Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
  • C08L3/00—Compositions of starch, amylose or amylopectin or of their derivatives or degradation products
  • C08L3/04—Starch derivatives, e.g. crosslinked derivatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/4816—Wall or shell material
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
  • C08B31/00—Preparation of derivatives of starch
  • C08B31/003—Crosslinking of starch
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
  • C08B31/00—Preparation of derivatives of starch
  • C08B31/003—Crosslinking of starch
  • C08B31/006—Crosslinking of derivatives of starch

Definitions

• the invention relates to a tough elastic material based on starch, which on the one hand has a high impact strength at low atmospheric humidities, on the other hand still has a high modulus of elasticity at high atmospheric humidities and has a high elasticity in a wide range of atmospheric humidities
• TPS plasticized thermoplastic starch
• Polyols are typically used as plasticizers.
• the strength of TPS is almost entirely in amorphous form.
• the properties of amorphous polymers are largely determined by the glass transition temperature Tg. Below Tg the condition is glassy, hard and brittle, above Tg it is soft. The difference between these two states is particularly pronounced in TPS. Since starch macromolecules are relatively rigid and rigid, high levels of plasticizer are required. Below Tg, TPS is extremely brittle and in particular very sensitive to high stress rates, above Tg TPS takes on the character of a sticky, highly viscous liquid with increasing temperature.
• TPS absorbs water from the atmosphere and the sensitivity of TRS to the air humidity RF is another problem that stands in the way of the use of TPS in practice.
• the relationship between RF and water content of a material is described by its sorption curve.
• Soft and hard capsules are a proven dosage form for pharmaceuticals and nutritional products. After taking the capsules, the capsule contents should generally be released as quickly as possible. Therefore, the materials with which soft and hard capsules are produced, or which are potentially suitable for this purpose, are at least hydrophilic, generally also water-soluble, such as gelatin, which is used to produce significantly more than 95% of today's capsules. Thus, the problem of the material properties that vary greatly with the RF also applies to these fields of application. Gelatin or The previous standard solution in the field of soft and hard capsules, containing 25 - 50% glycerin as plasticizer, has a water content of around 23% and a water content of around 85%, while the water content of around 85% is above 30%.
• Da 'Water is a very efficient plasticizers, the properties of plasticized gelatin are so heavily dependent on humidity.
• Their modulus of elasticity for example, a measure of rigidity and dimensional stability, is around 85% RH less by a factor of around 600 than at 23% RH, i.e. the material is comparatively stiff and hard at low air humidity, while it is hard at high humidity RF becomes very soft and the shape stability suffers.
• Other important material properties also vary in order of magnitude in the function of the RF.
• the increase in stickiness and oxygen permeability P0 2 is particularly problematic, which is a factor of about 100 when the RF increases from 0% to 75%.
• the use of gelatin capsules, particularly in humid climates is problematic and expensive packaging is necessary in order to protect the capsules from the moisture.
• Patent specification WO 01/37817 describes a soft capsule based on thermoplastic starch (TPS) with a high plasticizer content.
• TPS thermoplastic starch
• it has the serious disadvantage that it has a pronounced brittleness at low atmospheric humidities, so that the TPS soft capsule breaks and splinters in a dry environment with a glass-like fracture even under low stress.
• the TPS soft capsule becomes very soft and sticky and loses its shape stability.
• the TPS soft capsule is therefore clearly inferior to the gelatin soft capsule and the use of the TPS soft capsule is only possible with medium RF.
• Capsules based on TPS have so far not been feasible in the hard capsule area, where the requirements regarding toughness due to the stress on the capsules in high-speed filling machines are even greater.
• the object of the present invention is to provide a material on the basis of starch which has at least the following properties:
• Gas barrier properties especially low oxygen permeability 5.
• Optical properties transparency and colorlessness, but dyeable and printable
• the primary search was for a physical structure that can meet, preferably exceed, the requirements. It has the following characteristics:
• the base is given by a hydrophilic phase, which is water-soluble or swells and disintegrates in water.
• This phase is preferably amorphous or if it is in the partially crystalline state, the crystallites or ordered areas are ⁇ 500 nm. If they have larger dimensions, requirement 5 cannot be met.
• Amorphous phases generally exhibit brittle behavior at temperatures below the glass transition temperature Tg. Since the glass transition temperature varies for different properties and the tough-elastic material is used in a limited temperature range around room temperature, the dependence of this transition as a function of the RF is considered instead of the temperature dependence of the brittle-tough transition.
• RF Z is the RF, at RT the transition from brittle to tough behavior takes place.
• RF Z ⁇ 33%, preferably ⁇ 26%, more preferably ⁇ 20%, most preferably ⁇ 15% applies to a material that is tough at low RF. Consequently the amorphous phase shows a tough behavior at the given RF.
• This state is set using a suitable proportion of plasticizer.
• a polyol or a mixture of polyols with melting points that are as low as possible is preferably used as the plasticizer because their plasticizing effect is at a maximum and correspondingly small amounts have to be used.
• a high proportion of plasticizer increases the dependency of the properties on the RF.
• amorphous phases behave like highly viscous liquids, even if their viscosity is so high that they appear as solid bodies. Since water is several times more efficient than other plasticizers in hydrophilic systems with regard to the softening effect, this means that the amorphous phase becomes softer with increasing air humidity, loses stability and finally flows.
• a network is installed which has a lower dependency of the properties on the RF, since it is not possible to flow at high RF.
• This network preferably interpenetrates the amorphous phase and is coupled to this phase.
• covalent bonds i.e. chemical networks are insoluble in water and do not disintegrate even after swelling
• a network is introduced whose connection points are thermoreversible and / or can be dissolved again or become mechanically unstable by a solvent, in particular by adding water or gastric juice at 37 ° C.
• networks are also suitable that swell sufficiently so that they disintegrate in the swollen state under the action of low loads. This is particularly possible with thin films. If the network points are formed by at least partially ordered areas such as crystallites, these areas are ⁇ 500 nm to ensure transparency.
• Networks generally have good mechanical properties even at moderate network densities, ie high strengths and moduli of elasticity.
• a hydrophilic network is only slightly influenced in terms of mechanical properties by water absorption.
• the modulus of elasticity of a hydrophilic amorphous phase can vary by a factor of around 1000 in the range of normal air humidities
• the modulus of elasticity of a hydrophilic network varies by a factor of ⁇ 10, it can even in one wide range to be almost constant.
• the network density must therefore be set so that the contribution of the network to the modulus of elasticity and the strength at high water contents is at least comparable to the contribution of the amorphous phase.
• the contribution of the network in this area is preferably significantly greater than the contribution of the amorphous phase. In this case it is even possible to obtain almost constant moduli of elasticity in the range of around 30 - 70% humidity.
• a network with sufficient network density can compensate for the insufficient properties of the amorphous phase at high air humidities.
• hydrophilic networks are problematic with regard to water solubility, either the network density must be set so low that the network disintegrates after swelling in water due to minimal strength under low stress (which is the case in particular with thin films), or the network points are preferably through very small crystallites formed, which can dissolve in excess of water. The stability of the crystallites, which decreases with the size of the crystallites, is used.
• the structure after being adjusted, remains stable under changing conditions of humidity and temperature, i.e. it is set to an equilibrium state. This can be achieved through the manufacturing conditions, the network density being set to the required level.
• the elements listed basically point the way to various practical solutions based on different raw materials and recipes.
• the decisive points are the balance between amorphous phase and network, as well as the parameters of the network, which is strong enough on the one hand to ensure the mechanical properties of the material under changing conditions and on the other hand the solubility or the disintegration of the capsules in water or in Gastric juice not impossible.
• prior art networks do not meet this requirement.
• Previous networks based on starch for example, are practically completely insoluble in water and stable against decay, they are known to be opaque up to complete non-transparency, cannot be welded, and furthermore they only show low ductility in the range typically ⁇ 50% and have a disadvantageous effect on toughness out.
• An essential key to solving the problems mentioned is the size of the ordered areas that constitute the network points. This size can be set through the structural parameters of the raw materials used, in particular through the suitable choice of the network-active chain length CLn.na of the starch molecules used.
• VS existing strength
• starches do not form a homogeneous amorphous structure.
• Starches containing amylose in particular tend to retrogradate, which creates orderly areas, often with dimensions> 500nm. This affects transparency on the one hand (opacity), on the other hand, retrogated etched starches have a limited dissolution or disintegration behavior. Since the solubility in water can be made more difficult by introducing a network, the best possible solution or disintegration behavior of the base or the amorphous phase is an essential prerequisite.
• Retrogradation is primarily the result of the amylose portion of starches, with the amylose at least partially crystallizing.
• VS or mixtures of VS with an amylose content of ⁇ 25%, in particular ⁇ 22%, in particular ⁇ 19% are therefore preferred, i.e. Rice or sago starches or starches derived from tubers and roots such as potatoes, yams, canna, arrowroot or tapioca.
• starches derived from roots and tubers or waxy starches are also preferred, in particular tapioca starch, since their protein and lipid contents are lower in comparison with non-waxy cereal starches, which is also advantageous, inter alia, for transparency and clarity.
• Cereal starches and potato starches, in particular corn starch also have the disadvantage that various genetically modified variants of these starches are grown and purity is a priori problematic in terms of GMO proportions. Therefore starches are preferred from this point of view, of which no GMO variants are grown, for example sago or root starches, in particular tapioca starches.
• genetically modified starches can also be considered as VS.
• dextrins in particular pyrodextrins such as white dextrins, yellow or canary dextrins, modified dextrins, co-dextrins or British gums. They have good film-forming properties and, due to their irregular structure and the high degree of branching Qb of typically> 0.05, they are partially to practically completely stable with respect to retrogradation and therefore very readily water-soluble, and also long-term stable, i.e. aging.
• the use of dextrins has a positive effect on the quality of the weld seam of soft capsules, as they have good adhesive properties.
• Dextrins with low to medium degrees of conversion can be used as sole VS or together with other VS, while dextrins with high degrees of conversion are preferably used together with other VS. With regard to the optical properties, white dextrins are preferred.
• amylopectin can also retrograde, but to a much lesser extent and on a much larger time scale.
• the extent of the retrogradation of amylopectin and the stability of the retrog etched amylopectin regions against solubility or decay in water is determined by the length of the A-side chains of amylopectin.
• the shortest possible A-side chains are advantageous.
• starches are preferred with CLw ⁇ 18, preferably ⁇ 16, more preferably ⁇ 14, in particular ⁇ 13, most preferably ⁇ 12, i.e.
• waxy starches in particular waxy rice, tapioca starches or sago starches.
• the length of the A-side chains is also reflected in the more easily measurable properties of Blue Value (BV) and iodine affinity (IA), so that VS with amylopectin fractions of deep BV and deep IA are preferred.
• BV Blue Value
• IA iodine affinity
• VS starches or mixtures of such starches, which are modified and counteracted by the following treatments or combinations of these treatments. have been stabilized via retrogradation, preference being given to using starches with a priori low tendency to retrogradation, such as, for example, tubers or root starches:
• Oxidation for example periodate oxidation, chromic acid oxidation, permanganate oxidation, nitrogen dioxide oxidation, hypochlorite oxidation: oxidized starches); Esterification (for example acetylated starches, phosphorylated starches (monoesters), starch sulfates, starch xanthate); Etherification (for example, hydroxyalkyl starches, especially hydroxypropyl or hydroxyethyl starches, methyl starches, allyl starches, triphenylmethyl starches, carboxymethyl starches, diethylaminoethyl starches); Cross-linking (e.g. diphosphate starches, diadipate starches); Graft reactions; Carbamate reactions (starch carbamates).
• Esterification for example acetylated starches, phosphorylated starches (monoesters), starch sulfates, starch xanthate
• Etherification for example, hydroxyalkyl
• Starches with partially substituted hydroxyl groups show advantageous film-forming properties for use, high elongations, such as are required in particular for the production of films, and as a result of the substitution they are stabilized with respect to retrogradation, i.e. water soluble and transparent.
• These positive properties in the sense of the invention usually increase with the degree of substitution DS and the size of the substituted group.
• Starches with DS> 0.01, more preferably> 0.05, in particular> 0.10, most preferably> 0.15 are therefore preferred.
• the upper limit is given by regulatory provisions for food starches. From a technological point of view, however, modified starches with higher DS are also suitable and advantageous.
• substituted starches of particular interest are hydroxypropylated or hydroxyethylated or acetylated or phosphorylated or oxidized root and tuber starches or waxy starches with maximum permissible degrees of substitution of around 0.20 for food starches.
• VS chemically cross-linked starches
• distarch phosphates distarch adipates or inhibited starches (novation starches).
• Chemically crosslinked and simultaneously substituted starches are particularly preferred, with higher degrees of substitution also being preferred here.
• Suitable process measures in particular by checking the shear forces, can ensure that at least part of the chemical crosslinking within the starch grain is retained in the end product.
• the amorphous phase is a two-phase system containing network fragments of the original starch granules, whereby E- The modulus and strength of the capsule in the problematic area can be positively influenced by high atmospheric humidity, while the water solubility is not significantly impaired.
• discontinuous network fragments differ fundamentally from the physical networks essential for the solution.
• the required property profile cannot be achieved on the basis of the network fragments alone, but they can make a positive contribution in terms of an optimized solution.
• Another advantage of using substituted and chemically cross-linked starches is that a wide range of types with different degrees of substitution and cross-linking of these cheap commodity starches are commercially available in food quality.
• hydroxypropylated distarch phosphates examples are hydroxypropylated distarch phosphates, hydroxypropylated distarch adipates, acetylated distarch phosphates or acetylated distarch phosphates, which are based on starches of various origins such as corn, wheat, millet, rice, potato, tapioca et. are available.
• starches of interest are hydrolyzed starches such as acid-hydrolyzed starches or enzymatically hydrolyzed starches, as well as " chemically modified hydrolyzed starches, in particular based on starches with amylose contents of ⁇ 25%, provided that they have a reduced tendency to retrogradation, which is due to additional modification how oxidation or substitution is achieved.
• VS with a low, reduced or disappearing tendency to retrogradation are preferred.
• VS with higher amylose contents such as cereal starches, pea starches or high amylose-containing maize starch can, however, be used if measures are taken to prevent or minimize the retrogradation, e.g. through process measures such as freezing of the amorphous state and / or heat treatment with a defined water content , in particular in the case of low water content, and / or chemical modification of the VS such as, for example, substitution of hydroxyl groups, and / or measures relating to the recipe, substances which inhibit retrogradation being admixed.
• an amorphous state can on the one hand be achieved whereby water solubility and 'decay is guaranteed or otherwise retrogradation can have the effect minimized by the formation of a limited, but defined network is still possible, whereby a balance between toughness at low humidity and sufficient strength and rigidity can be achieved in high humidity.
• an additional network which is more network-compatible Starch (NS) is introduced, ie the required material properties can then be achieved on the basis of VS alone or a combination of VS.
• NS network-compatible Starch
• starches listed can be used both in native granular form (cooking starches) and physically modified (pregelatinized, cold water soluble, cold water swelling).
• plasticizers there is a wide range of known starch plasticizers to choose from, which have been described many times in the prior art (see, for example, WO 03/035026 A2 or WO 03/035044 A2).
• the polyols glycerol are mentioned here , Erythritol, xylitol, sorbitol, mannitol, galactitol, tagatose, lactitol, maltitol, maltulose, isomalt.
• plasticizers can each be used alone or in various mixtures.
• plasticizers particularly suitable for starch networks have melting points ⁇ 100 ° C., preferably ⁇ 70 ° C., more preferably ⁇ 50 ° C., most preferably ⁇ 30 ° C.
• Water is by far the most important plasticizer, around 2.5 times more effective than glycerin. Here is water but mostly not called plasticizers to distinguish water from other plasticizers.
• NS Starches containing or consisting of amyloses or amylose-like starches are used as NS.
• a mixture of different NS types is also referred to as NS.
• VS and NS can be materially identical, since in principle every NS can also be used as VS. The difference between VS and NS is therefore not material in all cases, rather the terms must also be understood in connection with the process.
• NS is treated in such a way that its potential for forming networks is optimally released, whereas this does not have to be the case with VS.
• the amyloses can be linear as well as branched and optionally modified.
• NS are amyloses from native starches, in particular amyloses obtained by fractionating starches with an amylose content> .23%, modified amyloses, in particular substituted amyloses or hydrolyzed amyloses, synthetic amyloses, cereal starches, pea starches, high amylose starches, in particular with an amylose content> 30 , preferably> 40, more preferably> 60, most preferably> 90, hydrolyzed starches, in particular hydrolyzed high amylose starches or sago starches, gelling dextrins, fluid starches, microcrystalline starches, starches from the field of fat replacers.
• NS can also have an intermediate fraction, such as those contained in starches containing high amylose and which can be obtained by fractionation.
• the intermediate fraction lies between amylose and amylopectin.
• LCA long chain amylose
• SCA short chain amylose
• Network-capable strengths can have LCA and / or SCA.
• SCA Short chain amylose
• SCA amylodextrins, linear dextrins, nail dextrins, lintnerized starches, erythrodextrins or achrodextrins, which represent different names and subgroups of SCA.
• SCA can be obtained, for example, by hydrolysis of LCA, LCA-amylopectin mixtures or amylopectin mixtures.
• SCA which is particularly suitable for advantageous networks is obtained, for example, by hydrolysis of starches originating from roots and tubers or from heterowaxy or waxy starches.
• the hydrolysis can be carried out chemically, such as, for example, acid hydrolysis and / or enzymatically, for example using amylases or combinations of amylases (alpha-amylase, beta-amylase, amyloglucosidase, isbamylase or pullulanase).
• Amylose-containing starches are obtained as SCA by combined acid / enzyme hydrolysis, and the two hydrolyses can be carried out simultaneously or in succession.
• different types of SCA can be obtained from the same strength.
• the characteristics of SCA are also influenced by the state of the native starch during hydrolysis, for example by the degree of swelling of the starch granules. Therefore a wide range of suitable SCA is available.
• Further types can be obtained by acid / enzyme hydrolysis or enzyme hydrolysis starting from waxy starches, SCA hydrolysates with DPn typically being obtained around 22, which are particularly suitable.
• SCA which is formed during the process of processing the starches into the NSF and finally the starch network, e.g. through pullulanase.
• LCA Long chain amylose
• the amylose contained in native starch is usually LCA with DPn> 100.
• the degree of polymerization DPn of LCA can be reduced, for example, by acid hydrolysis and / or enzymatic hydrolysis and / or oxidation to values ⁇ 100, so that appropriately modified native starches also have SCA can.
• Numerous processes for producing SCA, LCA and mixtures of SCA and LCA are described in the prior art. Both types of amylose are available on the one hand in pure form and are also present in different, optionally hydrolyzed, commercial starches in different proportions.
• the structural requirements for coupling the network to the amorphous or predominantly amorphous phase are given by the chain lengths CLw (A-AP) of the A side chains of the amylopectin fraction and by the chain lengths of the amylose 'fraction.
• the chain lengths CLw (A-AP) of A-side chains of amylopectin for amylopectins from starches with an amylose content ⁇ 30 are in the range of around 10-20, while high amylose starches have somewhat longer chain lengths CLw (A-AP).
• Amyloses on the other hand, can also have much longer chain lengths CLw (AM).
• chain lengths CL are typically in the range from 100 to 1000, with root and tuber starches having significantly longer chain lengths than cereal starches.
• chain lengths CL (SCA) are typically in the range from 100 to 1000, with root and tuber starches having significantly longer chain lengths than cereal starches.
• SCA short chain amyloses
• the chain lengths CL (SCA) ⁇ 100 and generally of about the same size as the degrees of polymerization DP (SCA), where CL (SCA) ⁇ DP (SCA). Since information on the weight average CLw is only rarely available for the various starches, the number average CLn of the chain length distribution and the number average DPn of the distribution of the degree of polymerization are used for a simplified discussion.
• CLw is slightly larger than CLn, although the difference in A-side chains of amylopectin is only slight because they have a narrow distribution, while the difference in SCA is larger and can be very large in LCA.
• the minimum chain length of amylose CLn (AM) or the minimum degree of polymerization of amylose DPn (AM) in order to use amylose to couple a network to the amorphous phase is approximately CLn (AM) - CLn (A-AP), ie around 10 - 20, - whereby advantageous couplings up to around CLn (AM) ⁇ 100 are possible.
• networks can also arise which are not coupled to the amorphous phase, ie which consist predominantly of amylose. These networks have disadvantageous properties with regard to the requirements, for example opacity at higher RF, water insolubility, significantly reduced elongations at break and toughness compared to coupled networks.
• SCA as NS or as a proportion of NS is suitable for the production of networks coupled to the amorphous phase, the stability of the crystallites forming the network points, ie their size, decreasing with decreasing CLn (AM) or DPn (AM) and the water solubility and the transparency of the substance increases.
• Advantageous networks are obtained with proportions psc A of SCA in% by weight dsb based on amylopectin and SCA in the range from 1-35, preferably 2-25, in particular 3-20, most preferably 4-14.
• Irregularities can be introduced into the chain length CLn (AM) by chemical reactions, in particular by substitution of hydroxyl groups of the anhydroclucose monomer unit, by oxidation or crosslinking.
• CLn chain length
• the network-active chain length is halved from CL to 1 / 2CL. It is therefore possible to obtain advantageous networks, for example by hydroxypropylation or acetylation, also on the basis of LCA.
• Advantageous degrees of substitution (DS) are in the range of approximately 0.01-0.50.
• Advantageous networks are obtained with proportions P CA of modified LCA in% by weight dsb based on amylopectin and LCA in the range 1-70, preferably 2-50, in particular 3-40, more preferably 4-35, most preferably 5-30.
• proportions of PLCA are higher than in the case of low degrees of modification.
• na> 100 can be obtained if suitable conditions are created for this through process measures, such as shaping at comparatively low water contents or low temperatures and / or heat treatment with RF in the range 20-60% and / or addition of RHS, the (large-scale) association of amylose to amylose networks being suppressed and the (small-scale) association of amylose with A-side chains being favored by amylopectin.
• RF in the range 20-60% and / or addition of RHS
• NS and possibly VS are activated and, in particular, stabilized before or during mixing with VS.
• the activation ensures that the amylose contained in NS is in an amorphous state, so that after mixing with VS a recombination can take place, which leads to a network.
• the stabilization makes it possible to influence the start of network formation and the type of network.
• Activation combined with stabilization of the NS is of particular importance. Stabilization is achieved by overheating the amylose to temperatures above the melting or dissolving process.
• foreign nucleating agents and / or methods for generating suitable germs can be used by supercooling the activated NS.
• stabilization, nucleation, hypothermia and foreign nucleating agents reference is made to the patent applications WO 03/035026 A2 and WO 03/035044 A2 for detailed information.
• the temperature of the recombination of the amylose to the desired network can be adjusted to low temperatures by the stabilization.
• RHS can be used to advantage for tough elastic materials based on VS alone or a combination of VS and NS.
• NSF network-compatible starch fluid
• the retr 'ogradationshemmende action of these substances is partly due to the reduction of the property of the strength as a plasticizer the water available, as well as in the dilution of the starch phase, whereby the diffusion of the starch macromolecules is difficult in both cases, and with respect to a crystallization existing incompatibility of RHS and strength.
• RHS examples include types of sugar such as glucose, galactose, fructose, sucrose, maltose, trehalose, lactose, lactulose, refiniosis, glucose syrup, high maltose com syrup, high fructose com syrup, hydrogenated starch hydrolysates et.
• polydextrose furthermore polydextrose, glycogen, oligosaccharides, mixtures of oligosaccharides, in particular with DE> 20, preferably> 25, more preferably> 30, most preferably> 70, maltodextrins, dextrins, pyrodextrins, in particular with degrees of branching Qb> 0.05, preferably> 0.10, even more preferably > 0.15, most preferably> 0.3.
• RHS also improve the water solubility per se, in some cases have a favorable influence on the sorption behavior and in particular the types of sugar reduce the oxygen permeability considerably, which is why they are particularly advantageous for this reason. If retrogradation-inhibiting substances are unable to completely suppress retrogradation, dextrins, pyrodextrins, maltodextrins, oligosaccharides and glycogen in particular enable the dimensions of the crystallites produced by retrogradation to be controlled down to dimensions, whereby the transparency is not impaired and water solubility or decomposition in water is achieved can be.
• disintegrants or disintegrants used in galenics are suitable as disintegrants, in particular fillers which are immersed in water. absorb a gas and / or swell strongly, which mechanically destabilizes and disintegrates.
• examples are carbonates and hydrogen carbonates of the alkali and alkaline earth ions, in particular calcium carbonate, and soy proteins (for example Emco-soy) or preferably strongly swelling starch particles such as sodium glycolates (sodium salt of carboxymethyl ether starch), for example Explotab, Vivastar or Primojel. Salts can also be used.
• Solvents are understood in particular as non-starch polysaccharides or hydrocolloids which have good water solubility or strong swellability in water and are miscible with NSF or are present as a separate phase therein.
• the usual natural or synthetic dyes such as those used for coloring, can be used. can be used to color gelatin capsules.
• starch In terms of printability, starch has advantages over gelatin. This is understandable because starch is used in large quantities in the paper industry, which means that the printability of paper can be improved.
• the stickiness is reduced compared to gelatin before the onset of network formation, since gelatin has a much higher water content at this point in time. With the formation of the network reduces the stickiness continuously, after the completion of the network there is practically no stickiness.
• the same sample can appear tough at low speeds and extremely brittle at high speeds. This is particularly the case with substances based on starch and in the area of the transition from brittle to tough behavior. Since high stress speeds also occur in practice, the impact strength is crucial. In addition to the impact strength, which is expressed as the energy absorbed during the break (impact work) in relation to the cross section of the sample, the elongation of the sample up to the break ⁇ «is also relevant as a measure of the deformability or toughness in the case of sudden stress.
• the toughness of TPS as well as of the tough elastic material according to the invention is primarily determined by the glass transition temperature Tg for a certain RF.
• the glass transition temperature is one way of characterizing a continuous phase transition in amorphous matter, characterized by an increase in the degrees of freedom of the components, resulting, for example, in increased heat capacity, thermal expansion, flexibility or increased toughness, the respective transition temperatures being able to have marked differences and a corresponding one at constant temperature Transition of the property depending on the plasticizer content can be observed.
• the optimal plasticizer or the optimal plasticizer combination the transition with regard to toughness as a function of the RF at RT, RFz, is decisive.
• RFz is ⁇ 30%, preferably ⁇ 20%, ie with these relatively low RF the material already has around half the maximum toughness.
• glycerin is used as the plasticizer, the range is 20 - 40% glycerin, depending on VS, NS and other formulation parameters such as For example, retrogradation-inhibiting substances, RF Z in the range of 15-30%, which ensures sufficient toughness in the problematic area of the lower RF.
• the toughness of the tough elastic material can also be further improved, in particular at RF ⁇ 33%, by adding a proportion of polyvinyl alcohol (PVA), in particular a proportion in% by weight in the range from 1-50, preferably 1.5-30, more preferably 2-20, in particular 3-15, most preferably 3-10.
• PVA polyvinyl alcohol
• any PVA types are possible, preference is given to PVA types with degrees of hydrolysis ⁇ 90%, more preferably ⁇ 80%, PVA preferably being added to the NSF in dissolved form becomes.
• a process is referred to as heat treatment, in which the material is stored in an atmosphere and the atmosphere has a course of air humidity and temperature as a function of time.
• the heat treatment can be used to control the network formation and, if necessary, the retrogradation in the capsule produced.
• the network formation is suppressed at RT and in the range of about 0-30% RF, while it takes place with increasing speed in the range of about 60-90% RF. If the RF is too high, turbidity can occur, which is why heat treatments are advantageously carried out in the middle range of air humidity.
• the heat treatment can be shortened, the suitable RF decreasing with increasing temperature.
• the duration of the heat treatment depends on the exact formulation and in particular on the degree of polymerization of the amylose and is in the range from hours to days.
• SCA offers advantages over LCA, i.e. short heat treatment times. Due to the greater mobility of the shorter molecules, heat treatment can also be omitted.
• Additives and / or fillers and / or resistant starches can be added to the tough-elastic material as additives.
• the process costs in the area of soft capsules are comparable to the process costs of gelatin capsules, except for the drying process. Since capsules are made based on the viscoplastic material with significantly lower water content compared to gelatin, the drying process can be reduced. With optimized process parameters, it can even be omitted entirely.
• the structure chosen to solve the task basically allows "various implementation options, whereby the parameters of the solution can be adapted and optimized in each case.
• the solution to the problem consists primarily in the selection of a suitable structure and the use of various polymer structures and mechanisms such as crystallization, nucleation, network formation or heat treatment, as a result of which an advantageous range of properties can be obtained.
• the invention discloses a new viscoplastic material based on starch which, in comparison with gelatin, has a flatter sorption isotherm and a flatter desorption isotherm, the equilibrium water contents generally being lower. This reduces the inevitable influence of RF, which reduces the range of material properties of the viscoplastic material compared to other substances that are suitable for capsules and edible films, and extends the range of applications.
• the tough elastic material has an amazing toughness at low RF, which, for example. compared to TPS, where toughness is critical, ie the limiting factor, is improved by a factor of> 100 and at the same time good dimensional stability, ie a high modulus of elasticity, can be obtained at high RF. With regard to the balance between toughness and dimensional stability, a better property profile could even be achieved compared to gelatin. In addition, lower oxygen permeabilities can be set, which means that the range of possible applications can be increased compared to common gelatine and TPS (eg oxidation-sensitive active ingredients). As a result of the improved sorption behavior, water absorption is also reduced, which also increases the application options. The improved sorption behavior and the reduced oxygen permeability improve, for example.
• the proposed solution thus fulfills the essential conditions for successfully replacing gelatin in the capsule area as a standard solution and setting new standards in the area of edible films.
• both soft and hard capsules can be obtained that meet the requirement profile and at least partially even have improved properties compared to gelatin.
• Example 1 The batch process was carried out using a heatable Brabender kneader with a chamber volume of 50 cm 3 .
• the VS was plasticized by adding water and plasticizer at mass temperatures of 80 - 90 ° C and 120 rpm for 3 minutes.
• a solution from NS was prepared and mixed into the melt.
• the homogenization was carried out at 100 rpm for 10 minutes, the mass temperature rising continuously to 90-105 ° C.
• the finished mixture was then removed and formed into 0.5mm films in a press, which typically contained about 20% water.
• the films were then stored at different RF until equilibrium and analyzed for their properties.
• Various formulations for tough elastic materials as well as for reference materials are listed in Table 1.
• TL1 solution temperature
• dT / dt cooling rate of the solution
• TL2 temperature of the solution when added to the VS melt
• C concentration of the solution
• the final water content after extrusion could be varied in the range 10 - 30% using a vacuum.
• the mixture was formed into a film of 0.6 mm thickness using a wide-angle nozzle and calibrated using a flat film take-off device (chili roll).
• the film can then be wound up and stored, processed further at a later time or it can also be bsw directly. processed into soft capsules via a rotary die system or into sachets via a welding and cutting system. If the film is stored temporarily, the water content should be around 25 - 35% at room temperature and around 15% at room temperature so that the network does not form. A very interesting state exists in the range of water contents of about 7 - 15% (provided that there is no or only a little developed network).
• the NSF is on the one hand in a state above the glass transition temperature Tg, ie the material is relatively soft and shows a very high elongation of typically 300% and more.
• the NSF in the NSF surprisingly remains in the molecularly disperse distribution for at least months. stood so that the good formability and weldability is preserved for as long.
• the network formation can then be triggered by an increase in the temperature and / or the water content, the material solidifying as a result of the onset of network formation and losing its weldability at low temperatures.
• Example 3 As example 1, but with NS solution added in G3, plasticizer in G2.
• Example 5 As example 1, but the NS solution and plasticizer are each metered into G2
• Example 6 (two-step process). In the first step, a preliminary product is produced, in contrast to Example 1 the throughput of plasticizer is 5 kg / h and granules are produced by strand or top granulation.
• These granules (5 kg / h) are plasticized in a processing extruder by adding the rest of the plasticizer content (0.7 kg / h) and water (1.5 kg / h) and formed into films or into an injection molded body such as hard capsules.
• the temperature of the processing extruder in the plasticizing zone is around 90 ° C. characteristics
• TPS soft 10, 11 and 12 show the basic problem of obtaining a material that can be used in a wide range of air humidity based on starch. These materials are relatively impact resistant at low RH of 20 - 30%, but with increasing humidity, water is quickly absorbed, which makes them very soft and sticky from around 40% RH, losing their firm character and gradually the properties of slowly flowing, highly viscous Accept liquids.
• the decrease of the E-moduli with the RF is dramatic, TPS soft 12 or so. varies in the RF range 20 - 40% by almost a factor of 1000. Such substances are extremely unsuitable for any application that is exposed to the atmosphere.
• the formulations tough elastic 10-1, 10-2, 11 and 12 have a defined network, whereby on the one hand the impact-resistant behavior at low RF is not impaired, but on the other hand the mechanical properties such as. the modulus of elasticity can be stabilized at medium to high RF. Surprisingly, a quasi plateau of the modulus of elasticity in the RF range of around 40 - 75% was obtained, whereby the modulus of elasticity remains almost constant. The level of the quasi plateau depends on the one hand on the chosen VS and on the type and proportion of the NS. The comparison of tough elastic 10-1 with 10% NS with tough elastic 10-2 with 15 NS shows the influence of the NS portion. " '
• the stress-strain curves of the tough-elastic material in the RF range of around 20 - 50% show a course that, for example, is comparable to the stress-strain curve of polyethylene, whereby a yield point, a subsequent plateau region and finally a hardening area can be determined.
• Figure 2 shows the elongations at break of the formulations of Figure 1.
• the elongations at break of the recipes Ten-elastic 10, 11 and 12 show a measure of around 45% RH. Maximum of a good 300% on and within a wide air humidity range of around 20 - 70%, elongations at break of at least 100% are obtained. This behavior reflects the excellent film-forming property in a wide water content range.
• the use of NS slightly reduces the maximum elongation at break compared to the formulations without NS, but here too it can be seen that the area of application for high RF can be significantly expanded by introducing a defined network.
• Figure 3 shows the behavior of the E-moduli in function of the RF for two typical tough elastic materials according to the invention (tough elastic 1 and 2) as well as for a soft (TPS soft 1) and a brittle TPS (TPS brittle 1) and for soft capsule gelatin demonstrated.
• soft capsule gelatin shows a linear decrease in the modulus of elasticity with increasing RF and varies in the RF range of around 20-85% by a factor of around 600.
• Elastic 1 and 2 have a significantly reduced range of variation in this RF range a factor of 100 and in particular a quasi plateau in the middle RF range. This is a significant advantage over gelatin. While gelatin and tough elastic 1 and 2 at 22% RH have comparable moduli of elasticity, the elastic moduli of tough elastic 1 and 2 at 85% RH are around 10 to 20 times higher, which significantly improves the dimensional stability at high RH.
• TPS soft 1 is based on a substituted starch with deep DS. This recipe shows what can be achieved in the most optimal case with respect to the modulus of elasticity at high RF if impact strength is to be maintained at the same time at low RF.
• the moduli of elasticity at higher RF are modest, however, at 58% RF only a value of 2MPa is obtained, while gelatin is still 8MPa, tough elastic 1 and 2 still 11 and 73MPa.
• the starch used for TPS soft 1 is not very suitable as VS for inventive tough-elastic materials. In particular, this property is not sufficient for applications where decay in water is essential.
• TPS brittle 1 shows E-moduli at higher air humidities, which are comparable to tough elastic 1.
• the impact strength at 32% RF with only 11 mJ / mm2 compared to 904mJ / mm2 with tough elastic 1 is extremely low, ie TPS brittle 1 is extremely brittle at low RF, the material breaks like glass with the slightest stress.
• the course of the tensile stress at 10% elongation as a function of the RF for the previously mentioned recipes is shown in Figure 4. The relationships regarding this property are analogous to the modulus of elasticity.
• TPS brittle 1 The course of the impact strength or impact work K as a function of the RF is shown for TPS brittle 1, TPS soft 1, and for tough elastic 1 and 21 in Figure 5.
• a starch-based material can be described as tough if the impact strength is at least 30mJ / mm2, but higher values are advantageous.
• TPS brittle 1 only becomes slightly tough above 40% RH, while tough elastic 1 becomes tough above 20% RH and tough elastic 21 even below 10% RH, i.e. even with extremely low air humidity, which normally hardly occurs, is tough.
• the transition from brittle to tough takes place at TPS soft 1 between 10 - 20% RH.
• the subsequent sharp decrease in impact strength at higher RF is due to the fact that the material becomes extremely soft with increasing RF and takes on the character of a highly viscous liquid.
• FIGs 3, 4 and 5 clearly show a basic problem of TPS.
• TPS is practically completely amorphous, is glass-like below the glass transition temperature Tg and is present as a highly viscous liquid above Tg. Useful properties can therefore only be obtained in the transition area between the two states within a narrow RF range.
• both toughness and strength properties can be achieved simultaneously in a wide RF range, with additional properties as required for specific applications being able to be set (eg transparency, decay in aqueous media, water solubility). It is also of particular advantage that the properties can be almost stabilized in an RF range of typically 40 - 75% (quasi-plateau of the modulus of elasticity and strength).
• Figure 6 shows the moduli of elasticity for various viscoplastic formulations as a function of the RF. On the one hand, it shows that the characteristic properties of the viscoplastic material according to the invention can be obtained by means of various formulations, on the other hand it is expressed that the level of the modulus of elasticity can be varied over a range comprising almost two decades.
• the property profile of the tough-elastic material depends not only on the recipe, but also on the manufacturing process.
• a comparison of the properties as produced for the same recipe by means of a batch process (Brabender kneader, tough elastic 1) and by means of a continuous extrusion process (tough elastic 1 E) can be seen in FIG. 7. It becomes clear that the modulus of elasticity after the extrusion process lies in the area of the quasi plateau and above at a significantly higher level, whereby values 3 to 5 times higher were obtained in comparison with tough elastic 1, i.e.
• the advantages of the tough elastic material are even more pronounced in the production by extrusion than the results based on the batch process.
• Figure 8 shows that the elasticity of tough elastic 1 E compared to tough elastic 1 decreases slightly in the area of the maximum at medium RF, but increases at low and high RF.
• the better properties resulting from the extrusion process compared to the Brabender process are common and based on factors such as. higher homogeneity, fewer material defects, shorter process times.
• the sorption isotherms of tough elastic 1, 16 and 17 are compared with the sorption isotherms of gelatin.
• Gelatin absorbs more water in the entire RF range compared to the tough elastic material with the same RF. This is one of the reasons why various properties of gelatin show a higher dependence on the RF.
• the water absorption of the viscoplastic material can be reduced by specific recipe measures, in particular by the composition of the plasticizer (viscoplastic 16, 17), so that various other properties are less dependent on the RF.
• good barrier properties to gases, in particular to oxygen are advantageous (damage to the contents by oxidation).
• Figure 11 shows that the oxygen permeability of tough elastic 1 compared to soft capsule gelatin is reduced by a factor of 2 to 3, making another advantage over gelatin obvious.
• the oxygen permeability can be further reduced through recipe measures, especially through the use of sugar.
• Tough elastic 17 has oxygen permeabilities reduced by a factor Vz in the RF range 0 - 75% compared to tough elastic 1, while this factor is even% in tough elastic 16.
• the advantage of such bags based on starch is on the one hand the price and on the other hand the very good biodegradability of starch.
• the tough elastic material can encapsulate aroma concentrates, whereby the aroma is only released during use and up to this point the aromas can be very well protected over a long period of time and maintain their quality (top notes).
• the stability of the viscoplastic material at high atmospheric humidity and the absence of stickiness in the entire RF area is a major advantage.
• the release of medicinal substances from capsules consisting of the viscoplastic material was examined, the results meeting the requirements for pharmacopoeia.
• the oxygen permeability measurements were carried out with an OX-TRAN 2/21 (MO ' CON Inc. 7500 Boone Avenue North, Minneapolis, USA) on films of 0.15 mm thickness, the oxygen permeabilities of starch film and gelatin film in a symmetrical arrangement at the same time were measured so that the relative values could be determined very precisely.
• K (RFz) is defined as the arithmetic mean of the toughness of the plateau in the brittle region Ks and the maximum toughness K after the brittle-tough transition. Since Ks «KM is usually K (RFz) ⁇ V KM P 02 [mlxcm / (cm 2 x24hxatm)] permeability coefficient for oxygen •
• AM [% by weight] amylose content, based on the starch, dsb PNS [% by weight] proportion of NS based on NS and VS, dsb PLCA [% by weight] proportion of LCA in% by weight dsb based on AP and LCA PSCA [% By weight] of SCA in% by weight of dsb based on AP and SCA P HS [% by weight] of RHS based on VS and NS and RHS PSM [% by weight] share of SM, based on VS and NS and SM p L [% by weight] share of LM, based on VS and NS and LM
• WM plasticizer can be a single plasticizer or a mixture of different plasticizers
• RHS RHS retrogradation inhibiting fabrics
• A-AP A side chains of amylopectin
• LCA2 LCA with DPn> 300; LCA2 can form networks both alone and in combination with other strengths. Mixtures of LCA2 and VS can form networks at high plasticizer contents and high temperatures
• NSF Networkable Starch Fluid Melt or solution containing a starch or a starch blend, and plasticizer; can be obtained as a strength network below under suitable conditions.
• An NSF has at least one VS and at least one NS
• VVP Cross-linked preliminary product obtained from NSF has an at least partially developed starch network
• IVP inhibited intermediate obtained from NSF has no or only a minimally developed network, the formation of a network is suppressed by procedural measures.
• An IVP is predominantly to completely amorphous
• KVP Pre-product containing germs obtained from NSF has a slightly developed network, the network elements of which act as germs in the processing of the KVP for the production of starch networks
• VS and NS are prepared separately, mixed to form an NSF and the NSF is processed directly into the end product • .
• TCP Together Continuous Process VS and NS are processed together to form an NSF and the NSF is processed directly into the end product
• VS and NS are prepared separately, mixed into an NSF and the NSF processed into a VP

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