CN1794979A - Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom. - Google Patents
Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom. Download PDFInfo
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- CN1794979A CN1794979A CN 200480014023 CN200480014023A CN1794979A CN 1794979 A CN1794979 A CN 1794979A CN 200480014023 CN200480014023 CN 200480014023 CN 200480014023 A CN200480014023 A CN 200480014023A CN 1794979 A CN1794979 A CN 1794979A
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Abstract
The present invention is directed to a homogeneous, thermoreversible gel film, and a method for preparing the same. The gel film comprises a film forming amount of low viscosity polymannan gum, e.g., low viscosity guar gum, and optionally at least one of a plasticizer, a second film former, a bulking agent, and a pH controlling agent. The invention also relates to soft capsules and solid dosage forms containing the gel film, and their perparation.
Description
Invention field
The present invention relates to homogeneous, thermoreversible gel film and preparation method thereof, wherein said gel film comprises film forming amount low viscosity polymanna (polymannan), and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.The invention still further relates to the soft capsule and the solid dosage forms that comprise gel film, and their preparation method.
Background of invention
Gelatin once was used for forming film for a long time, and these films are used to prepare soft capsule.Gelatin is the aminosal that is derived from ossein, and described ossein is generally by depressing that water boils animal bone and cartilage obtains adding.But from a business perspective, use gelatin to have several defectives, for example, can't use or be unwilling to use the capsular people who is derived from animal for those, with those worry the people of bovine spongiform encephalopathy (BSE) or " bovine spongiform encephalopathy " recently, the animal origin of gelatin is usually got rid of it outside these people's the scope of application.
For this reason, academia and industrial quarters are attempting to develop the succedaneum of gelatin for many years always, preferably can utilize existing numerous machinery and technology, as preparing soft capsule with mounted rotary die from gelatin replacer.
For example, Japanese Laid-Open Patent Application Kokai 61-10508A has disclosed the capsule by the polysaccharide composition preparation that comprises carrageenin and polyhydric alcohol at least.Carrageenin can use with other polysaccharide in whole or in part, as tamarind gum, pectin, gelatin, alginate, agar, Furcellaran, cellulose derivative, locust bean gum and guar gum.Polyhydric alcohol comprises Sorbitol, glucose, sucrose, ethylene glycol, diethylene glycol, 2,2'-ethylenedioxybis(ethanol)., Polyethylene Glycol, propylene glycol, polypropylene glycol, butanediol and glycerol.Soft capsule prepares with recessed punch die.
Japanese Laid-Open Patent Application Kokai 63-164858 has disclosed polysaccharide and polyhydric alcohol has/do not have the mixture of alkaline matter.It is said that the polysaccharide that is used for this application comprises natural polysaccharide, as carrageenin, alginic acid, alginate derivant, agar, locust bean gum, guar gum, tamarind seed polysaccharide, pectin, xanthan gum, Portugal's polymanna, chitin, Pullulan and cyclodextrin.Show that polysaccharide mixes with the fortified aqueous of at least one in polyhydric alcohol, sugar alcohol, monosaccharide, disaccharide and the oligosaccharide.It is said that mixture can be used to form the shell of soft capsule.This application provides three embodiment, relates to preparation soft capsule shell, and described shell comprises the bilayer of this invention mixture and gelatin composition, and the monolayer of this invention mixture and gelatin composition.
But United States Patent (USP) 5089307 has disclosed the edible film of heated sealant, and this film comprises at least one rete, and rete comprises the water soluble polysaccharide as major constituent, polynary alcohol and water.It is said that described film can be used as the sealing and the packaging material of dried foods, oily food etc.It is said that useful polysaccharide comprises alginic acid and salt (as sodium salt) thereof; Furcellaran; Carrageenin, as κ-, ι-and λ-carrageenin; Agar; Pectin is as high methoxyl and hypo-methoxy pectin; Natural gum is as tamarind gum, xanthan gum, guar gum, Caesalpinia spinosaKuntze glue, locust bean gum; Pullulan; Chitin derivative is as chitosan; Starch is as Semen Tritici aestivi, corn and potato starch; Dextrin; The edible water-soluble cellulose derivative is as carboxymethyl cellulose; The mixture of above-mentioned substance.The weight ratio of polyhydric alcohol and polysaccharide is preferably 1: 5-1: 1, and polysaccharide exists to be no less than 50% of active component total amount.
United States Patent (USP) 6331205 has disclosed and has been used for preparation and only contains carrageenin, is preferably the ι carrageenin, as the viscous aqueous compositions of the soft capsule or the hard capsule of gellant.This patent introduced ι-, λ-, μ-and v-carrageenin.Introduced the plasticizer that belongs to the polyhydroxy class, for example glycerol, Sorbitol, maltodextrin, dextrose, mannitol, xylitol, polyoxyethylene glycol 400-6000, natural glycerin ester and semi-synthetic and derivant thereof etc.Soft capsule it is said by adopting " Scherer " method to obtain.
United States Patent (USP) 6214376 has disclosed the gelatine-free capsules with the preparation of compositions that comprises the water solublity hydrophilic colloid layer, and described water solublity hydrophilic colloid layer comprises the gel film of κ carrageenin and plasticizer.It is said the gelatin-free soft capsule be with the κ carrageenin as main gel forming polymer (account at least form heat-convertible gel or help to form heat-convertible gel gummy weight 50%) make.Can add hydrolyzed starch,, help heat seal, and prevent that gelling salt from causing atomizing to improve solids content as maltodextrin.
United States Patent (USP) 6340473 has been introduced with having hydration temperature and has been less than about 90 ℃ modified starch and ι carrageenin and prepares soft capsule, employing be the rotating mould packaging apparatus.The weight ratio of modified starch and ι carrageenin be it is said the key that forms satisfied film.The weight ratio that is modified starch and ι carrageenin be it is said 1.5: 1.It is said that this patent inventor finds that the ι carrageenin can't generate acceptable film separately, modified starch also can't generate the acceptable film that can be used for sealing separately.The described theory of this patent is, the ι carrageenin plays elasticizer, and allowing does not have elastic modified starch film to have elasticity.
As everyone knows, the few film-forming composition of some solids content height, moisture forms high-viscous solution including (for example) hydrocolloid, makes hydrated film be difficult to form.The invention provides a kind of method, prepare solids content height, film that moisture is few with this high-viscous solution.
In addition, done many trials, prepared soft capsule as hydrocolloid with solids content height, film that moisture is few.But the trial of these preparation soft capsules all has above-mentioned shortcoming.Be that the known water colloid forms high-viscous solution, this solution is difficult to abundant hydration and formation film in conventional soft capsule preparation method.Therefore, the inventive method allows with this film preparation soft capsule.
Summary of the invention
As first kind of embodiment, the present invention relates to the homogeneous, thermoreversible gel film, described gel film comprises the low viscosity polymanna glue of film forming amount, as the low viscosity guar gum, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
As second kind of embodiment, the present invention relates to prepare the method for gel film of the present invention, comprise the steps: (1) in the equipment that enough shearing forces, temperature and the time of staying are provided to low viscosity polymanna glue, as the low viscosity guar gum, and choose any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heat, hydration, mixing, solubilising and the optional degassing, form the homogenizing melt composition, wherein temperature is equal to or higher than the solution temperature of fused mass; (2) the cooling melt composition forms gel film to the gelation temperature that is equal to or less than melt composition.
As the third embodiment, the present invention relates to soft capsule that comprises capsule wall and encapsulating substance and preparation method thereof, wherein capsule wall comprises gel film of the present invention.Described method comprise the steps: (1) in the equipment that enough shearing forces, temperature and the time of staying are provided to low viscosity polymanna glue, as the low viscosity guar gum, and choose any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heat, hydration, mixing, solubilising and the optional degassing, form the homogenizing melt composition, wherein temperature is equal to or higher than the solution temperature of melt composition; (2) directly by melt composition, perhaps cool off melt composition to the gelation temperature that is equal to or less than melt composition, form soft capsule.
As the 4th kind of embodiment, the present invention relates to comprise the solid dosage forms of the packing material of being sealed by homogeneous, thermoreversible gel film of the present invention; Hard capsule for example.
The accompanying drawing summary
Fig. 1 implements the sketch map that the present invention prepares the method for thin film and soft capsule with Stephan processor and extruding machine.
Fig. 2 implements the sketch map that the present invention prepares the method for thin film and soft capsule with fluid mixing apparatus shown in Figure 3 and extruding machine.Sketch map shows that film comes out from extruding machine, is just entering packaging apparatus.
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 the inventive 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 packaging apparatus.
Fig. 5 implements the sketch map that the present invention prepares thin film and soft capsule with fluid mixing apparatus shown in Figure 3, drum cooler and packaging apparatus.
Detailed Description Of The Invention
The gel mould of homogeneous, thermoreversible of the present invention uses the low viscosity polymanna glue of film forming amount. An example of this polymanna glue is the low viscosity guar gum. Found that guar gum commercially is used as emulsifying agent, stabilizing agent and thickener in many fields. In 1% aqueous solution, the viscosity in the time of 25 ℃ is generally at 2-8, the 000mPa scope. The inventor finds, the polymanna glue of particular type, and namely low viscosity polymanna glue (such as the low viscosity guar gum) can be used for preparing film of the present invention and soft capsule. Low viscosity polymanna/guar gum among the present invention, at 1% aqueous solution, the viscosity in the time of 25 ℃ is usually less than 8,000mPa, preferably 2-6,000mPa, 2-4 more preferably, 000mPa, 2-2 more preferably again, 000mPa, 2-1 more preferably also, 000mPa, 2-500mPa is preferably 2-100mPa. Should be understood that low viscosity polymanna and the guar gum of also having measured higher solids, such as ULV 225, when viscosity when 2% solid is measured is 25mPa. Such low viscosity guar gum can be from Indian Gum Industries, Ltd and/or its whole seller such as EDICOL COL ULV Guars, and for example ULV 225, and ULV 25, and ULV 50, and ULV 100, and ULV 200, and ULV 500 and ULV 1000 obtain. Should be understood that the combination that to adopt low viscosity polymanna/guar gum among the present invention. Should also be understood that the guar gum of food grade enzyme modification is also within the scope of the invention.
Notice, be generally considered to be the hydrocolloid of " non-gelling " such as guar gum. Make the inventor surprised be the gel mould that uses the low viscosity guar gum to show to be provided for the effective film intensity of making capsule. At this, by the benefit using the low viscosity guar gum to obtain to process etc.
Low viscosity polymanna/the guar gum of use film forming amount among the present invention (as, increase film-strength to the amount of gel mould), be different from trace low viscosity polymanna/guar gum, trace low viscosity polymanna/guar gum can not make film increase film properties. Therefore, for example, in gel mould of the present invention, the film forming amount of low viscosity polymanna/guar gum is the amount that whole film is increased film-strength. This film forming amount generally is at least 0.25% of xerogel film weight according to application, and better 0.5-90% is better, 0.5-50%, also 0.25-25% more preferably.
Here used " homogeneous membrane " refers to such film, and when detecting by an unaided eye, film is uniformly, does not have block, crack, should dissolve and undissolved particle, does not have insoluble particles skewness etc. " flake " (liquid and solids mixing state) or " glueballs " (non-homogeneous gel structure) do not meet the definition of used " homogeneous " here.
Gel film of the present invention is the homogeneous, thermoreversible gel film.They can be cast, and have extensive use as cast membrane, perhaps are used for subsequent treatment.
Here used " hot reversible film " is meant such film, fusing or mobile during heating.Here used fusion temperature is the temperature or the temperature range of gel film when softening or mobile.Here used word " gel film " refers to the thin film that the hydrocolloid by structure forms.
Gel-forming composition is characterised in that gelation temperature, and the molten gel compositions must be cooled to could form the self-supporting structure below this temperature.Randomly, fused mass can heat be cast, cooling then, and by dry further thickened solid (controlledly removing moisture), up to forming gel film by gel combination.The fusion temperature of heat-convertible gel film is higher than its gelation temperature.
The gel film that is applicable to preparation the present invention capsular homogeneous, thermoreversible can be chosen wantonly and comprise at least a in plasticizer, second film former, extender and the pH controlling agent.The component and the amount thereof that add in the gel film can change according to the required purposes of low viscosity guar gum gel film.
The example of this plasticizer comprises polyhydric alcohol, as glycerol, Sorbitol, maltose alcohol, lactose, corn starch, fructose, polydextrose, dissolved oil, propylene glycol and poly alkylene glycol, as Polyethylene Glycol.The amount of plasticizer can change according to the purposes and the required elasticity of gel film.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, better at least 10 weight %, better at least 20 weight %, 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 may be fully plasticizer-containing not.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 comprises at least a in the following material: natural and synthetic water colloid as, at least a λ carrageenin as κ carrageenin, kappa-2 carrageenan, ι carrageenin, and seldom has complete improved form, and their combination; Polymanna with viscosity higher than low viscosity guar gum of the present invention; Alginate, propylene glycol alginate; Pulullan polysaccharide (pullulan), gellan gum (gellan) (comprising high acyl group and low acyl group gellan gum); Dextran and pectin.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 3:6AG2S of the κ carrageenin of the prominent Eucheuma muricatum (Gmel.) Web.Van Bos. (Eucheuma cottonii) of ear (known usually Sargassum source) and 3:6AG content as the κ carrageenin less than about 10%; Be about 85% from the 3:6AG2S of the ι carrageenin of Eucheuma spinosum (Eucheuma Spinosum) (usually known Sargassum source) and the mol ratio of 3:6AG content as the ι carrageenin.The structure and the degree of functionality of κ carrageenin, kappa-2 carrageenan and ι carrageenin differ from one another.If desired, when using ι carrageenin, κ carrageenin or kappa-2 carrageenan as second film former, this carrageenin, with the total solution weight is benchmark, reduce in the 0.10 mole nacl solution of molecular weight carrageenin, containing 1.5% at 75 ℃ viscosity 19cps or littler, better less than 10cps.This viscosity test adopts BrookfieldLVF, and (Brookfield Engineering Laboratories, Inc) viscometer adopt the #1 spindle, and rotating speed is 60rpm, change 6 circle backs and measure viscosity.An example that can be used for alkyl cellulose ether of the present invention is a hydroxyethyl-cellulose.The example that can be used for modification alkyl cellulose ether of the present invention comprises hydroxypropyl cellulose and hydroxypropyl emthylcellulose.When gel film of the present invention contains second film former, low viscosity guar gum amount can the xerogel film in the film former gross weight at least 10%, at least 20%, at least 50%, or at least 80% exist.
Notice some second film former, the gelling property and the film-strength that can contain carrageenin as carrageenin have positive effect and negative effect.This useful cation comprises potassium and ammonium.These cationes can be present in the carrageenin, maybe can add from other organic or inorganic sources.These useful cationic amounts can gel film (comprising water) in 20% the existing of carrageenin dry weight.This amount can change according to the component in the system, required fusion temperature and seal temperature.
Other cationes can have adverse effect to the stability of carrageenin as calcium (as mentioned above), magnesium, aluminum and chromium, should make its content keep minimum, as be lower than 10% of the middle alginate dry weight of gel film (comprising water), are lower than 5%, are lower than 1%.
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 Process ingCorporation, Muscatine, Iowa), and C AraTex
TM75701 (available from Cerestar, Inc.).The example of starch hydrolysate comprises maltodextrin, also claims dextrin.Unmodified starch, as potato starch, when with the scope of the invention in hydrocolloid when combination, also can increase film-strength.Usually, modified starch is the product that starch is carried out the chemical treatment preparation, for example acid treated starches, enzyme treated starch, Oxytarch, crosslinked starch and other starch derivatives.Modified starch is preferably deutero-, and wherein side chain carries out modification with hydrophilic or hydrophobic group, forms the more complicated structure with 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, 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 be multi-functional.Promptly except being used as extender, they also can be used as second film former.When as the solubilizing agent and second film former, according to its purposes, for example be used to form soft capsule, their consumption accounts at least 10 weight % of xerogel film weight usually, is preferably at least 20 weight %, more is preferably at least 30 weight %.
The example that is used for pH controlling agent of the present invention comprises inorganic base and organic base.Preferred pH controlling agent comprises hydroxide, carbonate, citrate and phosphate.The pH controlling agent can be selected as being added with Yiyang ion source, as potassium.To some compositions, the pH controlling agent can be used to improve the stability of gel film.The amount of pH controlling agent generally accounts for the 0-4% of xerogel film, more is preferably 0-2%.
Discover that the disruptive force (for example) of xerogel film of the present invention (for example containing 80% solid or higher) is 1500g, 2500g at least at least, at least 4000g, at least 5000g, 6000g at least, available Texture AnalyzerTA-108S Mini Film Test Rig measures.
Find 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 still have in the gel film nearly 15%, 10%, 5% water consumingly with solid bond.
The thickness of dry film that is used for soft capsule is usually in the 0.5-3.0mm scope, and is more suitable in the 0.8-1.2mm scope.
Film of the present invention may comprise non-thermal reversibility glue.But for homogeneity and the thermal reversibility to gel film of the present invention not causes adverse effect, this non-thermal reversibility film should should be less than 40 weight % to be less than 50 weight % of low viscosity guar gum weight, and the more suitable 30 weight % that are less than exist.The example of this non-thermal reversibility glue comprises crosslinked and partial cross-linked natural gum, solidifies (for example crosslinked) pectin and/or alginate as calcium.Do not having under the situation of bivalent cation, active alginate of calcium and pectin, and their poor slightly refined form are considered to hot reversible glue.Reversible glue of other non-heat such as tragacanth help the thermal reversibility of kappa-2 carrageenan, its effect is by absorb water in its structure, thereby make kappa-2 carrageenan form finer and close three dimensional structure, when it is dissolved in the low amounts of water, provides and increased low viscosity polymanna/same effect of guar gum amount when not having second film former.
Usually with such prepared, this process using can provide the equipment of sufficiently high shearing force, temperature (being higher than gelation temperature) and the time of staying to gel film of the present invention, and to obtain the homogenizing melt composition, the cooling back forms gel.This can finish by heating, hydration, mixing, dissolving and optional degassing compositions in equipment usually.This equipment includes but not limited to Ross blender, Stephan datatron, conventional jet-propelled steamer, extruding machine and fluid mixing apparatus shown in Figure 3.Ross blender, Stephan datatron, extruding machine and conventional jet-propelled steamer 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 carry out the equipment of any one in these functions is an extruding machine.Extrusion melt can be sent into film forming or former (for example spread-coating case, as be used in the capsule forming machine), help evenly to cast continuous film, perhaps send extrusion melt to mould, so that from the fused mass conveying equipment, directly form film.Must be noted that, before limiting mobile/gel structure formation beginning, keep the state of fused mass.Can adopt adiabatic and preheating (in order to keep suitable temperature) delivery hose, guarantee smelt flow, be formed on casting roll or other one-tenth film spots, as beginning on extruding machine (restricted mobile, film-forming apparatus) or the mould up to required gel film.Can force (passing through pressure) fused mass by delivery hose above-mentioned with other processing methods (as preheating discharging/piston sample head (discharge/plunger-like head), as in the Ross processing system, seeing).Other thermal insulation also can help to keep the temperature of fused mass, as place teflon sheet immediately after removing mixing apparatus on melt surface.In addition, feed hose can be packed into and be arranged in thermal control fused mass charging (casting) case 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 of follow-up formation capsule film, keep temperature, the minimizing moisture loss of fused mass in the material feeding box and guarantee evenly (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, can directly film be sent into then and form capsular equipment, be stored under the temperature that to keep suitable membrane stage (to form capsule) until needed so far, perhaps be dried to desired moisture content, solid and texture level, until needed so far.This dry film has the character (can add water by any method) that absorbs moisture in its whole gel film matrix again, works as needs, and is for example rehydrated when 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/texture.
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 entrance point 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, withdraw from mixing chamber 52 then.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.
Next referring to Fig. 4, comprise with fluid mixing apparatus 10 preparation films and capsular system 100 being used for preparing and the film forming apparatus 60 of feed membrane 9 and form the capsule machine 80 of capsule 89.Film forming apparatus 60 comprises: fluid mixture equipment 10; First fluid supply equipment 62 is used for to fluid mixing apparatus 10 supply first fluids 4; Second fluid supplying apparatus 64 is used for to fluid mixing apparatus 10 supplies second fluid 6; Mixed serum service duct 70 is used for by fluid mixing apparatus 10 to former supply fused mass or mixed serum 8; The optional extruding machine 73 that links to each other with mixture service duct 70 is in order to mixture 8 extrusion molding film forming 9; Form the capsule machine 80 of capsule 89; The capsule 90 that is filled with content is delivered to subsequent processing, as conveyer belt 90 dry or packing.Extruding machine 73 can be the type that Wenger or Clextrel produce.
Capsule machine 80 can be R.P.Scherer Technologies (Paradise Valley, Nevada) the sort of traditional rotating mould capsule machine of Sheng Chaning.As shown in Figure 4, capsule machine 80 comprises capsule product storage tank 82, is used for placing the capsule product 81 that will seal.Capsule product 81 can comprise the food additive of liquid state, semi liquid state or powder medicaments, vitamin, extra-nutrition thing, pigment ball, colorant, agricultural active material and scheduled volume.Capsule machine 80 can link to each other with one or more rollers 77,77 ' and 78,78 ', so just film 9,9 ' can be moved in the capsule machine 80.Film 9 is delivered between heat block 86 and the roller die 88.With vacuum some part on the film 9 is moved in the depression that forms in rotating mould 88 surfaces.By vacuum action, a certain amount of capsule product 81 is conveyed into " compartment " that forms in the film 9.Mould 88,88 ' further rotation make in the engagement of film 9,9 ' between rotating mould 88,88 ' and are sealed.The capsule 89 of filling drops in the hopper 87,87 ', is put into then on the conveyer belt 90, sends to drying and packing.
Next referring to Fig. 5, capsule preparation system 100a is similar to shown in Figure 4, and wherein similarly label is represented similar parts.But in Fig. 5, film forming apparatus 60a comprises optional spread-coating case 72 and optional drum cooler or casting drum 74, replaces the extruding machine 73 in the system shown in Figure 4.System 100a comprises fluid mixing apparatus 10 and mixture service duct 70, and mixed slurry 8 is derived fluid mixing apparatus, delivers to spread-coating case 72.Spread-coating case 72 is applied to mixture 8 on the casting drum 74.Along with the cooling of mixture 8, film 9 forms on casting drum 74.After this, film 9 is delivered to capsule machine 80.Film 9 ' preferably forms by the mode identical with film 9 with second film forming apparatus (not shown).
As another aspect of the present invention, fused mass not necessarily will reach homogenizing in step (1).That is to say, when other equipment such as employing blender, pump and/or exhaust chamber, can melt composition is sent in pump, blender or the exhaust chamber at least one before or after, make fused mass reach homogenizing, as long as fused mass reached homogenizing before gelling.
Owing to show, the dry film intensity of gel film of the present invention reaches at least 2500 grams, and they are fit to the preparation soft capsule very much.Therefore, the present invention also relates to soft capsule by homogeneous thermoreversible low viscosity guar gum gel film preparation of the present invention, and the method for preparing this soft capsule.
The method for preparing soft capsule with low viscosity guar gum gel film of the present invention comprises any conventional packaging apparatus of use, for example traditional rotating mould equipment or recessed punch die.For example, in case form fused mass of the present invention, it can be cast on the drum, cooling is sent into rotation then and is sealed between the mould, heating film once more there, filling, sealing and cutting.To the better description of this traditional handicraft, can be referring to WO 98/42294.Perhaps, as the advantage of the present invention with respect to the traditional soft capsule preparation method thereof, available above-mentioned high shear force equipment with on its paint drum, is sent into traditional packaging apparatus while cooling off by the abundant hydration of fused mass then, is used for filling, sealing and cutting.This continued operation method can be saved the step that preparation is heated once more to abundant gelling and refrigerative film during capsule.Above-mentioned rotating mould method can be used to prepare the soft capsule that the present invention has any required form.
The cooling melt composition forms after the film of half gelling of the present invention or complete gelation, and before the preparation soft capsule, the moisture of such film is less than 50%, 25%, 15% of total composition weight in the film.
The packing material of soft capsule can be any material that is widely used in above-mentioned rotating mould method, comprise ingredient, agricultural composition, nutraceutical composition, composition for animals, food, cosmetics, personal nursing, industry etc., and can be liquid (comprising emulsion), suspension, dispersion etc.
The invention still further relates to the solid dosage forms that comprises the packing material of sealing by homogeneous, thermoreversible gel film of the present invention.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, thereby forms two and half shells, and the packing material that is generally powder is put in the shell, and two and half shells are lumped together, and forms hard capsule.Preparing the step that the method for this hard capsule is usually directed to is, metal needle or rod 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, or solid, as powder.Packing material can be ingredient, agricultural composition, nutritional labeling, composition for animals, food, cosmetic composition 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-infringement ability that hard capsule can strengthen product with gel film of the present invention.
The dissolution that also available gel film changes dosage form distributes.For example, can add the component that can produce 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.
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 calculated by weight.
Embodiment
Except as otherwise noted, following processes is to be used for preparing and to measure material among the embodiment 1-3 and film.Stephan UMC5 datatron is the laboratory scale mixing apparatus, and suitable high shear mixing, heating and the degassing can be provided the preparation of casting film in the laboratory.Suitable batch with Stephan UMC5 datatron is 1500g.
The aqueous dispersion for preparing starch like this: any salt/buffer agent and pH regulator agent are dissolved in the deionized water, add starch and/or maltodextrin (M100), mix, up to dissolution.Pure Cote
B760 and B790 starch can be available from Grain Processing Corporation, Muscatine, Iowa.Preparation hydrocolloid mixture in Stephan UMC5 datatron: the premixing plasticizer adds the dry hydrocolloid of premixing until evenly in batches, and each back that adds was with 200rpm stir about 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 300rpm.Mechanical agitation speed is increased to 2100rpm, while stirring mixture heated is arrived 85-95 ℃.After reaching target temperature, stirred the mixture 30 minutes, under continuous stirring, sample remained under the vacuum (50-60 crust) then 45 minutes.
Retention time under vacuum and temperature when finishing pours sample through in 1 quart of Mason glass jar of wide-mouth of preheating into.Record temperature and pH.Viscosity with the hot sample of Brookfield LVF viscometer determining.
Take out the fraction sample, general 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.One fritter placed through the gel of cold preservation be fixed on the invisible spectro wire stent, make gel piece not contact test tube wall, measure the fusion temperature of gel thus.Cover test tube with aluminium foil, open an aperture on the aluminium foil, so that with the temperature of digital temperature probe assay gel.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 contains cold running water (15 ℃).When sample cools off, measure temperature with temperature probe, and the sample for reference surface, to determine whether sample begins gelling.It is no longer mobile when cooling that gelation temperature is a sample, the temperature when filling up the indenture that probe stabs out.
Then, draw the wide gap of 3mm with the scraper plate that has the gap setting element, hot sample is cast on 177mm * 177mm * 5mm metallic plate, metallic plate is sprayed with PAM (lecithin) in advance, is convenient to the moving film material.Cover the plate that scribbles gel, in case moisture is from the cast membrane loss.The general cold preservation of cast membrane (being lower than 8 ℃) is half an hour at least, film is taken off test then.Do not need cold preservation in the film forming.The dry coating plate prepares the dry film bar in 40 ℃ of blowing-type baking ovens.Film obtains the intermediate value solid and is about 60% 40 ℃ of dryings 2 hours, and film is 40 ℃ of dried overnight, then generally obtains 80% or higher solid.(about 20 ℃) working sample character except as otherwise noted, generally at room temperature.The percent solids of dry film is determined by the solid cast membrane of preparation and the weight difference between dry film.Measure the disruptive force (BF) of cast membrane bar and dry film bar with Texture Analyzer TA-108S Mini Film TestRig.
Except as otherwise noted, Maltrin M100 is available from Grain Processing Corporation, and PureCote B760 is available from Grain Processing Corporation, and Sorbitol Special is available from SPIPolyols, and glycerol is available from VWR (EP/USP level).
Embodiment 1
Following Table II is listed the composition and the film properties of the prescription that uses low viscosity melon ear ULV 50 and low viscosity guar gum and kappa-2 carrageenan combined preparation.
Cgn A is a kappa-2 carrageenan, ratio is 1.5 to 3.0: 1 the κ carrageenin and the natural statistic copolymer of ι carrageenin, and the clarified extract as China fir algae (Gigartina skottsbergii) (main monoploid (gametocyte) plant) alkali treatment obtains respectively.Also there be a small amount of (total amount is below 5%) λ and θ-carrageenin from diploid (tetrasporaphite) plant.
Cgn B is a kappa-2 carrageenan, is that the clarified extract of mixture (main monoploid (gametocyte) plant) alkali treatment as China fir algae (Gigartina skottsbergii) and Sarcothaliacrispata obtains.Also there be λ and the θ-carrageenin of about 10-20% (total amount) from diploid (tetrasporaphite) plant.
The performance of kappa-2 carrageenan is listed in Table I.Use Brookfield LVF viscometer,, the solid viscosity in aqueous solution of 1.5 weight % is arranged 75 ℃ of mensuration with suitable speed and spindle.Use TXTM Texture analyser, mensuration is used 2 weight % sample Cgn A but is not added cation (#1), adds (#2) of 0.2 weight %KCl and adds 0.2%KCl and 0.2%CaCl
2The performance of (#3).In 25 ℃ of test gels, record disruptive force (gram) and penetrance (cm).
Table I: 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 II. use the preparation and the film properties of guar gum and kappa-2 carrageenan
| Component (g) | Embodiment 1-1 | Embodiment 1-2 | Embodiment 1-3 | Embodiment 1-4 | Embodiment 1-5 |
| 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 |
| Melon ear 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 | |||||
Though the intensity of some preparation is greater than other preparations, the preparation above all demonstrates enough dry film intensity, can be used for the manufacturing of soft capsule.Believe that gel film of the present invention is enough to prepare soft capsule in 16 hours dry film intensity of 40 ℃ of dryings on existing equipment.And 2 hours dry film intensity of 40 ℃ of dryings also is enough to prepare soft capsule as embodiment 1-3 to 1-5 on existing equipment.The mixture of embodiment 1-2 proof 55-45 weight % guar gum and kappa-2 carrageenan with have only guar gum (embodiment 1-1) to compare to have improved intensity.Comparing embodiment 1-4 and 1-5 show that needs keep the processing temperature of fused mass to be higher than gelation temperature, provide (the dry back) of finishing gel strength as embodiment 1-5, and ratio is at the film (embodiment 1-4) high at least 28% of 87 ℃ of casting when 95 ℃ of casting.Lower gel strength value is the pregelatinised reflection of film forming procedure possibility, causes low relatively gel strength.All films do not have syneresis when storing, and have kept their relative flexibility.
Generally, find that viscosity is to be maximum or near maximum under the testing equipment that adopts and the condition.Therefore, use the ancillary equipment with initial hydration/activating apparatus that other shearing and solids-enriched effect can be provided, fine maintenance process temperature is more than its high solid curing/gelation temperature (＞100 ℃) simultaneously.It is extrusion molding type equipment that the example of this ancillary equipment is not limited to, be enough to the temperature that keeps suitable and provide uniform mixing required shearing, and the fused mass that is used for 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 forms and function.
Use the low viscosity guar gum ULV 50 and the blend compositions of the combination of κ carrageenin or κ carrageenin and/or ι carrageenin to prepare film, described film properties is listed in Table III and Table IV.The carrageenin of use is described below.Carrageenin L has the κ carrageenin that viscosity is 10-15cp.
Table III
Use the film of low viscosity guar gum and κ carrageenin
| Component (g) | Embodiment 2-1 | Embodiment 2-2 | Embodiment 2-3 | Embodiment 2-4 |
| 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 | ||||
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for the manufacturing of soft capsule.
Use the combination of κ carrageenin and guar gum (embodiment 2-2) to improve film-strength with guar gum (embodiment 1-1) than single.
Add KCl (embodiment 2-3) and improved gelation temperature and 40% solid gel strength.In addition, the ratio that adds KCl and change over film component will 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, control cation bivalence can prevent desirably/make that gel sclerosis and fragility reduce to minimum.
Table IV 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 long heart card handkerchief algae (Kappaphycus alverezii) (ear dash forward Eucheuma muricatum (Gmel.) Web.Van Bos.).Cgn D is the clarification ι carrageenin extract of the alkali treatment of serration Eucheuma muricatum (Gmel.) Web.Van Bos. (Eucheuma denticulatum) (Eucheuma spinosum).Cgn C and Cgn D have low bivalence.
Table IV
Use the film of guar gum, κ carrageenin and ι carrageenin
| Component (g) | Embodiment 2-5 | Embodiment 2-6 | Embodiment 2-7 | Embodiment 2-2 |
| 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 | 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 |
| During casting | ||||
| 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 (%), Brix | 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 | ||||
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for the manufacturing of soft capsule.Top embodiment shows the situation that other carrageenin increase low viscosity guar gum film-strengths that adds.In addition, can strengthen and control gelling/fusion temperature by adding an amount of cation.
Embodiment 3
Table V 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 (M) and the unitary polyuronic acid copolymer of guluronic acid (G).KAHG is a kind of potassium alginate, and wherein alginate have high-caliber G unit, and extracts from Thallus Laminariae (Thallus Eckloniae) (Lanlinariahypezborean).KAHM is a kind of potassium alginate, and wherein alginate have high-caliber M unit, and extracts from horizontal stripe thunder pine algae (Lessonia trabeculata).
Table V is used the film of low viscosity guar gum, potassium alginate and carrageenin
| Component (g) | Embodiment 3-1 | Embodiment 3-2 | Embodiment 3-3 | Embodiment 3-4 | Embodiment 3-5 | Embodiment 3-6 |
| 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 | 88.2 | 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 |
| Average film thickness (mm) | 0.83 | 0.76 | 0.56 | 0.60 | 0.56 | 0.59 |
| *Temperature and the viscosity of fused mass before casting | ||||||
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for the manufacturing of soft capsule.
Table VI is listed the composition and the performance of the gel 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 120 RB are from FMC Corporation (Philadelphia, PA) sodium alginate of Huo Deing.
Table VI
Use the film of guar gum and alginate
| Component (g) | Embodiment 3-7 | Embodiment 3-8 | Embodiment 3-9 |
| 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 |
| Starch B760 | 220.8 | 220.8 | 220.8 |
| M100 | 0 | 0 | 15.0 |
| Sorbitol SP | 264.4 | 264.4 | 264.4 |
| Glycerol | 88.2 | 88.2 | 88.2 |
| Gross weight | 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 (%), | 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 |
| Average film thickness (mm) | 0.53 | 0.89 | 0.51 |
| BF(g) | 4780 | 7701 | 10850 |
| *Temperature and the viscosity of fused mass before casting | |||
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for the manufacturing of soft capsule.
Table VII is listed forming and performance of the gel 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 Corporation (Philadelphia PA) and Kibun respectively.
Table VII
Use the film of low viscosity guar gum and propylene glycol alginate
| Component (g) | Embodiment 3-10 | Embodiment 3-11 | Embodiment 3-12 | Embodiment 3-13 | Embodiment 3-14 |
| 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 | 4.3 | 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 |
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for preparation of soft capsule.
Embodiment 4
The fluid of Fig. 3 mixes
Following examples have illustrated the film with fluid mixing apparatus preparation shown in Figure 3.In these embodiments, part A and part B at room temperature from storage capsule separately as two strands independently logistics 4,6 enter two different inlets 42,44, logistics can be sent into the fluid mixing apparatus 10 that injects steam from these two inlets.Independently join on the vapor interface of logistics 4,6 in the mixed zone 52 of fluid mixing apparatus 10 for two strands.The independent solution of part A and part B pumps into fluid mixing apparatus 10 easily and mixes 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, scrape and paint homogeneous membrane 9.
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 blowing-type baking ovens, make fresh film 9 dryings.Measure the disruptive force of cast membrane bar and dry film bar with Texture Analyzer TA-108S Mini Film TestRig.The difference of measuring between the final weight of the initial weight of fresh film and dry film is determined percent solids.
For measuring gelation temperature, collect a part of fused mass 8 from the outlet 56 of mixing apparatus 10, be transferred to test tube, half of test tube is empty.Glass-stem thermometer is inserted fused mass 8.Allow material 8 cool off at ambient temperature.After every cooling once, thermometer is taken out from material 8.When a little 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 indenture can not be filled like this.Temperature when record forms permanent indenture.The gelation temperature of being reported is the scope between two temperature that write down.
Table VIII
The mixture that contains the LV guar gum
| The embodiment numbering | 4-1 | 4-2 | 4-3 |
| Part A (%) | |||
| | 0 | 4.0 | 4.2 |
| Carrageenin 1 | 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 | 36.9 | ||
| 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 | 65 | 70 | 55 |
| Gelation temperature (℃) | 60-65 | 46 | ＞100 |
| Wet film intensity (gram) | 460 | 3402 | 921 |
| Dry film intensity (gram) | 5299 | 6587 | 9234 |
Though the intensity of some preparation is greater than other preparations, preparation all demonstrates enough dry film intensity above all, can be used for the manufacturing of soft capsule.
Following Table I X and Table X provide further describing the component of enumerating among the embodiment in the above.
Table I X
Component is described
| Title | Trade name | Supplier | Describe |
| Low viscosity guar gum (LV guar gum) | Edicol ULV 50 | Indian Gum Industries，Ltd | |
| Glycerol | Callahan Chemical | 99.70％ | |
| Sorbitol | Sorbo | SPI Polyols | 70% sorbitol solution, USP/FCC |
| Starch | Pure-Cote B790 | Grain Processing Corporation |
Following table X provides the description of the various carrageenin that use among this embodiment.
Table X is to the description of carrageenin
| Labelling | The carrageenin type | Describe | Supplier |
| Carrageenin 1 | κ | From alkali processing, the clarifying κ-carrageenin extract of Kappaphycus alverezii (ear dash forward Eucheuma muricatum (Gmel.) Web.Van Bos.), bivalence content is low | FMC Corp. |
| | Low bivalence κ-2 | From the China fir algae, be mainly the processing of monoploid (gametocyte) plant alkaloid, clarifying low bivalence extract, this extract often is called " kappa-2 carrageenan ".Also comprise a small amount of (below 5% of total amount) 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 functionality. | FMC Corp. |
Embodiment 11
Polymanna glue prepares gel film below using: Rhizoma amorphophalli, locust bean gum (LBG) and CLBG/ guar gum, the clarified mixture of a kind of locust bean gum and guar gum (60/40 weight ratio).When with 1.5 aqueous solutions, when measuring for 75 ℃, the Brookfield viscosity of κ carrageenin is respectively 10-15cp, and the Brookfield viscosity of ι carrageenin is 30-50cp.Make the dry pre blend thing by these colloids.Weighing distilled water and glycerol add 1.2L rustless steel beaker.Under fully stirring the dry pre blend thing is added in the entry, be heated to 90 ℃ then, and kept 15 minutes, with complete hydrolysis glue at 90-95 ℃.Hot solution is poured in the container fast.The solution that casts in the petri diss is cooled to room temperature, forms thin film, in the forced ventilation baking oven, 45 ℃ of dried overnight are to constant weight then.Film properties is listed in the table below.
Table X I
Polymanna glue mixture preparation and performance
| Component (gm) | S | 1 | 2 | 3 | 4 |
| Distilled water | 195.0 | 195.0 | 195.0 | 195.0 | 195.0 |
| Glycerol | 50.0 | 50.0 | 50.0 | 50.0 | 50.0 |
| κcgn | 1.90 | 1.65 | 3.50 | 1.65 | 1.65 |
| ιcgn | 3.10 | 2.65 | 0 | 2.65 | 2.65 |
| Rhizoma amorphophalli | 0 | 0.70 | 1.50 | 0 | 0 |
| LBG | 0 | 0 | 0 | 0.70 | 0 |
| The CLBG/ guar gum | 0 | 0 | 0 | 0 | 0.70 |
| BF，gm | 955 | 1218 | 3244 | 1796 | 1903 |
| Penetrate cm | 2.1 | 1.6 | 1.4 | 1.6 | 1.9 |
| Rigidity | 455 | 761 | 2317 | 1123 | 1002 |
| Fusion temperature, ℃ | 36 | 43 | 39-43 | 49-52 | 45 |
| Gelation temperature, | 22 | 30 | 26 | 30 | 32 |
As described above and proof, the film of making according to the present invention can be used for the conventional capsule manufacturing equipment of preparation gelatine capsule in the past.The refuse that the hydrocolloid film that the present invention makes produces is few, and than the easier processing of gelatin basement membrane.
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 spirit and scope of the invention, can make various changes and modifications with reference to the specific embodiment.
Claims
(according to the modification of the 19th of treaty)
1. homogeneous, thermoreversible gel film, it comprises the low viscosity guar gum of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
2. film as claimed in claim 1, it is characterized in that, described second film former is selected from starch, starch derivatives, glucidtemns, cellulose gum, λ carrageenin, κ carrageenin, kappa-2 carrageenan, ι carrageenin, polymanna glue, alginate, propylene glycol alginate, pulullan polysaccharide, gellan gum, dextran, pectin, alkyl cellulose ether and the modification alkyl cellulose ether at least a, and described coloring agent is at least a polyhydric alcohol.
3. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount is at least 0.25% of a gel film weight.
4. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount is the 0.25-25% of gel film weight.
5. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 10%.
6. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 40%.
7. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 60%.
8. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 80%.
9. film as claimed in claim 1 is characterized in that described film has at least 2, the disruptive force of 500g.
10. film as claimed in claim 1 is characterized in that described film has at least 4, the disruptive force of 000g.
11. film as claimed in claim 1 is characterized in that, described film has at least 5, the disruptive force of 000g.
12. film as claimed in claim 1 is characterized in that, described film has at least 6, the disruptive force of 000g.
13. film as claimed in claim 1 is characterized in that, its solids content is at least 50% of gel film weight.
14. film as claimed in claim 1 is characterized in that, its solids content is at least 60% of gel film weight.
15. film as claimed in claim 1 is characterized in that, its solids content is at least 70% of gel film weight.
16. film as claimed in claim 1 is characterized in that, its solids content is at least 80% of gel film weight.
17. film as claimed in claim 1 is characterized in that, its solids content is at least 90% of gel film weight.
18. film as claimed in claim 1 is characterized in that, the viscosity of described low viscosity guar gum is less than 8000mPa.
19. soft capsule comprises capsule wall and entrapped material, described capsule wall comprises each described film among the claim 1-18.
20. soft capsule as claimed in claim 19 is characterized in that, the solids content of described capsule wall is at least 50%.
21. soft capsule as claimed in claim 19 is characterized in that, the described material of sealing be selected from medicine, vitamin, extra-nutrition thing, pigment ball, colorant, agricultural composition, cosmetics, flavoring agent or the food at least a.
22. prepare the method for each described gel film among the claim 1-18, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to described low viscosity guar gum, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of melt composition;
Described melt composition is cooled to is equal to or less than its gelation temperature, form gel film.
23. method as claimed in claim 22 is characterized in that, described melt composition direct at least a in input mixer, pump or the exhaust chamber before cooling.
24. method as claimed in claim 22 is characterized in that, described equipment is Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
25. prepare the method for the described soft capsule of claim 19, described soft capsule comprises each described gel film among the claim 1-18, described method comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to the low viscosity guar gum, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of fused mass;
(ii) directly make soft capsule, or described melt composition is cooled to be equal to or less than its gelation temperature, make soft capsule by said composition afterwards by described melt composition.
26. method as claimed in claim 25 is characterized in that, described equipment is Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
27. method as claimed in claim 25 is characterized in that, described melt composition is at least a in direct input mixer, pump or the exhaust chamber before making soft capsule.
28. a solid dosage forms comprises the packing material of being sealed by each described homogenizing, heat-convertible gel film among the claim 1-19.
29. solid dosage forms as claimed in claim 28 is characterized in that, described packing material is powder, sheet, capsule sheet, microcapsule or capsule.
30. solid dosage forms as claimed in claim 28 is characterized in that, described solid dosage forms is a hard capsule.
31. the homogeneous, thermoreversible gel film, it comprises the low viscosity polymanna of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
32. prepare the method for gel film, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to described low viscosity polymanna, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of melt composition;
Described melt composition is cooled to is equal to or less than its gelation temperature, form gel film.
33. soft capsule, comprise capsule wall and entrapped material, described capsule wall comprises homogenizing, heat-convertible gel film, and described gel film comprises the low viscosity polymanna of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
34. solid dosage forms comprises the material of being sealed by the homogeneous, thermoreversible gel film, the low viscosity polymanna of described gel film film forming amount, and choose any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
35. prepare the method for soft capsule, described method comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to the low viscosity polymanna, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of fused mass;
(ii) directly make soft capsule, or described melt composition is cooled to be equal to or less than its gelation temperature, make soft capsule by said composition afterwards by described melt composition.
36. film as claimed in claim 1 is characterized in that, described film is plasticizer-containing not.
37. film as claimed in claim 1 is made up of low viscosity guar gum, extender and water.
38. film as claimed in claim 37 is characterized in that, described extender is a corn syrup.
39. soft capsule comprises capsule wall and entrapped material, it is characterized in that, described capsule wall comprises each described film among the claim 36-38.
40. film as claimed in claim 31 is characterized in that, described film is plasticizer-containing not.
41. film as claimed in claim 40 is made up of low viscosity guar gum, extender and water.
42. film as claimed in claim 41 is characterized in that, described extender is a corn syrup.
43. soft capsule comprises capsule wall and entrapped material, it is characterized in that, described capsule wall comprises each described film among the claim 40-42.
Claims (35)
1. homogeneous, thermoreversible gel film, it comprises the low viscosity guar gum of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
2. film as claimed in claim 1, it is characterized in that, described second film former is selected from starch, starch derivatives, glucidtemns, cellulose gum, λ carrageenin, κ carrageenin, kappa-2 carrageenan, ι carrageenin, polymanna glue, alginate, propylene glycol alginate, pulullan polysaccharide, gellan gum, dextran, pectin, alkyl cellulose ether and the modification alkyl cellulose ether at least a, and described coloring agent is at least a polyhydric alcohol.
3. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount is at least 0.25% of a gel film weight.
4. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount is the 0.25-25% of gel film weight.
5. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 10%.
6. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 40%.
7. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 60%.
8. film as claimed in claim 1 is characterized in that, described low viscosity guar gum amount be in the gel film the second film former total amount at least 80%.
9. film as claimed in claim 1 is characterized in that described film has at least 2, the disruptive force of 500g.
10. film as claimed in claim 1 is characterized in that described film has at least 4, the disruptive force of 000g.
11. film as claimed in claim 1 is characterized in that, described film has at least 5, the disruptive force of 000g.
12. film as claimed in claim 1 is characterized in that, described film has at least 6, the disruptive force of 000g.
13. film as claimed in claim 1 is characterized in that, its solids content is at least 50% of gel film weight.
14. film as claimed in claim 1 is characterized in that, its solids content is at least 60% of gel film weight.
15. film as claimed in claim 1 is characterized in that, its solids content is at least 70% of gel film weight.
16. film as claimed in claim 1 is characterized in that, its solids content is at least 80% of gel film weight.
17. film as claimed in claim 1 is characterized in that, its solids content is at least 90% of gel film weight.
18. film as claimed in claim 1 is characterized in that, the viscosity of described low viscosity guar gum is less than 8000mPa.
19. soft capsule comprises capsule wall and entrapped material, described capsule wall comprises each described film among the claim 1-18.
20. soft capsule as claimed in claim 19 is characterized in that, the solids content of described capsule wall is at least 50%.
21. soft capsule as claimed in claim 19 is characterized in that, the described material of sealing be selected from medicine, vitamin, extra-nutrition thing, pigment ball, colorant, agricultural composition, cosmetics, flavoring agent or the food at least a.
22. prepare the method for each described gel film among the claim 1-18, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to described low viscosity guar gum, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of melt composition;
Described melt composition is cooled to is equal to or less than its gelation temperature, form gel film.
23. method as claimed in claim 22 is characterized in that, described melt composition direct at least a in input mixer, pump or the exhaust chamber before cooling.
24. method as claimed in claim 22 is characterized in that, described equipment is Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
25. prepare the method for the described soft capsule of claim 19, described soft capsule comprises each described gel film among the claim 1-18, described method comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to the low viscosity guar gum, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of fused mass;
(ii) directly make soft capsule, or described melt composition is cooled to be equal to or less than its gelation temperature, make soft capsule by said composition afterwards by described melt composition.
26. method as claimed in claim 25 is characterized in that, described equipment is Ross blender, Stephan datatron, extruding machine, jet boiler or fluid mixing apparatus.
27. method as claimed in claim 25 is characterized in that, described melt composition is at least a in direct input mixer, pump or the exhaust chamber before making soft capsule.
28. a solid dosage forms comprises the packing material of being sealed by each described homogenizing, heat-convertible gel film among the claim 1-19.
29. solid dosage forms as claimed in claim 28 is characterized in that, described packing material is powder, sheet, capsule sheet, microcapsule or capsule.
30. solid dosage forms as claimed in claim 28 is characterized in that, described solid dosage forms is a hard capsule.
31. the homogeneous, thermoreversible gel film, it comprises the low viscosity polymanna of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
32. prepare the method for gel film, it comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to described low viscosity polymanna, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of melt composition;
Described melt composition is cooled to is equal to or less than its gelation temperature, form gel film.
33. soft capsule, comprise capsule wall and entrapped material, described capsule wall comprises homogenizing, heat-convertible gel film, and described gel film comprises the low viscosity polymanna of film forming amount, and chooses any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
34. solid dosage forms comprises the material of being sealed by the homogeneous, thermoreversible gel film, the low viscosity polymanna of described gel film film forming amount, and choose any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent.
35. prepare the method for soft capsule, described method comprises the steps:
(i) in the equipment that enough shearing forces, temperature and the time of staying are provided to the low viscosity polymanna, and the compositions of choosing any one kind of them at least in plasticizer, second film former, extender and the pH controlling agent heats, hydration, mixing, solubilising and the optional degassing, form homogenizing, hot reversible melt composition, wherein temperature is equal to or higher than the solution temperature of fused mass;
(ii) directly make soft capsule, or described melt composition is cooled to be equal to or less than its gelation temperature, make soft capsule by said composition afterwards by described melt composition.
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46272103P | 2003-04-14 | 2003-04-14 | |
| US60/462,617 | 2003-04-14 | ||
| US60/462,785 | 2003-04-14 | ||
| US60/462,758 | 2003-04-14 | ||
| US60/462,792 | 2003-04-14 | ||
| US60/462,721 | 2003-04-14 | ||
| US60/462,783 | 2003-04-14 | ||
| US60/462,793 | 2003-04-14 | ||
| US60/462,794 | 2003-04-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1794979A true CN1794979A (en) | 2006-06-28 |
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 200480013903 Pending CN1791382A (en) | 2003-04-14 | 2004-04-14 | Process for making gel films |
| CN 200480014023 Pending CN1794979A (en) | 2003-04-14 | 2004-04-14 | Homogeneous, thermoreversible gel containing reduced viscosity carrageenan and products made therefrom. |
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 200480013903 Pending CN1791382A (en) | 2003-04-14 | 2004-04-14 | Process for making gel films |
Country Status (1)
| Country | Link |
|---|---|
| CN (4) | CN1791385A (en) |
Cited By (2)
| 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 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102206362B (en) * | 2011-04-28 | 2012-06-27 | 福建农林大学 | Instant noodle flavoring package coating and preparation method thereof |
| CA2997734C (en) * | 2013-09-13 | 2022-01-04 | Phood Station | Encapsulated food products and methods of making same |
| 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 |
| 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 |
| 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 200480013903 patent/CN1791382A/en active Pending
- 2004-04-14 CN CN 200480014023 patent/CN1794979A/en active Pending
Cited By (5)
| 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 |
| US10548978B2 (en) | 2016-09-01 | 2020-02-04 | International Business Machines Corporation | Microcapsule having a microcapsule shell material that is rupturable via a retro-dimerization reaction |
| US11007268B2 (en) | 2016-09-01 | 2021-05-18 | 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 |
| US10610980B2 (en) | 2016-11-07 | 2020-04-07 | International Business Machines Corporation | Self-heating solder flux material |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100569224C (en) | 2009-12-16 |
| CN1791385A (en) | 2006-06-21 |
| CN1791382A (en) | 2006-06-21 |
| CN1791389A (en) | 2006-06-21 |
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