50 | 43-47 | 53-60 | 80-85 | 49-52 |
| Wet film intensity (gram) | 267 | 214 | 983 | 2693 | 975 |
| Dry film intensity (gram) | 2958 | 6798 | 4594 | 6457 | 7017 |
| Average film thickness (mm) (% solid) | 1.3(74％) 1.7(59％) |
Table 2
The mixture that contains propylene glycol alginate
| The embodiment numbering | 2A | 2B | 2C | 2D | 2E |
| Part A (%) | |||||
| Carrageenin C | 2.7 | 3.2 | 3.2 | 4.0 | 0.0 |
| Carrageenin B | 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 |
| K 2CO 3 | 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 | 48 | 50 | Not test | 58 | 57 |
| Gelation temperature (℃) | 35-40 | Not test | Not test | 58-66 | 63-71 |
| Wet film intensity (gram) | 60 | 117 | Not test | 337 | 822 |
| Dry film intensity (gram) | 2408 | 3069 | 4335 | 4561 | 4795 |
| Average film thickness (mm) (% solid) | 1.2(91％) 1.1(57％) |
Table 2 is shown as the combination that membrane can be a hydrocolloid, as carrageenin and PGA.In addition, adding salt pair film properties such as intensity, gelation temperature and pH are influential.
Table 3
The mixture that contains the low viscosity guar gum
| The embodiment numbering | 3A | 3B | 3C |
| Part A (%) | |||
| Carrageenin E | 0 | 4.0 | 4.2 |
| Carrageenin B | 4.3 | 0.0 | 0.0 |
| The ULV guar gum | 4.6 | 4.9 | 5.1 |
| Glycerol | 33.5 | 33.5 | 27.0 |
| Sorbitol | 0.0 | 0.0 | 8.1 |
| Part B (%) | |||
| Starch | 20.7 | 20.7 | 21.8 |
| Water | |||
| The mixing chamber temperature (℃) | 108 | 108 | 108 |
| Outlet temperature (℃) | 102 | 102 | 102 |
| Viscosity, cP (95 ℃) | 7900 | 7800 | 69000 |
| pH | 6.5 | 5.6 | 5.5 |
| The % solid | 57 | 57 | 55 |
| Gelation temperature (℃) | 60-65 | ＞100 | ＞100 |
| Wet film intensity (gram) | 460 | 3402 | 921 |
| Dry film intensity (gram) | 5299 | 6587 | 9234 |
Table 3 is shown as the combination that membrane can be a hydrocolloid, as carrageenin and guar gum.
Table 4
The mixture that contains PES
| The embodiment numbering | 4A | 4B |
| Part A (%) | ||
| Carrageenin G | 0.0 | 8.9 |
| Carrageenin F | 8.9 | 0.0 |
| Glycerol | 33.5 | 33.5 |
| Part B (%) | ||
| Starch B790 | 20.7 | 20.7 |
| Water | 36.9 | 36.9 |
| The mixing chamber temperature (℃) | 108 | 108 |
| Outlet temperature (℃) | 102 | 102 |
| Viscosity, cP (95 ℃) | ＞100K | 8400 |
| pH | 7.5 | 8 |
| The % solid | 46 | 49 |
| Gelation temperature (℃) | ＞100 | ＞100 |
| Wet film intensity (gram) | 722 | 360 |
| Dry film intensity (gram) | 1095 | 4213 |
Table 4 explanation can be handled PES and enriching PES in mixing apparatus 10.Enriching PES provides some advantage, as low outlet viscosity, and forms the high strength dry film.Below table 5 and table 6 detailed description of the component that this embodiment is listed is provided.
Table 5
The description of component
| Title | Trade name | Supplier | Describe | |
| Gelatin | Kind and Knox | 150 Bloom, Type B | ||
| Propylene glycol alginate (PGA) | Protanal BV 4830 | FMC Corporation | ||
| Low viscosity guar gum (LV guar gum) | Edicol ULV 50 | Indian Gum Industries，Ltd | ||
| Glycerol | Callahan Chemical | 99.70％ | ||
| Sorbitol | | SPI Polyols | 70% sorbitol solution, USP/FCC | |
| Starch | Pure-Cote B790 | Grain Processing Corporation |
Table 6
Description to carrageenin
| Labelling | The carrageenin type | Describe | Supplier |
| Carrageenin A | ι | From clarification ι-carrageenin extract that Eucheuma denticulatum (Eucheuma spinosum) obtains through alkali treatment, bivalence content is low | FMC Corp. |
| Carrageenin B | κ | From clarification κ-carrageenin extract that Kappaphycus alverezii (Eucheuma cottonii) obtains through alkali treatment, bivalence content is low | FMC Corp. |
| Carrageenin C | κ-2 | From China fir algae (Gigartina skottsbergii) and Sarcothalia crispata, be mainly the low bivalence extract of monoploid (gametocyte) the plant mixture clarification that processing obtains through alkali, this extract often is called " kappa-2 carrageenan ".Also comprise λ and the θ carrageenin of 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. |
| Carrageenin D | Special low bivalence κ | From the alkali treatment of Kappaphycus alverezii (Eucheuma cottonii) process, be converted into pure sodium salt, remove the κ-carrageenin extract of bivalent cation | FMC Corp. |
| Carrageenin E | Low bivalence κ-2 | From China fir algae (Gigartina skottsbergii), be mainly the low bivalence extract of monoploid (gametocyte) the plant clarification that processing obtains through alkali, this extract often is called " kappa-2 carrageenan ".Also comprise a small amount of (be lower than total amount 5%) λ and θ carrageenin 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. |
| Carrageenin F | PES κ | Kappaphycus alverezii (Eucheuma cottonii) is through the not clarification Eucheuma algal product (containing κ-carrageenin) of alkali treatment, and bivalence content is low | FMC Corp. |
| Carrageenin G | Enriching PES κ | Kappaphycus alverezii (Eucheuma cottonii) is through not clarification, the pregelatinised κ-carrageenin extract of alkali treatment, bivalence content is low, press US6, embodiment 5 preparations in 479,649 | FMC Corp. |
Such as top description and show that film prepared according to the methods of the invention can be used on the conventional capsules that is used for preparing gelatine capsule originally and prepares on the equipment.
The method of embodiment 2-7
Except as otherwise noted, following processes is to be used for preparing and to measure material among the embodiment 2-7 and film.Stephan UMC5 datatron is the laboratory mixing apparatus, can be to carrying out suitable high shear mixing, heating and the degassing by the preparation of casting film in laboratory.The suitable batch process scale of Stephan UMC5 datatron is 1500g.
The aqueous dispersion for preparing starch like this: any required salt/buffer agent and pH regulator agent are dissolved in the deionized water, add starch and/or maltodextrin (M100), mix, up to they dissolution.PureCote
B760 and B790 starch can be available from Grain Processing Corporation, Muscatine, Iowa.
Preparation hydrocolloid mixture in Stephan UMC5 datatron: the premixing plasticizer adds premixed dry hydrocolloid 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 continue 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 can't flow in refrigerative process again, the temperature the when indenture that probe can not be stabbed out fills 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 that scribbles gel, in case moisture scatters and disappears from cast membrane.Cast membrane is generally wanted cold preservation (being lower than 8 ℃) half an hour at least, film is taken off test then.Film forming does not need cold preservation.Dry coating plate in 40 ℃ of blast furnaces, preparation desciccator diaphragm bar.Film was 40 ℃ of dryings 2 hours, and the intermediate value solids content that obtains is about 60%.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 preparation solid level 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).
Table 8 is listed the composition and the film properties of the preparation that uses low viscosity guar gum ULV50 and kappa-2 carrageenan combined preparation.
Cgn A is that the clarified extract that can be used as after China fir algae (Gigartina skottsbergii) (mainly being monoploid (gametocyte) plant) alkali treatment obtains by the kappa-2 carrageenan of definition here.Also there be a small amount of (total amount is less than 5%) λ and θ-carrageenin from diploid (tetrasporaphite) plant.The bivalent cation of Cgn A and potassium cationic content are low, as shown in table 7.
Cgn B 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.Also comprise λ and the θ carrageenin of 10-20% (total amount) from diploid (tetrasporaphite) plant.
The kappa-2 carrageenan performance is listed in table 7.Use Brookfield LVF viscometer, adopt appropriate speed and spindle, measure the solid viscosity in aqueous solution of 1.5 weight % at 75 ℃.Use TXTM Texture analyser, measure 2% hydrogel (#1) that uses 2 weight % sample Cgn A-B but do not add the cation preparation respectively, add (#2) of 0.2 weight %KCl and add 0.2%KCl and 0.2%CaCl
2The performance of (#3).At 25 ℃ of test gels, write down disruptive force (gram) and penetrate (mm).
Table 7: the performance of kappa-2 carrageenan
| Cgn A | Cgn B | |
| Cation exchange | Be | Not |
| Mg，％ | 0.05 | 0.05 |
| Ca，％ | 0.15 | 0.45 |
| K，％ | 0.67 | 13.40 |
| Na，％ | 7.40 | 0.90 |
| Viscosity mPs | 98 | NT |
| pH | 10.1 | “ |
| 2% hydrogel | ||
| BF(g) | 0 | “ |
| 2% hydrogel (KCl) BF (g) | ||
| 38 | “ | |
| 2% hydrogel (KCl+CaCl 2) | ||
| BF(g) | 181 | “ |
Table 8
Use the preparation and the film properties of LV guar gum and kappa-2 carrageenan
| Component (g) | Embodiment 2-1 | Embodiment 2-2 | Embodiment 2-3 | Embodiment 2-4 | Embodiment 2-5 |
| Water | 836.3 | 836.3 | 836.3 | 836.3 | 836.3 |
| Cgn B | 0.0 | 40.5 | 20.3 | 0.0 | 0.0 |
| Cgn A | 0.0 | 0.0 | 20.3 | 40.5 | 40.5 |
| Guar gum ULV 50 | 90.0 | 49.5 | 49.5 | 49.5 | 49.5 |
| Starch B760 | 220.8 | 220.8 | 220.8 | 220.8 | 220.8 |
| KCl | 0.0 | 0.0 | 0.0 | 4.5 | 4.5 |
| Sorbitol SP | 264.4 | 264.4 | 264.4 | 264.4 | 264.4 |
| Glycerol | 88.2 | 88.2 | 88.2 | 88.2 | 88.2 |
| Gross weight (g) | 1500.00 | 1500.00 | 1500.00 | 1500.00 | 1500.00 |
| Temperature, | 90 | 90 | 90 | 87 | 95 |
| Viscosity, mPas * | ＞50000 | ＞50000 | ＞50000 | ＞50000 | ＞50000 |
| Gelling, ℃ | 47 | 68-69 | 69 | 50 | 54-65 |
| Fusing, | 78 | 85-87 | 86-88 | 67-68 | 76-83 |
| pH | 4.8 | 5.8 | 5.9 | 5.2 | 5.2 |
| Cast membrane | |||||
| Solid (%) is estimated | 42 | 45 | 42 | 40.2 | 45 |
| BF(g) | ＜40 | 239 | 349 | 130 | 330 |
| Dry film (40 ℃, 2 hours) | |||||
| Solid (%) is estimated | 65 | 60 | 60 | 63 | 66 |
| BF(g) | 722 | 953 | 2189 | 1194 | 1631 |
| Dry film (40 ℃, 16 hours) | |||||
| Solid (%) is estimated | 86 | 87 | 75 | 84 | 84 |
| BF(g) | 4436 | 7476 | 6901 | 6276 | 8733 |
| *Temperature and the viscosity of fused mass before casting | |||||
Gel film of the present invention is enough to prepare soft capsule in the dry film intensity of 40 ℃ of dryings after 16 hours on existing equipment.And 2 hours dry film intensity of 40 ℃ of dryings also is enough to prepare soft capsule as embodiment 2-3 to 2-5 on existing equipment.The mixture of embodiment 2-2 proof 55-45 weight % guar gum and kappa-2 carrageenan with have only guar gum (embodiment 2-1) to compare to have improved intensity.Comparing embodiment 2-4 and 2-5 show that the processing temperature of needs maintenance fused mass is higher than gelation temperature, and as final (dry back) gel strength that embodiment 2-5 provides, ratio is at the film (embodiment 2-4) high at least 28% of 87 ℃ of casting when 95 ℃ of casting.Lower gel strength reflects in the film forming procedure, and pregelatinization may take place, and causes relatively low gel strength.All films do not have syneresis when storing, and have kept their relative flexibility.
Found that viscosity is maximum or approaching maximum under testing equipment that adopts and condition.Therefore, using has the ancillary equipment of initial hydration/activating apparatus that other shearing and solids-enriched effect can be provided, and keeps process temperature to be higher than the curing/gelation temperature (＞100 ℃) of its high solid simultaneously.It is extrusion molding type equipment that such ancillary equipment is not limited to, as long as can keep necessary temperature and provide uniform mixing required shearing, and the fused mass that is used in direct film forming or capsule casting is shaped, or making fused mass be configured as required form such as the required solid concentration of thin film, described thin film can be used as film or further is processed into other dosage forms and function.
Embodiment 3
Use the low viscosity guar gum ULV 50 and the mixture of the combination of κ carrageenin or κ carrageenin and/or ι carrageenin to prepare film, described film properties is listed in table 9 and table 10 respectively.The following describes the carrageenin of use.Carrageenin L is that a kind of viscosity is the κ carrageenin of 10-15cp.
Table 9
Use the film of low viscosity guar gum and κ carrageenin
| Component (g) | Embodiment 3-1 | Embodiment 3-2 | Embodiment 3-3 | Embodiment 3-4 |
| Water | 836.3 | 836.3 | 836.3 | 836.3 |
| Cgn L | 40.5 | 40.5 | 40.5 | 40.5 |
| Guar gum ULV 50 | 49.5 | 49.5 | 49.5 | 49.5 |
| Starch B760 | 0 | 220.8 | 220.8 | 0 |
| Starch B790 | 220.8 | 0 | 0 | 0 |
| M-100 | 0 | 0 | 0 | 220.8 |
| KCl | 0 | 0 | 4.5 | 4.5 |
| Sorbitol SP | 264.4 | 264.4 | 264.4 | 264.4 |
| Glycerol | 88.2 | 88.2 | 88.2 | 88.2 |
| Gross weight | 1500.0 | 1500.0 | 1500.0 | 1500.0 |
| Temperature, | 90 | 90 | 90 | 90 |
| Viscosity, mPas * | 16000 | ＞50000 | 36750 | 27100 |
| During casting | ||||
| Gelling, ℃ | 36 | 53 | 57 | 56 |
| Fusing, ℃ | 61 | 75-77 | 76-78 | 75-78 |
| pH | 5.3 | 5.2 | 5.1 | 5.3 |
| Cast membrane | ||||
| Solid (%) is estimated | 41.5 | 40 | 45 | 43 |
| BF(g) | 170 | 227 | 283 | 217 |
| Dry film (40 ℃, 2 hours) | ||||
| Solid (%) is estimated | 69 | 65 | 64 | 66 |
| BF(g) | 1368 | 1574 | 1144 | 1236 |
| Dry film (40 ℃, 16 hours) | ||||
| Solid (%) is estimated | 84 | 85 | 85 | 83 |
| BF(g) | 5541 | 7638 | 7029 | 5671 |
| *Temperature and the viscosity of fused mass before casting | ||||
Use κ carrageenin and guar gum combination (embodiment 3-2) than only using guar gum (embodiment 2-1) to improve film-strength.
Add KCl (embodiment 3-3) and improved gelation temperature and 40% solid gel strength.In addition, the ratio that adds KCl and change over membrane component can be controlled cast membrane intensity and gel fusion temperature.When κ carrageenin and low viscosity guar gum of the present invention were used in combination, the control bivalent cation can prevent/reduce gel sclerosis and fragility satisfactorily.
Table 10 is listed the composition and the performance of the film that uses low viscosity guar gum ULV 50 and κ and the formation of ι carrageenin.Cgn C is the clarification κ carrageenin extract of the alkali treatment of Kappaphycus alverezii (Eucheuma cottonii).Cgn D is the clarification ι carrageenin extract of the alkali treatment of Eucheuma denticulatum (Eucheuma spinosum).Cgn C and Cgn D have low bivalence.
Table 10
Use the film of LV guar gum, κ carrageenin and ι carrageenin
| Component (g) | Embodiment 3-5 | Embodiment 3-6 | Embodiment 3-7 | Embodiment 3-8 |
| Water | 836.3 | 836.3 | 836.3 | 836.3 |
| Cgn C | 0 | 13.5 | 27 | 40.5 |
| Cgn D | 40.5 | 27 | 13.5 | 0 |
| Guar gum ULV 50 | 49.5 | 49.5 | 49.5 | 49.5 |
| Starch B760 | 220.8 | 220.8 | 220.8 | 220.8 |
| Sorbitol SP | 264.4 | 264.4 | 264.4 | 264.4 |
| Glycerol | 88.2 | 88.2 | 88.2 | 88.2 |
| Gross weight | 1500.0 | 1500.0 | 1500.0 | 1500.0 |
| Temperature, ℃ * | 93 | 90 | 90 | 90 |
| Viscosity, mPas * | 46100 | 41250 | 41500 | ＞50000 |
| Cast membrane | ||||
| Gelling, | 70 | 46 | 43 | 53 |
| Fusing, ℃ | 85-90 | 65-66 | 56-62 | 75-77 |
| PH | 5.8 | 5.4 | 5.4 | 5.2 |
| Cast membrane | ||||
| Solid (%) is estimated | 39 | 43 | 41 | 40 |
| BF(g) | 102 | 48 | 95 | 227 |
| Dry film (40 ℃, 2 hours) | ||||
| Solid (%) is estimated | 63 | 60 | 60 | 65 |
| BF(g) | 1068 | 282 | 679 | 1574 |
| Dry film (40 ℃, 16 hours) | ||||
| Solid (%) is estimated | 82 | 80 | 80 | 85 |
| BF(g) | 5915 | 6067 | 5549 | 7638 |
| *Temperature and the viscosity of fused mass before casting | ||||
Top embodiment shows the situation that other carrageenin improve low viscosity guar gum film-strengths that adds.Can further strengthen and control gelling/fusion temperature by adding an amount of cation.
Table 11 has been listed the composition and the performance of the film of the mixture formation of using guar gum and potassium alginate and/or carrageenin.Alginate are to comprise mannuronic acid salt (M) and the unitary poly-polysaccharide aldehyde hydrochlorate of gulose aldehyde acid salt (G) (polyuronate) copolymer.KAHG is a kind of potassium alginate, and wherein alginate have the G unit of higher level, and can extract from Thallus Laminariae (Thallus Eckloniae) (Laminaria hyperborean).KAHM is a kind of potassium alginate, and wherein alginate have higher M unit, and can extract from Lessonia nigressens.
Table 11
Use the film of low viscosity guar gum, potassium alginate and carrageenin
| Component (g) | Embodiment 4-1 | Embodiment 4-2 | Embodiment 4-3 | Embodiment 4-4 | Embodiment 4-5 | Embodiment 4-6 |
| 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 |
| Cgn L | 30 | 30 | 0 | 30 | 30.0 | 30 |
| Guar gum ULV 50 | 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 | V | 88.2 | 88.2 |
| Gross weight | 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 |
| Gelling, ℃ | 42 | 41 | 50-51 | 53 | 39 | 55 |
| Fusing, ℃ | 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 | ||||||
| Solid (%) is estimated | 40 | 40 | 40 | 40 | 38 | 41 |
| BF(g) | ＜40 | ＜40 | ＜40 | 188 | ＜40 | 185 |
| Dry film (40 ℃, 2 hours) | ||||||
| Solid (%) is estimated | 66 | 62 | 63 | 64 | 62 | 66 |
| BF(g) | 370 | 248 | 445 | 1811 | 502 | 1265 |
| Dry film (40 ℃, 16 hours) | ||||||
| Solid (%) is estimated | 81 | 79 | 85 | 80 | 77 | 80 |
| BF(g) | 3826 | 4253 | 4144 | 7960 | 6918 | 8301 |
| *Temperature and the viscosity of fused mass before casting | ||||||
Table 12 is listed the composition and the performance of the film that uses low viscosity guar gum ULV 50 and the preparation of sodium alginate mixture.Protanal LFR 5/60, Protanal LF 20/40 and Protanal SF 120RB are from FMCCorporation (Philadelphia, PA) sodium alginate of Huo Deing.
Table 12
Use the film of guar gum and alginate
| Component (g) | Embodiment 4-7 | Embodiment 4-8 | Embodiment 4-9 |
| Water | 836.3 | 836.3 | 836.3 |
| LFR5/60 | 40.5 | 0 | 0 |
| LF20/40 | 0 | 40.5 | 0 |
| SF120RB | 0 | 0 | 30 |
| Guar gum ULV 50 | 49.5 | 49.5 | 45 |
| 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 | 1500.0 | 1500.0 | 1500.0 |
| Temperature, | 90 | 94 | 93 |
| Viscosity, mPas * | 31650 | ＞50000 | ＞50000 |
| Gelling, ℃ | 50 | NA | NA |
| Fusing, ℃ | 70-71 | ＞95 | ＞93 |
| pH | 5.6 | 5.5 | 5.6 |
| Cast membrane | |||
| Solid (%) is estimated | 40 | 40 | 40 |
| BF(g) | ＜40 | 102 | 110 |
| Dry film (40 ℃, 2 hours) | |||
| Solid (%) is estimated | 60 | 64 | 67 |
| BF(g) | 617 | 1250 | 1126 |
| Dry film (40 ℃, 16 hours) | |||
| Solid (%) is estimated | 80 | 80 | 94 |
| BF(g) | 4780 | 7701 | 10850 |
| *Temperature and the viscosity of fused mass before casting | |||
Table 13 is listed forming and performance of the film that is combined to form by low viscosity guar gum ULV50 and propylene glycol alginate.Protanal ester BV4830 and Protanalt ester SLF3 are the propylene glycol alginates that obtains from FMC BioPolymer (Philadelphia PA).
Table 13
Use the film of low viscosity guar gum and propylene glycol alginate
| Component (g) | Embodiment 4-10 | Embodiment 4-11 | Embodiment 4-12 | Embodiment 4-13 | Embodiment 4-14 |
| Water | 836.3 | 840.3 | 840.3 | 840.3 | 836.3 |
| BV4830 | 12.0 | 0 | 91.2 | 0 | 12.0 |
| SLF-3 | 0 | 85.5 | 0 | 114 | 0 |
| HEC | 0 | 1.8 | 1.9 | 2.4 | 0 |
| Cgn L | 40.5 | 0 | 24 | 0 | 40.5 |
| Guar gum ULV 50 | 37.5 | 30 | 0 | Do not have | 37.5 |
| B760 | 220.8 | 207.8 | 207.8 | 207.8 | 220.8 |
| M-100 | 0 | 0 | 0 | 0 | |
| Sodium citrate | 0 | 2.7 | 0 | 3.6 | |
| Potassium citrate | 0 | 0 | 2.9 | 0 | |
| KCl | 0 | 0 | 2.4 | 0 | |
| Sorbitol SP | 264.4 | 248.8 | 248.8 | 248.8 | 264.4 |
| Glycerol | 88.2 | 83.0 | 83.0 | 83 | 88.2 |
| Temperature, ℃ * | 90 | 87 | 90 | 91 | 90 |
| Viscosity, mPas * | 23100 | 16500 | 25000 | 3250 | 23100 |
| Gelling, ℃ | 46 | 34-38 | 43-46 | 34-35 | 46 |
| Fusing, ℃ | 60-68 | 62-64 | 56-62 | 58-60 | 60-68 |
| pH | 4.6 | 4.5 | 6.3 | 4.4 | 4.6 |
| Cast membrane | |||||
| Solid (%) is estimated | 41.5 | 41 | 45 | 39 | 41.5 |
| BF(g) | 147 | 40 | 231 | ＜40 | 147 |
| Dry film (40 ℃, 2 hours) | |||||
| Solid (%) is estimated | 60 | 65 | 55 | 74 | 60 |
| BF(g) | 592 | 355 | 842 | 1877 | 592 |
| Dry film (40 ℃, 16 hours) | |||||
| Solid (%) is estimated | 80 | 77 | 78 | 85 | 80 |
| Average film thickness (mm) | 0.62 | 0.60 | 0.75 | 0.67 | 0.62 |
| BF(g) | 7214 | 3317 | 9599 | 4677 | 7214 |
Embodiment 5
Table 14 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 the clarified extract through alkali treatment of Kappaphycus alaverei (Euchema cottonii).
Table 14
Compositions based on the propylene glycol alginate mixture
| Component (g) | Embodiment 5-1 | Embodiment 5-2 | Embodiment 5-3 |
| 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 | ||
| 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 mPas* | 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 | |||
| Solid (%) is estimated | 45 | 38 | 36 |
| BF(g) | 136 | 89 | 113 |
| Dry film (16 hours, 40 ℃) | |||
| Solid (%) is estimated | 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 15 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 15
Alginate film with the kappa-2 carrageenan preparation
| Component (g) | Embodiment 5-4 | Embodiment 5-5 |
| Water | 834.7 | 834.7 |
| κ-2Cgn | 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 |
| Solid | 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 |
*Temperature and the viscosity of fused mass before casting
In embodiment 5-4, 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 5-5, intensity increase and the reason of processing viscosity degradation to be the content of propylene glycol alginate higher.
As shown below, Cgn A is from China fir algae (Gigartina skottsbergii), mainly uses monoploid (gametocyte) the plant clarification kappa-2 carrageenan extract that processing obtains through alkali, reclaims through the alcohol precipitation.Also there is the λ from diploid (tetrasporaphite) plant of a small amount of (less than 5% total amount)-and θ-carrageenin.
Cgn B obtains by following method, Cgn A is dissolved in the water, and reclaims after drying by the alcohol precipitation.By dissolved carrageenin and oxidant reaction, obtain the sample of different molecular weight, be Cgn C-F.After the oxidation step but before the alcohol precipitation, in sample Cgn C-E, add sodium hydroxide, with the pH of control end product.
The kappa-2 carrageenan performance is listed in table 16.Use Brookfield LVF viscometer, adopt certain speed and spindle, the solid viscosity in aqueous solution of 1.5 weight % is arranged 75 ℃ of mensuration.Use TXTM Texture analyser, measure 2% hydrogel (#1) that uses 2 weight % sample Cgn A-F but do not add the cation preparation, add (#2) of 0.2 weight %KCl and add 0.2%KCl and 0.2%CaCl
2The performance of (#3).At 25 ℃ of test gels, write down disruptive force (gram) and penetrate (mm).
Following Cgn A-F is the example that can be used for kappa-2 carrageenan of the present invention.
Table 16
The performance of kappa-2 carrageenan A-F
| Cgn A | Cgn B | Cgn C | Cgn D | Cgn E | Cgn F | ||
| Test | |||||||
| Oxidation processes | Not | Not | Be | Be | Be | Be | |
| Mg，％ | 0.11 | 0.34 | 0.19 | 0.19 | 0.19 | 0.19 | |
| Ca，％ | 0.34 | 0.29 | 0.34 | 0.39 | 0.52 | 0.40 | |
| K，％ | 12.9 | 8.46 | 8.59 | 8.87 | 8.74 | 8.95 | |
| Na，％ | 0.22 | 0.42 | 0.51 | 0.57 | 0.65 | 0.38 | |
| Viscosity mPs * | 175 | 144 | 48 | 24 | 14 | 11 | |
| PH | 9.4 | 9.42 | 8.93 | 9.03 | 9.16 | 6.7 | |
| 2% hydrogel | BF(g) | 211 | 38 | 21 | 18 | 11 | 12 |
| Penetrate (mm) | 7.4 | 13.9 | 11.5 | 9.0 | 7.8 | 16.1 | |
| 2% hydrogel (KCl) | BF(g) | 308 | 162 | 126 | 107 | 70 | 51 |
| Penetrate (mm) | 7.4 | 9.9 | 7.8 | 7.6 | 7.3 | 6.1 | |
| 2% hydrogel (KCl+CaCl 2) | BF(g) | 487 | 349 | 514 | 445 | 356 | 158 |
| Penetrate (mm) | 3.6 | 3.1 | 6.4 | 5.3 | 5.0 | 1.7 | |
| *75 ℃, in 1.5% solid deionized water solution, measure viscosity | |||||||
In the following table 17, according to shown in preparation Cgn D and E and casting film.Preparation and film properties are listed in table 17.All preparations all are considered within the scope of the invention, although some can more be better than another kind to special-purpose.
Table 17
Kappa-2 carrageenan preparation and film properties
| Component (g) | Embodiment 6-1 | Embodiment 6-2 | Embodiment 6-3 | Embodiment 6-4 |
| Water | 834.7 | 834.7 | 666 | 497.4 |
| Cgn D | 0 | 75 | 75 | 75 |
| Cgn E | 75 | 0 | 0 | 0 |
| M-100 | 227.3 | 227.3 | 292.3 | 357.2 |
| Sorbitol SP | 272.2 | 272.2 | 349.9 | 427.7 |
| Glycerol | 90.8 | 90.8 | 116.8 | 142.7 |
| Temperature, ℃ * | 81.1 | 82 | 85 | 92 |
| Viscosity, mPas * | 4000 | 13700 | 22350 | ＞50000 |
| Solid (estimation) | 40.1％ | 40.1％ | 50.1％ | 60.0 |
| Gelling, ℃ | 55-57 | 54-55 | 62 | 77-78 |
| Fusing, ℃ | 73-75 | 77-80 | 85 | 90-92 |
| As cast membrane | ||||
| BF(g) | 312 | 318 | 404 | 476 |
| BF(g/mm) | 280 | 303 | 420 | 448 |
| Dry film (estimating 80% solid) (16 hours, 40 ℃) | ||||
| Average film thickness (mm) | 1.5 | 1.0 | 0.87 | 1.1 |
| BF(g) | 5755 | 5220 | 5613 | 3218 |
| *Temperature and the viscosity of fused mass before casting | ||||
Data show in the table above: among embodiment 6-2 and the embodiment 6-1, (be respectively 13 by Cgn D molecular weight being reduced to the viscosity that Cgn E (be expressed as viscosity and be respectively 24mPas and 14mPas) is controlled at melt under the processing temperature, 700mPas and 4000mPas), and to not obviously influence of film properties.
To certain preparation, cast material increases its fusion temperature with solid content and raises (embodiment 6-2,6-3 and 6-4), and in embodiment 6-2,6-3 and 6-4, gelation temperature increases with solid and raises, up to gelation temperature near melt temperature.Before the casting, gelation shows as cast membrane in embodiment 6-4 gel strength descend and the viscosity height of molten condition (＞50,000mPa), reason is that gelation temperature is near fusion temperature.This shows, the film of greater strength if desired then needs fusion temperature remained on during processing and is higher than gelation temperature.Stirring can cause the gel structure that ruptures and reduce intensity under the gelation temperature being lower than.
Embodiment 7
Kappa-2 carrageenan is as China fir algae (Gigartina skottsbergii) and Sarcothalia crispata, and the clarified extract after the alkali treatment of main monoploid (gametocyte) plant obtains.Also exist the λ of about 10-20% (total amount) from diploid (tetrasporaphite) plant-with the θ carrageenin.Reclaim this extract, ion exchange subsequently provides the kappa-2 carrageenan that hangs down bivalence.The character of the kappa-2 carrageenan (Cgn G-J) of low bivalent cation is shown in table 18.Can think that Cgn G-J is within the scope of the invention.
Table 18
Low bivalent cation kappa-2 carrageenan performance
| Cgn G | Cgn H | Cgn I | Cgn J | ||
| Cation exchange | Be | Be | Be | Be | |
| Mg，％ Ca，％ K，％ Na，％ | 0.07 | 0.02 | 0.03 | 0.05 | |
| 0.06 | 0.01 | 0.16 | 0.15 | ||
| 2.19 | 1.00 | 0.00 | 0.67 | ||
| 5.12 | 7.70 | 6.90 | 7.40 | ||
| | 6 | 18 | 45 | 98 | |
| pH | 8.12 | 8.7 | 9.6 | 10.1 | |
| 2% hydrogel | BF(g) | 0 | 0 | 0 | 0 |
| 2% hydrogel (KCl) | BF(g) | 0 | 13 | 29 | 38 |
| 2% hydrogel (KCl+CaCl 2) | BF(g) | 30 | 93 | 112 | 181 |
Use the composition and the corresponding film properties thereof of the film of the kappa-2 carrageenan sample Cgn G-J that hangs down bivalent cation content to list in table 19.Below all preparations all be considered within the scope of the invention, although some can more be better than another kind to special-purpose.
Table 19
Use the film of low bivalent cation kappa-2 carrageenan
| Component (g) | Embodiment 7-1 | Embodiment 7-2 | Embodiment 7-3 | Embodiment 7-4 |
| Water | 834.7 | 834.7 | 834.7 | 834.7 |
| Cgn J | 75 | 0 | 75 | 75 |
| Cgn I | 0 | 75 | 0 | 0 |
| KCl | 0 | 0 | 9.0 | 9.0 |
| Starch B790 | 0 | 0 | 0 | 227.3 |
| M-100 | 227.3 | 227.3 | 227.3 | 0 |
| Sorbitol SP | 274.9 | 274.9 | 274.9 | 274.9 |
| Glycerol | 91.7 | 91.7 | 91.7 | 91.7 |
| Temperature, | 89 | 87 | 87 | 87 |
| Viscosity, mPas * | 5800 | 5800 | 6250 | 10300 |
| Solid (estimation) | 40％ | 40％ | 41％ | 40％ |
| Fusing, ℃ | 45-48 | 43 | 66-71 | 70 |
| Gel, ℃ | 35 | 31 | 52 | 48 |
| As cast membrane | ||||
| BF(g) | ＜40 | ＜40 | 281 | 237 |
| Dry film (estimating 80% solid) | ||||
| Average film thickness (mm) | - | - | 0.97 | 0.88 |
| BF(g) | 3468 | 3697 | 3236 | 7603 |
| *Temperature and the viscosity of fused mass before casting | ||||
Ion exchange kappa-2 carrageenan (I and J) provides relative more weak casting gel film with polyhydric alcohol and maltodextrin (as extender) combination, and disruptive force can be ignored during its 40% solid.Believe it is because the quantity not sufficient of potassium cationic needs potassium cationic to promote carrageenin to form Double helix (double helix) (being gelling) more completely under the temperature that makes it as the primary structure agent.Embodiment 7-1 and 7-2 are the gel filies with relatively low fusion temperature and gelation temperature.Even the gelling potentiality can not maximize (because the potassium amount is lower), embodiment 7-1 and 7-2 show 3468 and 3697 disruptive force respectively.Embodiment 7-3 proof adds the effect of potassium ion to Cgn J in the structure that kappa-2 carrageenan forms.Though softer, casting intensity provides and has been enough to take off the required intensity of film from moulding plate.Compare with embodiment 7-1, improved fusion temperature and confirmed that with gelation temperature the structure that is become by the Cgn J-shaped that adds potassium ion among the embodiment 7-3 has improved fusion temperature and gelation temperature.The disruptive force of this dry film is still similar with embodiment 7-1 and 7-2.
Embodiment 7-4 proof is substituted the effect of maltodextrin (embodiment 7-3) by modified starch (B790).Though viscosity improves, gelation temperature and fusion temperature are similar to the embodiment 7-3 that comprises maltodextrin.The cast membrane intensity of embodiment 7-4 is also suitable with embodiment 7-3.The dry film intensity of embodiment 7-4 is greater than the twice of embodiment 7-3.This clearly illustrates that, when starch and kappa-2 carrageenan and potassium cationic the gelling ion of kappa-2 carrageenan (that is, to) the structure synergism between starch and the kappa-2 carrageenan when existing together.Can provide potassium ion by direct adding inorganic salt, organic salt or their combination, or potassium ion can be included in other components.More the be easy to get condition of gel formation of the kappa-2 carrageenan that use contains residual process salt makes the synergism maximum of gel structure and starch.Form uniform kappa-2 carrageenan/starch gel structure by casting fused mass under sufficiently high temperature, can prevent pregelatinization.
List other preparations of the present invention below.
Table 20: kappa-2 carrageenan film
| Component (g) | Embodiment 7-5 | Embodiment 7-6 | Embodiment 7-7 |
| Water | 834.7 | 834.7 | 825 |
| Cgn H | 61.4 | 0 | 0 |
| Cgn G | 0 | 0 | 90 |
| Cgn I | 0 | 75.0 | 0 |
| Calcium sulphate dihydrate | 1.7 | 0 | 0 |
| KCl | 0 | 15.0 | 0 |
| Starch B760 | 0 | 0 | 225 |
| M-100 | 227.3 | 227.3 | 0 |
| Sorbitol SP | 275.4 | 272.2 | 272.2 |
| Glycerol | 91.9 | 90.8 | 90.8 |
| Temperature, | 82 | 88 | 75 |
| Viscosity, mPas * | 6500 | 16150 | 18250 |
| Solid (estimation) | 39 | 42 | 40 |
| Fusing, ℃ | 74-77 | 85 | 62-65 |
| Gelling, | 56 | 60-65 | 42 |
| pH | 5.8 | 6.9 | 6.9 |
| As cast membrane | |||
| BF (g), about 40%, 40 ℃ of | 338 | 302 | 117 |
| BF (g), about 60%, 40 ℃ of dryings, 16 hours | 766 | NT | 536 |
| Average film thickness (mm) | - | 0.62 | |
| BF (g), about 80%, NT=does not test | 3227 | 4470 | 6073 |
| NT=does not test | |||
| *Temperature and the viscosity of fused mass before casting | |||
Preparation embodiment 7-5, it has the cations that equates with embodiment 5-1.Two samples all show same gel melt property.Compare with the Cgn H (6cps) among the embodiment 7-5, the Cgn E (14cps) of higher molecular weight provides more structural support to gel film among the embodiment 5-1, shown in the higher disruptive force of dry film.The higher dry film intensity of embodiment 7-7 shows uses modified starch and the combination of low-molecular-weight kappa-2 carrageenan, the integral membrane structure can be provided and show kappa-2 carrageenan and starch complexation mutually.
Embodiment 8
To heat mixed compositions, in conventional polymer film casting equipment, form film as arbitrary compositions among the embodiment 1-7, method is that the melt composition with control thickness is sent on the going barrel that is controlled at uniform temperature, makes the film of formation be suitable for subsequently processing and processing.In the film that becomes the membrane operations downstream to make is carried by the reverse rotation mould of a series of rollers to the normal gelatin capsule device, with form, the capsule of cutting and filling various sizes.In this process, two film surfaces under melting condition (that is, the local pressure that is enough to two films are fused together with local temperature time) contacts.The capsule that unloads formation is used for further processing.The capsule that reclaims has the sufficient mechanical strength that can bear processing, packing and condition of storage.
Embodiment 9
Soft capsule embodiment
Use Technophar SGM1010 soft capsule equipment, this equipment has 7.25 inches long, that diameter is 4 inches moulds, and preparation contains the soft capsule (7.5 ellipse) of mineral oil (following surface compositions A).Form the fused mass of capsule shells by following method preparation: in Ross DS40 chuck vacuum mixer, 33.89 pounds of glycerol are housed, in the glycerol material, add 11.35 pounds of kappa-2 carrageenans, and disperseed 5 minutes with maximal rate.In this mixture, add other 11.35 pounds of kappa-2 carrageenans, redispersion 5 minutes.Then, the pre-composition that in this blender, adds 50 pounds of PureCote B790 modified starches and 94.1 pounds of deionized waters.Blender is added a cover closure, takes out 26 inches vacuum, removes air.With the disperser mixed content thing under planetary-type mixer under the maximal rate and 1/3 maximal rate 30 minutes.Lock this vacuum, then, by in this blender chuck, provide low-pressure steam (＜10psig) be heated to 90 ℃, the content in the mixer simultaneously.After temperature reached 90 ℃, disperser speed was brought up to 2/3 maximal rate gradually, and fused mass was kept 45 minutes at least 90 ℃.Use increased pressure board make this fused mass as required from the flexible pipe of the electrical heating (about 125 ℃) of Ross blender by controlling temperature to the spread-coating case of adding a cover, disperse this fused mass.The cast membrane that forms in the spread-coating case is continuous and smooth.With roller film is sent in the capsule finishing die, forms capsule, filling mineral oil rear enclosed.Capsular seal temperature is 62 ℃, and sealing load is about 2 crust.When ribbon thickness has improved sealability when 0.28 inch is reduced to 0.16 inch.Capsule under 80 and 19%RH through dry 72 hours of tunnel type.After the drying, it is good that the capsule sealing integrity keeps.The cast membrane of being made by this preparation is for amber deeply, muddiness, slightly Sargassum abnormal smells from the patient.The disruptive force of this film (0.3mm is thick) is 310g when 58% solid.The disruptive force of the film of (about 80% solid) is 3309g after 40 ℃ and 40%RH drying.See table the A in 21.
According to top method and apparatus, use comprises 39.7 pounds of Sorbitol SP, 59.5 pounds of glycerol, the kappa-2 carrageenan of 19.6 pounds of sodium ion exchanges, 44.6 second preparation of pound PureCote B760 starch and 92.6 pounds of water has also prepared the other soft capsule (following surface compositions B) of sealing mineral oil.Sorbitol SP is joined in the starch/water pre-composition.The film odorlessness that the use said preparation is made, transparent has medium color and luster.The thickness of cast membrane is 0.6mm, and disruptive force is 263g during 55% solid.The membrane sample thickness of dried overnight (about 80% solid) is 0.7mm under 40 ℃ and 40%RH, and disruptive force is 6463g.When being sent to the capsule mould on roller, cast membrane has more elasticity, and can stretch.Adopt 42 ℃ of capsule seal temperatures and 0.5 crust sealing load, form capsule.Mineral oil is encapsulated.
Measure per half capsular weight, film thickness, and burst strength.Adopt the extruding capsule to measure burst strength to breaking.The speed of extruding probe is 1mm/sec.Each condition is measured 10 capsules.Capsular burst strength when shell intensity is capsule seam horizontal positioned.When vertically placing, seam measures 10 capsular joint strengths.The results are shown in table 21.Two kinds of kappa-2 carrageenan films all are flexible, and shown in explosive distance, two kinds of films can be made into the high-strength sealing capsule, shown in the capsule burst strength, this intensity is approximately identical with the intensity of capsule seam with capsule shells, and capsule does not break on seam, but breaks at seam top (away from pressure spot).
Table 21
The capsule performance
| Capsule formula | Capsules weight (mg) | Film wets/filling weight (mg) | | Shell explosive distance mm | Shell intensity newton | Seam explosive distance mm | Joint strength newton |
| Prescription A | 471 | 151/320 | 357/312 | 6.3 | 206 | 6.3 | 210 |
| Prescription B | 499 | 187/312 | 420/370 | 5.3 | 124 | 5.1 | 105 |
Though describe the present invention in detail, it will be apparent to those skilled in the art that 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)
1. one kind prepares method homogenizing, hot reversible gel film, and it comprises the steps:
(i) in the equipment of enough shearing force, temperature and time of staying is provided to film-forming composition heating, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is sent at least one in blender, pump or the exhaust chamber;
(iii), form described gel film being equal to or less than the melt composition cooling that makes described homogenizing under the temperature of its gelation temperature.
2. the method for claim 1 is characterized in that, described film-forming composition comprises at least a hydrocolloid film former, and optional plasticizer, extender, pH controlling agent and second film former.
3. the method for claim 1 is characterized in that, described equipment is the Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
4. the method for claim 1 is characterized in that, described melt composition solids content is at least 50%.
5. the method for claim 1 is characterized in that, described melt composition solids content is at least 60%.
6. the method for claim 1 is characterized in that, described melt composition solids content is at least 70%.
7. the method for claim 1 is characterized in that, described melt composition solids content is at least 80%.
8. the method for claim 1 is characterized in that, described melt composition solids content is at least 90%.
9. the method for claim 1 is characterized in that, described gel film has the disruptive force of 1000g at least.
10. the method for claim 1 is characterized in that, described gel film has the disruptive force of 2500g at least.
11. the method for claim 1 is characterized in that, described gel film has the disruptive force of 4000g at least.
12. the method for claim 1 is characterized in that, described gel film has the disruptive force of 5000g at least.
13. the method for claim 1 is characterized in that, described gel film has the disruptive force of 6000g at least.
14. as each described method among the claim 1-13, it is characterized in that described melt composition is sent into pump, in blender or the exhaust chamber at least one.
15. method as claimed in claim 2 is characterized in that, described hydrocolloid is be selected from carrageenin, alginate, glucomannan or galactomannan at least a; Described plasticizer is to be selected from least a in glycerol, Sorbitol, maltose alcohol, lactose and the poly alkylene glycol; Described second film former is to be selected from least a in starch, starch derivatives, glucidtemns, cellulose gum, hydrocolloid, alkyl cellulose ether and the modification alkyl cellulose ether; Described extender is be selected from microcrystalline Cellulose, Microcrystalline Starch, starch, starch derivatives, inulin and glucidtemns at least a.
16. method as claimed in claim 15 is characterized in that, described carrageenin is to be selected from least a in ι carrageenin, κ carrageenin and the kappa-2 carrageenan; Described alginate are propylene glycol alginates; Described glucomannan is a Rhizoma amorphophalli, and described galactomannan is a guar gum.
17. the method for claim 1 is characterized in that, under atmospheric pressure the solution temperature of the melt composition of described homogenizing is higher than its boiling point, and be higher than that atmospheric pressure heats, hydration, mixing and dissolving.
18., it is characterized in that the described fugitive constituent that removes carries out as each described method among the claim 1-17 in extruding machine.
19., it is characterized in that described melt composition sent into directly that described blender outgases, decompression and pumping as each described method among the claim 1-17 before being cooled to its gelation temperature or being lower than this temperature.
20. the homogenizing that makes by each method among the claim 1-19, reversible, high solid, the low-moisture film of heat.
21. one kind prepares the soft capsule method, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating high solid, low-moisture, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is sent at least one in blender, pump or the exhaust chamber;
(iii) described melt composition is cooled to the temperature that is equal to or less than its gelation temperature, forms described homogenizing, hot reversible gel film;
(iv) make soft capsule by described gel film.
22. method as claimed in claim 21 is characterized in that, described film-forming composition comprises at least a hydrocolloid, and optional plasticizer, extender, pH controlling agent and second film former.
23. method as claimed in claim 21 is characterized in that, described equipment is the Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
24. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 50%.
25. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 60%.
26. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 70%.
27. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 80%.
28. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 90%.
29. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 1000g at least.
30. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 2500g at least.
31. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 4000g at least.
32. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 5000g at least.
33. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 6000g at least.
34. as each described method among the claim 21-33, it is characterized in that, described melt composition is sent into have pump, in blender and the exhaust chamber at least one the extruding machine.
35. method as claimed in claim 22 is characterized in that, described hydrocolloid is be selected from carrageenin, alginate, glucomannan or galactomannan at least a; Described plasticizer be selected from glycerol, Sorbitol, maltose alcohol, lactose and the poly alkylene glycol at least a; Described second film former is to be selected from least a in starch, starch derivatives, glucidtemns, cellulose gum, κ carrageenin, ι carrageenin, kappa-2 carrageenan, alginate, propylene glycol alginate, polymanna glue (polymannan gum), pulullan polysaccharide, dextran, pectin, gellan gum, alkyl cellulose ether and the modification alkyl cellulose ether; Described extender is to be selected from least a in microcrystalline Cellulose, Microcrystalline Starch, starch, starch derivatives, glucidtemns, inulin and the glucidtemns.
36. method as claimed in claim 35 is characterized in that, described carrageenin is to be selected from least a in ι carrageenin, κ carrageenin and the kappa-2 carrageenan; Described alginate are propylene glycol alginates; Described glucomannan is a Rhizoma amorphophalli, and described galactomannan is a guar gum.
37. method as claimed in claim 21 is characterized in that, under atmospheric pressure the solution temperature of the melt composition of described homogenizing is higher than its boiling point, and be higher than that atmospheric pressure heats, hydration, mixing and dissolving.
38., it is characterized in that the described fugitive constituent that removes carries out as each described method among the claim 21-37 in extruding machine.
39., it is characterized in that described melt composition sent into directly that described blender outgases, decompression and pumping as each described method among the claim 21-37 before being cooled to its gelation temperature or being lower than this temperature.
40. the soft capsule that makes by each method among the claim 21-39.
41. a manufacturing comprises the method for the solid dosage forms of the packing material of being sealed by reversible gel film homogenizing, hot, it may further comprise the steps:
(i) prepare reversible gel film described homogenizing, hot with each method among the claim 1-19;
(ii) described packing material is packed in the described gel film.
42. method as claimed in claim 41 is characterized in that, described packing material is powder, sheet, capsule sheet, microcapsule or capsule.
43. solid dosage forms as claimed in claim 41 is characterized in that, described solid dosage forms is a hard capsule.
44. a method for preparing the gel film delivery system that comprises homogenizing active substance and homogenizing, hot reversible gel film, it may further comprise the steps:
(i) prepare melt composition with each method among the claim 1-19;
The active substance that (ii) before or after forming this melt composition, adds effective dose;
(iii), form the gel film that comprises described active substance being equal to or less than the described melt composition cooling that will contain described active substance under the temperature of its gelation temperature.
45. method as claimed in claim 44, it is characterized in that described active substance comprises at least a oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, toner, sweeting agent, flavoring agent, aromatic, food.
46. a delivery system, it is that method by claim 44 makes.
47. one kind prepares method homogenizing, hot reversible gel film, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii), form described gel film being equal to or less than the melt composition cooling that makes described homogenizing under the temperature of its gelation temperature.
48. method as claimed in claim 47 is characterized in that, described equipment is the Ross blender.
49. a method of making soft capsule, it may further comprise the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating high solid, low-moisture, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is cooled to the temperature that is equal to or less than its gelation temperature, forms homogenizing, hot reversible gel film;
(iii) make soft capsule by described gel film.
50. method as claimed in claim 49 is characterized in that, described equipment is the Ross blender.
51. method as claimed in claim 2 is characterized in that, described film-forming composition is plasticizer-containing not.
52. method as claimed in claim 2 is characterized in that, described film-forming composition contains extender, and described extender is a corn syrup, and described at least a hydrocolloid film former is a carrageenin.
53. homogenizing, hot reversible gel film by the method for claim 51 or 52 makes is characterized in that, the solids content of described gel film be in the described gel film all components weight at least 80%.
Claims (50)
1. one kind prepares method homogenizing, hot reversible gel film, and it comprises the steps:
(i) in the equipment of enough shearing force, temperature and time of staying is provided to film-forming composition heating, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is sent at least one in blender, pump or the exhaust chamber;
(iii), form described gel film being equal to or less than the melt composition cooling that makes described homogenizing under the temperature of its gelation temperature.
2. the method for claim 1 is characterized in that, described film-forming composition comprises at least a hydrocolloid film former, and optional plasticizer, extender, pH controlling agent and second film former.
3. the method for claim 1 is characterized in that, described equipment is the Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
4. the method for claim 1 is characterized in that, described melt composition solids content is at least 50%.
5. the method for claim 1 is characterized in that, described melt composition solids content is at least 60%.
6. the method for claim 1 is characterized in that, described melt composition solids content is at least 70%.
7. the method for claim 1 is characterized in that, described melt composition solids content is at least 80%.
8. the method for claim 1 is characterized in that, described melt composition solids content is at least 90%.
9. the method for claim 1 is characterized in that, described gel film has the disruptive force of 1000g at least.
10. the method for claim 1 is characterized in that, described gel film has the disruptive force of 2500g at least.
11. the method for claim 1 is characterized in that, described gel film has the disruptive force of 4000g at least.
12. the method for claim 1 is characterized in that, described gel film has the disruptive force of 5000g at least.
13. the method for claim 1 is characterized in that, described gel film has the disruptive force of 6000g at least.
14. as each described method among the claim 1-13, it is characterized in that described melt composition is sent into pump, in blender or the exhaust chamber at least one.
15. method as claimed in claim 2 is characterized in that, described hydrocolloid is be selected from carrageenin, alginate, glucomannan or galactomannan at least a; Described plasticizer is to be selected from least a in glycerol, Sorbitol, maltose alcohol, lactose and the poly alkylene glycol; Described second film former is to be selected from least a in starch, starch derivatives, glucidtemns, cellulose gum, hydrocolloid, alkyl cellulose ether and the modification alkyl cellulose ether; Described extender is be selected from microcrystalline Cellulose, Microcrystalline Starch, starch, starch derivatives, inulin and glucidtemns at least a.
16. method as claimed in claim 15 is characterized in that, described carrageenin is to be selected from least a in ι carrageenin, κ carrageenin and the kappa-2 carrageenan; Described alginate are propylene glycol alginates; Described glucomannan is a Rhizoma amorphophalli, and described galactomannan is a guar gum.
17. the method for claim 1 is characterized in that, under atmospheric pressure the solution temperature of the melt composition of described homogenizing is higher than its boiling point, and be higher than that atmospheric pressure heats, hydration, mixing and dissolving.
18., it is characterized in that the described fugitive constituent that removes carries out as each described method among the claim 1-17 in extruding machine.
19., it is characterized in that described melt composition sent into directly that described blender outgases, decompression and pumping as each described method among the claim 1-17 before being cooled to its gelation temperature or being lower than this temperature.
20. the homogenizing that makes by each method among the claim 1-19, reversible, high solid, the low-moisture film of heat.
21. one kind prepares the soft capsule method, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating high solid, low-moisture, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is sent at least one in blender, pump or the exhaust chamber;
(iii) described melt composition is cooled to the temperature that is equal to or less than its gelation temperature, forms described homogenizing, hot reversible gel film;
(iv) make soft capsule by described gel film.
22. method as claimed in claim 21 is characterized in that, described film-forming composition comprises at least a hydrocolloid, and optional plasticizer, extender, pH controlling agent and second film former.
23. method as claimed in claim 21 is characterized in that, described equipment is the Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
24. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 50%.
25. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 60%.
26. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 70%.
27. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 80%.
28. method as claimed in claim 21 is characterized in that, described melt composition solids content is at least 90%.
29. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 1000g at least.
30. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 2500g at least.
31. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 4000g at least.
32. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 5000g at least.
33. method as claimed in claim 21 is characterized in that, described gel film has the disruptive force of 6000g at least.
34. as each described method among the claim 21-33, it is characterized in that, described melt composition is sent into have pump, in blender and the exhaust chamber at least one the extruding machine.
35. method as claimed in claim 22 is characterized in that, described hydrocolloid is be selected from carrageenin, alginate, glucomannan or galactomannan at least a; Described plasticizer be selected from glycerol, Sorbitol, maltose alcohol, lactose and the poly alkylene glycol at least a; Described second film former is to be selected from least a in starch, starch derivatives, glucidtemns, cellulose gum, κ carrageenin, ι carrageenin, kappa-2 carrageenan, alginate, propylene glycol alginate, polymanna glue (polymannan gum), pulullan polysaccharide, dextran, pectin, gellan gum, alkyl cellulose ether and the modification alkyl cellulose ether; Described extender is to be selected from least a in microcrystalline Cellulose, Microcrystalline Starch, starch, starch derivatives, glucidtemns, inulin and the glucidtemns.
36. method as claimed in claim 35 is characterized in that, described carrageenin is to be selected from least a in ι carrageenin, κ carrageenin and the kappa-2 carrageenan; Described alginate are propylene glycol alginates; Described glucomannan is a Rhizoma amorphophalli, and described galactomannan is a guar gum.
37. method as claimed in claim 21 is characterized in that, under atmospheric pressure the solution temperature of the melt composition of described homogenizing is higher than its boiling point, and be higher than that atmospheric pressure heats, hydration, mixing and dissolving.
38., it is characterized in that the described fugitive constituent that removes carries out as each described method among the claim 21-37 in extruding machine.
39., it is characterized in that described melt composition sent into directly that described blender outgases, decompression and pumping as each described method among the claim 21-37 before being cooled to its gelation temperature or being lower than this temperature.
40. the soft capsule that makes by each method among the claim 21-39.
41. a manufacturing comprises the method for the solid dosage forms of the packing material of being sealed by reversible gel film homogenizing, hot, it may further comprise the steps:
(i) prepare reversible gel film described homogenizing, hot with each method among the claim 1-19;
(ii) described packing material is packed in the described gel film.
42. method as claimed in claim 41 is characterized in that, described packing material is powder, sheet, capsule sheet, microcapsule or capsule.
43. solid dosage forms as claimed in claim 41 is characterized in that, described solid dosage forms is a hard capsule.
44. a method for preparing the gel film delivery system that comprises homogenizing active substance and homogenizing, hot reversible gel film, it may further comprise the steps:
(i) prepare melt composition with each method among the claim 1-19;
The active substance that (ii) before or after forming this melt composition, adds effective dose;
(iii), form the gel film that comprises described active substance being equal to or less than the described melt composition cooling that will contain described active substance under the temperature of its gelation temperature.
45. method as claimed in claim 44, it is characterized in that described active substance comprises at least a oral cavity nursing agent, breath freshener, medicament, nutrient, salivation stimulant, vitamin, mineral, toner, sweeting agent, flavoring agent, aromatic, food.
46. a delivery system, it is that method by claim 44 makes.
47. one kind prepares method homogenizing, hot reversible gel film, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii), form described gel film being equal to or less than the melt composition cooling that makes described homogenizing under the temperature of its gelation temperature.
48. method as claimed in claim 47 is characterized in that, described equipment is the Ross blender.
49. a method of making soft capsule, it may further comprise the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to film-forming composition heating high solid, low-moisture, hydration, mixing, dissolving and the randomly degassing, form the melt composition of homogenizing, wherein, described temperature is equal to or higher than the solution temperature of described compositions;
(ii) described melt composition is cooled to the temperature that is equal to or less than its gelation temperature, forms homogenizing, hot reversible gel film;
(iii) make soft capsule by described gel film.
50. method as claimed in claim 49 is characterized in that, described equipment is the Ross blender.
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46272103P | 2003-04-14 | 2003-04-14 | |
| US60/462,785 | 2003-04-14 | ||
| US60/462,721 | 2003-04-14 | ||
| US60/462,792 | 2003-04-14 | ||
| US60/462,758 | 2003-04-14 | ||
| US60/462,793 | 2003-04-14 | ||
| US60/462,794 | 2003-04-14 | ||
| US60/462,617 | 2003-04-14 | ||
| US60/462,783 | 2003-04-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1791382A true CN1791382A (en) | 2006-06-21 |
Family
ID=36788720
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480014006 Pending CN1791385A (en) | 2003-04-14 | 2004-04-14 | Homogeneous, thermoreversible alginate films transportation system |
| CNB2004800139076A Expired - Lifetime CN100569224C (en) | 2003-04-14 | 2004-04-14 | The gel film and the soft capsule prepared therefrom that contain the homogeneous, thermoreversible of kappa-2 carrageenan |
| CN 200480014023 Pending CN1794979A (en) | 2003-04-14 | 2004-04-14 | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom. |
| CN 200480013903 Pending CN1791382A (en) | 2003-04-14 | 2004-04-14 | Process for making gel films |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200480014006 Pending CN1791385A (en) | 2003-04-14 | 2004-04-14 | Homogeneous, thermoreversible alginate films transportation system |
| CNB2004800139076A Expired - Lifetime CN100569224C (en) | 2003-04-14 | 2004-04-14 | The gel film and the soft capsule prepared therefrom that contain the homogeneous, thermoreversible of kappa-2 carrageenan |
| CN 200480014023 Pending CN1794979A (en) | 2003-04-14 | 2004-04-14 | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom. |
Country Status (1)
| Country | Link |
|---|---|
| CN (4) | CN1791385A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206362A (en) * | 2011-04-28 | 2011-10-05 | 福建农林大学 | Instant noodle flavoring package coating and preparation method thereof |
| CN105534945A (en) * | 2015-12-29 | 2016-05-04 | 仙乐健康科技股份有限公司 | Plant type enteric soft capsule |
| CN107982095A (en) * | 2017-10-19 | 2018-05-04 | 珀莱雅化妆品股份有限公司 | A kind of preparation method with crease-resistant slow-release solid microballoon |
| US20200221752A1 (en) * | 2013-09-13 | 2020-07-16 | Phood Station | Encapsulated food products and methods of making same |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9878039B1 (en) | 2016-09-01 | 2018-01-30 | International Business Machines Corporation | Microcapsule having a microcapsule shell material that is rupturable via a retro-dimerization reaction |
| US10328535B2 (en) | 2016-11-07 | 2019-06-25 | International Business Machines Corporation | Self-heating solder flux material |
| CN114762527B (en) * | 2021-01-15 | 2023-07-25 | 广东富味健康科技有限公司 | Tasty and refreshing tablet containing active probiotics and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5089307A (en) * | 1989-05-23 | 1992-02-18 | Mitsubishi Rayon Co., Ltd. | Edible film and method of making same |
| US5342626A (en) * | 1993-04-27 | 1994-08-30 | Merck & Co., Inc. | Composition and process for gelatin-free soft capsules |
| FR2767070B1 (en) * | 1997-08-08 | 1999-09-17 | Laurence Paris | AQUEOUS VISCOUS COMPOSITION, LIMPID OR NOT, FOR THE MANUFACTURE OF SOFT CAPSULES AND HARD CAPSULES, AND METHOD FOR MANUFACTURING FILMS FOR SUCH CAPSULES |
| US6214376B1 (en) * | 1998-08-25 | 2001-04-10 | Banner Pharmacaps, Inc. | Non-gelatin substitutes for oral delivery capsules, their composition and process of manufacture |
-
2004
- 2004-04-14 CN CN 200480014006 patent/CN1791385A/en active Pending
- 2004-04-14 CN CNB2004800139076A patent/CN100569224C/en not_active Expired - Lifetime
- 2004-04-14 CN CN 200480014023 patent/CN1794979A/en active Pending
- 2004-04-14 CN CN 200480013903 patent/CN1791382A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206362A (en) * | 2011-04-28 | 2011-10-05 | 福建农林大学 | Instant noodle flavoring package coating and preparation method thereof |
| CN102206362B (en) * | 2011-04-28 | 2012-06-27 | 福建农林大学 | Instant noodle flavoring package coating and preparation method thereof |
| US20200221752A1 (en) * | 2013-09-13 | 2020-07-16 | Phood Station | Encapsulated food products and methods of making same |
| CN105534945A (en) * | 2015-12-29 | 2016-05-04 | 仙乐健康科技股份有限公司 | Plant type enteric soft capsule |
| CN105534945B (en) * | 2015-12-29 | 2020-12-25 | 仙乐健康科技股份有限公司 | Plant type enteric soft capsule |
| CN107982095A (en) * | 2017-10-19 | 2018-05-04 | 珀莱雅化妆品股份有限公司 | A kind of preparation method with crease-resistant slow-release solid microballoon |
| CN107982095B (en) * | 2017-10-19 | 2020-03-27 | 珀莱雅化妆品股份有限公司 | Preparation method of sustained-release solid microspheres with anti-wrinkle effect |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1794979A (en) | 2006-06-28 |
| CN1791389A (en) | 2006-06-21 |
| CN100569224C (en) | 2009-12-16 |
| CN1791385A (en) | 2006-06-21 |
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