RU2341250C2 - Homogeneous thermal reversible gel film containing cappa-2-carraginan, and soft capsules produced thereof - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention refers to medicine and is intended for homogeneous thermal reversible gel film including filming amount of cappa-2-carraginan and optionally at least one component among plasticizer, the second filming agent, bulking agent, and the pH regulating agent; and method of production thereof. This invention is also intended for soft capsules and solid forms containing gel film, as well as methods of production thereof.

EFFECT: allows for production of soft capsules based on gel films.

44 cl, 5 dwg, 17 tbl, 9 ex

Description

Related Applications

This application claims priority in accordance with provisional patent application US No. 60/462785, filed April 14, 2003

FIELD OF THE INVENTION

The present invention is directed to a homogeneous thermally reversible gel film containing a film-forming amount of kappa-2-carrageenan and optionally at least one plasticizer, a second film former, a filler, a pH adjuster; and methods for their preparation. The present invention is also directed to soft capsules and solid forms containing a gel film, as well as methods for their preparation.

BACKGROUND OF THE INVENTION

Gelatin is widely used to form films used in soft capsules. It is a hydrolyzed protein from collagen, usually obtained by digesting animal bones and cartilage with water under pressure. However, the use of gelatin has some commercial drawbacks, for example, its animal origin often hinders its availability for those who cannot or do not want to take capsules made from animals, and recent concerns about bovine spongiform encephalopathy, BSE, or "mad cow disease."

As a result, the scientific community and industry have been trying for many years to develop alternatives to gelatin that most apparatuses and methods, such as rotating heads, can desirably use to make soft capsules from alternative gelatin materials.

For example, Japanese patent application Kokai No. 61-10508A discloses capsules obtained from a polysaccharide composition comprising at least carrageenan and a polyhydric alcohol. Carrageenan can be used in whole or in part with other polysaccharides, such as tamarind seed gum, pectin, gelatin, alginates, agar, fursellaran, cellulose derivatives, robinia bean gum and guar gum. Polyhydric alcohols include sorbitol, glucose, sucrose, ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol, butanediol and glycerol. Soft capsules are obtained from concave stamping heads.

Japanese patent application Kokai No. 63-164858 discloses mixtures of polysaccharides and polyols with / without alkaline substances. It is understood that the extensive list of polysaccharides that can be used in this application includes natural polysaccharides such as carrageenan, alginic acid, alginate derivatives, agar, robinia bean gum, guar gum, tamarind seed polysaccharides, pectin, xanthan gum, glucan, , pullulan and cyclodextrin. It is claimed that polysaccharides are combined with a concentrated aqueous solution of at least one polyhydric alcohol, a sugar alcohol, a monosaccharide, a disaccharide or an oligosaccharide. It is claimed that the mixtures are suitable for forming capsule shells. Three examples indicate that the manufacture of shells for soft capsules has double layers of a mixture with gelatin and a single layer consisting of a mixture of the invention with gelatin. Specific carrageenans are not mentioned.

US Pat. No. 5,089,307 discloses edible thermally sealed films comprising at least a layer of a film containing a water-soluble polysaccharide as a major component, polyhydric alcohol and water. The films are claimed to be suitable for sealing and packaging materials for dried foods, oily foods and the like. Imposed polysaccharides include alginic acid and its salts (such as sodium salt); fursellaran; carrageenan such as kappa, iota and lambda carrageenans, agar, pectin such as high-methoxy and low-methoxy pectins; gums such as tamarind gum, xanthan gum, guar gum, tara seed gum, robinia bean gum; pullulan; chitin derivatives such as chitosan; starch, such as wheat, corn or potato starches; dextrin; edible water-soluble cellulose derivatives such as carboxymethyl cellulose and mixtures of the foregoing. Preferably, a weight ratio of polyhydric alcohol to polysaccharides in an amount of from 1: 5 to 1: 1 is used, and polysaccharides are present in an amount of at least 50% of the total amount of active components. The patent does not indicate that such films can be used in the manufacture of soft and hard capsules.

US Pat. No. 6,331,205 discloses viscous aqueous compositions for the manufacture of soft or hard capsules containing carrageenan, preferably iota-carrageenan as the sole gelling agent. Iota-, lambda-, mu- and nu-carrageenans are disclosed as types of carrageenans that can be used in the invention, and it is claimed that they are extracted from many different algae used depending on the extraction method. Plasticizers such as those belonging to the class of polyoxyls are disclosed, for example glycerol, sorbitol, maltodextrins, dextrose, mannitol, xylitol, polyoxyethylene glycol 400 to 6000, natural and semi-synthetic glycerides and their derivatives, etc. It is mentioned that soft capsules are prepared by adapting the "Scherer" method. It has been argued that films made from kappa-carrageenan have problems causing syneresis in the production of soft and hard capsules. There is no description of any specific iota-carrageenans, kappa-carrageenans, kappa-2-carrageenans, etc.

US Pat. No. 6,214,376 discloses gelatin-free capsules obtained from compositions containing water-soluble hydrophilic colloidal layers containing gel films of kappa-carrageenan and a plasticizer. It is mentioned that gelatin-free soft capsules are obtained from kappa-carrageenan as the main gel-forming polymer (at least 50% by weight of the gums forming thermo-reversible gels or promoting the formation of thermo-reversible gels). Hydrolyzed starches, such as maltodextrin, can be added to increase the concentration of solids, promote thermal sealing and prevent clouding caused by thickening of salts. Other types of gums, such as iota carrageenan, are recommended to be minimized, most preferably to less than 0.5% of the total film composition.

US patent No. 6340473 requires the use of modified starch having a hydration temperature of less than 90 ^about C and iota-carrageenan for the production of soft capsules using a rotary stamping encapsulating apparatus. It is argued that the mass ratio of modified starch to iota-carrageenan is crucial in the formation of a satisfactory film. This mass ratio of modified starch to iota-carrageenan is indicated as 1.5: 1. The authors unexpectedly found that one iota-carrageenan does not produce an acceptable film and that modified starch alone does not produce a film acceptable for encapsulation. The theory is stated that iota-carrageenan functions as an elasticizing agent, making an inelastic film of modified starch elastic. It is argued that carrageenans are combined with hundreds of different products on the market that have different functional groups. It is claimed that Euchema spinosum is a seaweed source of iota-carrageenan, and it is claimed that not all carrageenans are suitable for the invention, for example, it is claimed that kappa-carrageenan is not a substitute for iota-carrageenan.

It is known that some film-forming compositions with a high solids content and low humidity, containing, for example, hydrocolloids, form solutions with high viscosity, which makes the formation of hydrated films difficult to achieve. The present invention relates to a method for producing films with a high solids content, low moisture content from such high viscosity solutions.

Additionally, there have been many attempts to obtain soft capsules from films with a high solids content and low humidity, such as hydrocolloids. However, such attempts to obtain soft capsules have the disadvantages mentioned above. So, it is known that hydrocolloids form solutions with high viscosity, which are rather difficult to hydrate and form a film in the conventional method for the production of soft capsules. Therefore, the method according to the invention allows the production of soft capsules from such films.

Summary of the invention

In a first embodiment, the present invention is directed to a homogeneous thermoreversible gel film containing a film-forming amount of kappa-2-carrageenan and optionally at least one plasticizer, a second film former, a filler, and a pH adjusting agent.

In a second embodiment, the present invention is directed to a method for producing gel films, the process comprising the steps of: (i) heating, hydrating, mixing, dissolving and optionally deaerating the kappa-2-carrageenan composition and optionally at least one of: a plasticizer, a second film former, filler and pH adjusting agent in an apparatus providing sufficient shear, temperature and processing time for forming a homogeneous thermo-reversible molten composition thereof, where the temperature is are equal to or higher than the dissolution temperature of the molten composition; and (ii) cooling the molten composition to or above a gel-forming temperature to form a gel film.

In a third embodiment, the present invention is directed to soft capsules comprising capsule shells and an encapsulated substance, wherein the capsule shells include gel films of the present invention, as well as a process for their preparation. The method includes the steps of: (i) heating, hydrating, mixing, dissolving and, optionally, deaerating the kappa-2-carrageenan composition and optionally at least one of: a plasticizer, a second film former, a filler, and a pH adjuster in the apparatus providing sufficient shear temperature and residence time for the formation of their homogeneous, thermoreversible, molten composition, where the temperature is equal to or higher than the dissolution temperature of the molten composition; and (ii) obtaining soft capsules directly from the molten composition, or it is allowed to cool the molten composition to a gel-forming temperature or lower and then obtain soft capsules from it.

In a fourth embodiment, the present invention is directed to solid forms comprising a filling material encapsulated in a homogeneous thermo-reversible gel film of the present invention, for example, hard capsules.

Brief Description of the Drawings

Figure 1 is a diagram of a method of manufacturing films and soft capsules according to the present invention, using a Stefan processor together with an extruder.

Figure 2 is a diagram of a method according to the present invention for producing films and soft capsules using the fluid mixer of Figure 3 and an extruder. The diagram shows a film exiting the extruder into an encapsulation apparatus.

Figure 3 is a side view of a partial section of a fluid mixer for mixing the first and second fluids with steam, which can be used in the method according to the invention.

Figure 4 is another variant of the circuit of Figure 2, showing a film exiting the extruder into an encapsulation apparatus.

Figure 5 is a diagram of a method according to the invention for producing films and soft capsules using the fluid mixer of Figure 3, a cooling drum and an encapsulation apparatus.

DETAILED DESCRIPTION OF THE INVENTION

Carrageenan is a commercially significant galactan polysaccharide found in red seaweed. All carrageenans contain repeating structural units of galactose, joined by alternating α1 → 3 and β1 → 4 glycosidic bonds, and are sulfated to widely varying degrees. Types of carrageenans can vary, in particular, by the degree and position of their sulfation, as well as the alga from which they are derived. For example, iota-carrageenan has a repeating unit of D-galactose-4-sulfate-3,6-anhydro-D-galactose-2-sulfate, providing a sulfate ester content of from about 25% to 34%. Iota-carrageenan can be obtained, for example, from Eucheuma denticulatum (also called "Spinosum"). Kappa-carrageenan has a repeating structural unit of D-galactose-4-sulfate-3,6-anhydro-D-galactose and is obtained, for example, from Kappaphycus alvarezii (also called "Eucheuma cottonii" ). In contrast, kappa-2-carrageenan described by R. Falshaw, HJ Bixler and Johndro, Structure and Performance of Commercial Kappa-2-Carrageenan Extracts, Food Hydrocolloids 15 (2001 ) 441-452 and H. Bixler, K. Johndro and R. Falshaw, Kappa-2-carrageenan: structure and perfomance of commercial extracts II, Food Hydrocolloids 15 (2001) 619-630 as a copolymer comprising a certain number of structural repeating kappa (3: 6-anhydrogalactose (3: 6-AG)) and repeating iota structural units (3: 6-anhydrogalactose-2-sulfate (3: 6-AG-2-S)) covalently linked to the copolymer backbone and is obtained from certain algae Gigartinaceae. The above links state that such kappa-2-carrageenan has distinctly excellent properties compared to a simple mixture of kappa and iota-carrageenan. Other references discussing kappa-2-carrageenan are provided in these publications. Kappa-2-carrageenan extracted from Gigartina atropurpurea is described by R. Falshaw, HJ Bixler and Johndro, Structure and Performance of Commercial Kappa-2-Carrageenan Extracts III, Food Hydrocolloids 17 (2003) 129-139. While historically there has been great confusion about the physical nature of kappa-2-carrageenans, recent studies, such as the aforementioned, instantly found that kappa-2-carrageenans are copolymers containing repeating covalently linked structural units of kappa and iota (in a certain proportion of parts kappa and iota) in the main chain of the copolymer with a clear difference from physical mixtures of kappa and iota polymers.

For the purposes of this document, kappa-2-carrageenan has a molar ratio of 3: 6AG-2S to 3: 6AG from 25% to 50%, iota-carrageenan has a molar ratio of 3: 6AG-2S to 3: 6AG from 80 to 100% and kappa-carrageenan has a molar ratio of 3: 6AG-2S to 3: 6AG in less than kappa-2-carrageenan. For example, kappa-carrageenan from Eucheuma cottonii, commonly known and used as a source of kappa-carrageenan algae, has a molar ratio of 3: 6AG2S to 3: 6AG of less than about 10%; and the Spinosum iota-carrageenan , commonly known and used as a source of algae iota-carrageenan, has a molar ratio of 3: 6AG2S to 3: 6AG of more than about 85%. On average, kappa-2-carrageenan includes a ratio of repeating structural units of kappa (3: 6-AG) to repeating structural units of iota (3: 6-AG-2-S) between 1.0 to 3.0: 1, more preferably , from 1.5 to 3.0: 1 (more preferably relates to the desired application). The molar ratio of the content of 3: 6AG-2S to 3: 6AG from 25 to 50% is contained in kappa-2-carrageenan regardless of the degree of its modification and the content of the precursor (for example, repeating structural units mu and nu). Thus, only kappa-2-carrageenan satisfying a molar ratio of 3: 6AG-2S to 3: 6AG of 25 to 50%, regardless of the degree of its modification, is within the scope of the present invention.

The kappa-2-carrageenan used in the present invention can be obtained either purified or isolated from seaweed species within classes, for example, Gigartina algae, such as Gigartina radula, Gigartina corymbifera, Gigartina skottsbergii, Iridaea cordata, Sarcothaia crispata and Mazzaella laminario . The seaweed sources of kappa-2-carrageenan in the present invention are used only as producing kappa-2-carrageenan having a molar content of 3: 6AG-2S to 3: 6AG described herein. The kappa-2-carrageenan used in the present invention can naturally occur in the above-described algae or can be modified from these algae to increase the amount of 3: 6AG-2S and 3: 6AG components in the kappa-2-carrageenan from its predecessors (e.g. 3 : 6AG-2S component of kappa-2-carrageenan modified from its precursor by alkali treatment and 3: 6AG component of kappa-2-carrageenan modified from its precursor by alkali treatment). Recovery and modifying technologies well known in the art include publications by Falshaw, Bixler and Johndro. For example, kappa-2-carrageenan may be modified during its reduction from a particular Gigartinacean algae as a result of alkali treatment at elevated temperatures. Recovery methods include optionally completely or partially filtering the insoluble starting material or using unfiltered material. When the nu and mu precursors in kappa-2-carrageenan are modified in 3: 6AG-2S and 3: 6AG, respectively, such a modification can be completed (for example, 100% nu and mu precursors in kappa-2-carrageenan are modified in 3: 6AG- 2S and 3: 6AG, respectively) or less than fully finished (for example, less than 100% nu and mu precursors in kappa-2-carrageenan are modified in 3: 6AG-2S and 3: 6AG, respectively). It is understood that during the reduction of kappa-2-carrageenan from the above-described seaweed, small or trace amounts of other carrageenans (e.g., lambda carrageenans) can be detected and they can be used with kappa-2-carrageenan in the present invention.

One of the surprising aspects of the present invention is the functionality of kappa-2-carrageenan compared to kappa-carrageenans, iota-carrageenans and simple dry mixtures of kappa and iota-carrageenans containing the same level of 3: 6-AG-2-S. So, iota and kappa carrageenans are gelling carrageenans. In contrast, kappa-2-carrageenans are known as weakly gel-forming. As a result, it was expected that such weakly gel-forming carrageenans would form weak gel films. However, to the surprise of the applicants, it was found that kappa-2-carrageenan forms surprisingly strong gel films. It is usually observed that the aqueous gel stability of kappa carrageenan clearly decreases with a decrease in the content of 3: 6-AG-2-S (for example, from 1500 g to 300 g for 1% water), i.e. there should be a structural effect of these additional sulfuric acid esters on the spiral aggregation and oxygen binding between such aggregated helices. This trend continues for kappa-2 (25-50%, more preferably 25-40% 3: 6-AG-2-S for these applications) with water gels as lower than 150 g and is probably consistent with their structural variability. Iota-carrageenan (for example, from 80 to 100% 3: 6-AG-2-S) is however more structurally ordered, thus contributing to a more uniform three-dimensional structure of this water gel, providing a strong water gel, as shown, its resistance to a gap of more than 300 g. It is an idea that is not yet related to any theory that simple physical mixtures of kappa and iota-carrageenans are partly antagonistic in terms of gel strength, more likely the corresponding mutual interaction of their absolute gel structures is more likely to develop that occurs at individual cooling temperatures. The obtained strength value for a dry mixed aqueous gel based on a physical mixture of kappa and iota carrageenans is even higher than for the strength of an aqueous gel kappa-2-carrageenan. It is also possible to achieve this antagonistic effect by separately hydrating and dissolving the kappa and iota carrageenans and uniformly combining the solutions while maintaining the temperature of their solutions above the gel-forming and draining or mixing, cooling to the initiation of gel formation. This decrease in gel strength (structural weakening) is exacerbated by extraction, viscosity reduction (small molecules) and divalent addition. Thus, based on the traditional strength of the gel and structural measurements, it is not intended to designate kappa-2-carrageenan for use in gel films.

However, as discovered by the applicants, when kappa-2 is used to make gel films, it demonstrates amazing film strength and mechanical integrity, far exceeding expectations based on traditional (prior art) molecular crosslinking in comparison with aqueous gels. It also shows full compatibility with traditional film and capsule film ingredients such as starch, moisturizer, etc. There is also reason to believe that the statistical structure of the kappa-2-carrageenan copolymer gel in such gel films and film compositions is ideal, contributing to the final structural stability of the onset of gelation with no need or tendency to change with time or during the drying process of the film. During gel formation, the structural bonds of the heterogeneous structure of kappa-carrageenan continue to harden, iota-carrageenan, which is also elastic and does not condense, and physical / mixtures of kappa / iota (as opposed to kappa-2 copolymers) show structural interactions. This amazing strength of kappa-2-carrageenan film also provides the ability to control the molecular weight of carrageenan to better balance the viscosity process and film strength required for machining into capsules, this regulation makes it possible to cast films at a lower humidity level while maintaining other necessary film properties .

Kappa-2-carrageenan is used in the present invention in a film-forming amount (for example, an amount adding film strength to a gel film), which is determined from trace amounts of kappa-2-carrageenan that do not add additional properties to the film. So, for example, the gel film of the invention contains the second film former discussed above, the film-forming amount of kappa-2-carrageenan is an amount that adds strength to the film in general. Such film-forming amounts are usually at least 0.5% by weight of a dry gel film, preferably from 0.5% to 90%, more preferably from 0.5% to 50%, more preferably from 0.5 to 25%, more preferably from 1.5% to 25% by weight of the dry gel film, depending on the application.

For the purposes of this document, “homogeneous film” means a film which, when viewed with the naked eye, is visually uniform and free from defects such as lumps, cracks, insoluble particles that were supposed to dissolve, inhomogeneous distribution of insoluble particles, etc. “Fish eyes” (mixed liquid and solid states) or “gel balls” (heterogeneous gel structure) must not satisfy the definition of “homogeneous” as used here.

The gel films of the invention are homogeneous thermally reversible gel films. They can be obtained by casting and used in a wide variety of applications as cast films or resulting from processing.

As used herein, “heat reversible film” means a film that has a melting point. As used herein, the melting temperature is the temperature or temperature range above which the gel film softens or flows.

As used herein, the phrase “gel films” refers to a thin membrane or three-dimensional network formed from structured kappa-2-carrageenan. The film-forming composition is characterized by the temperature of the gel, the temperature below which the molten mass of the gel composition must be cooled to form an independent structure. If necessary, the molten mass can be cast hot and allowed to cool, as well as dried, contributing to the concentration of solids (controlled removal of moisture), while the gel film is formed from the gel composition. The melting temperature of the thermally reversible gel film is higher than the temperature of the gel.

The gel film of the invention desirably contains soluble gelling cations that contribute to the formation of a carrageenan structure, i.e. gelation. Such useful cations include potassium, sodium and ammonium. These cations can be present in Kappa-2-carrageenan or added to it from other organic and inorganic sources, at various points in the process, while the temperature of the molten mass is maintained above the gel-forming. These beneficial cations may be present in an amount of less than 50% dry weight of kappa-2-carrageenan in a gel film (including water). This amount may vary depending on the network components, the desired melting and pouring temperatures, and the processing properties and equipment selection.

Other soluble cations such as calcium, magnesium, aluminum and chromium can otherwise affect stability and may be added in a minimal amount, for example, less than 10%, less than 5%, less than 1% of the dry weight of kappa-2-carrageenan in gel film (including water). Binding and gelling agents can be added in amounts sufficient to minimize the solubility of the aforementioned cations (and participating activity), ensuring that the gel network of the binding agent or the resulting substance is not improperly affected.

The molecular weight of kappa-2-carrageenan is usually above 100,000 Daltons, preferably from 100,000 to 1,000,000, more preferably from 100,000 to 450,000, more preferably from 100,000 to 350,000, depending on the application.

In some applications, it is desirable to lower the gelation temperature of kappa-2-carrageenan. Gelled network of kappa-carrageenan 2 having a high average molecular weight, has a gelling temperature of at least 59 ^{° C} and 35 ^{° C} in a potassium / sodium and calcium forms respectively. So, a substitute potassium cation with a sodium cation is one of the ways to lower the gelation temperature of kappa-2-carrageenan. It was generally believed that the gelation temperature was dependent on the molecular weight of kappa-2-carrageenans. However, Applicants unexpectedly subsequently discovered that in high hardness networks having at least 50% solids, the use of kappa-2-carrageenan having a reduced molecular weight (for example, having a viscosity of 19 cP or less, more preferably less than 10 at 75 ^° C in a 0.10 molar solution of sodium chloride containing 1.5% carrageenan with a reduced molecular weight by weight based on the total weight of the solution; this viscosity determination can be performed using a Brookfield LVF viscometer (Brookfield Engineering Laboratori es, Inc.) №1 spindle at 60 rpm. / min and determining the viscosity after six turns) may further lower the temperature of gelation of kappa-carrageenan-2, for example from 35 ^{° C to} 25 ° C in the sodium form and ^about 59 C to 57 ^° C in potassium / calcium form. Lowering the gelation temperature of structures generated by kappa-2-carrageenan can have a beneficial effect in processing the gel films of the present invention, for example in the production of soft capsules, hard capsules and other solid forms by reducing the amount of heat used in the manufacturing process and minimizing the residual stress in the dried film .

The homogeneous heat-reversible gel film of the invention may optionally contain at least one of the following components: a plasticizer, a second film former, a filler, and a pH control agent. The components are added to the gel film and their amounts may vary depending on the desired use of the kappa-2 gel film.

Examples of such a plasticizer include polyols such as glycerol, sorbitol, maltitol, lactitol, corn starch, fructose, polydextrose, soluble oil or polyalkylene glycols such as propylene glycol and polyethylene glycol. The amount of plasticizer may vary depending on the use of the gel film and its desired elasticity. For example, such plasticizers can usually be used in an amount of at least 5%, more preferably at least 10%, more preferably at least 20%, more preferably at least 30% by weight of all components, including water in a dry film, if the desired gel film should have greater elasticity; for example, a film is used to make soft capsules. For other applications, such as hard capsules, where a less flexible film is desired, the plasticizer may be present in an amount of 0% to 20% by weight of all components in the dry film. It is possible that the gel film of the present invention does not contain a plasticizer at all.

Examples of a second film former that can be used in the present invention include at least one of the following components: starch, hydrolyzed starch, starch derivatives, cellulose gum, hydrocolloid, alkyl cellulose ether or modified alkyl cellulose ether. Examples of the hydrocolloid include at least one of the following compounds: kappa-carrageenan; Iota carrageenan, kappa and iota carrageenans having a reduced molecular weight (e.g., viscosity of 19 cps or less, more preferably less than 10 cps at ⁷⁵ ° C, measured in 0.10 molar sodium chloride containing 1.5% carrageenan with a reduced molecular weight by weight based on the total weight of the solution; this viscosity determination can be performed using a Brookfield LVF viscometer (Brookfield Engineering Laboratories, Inc.) with spindle No. 1 at 60 rpm and determination of viscosity after six revolutions), and their incomplete modified species ty; alginates including potassium alginate, sodium alginate, ammonium alginate and propylene glycol alginate; polikamedi (e.g., typically having a viscosity of less than about 1000 mPa · s, measured at 1 wt% in water at ²⁵ ° C.), such as guar gum, low viscosity; pullunan, gellan (including high and low acyl gellan); dextran, pectin, and combinations thereof. For example, an alkyl cellulose ester that can be used in the present invention is hydroxyethyl cellulose. Examples of modified alkyl cellulose esters that can be used in the present invention are hydroxypropyl cellulose and hydroxypropyl methyl cellulose. The film former in the gel film can only be kappa-2-carrageenan. When the gel film of the invention contains a second film former, kappa-2-carrageenan may be present in an amount of at least 10%, at least 20%, at least 50%, or at least 80% by weight of the total amount of film former in the dry film.

The dried film is the remainder of the film obtained by casting after a controlled removal of moisture. Combinations of ingredients such as kappa-2-carrageenan and optionally starch, polyol and water for processing are dispersed, hydrated, dissolved and, optionally, deaerated during the process options described herein. The resulting homogeneous mass is poured or molded to the desired level of hardness (it is necessary to achieve the intended final product). The system obtained by casting is formed by gravitational or controlled forces and subsequently immediately further processed (since the production of soft gel capsules) or the mass obtained by casting is further processed by various methods used for uniform and controlled removal of water until the desired moisture level is reached. The controlled removal of water from the casting system provides additional hardening / alignment of the homogeneous film ingredients in a dense structure that can further enhance the film's performance. Removing moisture is limited in that moisture does not bind the molecular surface of various hydrocolloid and carbohydrate components. The film is dried when the initial film obtained by casting does not lose additional weight under the influence of various drying methods during dehydration / dehydration treatment. Reducing the moisture content to a constant level also gives stability to the film and, optionally, the content (if embedded or clothed or captured, etc.) of water activity is also reduced by processing.

Examples of filler include non-colloidal (vegetable) cellulose, microcrystalline (vegetable) cellulose, microcrystalline starch, modified and unmodified starch, derivatives and fractions of starch, inulin, starch hydrolysates, sugar, corn syrup and polydextrose. As described herein and in the formula, the term “modified starch” includes such starches and hydroxypropylated starches, acid-reduced starches and the like. Examples of modified starches that can be used in the present invention include ^{Pure Cote TM, B760, B790,} B793, B795, M250 and M180, Pure-Dent ^TM B890 and Pure-Set ^TM B965, commercially available from the Grain Processing Corporation of Muscatine, Iowa , and CAraTex ^TM 75701, available from Cerestar, Inc. Examples of starch hydrosylates include maltodextrin, also known as dextrin. Unmodified starches, such as potato starch, can also contribute to film strength when combined with hydrocolloids within the scope of the present invention. In general, modified starches are products obtained by chemically treating starches, for example treating starches with an acid, treating starches with enzymes, oxidized starches, structured starches and other derivatives of starches. Modified starches are preferred in which the side chain is modified with hydrophilic or hydrophobic groups, thereby forming a more complex structure with strong interaction between the side chains.

The amount of filler used in the present invention is usually from 0 to 20% by weight of the dry film, but if necessary, a larger amount, for example at least 20%, more preferably at least 30% by weight of the dry film can be used.

It is noted that starches, derivatives of starches and starch hydrolysates can be multifunctional. So, in addition to being used as fillers, they can be used as a second film former. When they are used as fillers and as second film formers, they are usually used in an amount of at least 10%, preferably at least 20%, more preferably at least 30% by weight of the dry film, depending on the application; for example, soft capsules.

Examples of a pH adjusting agent that may optionally be used in the present invention include bases such as hydroxides, carbonates, citrates and phosphates, mixtures thereof and salts thereof (e.g. sodium citrate). The pH adjusting agent may be selected as a source of attached beneficial cations, such as potassium or sodium. For some compositions, a pH adjusting agent can be used to improve the stability of the gel film. The amount of pH adjusting agent is usually from 0 to 4%, preferably from 0 to 2%.

The gel films of the invention may also contain colorants and flavors, such as sugar, corn syrup, fructose, sucrose, aspartame, sucrolose, sorbitol, mannitol, maltitol and the like, other components such as plasticizers, fillers, second film formers, etc. One embodiment of the gel film of the invention comprises kappa-2-carrageenan, a flavor, and water in a high solids system; for example, higher than 50%, 60%, 65%, 75%, 80%, 85%, 90% solids.

It has been found that the dry gel films (e.g., 80% solids or higher) of the invention have, for example, a tensile strength of at least 1500, at least 2500 grams, at least 4000 grams, at least 5000 grams and at least 6000 grams as determined using Texture Analyzer TA-108C Mini Film Test Rig. For less hard gel films, it has been found that they have a tear strength of at least 50 grams, at least 100 grams, at least 200 grams, at least 500 grams, at least 1000 grams, as determined by a similar method.

It has been found that the films of the invention have a solids content of at least 50%, at least 60%, at least 70%, at least 80% and at least 90% of all gel film components. It is understood that 15%, 10%, or 5% of water can remain strongly associated with a solid in a gel film.

The thickness of the film commonly used for soft capsules is in the range of 0.5 to 3.0 mm, more preferably 0.8 to 1.2 mm.

It is possible that the gel films of the invention may contain non-heat reversible gums. However, without adversely affecting the homogeneity and thermo-reversible nature of the gel film of the invention, such non-heat-reversible gums can be present in an amount of less than 50% by weight of kappa-2-carrageenan, preferably less than 40%, more preferably less than 30% . Examples of such non-heat reversible gums include crosslinked gums such as pectins and / or calcium alginates (e.g. crosslinked). Calcium-reactive alginates and pectins, as well as their less purified forms, are considered as thermoreversible gums in the absence of divalent cations. Other non-irreversible gums, such as tragacanth gum, promote the thermal reversibility of kappa-2-carrageenan by absorbing water in its structure, thus causing the formation of kappa-2-carrageenan into a dense three-dimensional structure, since it is solubilized in less water, providing the same effect. as well as a result of an increase in the amount of kappa-2-carrageenan without secondary film formers. Additional film formers, such as polymannans, can form continuous scaffolds on their own or through synergies with other components during activation and the casting process.

The kappa-2-carrageenan gel films of the invention are usually produced by a method using a device that allows a sufficiently high shear, temperature (above the gelation temperature) and a constant temperature to ensure the homogeneity of the molten mass of the composition and gel formation upon cooling. Such a device includes, but is not limited to, Ross mixers, Stefan processors, traditional inkjet cooking chambers, extruders, and a fluid mixing device, as shown in Figure 3. Ross mixers, Stefan processors, traditional inkjet cooking chambers are readily commercially available. Before cooling, the molten mass can be fed into at least one of the following devices: a pump, mixer or degasser. An example of a device that performs some of these functions is an extruder. The extruded molten mass can also be sent to a film forming or forming device (for example, a spreading machine used as a capsule forming machine), which helps to uniformly cast a continuous film, or through a matrix that allows direct film or total extrudate formation from the molten mass, filed equipment. Care must be taken to maintain the molten mass above the initiation of the formation of a coupled flow / gel structure. To ensure the flow of molten mass before initiating the desired gel film formation on the casting rollers or at other film forming points, such as an extruder (flow restricting film forming device) or die, transfer hoses can be used that are insulated and heated (to maintain proper temperatures). Additional processing methods (such as heating the outlet / plunger head, as seen in the Ross method system) can pump (by pressure) the molten mass through the transfer hoses described above. Additional insulation can help maintain the temperature of the molten mass by using a Teflon disk originally located on the surface of the molten mass immediately after removing the mixing device. In addition, the supply hoses can be placed in controlled-heating molten mass supply (injection) blocks located on the capsule-making device, directly in the blocks or via optional modification of the supply blocks placed in the upper half of the body / shell, which helps maintain the temperature of the molten mass in the feed units, reduces moisture loss and maintains uniformity (centering) of the filling of the unit during the extended capsule film formation process. It is understood that other methods for maintaining the temperature of the molten mass can be used to form capsule films. These methods include, but are not limited to: extruding the molten mass through dies / holes in the film, which can be immediately fed to the capsule forming device, stored at a temperature that maintains the desired film properties (until capsule formation), as long as necessary. or dried to the desired levels of moisture, hardness and texture, as long as necessary. Such dried films tend to reabsorb water (water is introduced by some means) throughout the gel film structure and can be rehydrated when necessary, for example in the manufacture of soft capsules or other solid forms. Humidity is introduced into the film to achieve the desired moisture content, and strength / texture is achieved, which will allow the introduction of the film into a capsule manufacturing device for producing soft capsules.

As used herein, “fluid mixing device” means the device shown in FIG. 3. FIG. 3 shows a device for mixing fluids 10. A device for mixing fluids 10 is for mixing steam 2 with a first fluid or suspension 4 and a second fluid or suspension 6, producing a molten mass or suspended mixture 8.

A device for mixing fluids 10 includes a first housing 20 having a first inlet 22 through which steam 2 enters the housing 22, the nozzle portion 24, from which the steam 2 enters the housing 20 and the nozzle needle or rod 26 located on the nozzle portion 24 The actuator 30 is connected to the first housing 20 to control the final velocity and final pressure of the first fluid 2 in the nozzle portion 24. The actuator 30 may be of the type manufactured by Fisher Controls USA.

The fluid mixing device 10 further includes a mixing housing 40 connected to the first housing 20 on the nozzle portion of the first housing 20. The second housing 40 includes a second inlet 42 through which the first fluid 4 enters the second housing 40 and the third inlet 44 through which the second fluid 6 enters the second body 40. The inlets 42 and 44 are located below the first inlet 22. As shown in FIG. 3, the second inlet 42 and third inlet 44 are arranged on a common panel and spaced radially relative to each other, more preferably the opposing (i.e., spaced by 180 ^o) relative to the central axis Y of the mixing device 10. The second body 40 is typically looks like a cylindrical mixing chamber 52, which in turn determines the passage of flow distributed along the axis of the mixing chamber 52 from the inlet 54 of the mixing chamber to the outlet 56 of the chamber 52. The nozzle needle 26 is Xia movable actuator device 30 between the raised and lowered positions in the input section 54 to control the flow rate of steam in the mixing chamber 2 52.

The nozzle portion 24 of the first body 20 directs the steam 2 to the inlet 54 of the mixing chamber 52. The second inlet 42 and the third inlet 44 radially direct the first fluid 4 and the second fluid 6, respectively, to the mixing chamber 52. Steam 2, the first fluid 4 and the second fluid 6 is mixed in the mixing chamber 52, forming a molten mass or mixture 8 that leaves the mixing chamber 52. The molten mass 8, which can take the form of a formed product or form into a film, such as by casting mixture 8 onto a cooling drum or by passing mixture 8 through an extruder.

Regarding the following FIG. 4, a film and capsule manufacturing system 100 with a fluid mixing device 10 includes a film manufacturing unit 60 for manufacturing and supplying a film 9 and a capsule manufacturing device 80 for forming capsules 89. A film manufacturing unit 60 includes: a fluid mixing device 10 ; a first fluid supply device 62 for supplying a first fluid 4 to the fluid mixing device 10; a second fluid supply device 64 for supplying a second fluid 6 to the fluid mixing device 10; a feed path of the suspended mixture 70 for supplying the molten mass or the suspended mixture 8 from the fluid mixing device to the forming device; an optional extruder 73 in fluid communication with by feeding a suspended mixture 70, which extrudes the mixture 8 into a film 9; a capsule making device 80 for forming capsules 89; and a conveyor belt 90 for transporting filled capsules 90 for further processing, such as drying or packaging. Extruder 73 may be of the type manufactured by Wenger or Clextrel.

The capsule making device 80 may be a conventional rotational die for making capsules of the type made by R.P. Schrerer Technologies of Paradise Valley, Nevada. As shown in FIG. 4, the capsule manufacturing apparatus includes a capsule substance storage container 82, which contains the capsule substance 81 for encapsulation. Capsule substance 81 may include liquid, semi-liquid or powder medications, vitamins, food additives, colored balls, pigments, agricultural and food additives. The capsule manufacturing device 80 may be coupled to one or more rollers 77, 77 'and 78, 78' such that the films 9, 9 'can be drawn inside the capsule manufacturing device 80. The film 9 is fed between the heating unit 86 and the roller die 88. Parts of the film 9 are fed by vacuum into the recesses formed on the surface of the rotary die 88. The amount of capsule material 81 is delivered to the chamber formed in the film 9 under the influence of vacuum. A further rotational movement of the dies 88, 88 'solders the films 9, 9' together in the clamp between the rotational dies 88, 88 '. The filled capsules 89 fall into the receivers 87, 87 'and are transferred to the conveyor 90 for drying and packaging.

Regarding the following FIG. 5, the capsule manufacturing system 100a is similar to that shown in FIG. 4, where the similar features mentioned refer to similar elements. In FIG. 5, however, the film manufacturing unit 60a optionally includes a distribution chamber 72, and optionally a cooling drum or casting drum 74 in place of the extruder 73 in the system of FIG. 4. The system 100a includes a fluid mixing device 10 and a suspension mixture supply path 70, directing the suspended mixture 8 from the fluid mixing device to the distribution chamber 72. The distribution chamber 72 applies the mixture 8 to the injection drum 74. A film 9 is formed on the injection molding drum 74 when mixture 8 cools. After that, the film 9 is supplied to the capsule manufacturing apparatus 80. The film 9 'is preferably formed in the same manner as the film 9 by means of a second film-making unit (not shown).

The fluid mixing device 10 is adapted to produce a mixture for making a film, more preferably an edible film for producing edible capsules or strips. Incompatible film components are usually located in different injected fluid streams so that the incompatible components together come to the first stage of interaction with steam injection in the mixing chamber 52 of the fluid mixing device. While FIG. 3 shows steam inlets of both the first and second fluids, one or more additional inlets for one or more additional fluids may be provided. Preferably, the housings 20, 40 and other components of the fluid mixing device 10 are constructed of high quality stainless steel.

As another aspect of the present invention, it is noted that the molten mass does not need to inevitably achieve homogeneity in step (i). Thus, the homogeneity of the molten mass can be achieved before or after the molten composition is fed into at least one of the following devices: a mixer, a pump, or a device for removing volatiles, ensuring the molten mass reaches homogeneity before gelation.

The gel films of the invention shown below have a dry film strength of at least 2500 grams and are well adapted to the manufacture of soft capsules. Thus, the present invention is also directed to soft capsules made from homogeneous thermo-reversible kappa-2-carrageenan gel films of the invention, as well as methods for making such soft capsules.

A method of manufacturing soft capsules from kappa-2-carrageenan gel films involves the use of any conventional encapsulating device, for example a conventional rotational stamping device or a concave embossing stamp. For example, upon receipt of the molten mass according to the invention, it can be cast onto drums, cooled and then fed between rotating encapsulation dies, where the films are again heated, filled, sealed and cut. For a detailed description of the conventional process, see WO 98/42294. Alternatively, and as an advantage of the present invention over known methods for manufacturing soft capsules, the use of a shear device described above provides a sufficiently hydrated molten mass to be applied to the drum, where it is cooled and then fed to a conventional encapsulating device for filling, sealing and separation. This continuous type method can be used to eliminate the step of re-heating fully gelled and chilled films. The above rotational stamping method can be used to make the soft capsules of the invention having any desired shape.

Soft capsule filling materials can be materials widely used in the above rotational stamping method, including pharmaceutical ingredients, agricultural ingredients, nutritional ingredients, veterinary ingredients, food, cosmetics, personal care products, industrial, i.e. may be a liquid, solid, suspension, dispersion, and the like.

The present invention is also directed to a solid form comprising a filler material encapsulated in a homogeneous thermally reversible gel film according to the invention. One type of such solid form is a hard capsule. Hard capsules, as described herein, are solid forms that are traditionally used, for example, in the pharmaceutical industry, whereby two halves of a shell are formed, the filling material, usually a powder, is located in the shells and the two halves are joined together to form hard capsule. One way to make such hard capsules typically involves immersing metal pins or rods in the molten composition of the invention and forming a gel film around the rods. The gel film is dried and then removed from the rods. These methods are well known in the industry as methods for the manufacture of hard capsules. Hard capsule filling materials may be any filling materials commonly used in such dosage forms. Typically, filling materials can be liquids (including emulsions) or solid substances such as powders. The filling materials may be pharmaceutical ingredients, agricultural ingredients, nutritional ingredients, veterinary ingredients, food products, cosmetic ingredients, and the like.

The solid form can also encapsulate a powder, tablet, microcapsule or capsule in accordance with known techniques. For example, encapsulating a hard capsule with a gel film of the invention may provide protective sealing / reflective properties.

A gel film can also be used to modify the dissolution parameters of dosage forms. For example, the gel films of the invention contain additional components that can create solid dosage forms that can be released immediately, controlled, enteric or sustained release, or can be released upon activation by known phenomena, conditions or processes. The definitions of “immediate release,” “delayed release,” and “enteric” can be found in U.S. Pharmacopeia and are incorporated herein by reference.

The present invention is now described in more detail by reference to the following examples, but it is understood that the invention should not be construed as being limited to them. Unless otherwise specified, all parts, percentages, ratios, etc. presented by weight.

Examples

Unless otherwise specified, the following methods are used to obtain and evaluate materials and films in Examples 1-4. The Stefan UMC5 processor is a laboratory mixing device that provides suitable high mixing shear, heating and deaeration of compositions that are obtained by film-casting in a laboratory. A suitable used load size for the Stefan UMC5 processor is 1,500 grams.

An aqueous starch dispersion is prepared by dissolving any salts / buffers and pH modifiers in deionized water. Starch and / or maltodextrin (M100) is added and mixed until dissolved / dispersed. Pure Cote® B760 and B790 Starches are available from Grain Processing Corporation of Muscatine, Iowa.

The hydrocolloid mixture is obtained in the Stefan UMC5 processor by pre-mixing the plasticizers until uniform and adding pre-mixed dry hydrocolloids in portions with stirring for approximately 30 seconds at 200 rpm after each addition. Sorbitol Special and glycerin are used as plasticizers. Sorbitol Special is an aqueous solution of sorbitol and sorbitol anhydrides at 76% solids, supplied by SPI Polyols, Inc (New Castle, Delaware).

The starch dispersion is added to the non-aqueous hydrocolloid mixture and mixed at 300 rpm for 5 minutes. Mechanical stirring was increased to 2100 rev / min, and the mixture was heated from 85 ^{° C} to 95 ° ^C under stirring. When the target temperature is reached, the mixture is stirred for 30 minutes, then the sample is kept under vacuum (50-60 bar) with continued stirring for an additional 45 minutes.

When the holding time under vacuum at temperature ends, the sample is poured into a preheated quarton vessel of Mason with a wide neck. Temperature and pH are recorded. Viscosity is measured on a hot sample using a Brookfield LVF viscometer.

A small portion of the sample is taken and cooled usually overnight before measuring gel / melt properties and solids content using an Atago E handheld refractometer (Gardco, Pompano Beach, FL). The melt temperature is determined by placing a small fragment of the cooled gel on a wire string stand inside the tube so that the fragment does not come into contact with the tube wall. The tube is sealed with aluminum foil with a small hole to allow measurement of gel temperature using a digital Tempermeter probe. The tube was immersed in a heating bath so that a fragment is below the surface of hot water at about 100 ° ^C. For samples that have a melt temperature above 90 ^{° C,} using a bath of silicone oil. The melt temperature is recorded when the gelled sample becomes wet in appearance, softened and can be mixed (note the temperature range). As soon as the sample melts, the test tube is transferred to a second glass containing cold tap water (15 ^° C). To record the temperature, a temperature sensor is used as the sample cools and the surface of the sample is probed to determine the onset of gel formation of the sample. The temperature of the gel is the temperature during cooling, when the sample no longer flows to fill the recess made by the sensor.

The hot sample is then cast using a leveling stick with a clearance hole of 3 mm to a metal plate measuring 177 mm by 177 mm by 5 mm onto which RAM (lecithin) is previously sprayed to facilitate easy removal of the film material. Gel coated plates are closed to avoid moisture loss from the cast film. Cast films are typically cooled (to less than 8 ^° C.) for half an hour to remove the film for testing. Cooling is not required for film formation. The dried film obtained by drying the coated strip plate in an air-ventilation oven heated to 40 ° ^C. The films were dried for 2 hours at 40 ^{° C,} have an intermediate solids content of approximately 60%, while the films dried in overnight ^at 40 ° C, have a solids content of 80% or above. The test properties are measured at room temperature (approximately 20 ° ^C), unless otherwise indicated. The percentage of solids in the dried film is determined by the difference in mass of the cast film in the form of the contained level of solids and the dried film. The tensile strength (UR) is measured on cast and dried film strips using the structure analyzer Texture Analyzer TA-108S Mini Film Test Rig.

Unless otherwise indicated, Maltrin M100 is obtained from Grain Processing Corporation, Pure-Cote B760 is obtained from Grain Processing Corporation, Sorbitol Special is obtained from SPI Polyols and Glycerin is obtained from VWR (EP / USP purity category).

Example 1

As described above, Cgn A is obtained as an alkali-treated, clarified extract of Gigartina skottsbergii , essentially haploid (gametophyte) plants, and is recovered by precipitation with alcohol. Minor levels (total below 5%) of lambda and theta carrageenans from diploid (tetrasporophytic) plants are also presented.

Cgn B is obtained by dissolving Cgn A in water and recovered by precipitation with alcohol and drying. Samples with different molecular weights are obtained by the reaction of dissolved carrageenan with an oxidizing agent to obtain Cgn C-F. Sodium hydroxide is added to the Cgn CE samples after the oxidation step and before alcohol precipitation to adjust the pH of the resulting product. The properties of kappa-carrageenan 2 are shown in Table 1. The viscosity of an aqueous solution at 1.5 wt.% Solids measured at ⁷⁵ ° C using a Brookfield LVF viscometer at suitable speeds and types of spindles. Properties of 2% aqueous gels obtained using 2 wt.% Kgn AF samples (# 1) without added cations, (# 2) with 0.2 wt.% Added KCl and (# 3) with 0.2 wt. % added KCl and 0.2% CaCl _2, respectively, are characterized using a TXTM structure analyzer. Gels were tested at ²⁵ ° C and recorded rupture force (in grams) and permeability (in centimeters).

Kghi (carrageenans) A-F below are kappa-2-carrageenans that can be used in the present invention.

Table I
Properties of Kappa-2-Carrageenans AF Kgn A Kgn In Kgn S Kgn D Kgn E CNF F Oxidation Test No No Yes Yes Yes Yes Mg,% 0.11 0.34 0.19 0.19 0.19 0.19 Ca,% 0.34 0.29 0.34 0.39 0.52 0.40 K,% 12.9 8.46 8.59 8.87 8.74 8.95 Na,% 0.22 0.42 0.51 0.57 0.65 0.38 Viscosity, MPa · s 175 144 48 24 fourteen eleven pH 9,4 9.42 8.93 9.03 9.16 6.7 2% water gel Ur (g) 211 38 21 eighteen eleven 12 Permeability (cm) 7.4 13.9 11.5 9.0 7.8 16.1 2% water gel
(KCl) Ur (g) 308 162 126 107 70 51 Permeability (cm) 7.4 9.9 7.8 7.6 7.3 6.1 2% water gel
(KCl + CaCl ₂ ) Ur (g) 487 349 514 445 356 158 Permeability (cm) 3.6 3,1 6.4 5.3 5,0 1.7

* Viscosity is measured at 1.5% solids in deionized water at 75 ^about C.

In Table II below, Crs D and E are prepared in the form as presented, and obtained by casting in the form of films. The composition and properties of the films are shown in Table II. It is believed that all compositions are within the scope of legal protection of the present invention, although some may be more preferred for a particular application than others.

Table II
Kappa-2-carrageenan compositions and film properties Note 1-1 Note 1-2 Note 1-3 Note 1-4 Ingredients (g) Water 834.7 834.7 666 497.4 Kgn D 0 75 75 75 Kgn E 75 0 0 0 M-100 227.3 227.3 292.3 357.2 Sorbitol SP 272.2 272.2 349.9 427.7 Glycerol 90.8 90.8 116.8 142.7 Temp, ^o C * 81.1 82 85 92 Viscosity, MPa · s 4000 13700 22350 > 50,000 Solids (ust.) 40.1% 40.1% 50.1% 60.0% Gel, ^o C 55-57 54-55 62 77-78 Melt, ^about With 73-75 77-80 85 90-92 In the form of a cast film Ur (g)
Dried film (set. 80% solids)
(16 hours ^at 40 ° C) 312 318 404 476 Avg film thickness (mm) 1,5 1,0 0.87 1,1 Ur (g) 5755 5220 5613 3218

* Temperature and viscosity of the molten mass before casting.

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength than others.

The above table shows that in Example 1-2 and Example 1-1, the viscosity of the molten mass at the processing temperature (13700 mPa · s and 4000 mPa · s, respectively) is regulated by reducing the molecular weight of Cgn D to Cgn E (expressed as a viscosity of 24 mPa · S and 14 MPa · s, respectively) with a slight effect on the properties of the film.

The melting temperature of the casting material increases (Examples 1-2, 1-3, and 1-4) as the solids content of the composition increases. In examples 1-2, 1-3 and 1-4, the temperature of the gel increases as the solids content increases until the temperature of the gel approaches the temperature of the molten mass. The gelation before casting, as indicated by the increased strength of the gel of the cast film and the high viscosity of the molten state (> 50,000 mPa · s) in Example 1-4, is due to the approximation of the gel temperature to the temperature of the molten mass. This indicates the desirability of maintaining the temperature of the molten mass above the gelation temperature during processing, if it is desirable to obtain more durable films. Stirring at temperatures below the temperature of the gel leads to a disturbed gel structure and reduced strength. Technological equipment suitable for use should adequately hydrate, homogenously mix and easily transport the molten mass for further processing as such or for further operations such as molding or casting of the film.

Example 2

Kappa-2-carrageenan is obtained as an alkali-treated, clarified extract of a mixture of Gigartina skottsbergii and Sarcothalia _rispate , mainly haploid (gametophyte) plants, and is recovered by precipitation with alcohol. Also present are approximately 10-20% (total) of lambda and theta carrageenans from diploid (tetrasporophytic) plants. The extract is recovered and subsequently subjected to ion exchange to obtain kappa-2-carrageenan with low divalency. The properties of kappa-2-carrageenans with a low content of divalent cations (Cgn GJ) are shown in Table III. GJ carrageenans are believed to be covered by the scope of the claims of the invention.

Table III Kgn G Kgn H Kgn I Kgn J Cation exchange Yes Yes Yes Yes Mg,% 0,07 0.02 0,03 0.05 Ca,% 0.06 0.01 0.16 0.15 K,% 2.19 1.00 0.00 0.67 Na,% 5.12 7.70 6.90 7.40 Viscosity, MPa · s 6 eighteen 45 98 Viscosity, MPa · s 9 twenty 41 pH 8.12 8.7 9.6 10.1 2% water gel
Ur (g) 0 0 0 0 2% water gel
(KCl)
Ur (g) 0 13 29th 38 2% water gel
(KCl + CaCl ₂ )
Ur (g) thirty 93 112 181

Carrageenans * H, I and J was measured at ⁷⁵ ° C at 1.5% solids Kappa-2-Carrageenan in 0.10 molar sodium chloride.

Film compositions using kappa-2-carrageenans Kgn G-J samples with a low content of divalent cations and the corresponding properties of the films are presented in Table IV. It is believed that all compositions are within the scope of legal protection of the present invention, although some may be more preferred for a particular application than others.

Table IV
Films using kappa-2-carrageenan with a low content of divalent cations Note 2-1 Note 2-2 Note 2-3 Note 2-4 Ingredients
(g) Water 834.7 834.7 834.7 834.7 Kgn J 75 0 75 75 Kgn I 0 75 0 0 Kcl 0 0 9.0 9.0 B790 starch 0 0 0 227.3 M-100 227.3 227.3 227.3 0 Sorbitol SP 274.9 274.9 274.9 274.9 Glycerol 91.7 91.7 91.7 91.7 Pace. ^about C * 89 87 87 87 Viscosity, MPa · s 5800 5800 6250 10300 Solids (established) 40% 40% 41% 40% Melt, ^about With 45-48 43 66-71 70 Gel, ^o C 35 31 52 48 In the form of a cast film Ur (g) <40 <40 281 237 Dried film Solids (established. ~ 80%) Avg film thickness (mm) - - 0.97 0.88 Ur (g) 3468 3697 3236 7603

* Temperature and viscosity of the molten mass before casting.

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

Ion-exchanged kappa-2-carrageenans (I and J) in combination with polyols and maltodextrin (as a filler) provide a relatively less strong cast film with a slight tensile strength at 40% solids content. It is believed that this is due to insignificant amounts of potassium cations, which are desirable for more complete activation of the formation of a double helix of carrageenan (i.e. gel formation) at temperatures that allow carrageenan to be the primary structuring agent. Examples 2-1 and 2-2 are gel films having relatively lower gel and melt temperatures. Even though the gelation potential is not maximum (due to lower potassium levels), Examples 2-1 and 2-2 exhibit a tensile strength of 3468 and 3697, respectively. Example 2-3 demonstrates the effect of adding potassium ions to the structure of Kappa-2-carrageenan in Cgn J. The casting force, although soft, provides sufficient force to remove the film from the casting plate. The development of the structure through Kgh J, together with the addition of potassium ions, is confirmed by an increase in the temperature of the melt and gel in Example 2-3, compared with Example 2-1. The tensile strength of the dried film remains comparable with Examples 2-1 and 2-2.

Example 2-4 demonstrates the effect of replacing the maltodextrin in Example 2-3 with modified starch (B790). While viscosity increases, gel and melt temperatures remain relatively similar to Example 2-3, which contains maltodextrin. The strength of the cast film of Example 2-4 is also relatively equal to Example 2-3. The strength of the dried film of Example 2-4 is more than doubled compared to Example 2-3. This clearly indicates the structural synergy between starch and kappa-2-carrageenan when they are both present together with potassium ions (i.e. gelling ions for kappa-2-carrageenan). Potassium ions can be provided by direct addition of inorganic salts, organic salts or combinations thereof, or contained in additional ingredients. The use of kappa-2-carrageenan containing residual salts from the treatment may contribute to desirable gel conditions that maximize gel structure and synergy with starch. The homogeneous gel structure of kappa-2-carrageenan / starch is formed by casting molten mass at sufficiently high temperatures to prevent premature gelation.

Immediately below are additional compositions of the invention.

Table v
Kappa-2-carrageenan films Note 2-5 Note 2-6 Note 2-7 Ingredients (g) Water 834.7 834.7 825 CNN N 61,4 0 0 Kgn G 0 0 90 Kgn I 0 75.0 0 Calcium Sulphate Dihydrate 1.7 0 0 Potassium chloride 0 15.0 0 B760 starch 0 0 225 M-100 227.3 227.3 0 Sorbitol SP 275.4 272.2 272.2 Glycerol 91.9 90.8 90.8 Temp., ^O C 82 88 75 Viscosity, MPa · s 6500 16150 18250 Solids identified 39 42 40 Melt, ^about With 74-77 85 62-65 Gel, ^o C 56 60-65 42 pH 5.8 6.9 6.9 In the form of cast films SD (g) at ~ 40% 338 302 117 The dried 2 hours at 40 ^C. SD (g) at ~ 60% 766 NT 536 The dried overnight for 16 hours at 40 ^C. Avg film thickness (mm) - 0.62 SD (g) at ~ 80% 3227 4470 6073

NT = not tested

* Temperature and viscosity of the molten mass before casting.

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

Example 2-5 was obtained to determine the content of cations equivalent to example 1-1. Both samples show the same properties of the gel melt. The higher molecular weight Kgn E (14 tsvs) in Example 1-1 provides more structural support for the gel film compared to Kgn H (6 tsvs) in Example 2-5, as shown by the higher strength of the dried film. The higher film strength of Example 2-7 shows that the use of modified starch in combination with a controlled / reduced molecular weight of kappa-2-carrageenan provides the overall structure of the film and indicates the combination of kappa-2-carrageenan with starch.

Example 3

Table VI: "Film compositions and properties of films containing kappa-2-carrageenans mixed with alginates." KAHG is a potassium alginate from Laminaria hyperborean having a high level of guluronic (G) structural units. KAHG has a viscosity of 5 cP, measured in a 1% aqueous solution at 25 ° ^C and ion content equal to 15.73% of potassium, 0.63% sodium, 0.07% Mg and not containing calcium. Protanal® BV4830 ester is propylene glycol alginate available from FMC BioPolymer (Philadelphia, PA).

Table VI
Kappa-2-carrageenan and alginate mixtures Note 3-1 Note 3-2 Ingredient Water 55.6% 55.6% Kgn G Kgn S 2.7% 3.6% Kahg 2.1% BV4830 1.2% 2.4% B760 starch M-100 15.0% 15.0% Sorbitol SP 18.0% 18.0% Glycerol 6.0% 6.0% Temp., ^O C 87 84 Viscosity, MPa · s 4250 1050 Solids 40 37 Melt, ^about With 77-78 74-79 Gel, ^o C 54 52 pH 4.8 5.5 Cast Film (Inst. 40%) Ur (g) 142 168 Dried film (set 80%) Average film thickness (mm) 0.62 0.48 Ur (g) 3409 4004

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

In Example 3-1, a potassium ion is provided by potassium alginate. Example 3-2 shows that propylene glycol alginate adds strength to kappa-2-carrageenan and reduces processing viscosity.

Example 4

Table VII presents a film obtained using mixtures of Kappa-2-carrageenan with Edicol ULV 50, a low viscosity guar gum from Indian Gum Industries.

Kgn K is kappa-2-carrageenan obtained in the form of an alkali-treated, clarified extract of Gigartina skottsbergii , essentially haploid (gametophytic) plants. Minor levels (total below 5%) of lambda and theta carrageenans from diploid (tetrasporophytic) plants are also presented. Cgn K has a low content of divalent cations and a low content of potassium ion, as shown in Table I.

Kgn L is a kappa-2-carrageenan obtained in the form of an alkali-treated, clarified extract of a mixture of Gigartina skottsbergii and Sarcothalia crispata , mainly haploid (gametophyte) plants. Also present are approximately 10-20% (total) of lambda and theta carrageenans from diploid (tetrasporophytic) plants. The properties of Kgn K and L are as follows.

Table VII
Properties of kappa-2-carrageenan Kgn K Kgn L Cation exchange Yes No Mg,% 0.05 0.05 Ca,% 0.15 0.45 K,% 0.67 13.40 Na,% 7.40 0.90 Viscosity, MPa · s 98 NT pH 10.1 NT 2% water gel Ur (g) 0 " 2% aqueous gel (KCl) Ur (g) 38 " 2% aqueous gel (KCl + CaCl ₂ ) Ur (g) 181 "

Table VIII shows the compositions and properties of the films for compositions prepared using low viscosity guar gum in combination with kappa-2-carrageenans.

Table VIII
Kappa-2-carrageenan guar compositions and films Note 4-1 Note 4-2 Note 4-3 Note 4-4 Ingredients (g) Water 836.3 836.3 836.3 836.3 Kgn L 40.5 20.3 0,0 0,0 Kgn K 0,0 20.3 40.5 40.5 GUAR ULV 50 49.5 49.5 49.5 49.5 B760 starch 220.8 220.8 220.8 220.8 Potassium chloride 0,0 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 Total weight (g) 1,500.0 1,500.0 1,500.0 1,500.0 Temp., ^O C 90 90 87 95 Viscosity, MPa · s > 50,000 > 50,000 > 50,000 > 50,000 For casting Gel, ^o C 68-69 69 fifty 54-65 Melt, ^about With 85-87 86-88 67-68 76-83 pH 5.8 5.9 5.2 5.2 Cast film Solids, mouth. 45% 42% 40.2% 45% Ur (g) 239 349 130 330 Dried film (2 hours 40 ^about C) Solids, mouth. 60% 60% 63% 66% Ur (g) 953 2189 1194 1631 Dried film (16 hours 40 ^about C) Solids, mouth. 87% 75% 84% 84% Ur (g) 7476 6901 6276 8733

* Temperature and viscosity of the molten mass before casting.

All of the above compositions of the invention show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

Example 5

The following examples represent films obtained using the fluid mixing device of Figure 3. In these examples, part A and part B are pumped from separate prefabricated containers at ambient temperature, in the form of two separate streams 4, 6 into two different inlets 42, 44, which provide steam injection in a device for mixing fluids. Two separate streams 4, 6 are combined at the interface between the vapor phase in the mixing zone 52 of the fluid mixing device 10. Separate solutions of part A and part B are easily pumped into the fluid mixing device 10 and mixed with steam 2. Steam 2 is introduced into the zone mixing at a pressure of 120 psi. The resulting molten mass or suspension mixture 8 flows from the outlet 56 of the fluid mixing device 10. The mixture 8 is poured onto a smooth surface and distributed to form a homogeneous film 9.

To measure the viscosity of mixture 8, approximately 500 ml of mixture 8 is collected from outlet 56 and poured into a vessel. The temperature, pH, and viscosity is measured for a given sample at 95 ^° C for viscosity measurements using a Brookfield viscometer LVF. Use a suitable combination of speed and spindle so that you can take readings. The scale readings are converted to dynamic viscosity (cP).

To measure the strength of the film and the level of solids, the molten mass 8 is collected from the outlet 56, then it is cast using a bar for distribution with a gap size of 3 mm onto a stainless steel metal plate. Original films 9 or “fresh films” are collected. Part fresh film 9 is dried by placing them into a heated ^to 40 ° C air oven. Tear strength is measured on fresh and dried film strips using the Texture Analyzer TA-108S Mini Film Test Rig. The percentage of solids is determined by measuring the difference between the initial mass of fresh film and the final mass of dried films.

To measure the temperature of the gel, part of the molten mass 8 is collected from the outlet 56 of the mixing device 10 and transferred to a test tube. Half of the tube remains empty. A glass thermometer is introduced into the molten mass 8. The material 8 is allowed to cool at room temperature. After each degree of cooling, the thermometer is removed from the material 8. When a small recess is observed on the surface of the mass 8, this temperature is recorded. The thermometer is reintroduced into mass 8, which is allowed to cool further. The thermometer is removed and reintroduced at each degree of cooling until a constant recess is formed in mass 8, so that the recess is not re-filled. The temperature at which a permanent recess is formed is recorded. The gel temperature shown is the interval between the two recorded temperatures.

Table IX
Mixtures containing kappa-2-carrageenan Example No. 5-1 5-2 5-3 Part A (%) Kappa-2-carrageenan A 7.0 8.4 8.9 Glycerol 26.5 31.8 33.5 Part B (%) Starch 16,4 19.7 20.7 Water 50,0 40,0 36.9 Pace. in the mixing chamber ( ^o C) 107 107 108 Release temperature ( ^o C) 101 102 102 Viscosity cps (95 ° ^C) 7300 5200 48000 pH 7.3 NT 8 % solids 53 54 65 Pace. gel ( ^o C) 46-50 43-47 53-60 The strength of the wet film (grams) 267 214 983 Dry Film Strength (grams) 2958 6798 4594 Avg film thickness (mm)
(% solids) 1.3 (74%)
1.7 (59%)

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

Table X
Mixtures containing kappa-2-carrageenan and PGA Example No. 5-4 5-5 5-6 5-7 Part A (%) Kappa-2-carrageenan A 2.7 3.2 3.2 4.0 Pga 3.3 3.9 3.9 4.9 Glycerol 22.4 26.5 26.5 33.5 Part B (%) KOH 0,0 0,0 0.1 0,0 K ₂ CO ₃ 0,0 0,0 0,0 0.3 Starch 13.9 16,4 16,4 20.7 Water 57.8 50,0 49.9 36.6 Pace. In the mixing chamber ( ^o C) 108 107 108 107 Release temperature ( ^o C) 102 102 102 101 Viscosity cps (95 ° ^C) 5500 4650 2200 12400 pH 4.1 4.2 8.7 6.3 % solids 48 fifty NT 58 Pace. gel ( ^o C) 35-40 NT NT 58-66 The strength of the wet film (grams) 60 117 NT 337 Dry Film Strength (grams) 2408 3069 4335 4561 Avg film thickness (mm)
(% solids) 1.2 (91%)
1.1 (57%)

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

Table XI
Mixtures containing kappa-2-carrageenan and guar LV Example No. 5-8 5-9 Part A (%) Kappa-2-carrageenan B 4.0 4.2 Guar ULV 4.9 5.1 Glycerol 33.5 27.0 Sorbitol 0,0 8.1 Part B (%) Starch 20.7 21.8 Water Pace. in the mixing chamber ( ^o C) 108 108 Release temperature ( ^o C) 102 102 Viscosity cps (95 ° ^C) 7800 69000 pH 5,6 5.5 % solids 57 55 Pace. gel ( ^o C) > 100 > 100 The strength of the wet film (grams) 3402 921 Dry Film Strength (grams) 6587 9234

All of the above compositions show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others.

The following Tables XII and XIII provide descriptions of the components indicated in this example.

Table xii
Component Descriptions Name Trade name Provider Description Propylene Glycol Alginate (PGA) Protanal BV 4830 FMC Corporation Low viscosity guar gum (LV guar) 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

Table XIII
Descriptions of Carrageenans Link Description Provider Kappa-2-carrageenan A An alkali-treated, clarified, low divalent extract of a mixture of Gigartina skottsbergii and Sarcothalia crispata , mainly haploid (gametophytic) plants, this extract is commonly known as "kappa-2-carrageenan". Includes approximately 10-20% (total) of lambda and theta carrageenans from diploid (tetrasporophytic) plants. It is defined as a natural statistical block copolymer of kappa and iota-carrageenan in a ratio of approximately 1.0 to 3.0: 1, respectively, and has significantly different functional groups compared to mixed individual natural polymers of kappa and iota-carrageenan in same ratio. FMC Corporation Kappa-2-carrageenan B An alkali treated, clarified, low divalent extract of Gigartina skottsbergii essentially haploid (gametophyte) plants, this extract is commonly known as "kappa-2-carrageenan". Also includes minor levels (below 5% of total) lambda and theta carrageenans from diploid (tetrasporophytic) plants. It is defined as a natural statistical block copolymer of kappa and iota-carrageenan in a ratio of approximately 1.0 to 3.0: 1, respectively, and has significantly different functional groups compared to mixed individual natural polymers of kappa and iota-carrageenan in same ratio. FMC Corporation

As described and demonstrated above, the films obtained in accordance with the invention can be used in traditional capsule manufacturing equipment previously used to make gelatin capsules. Hydrocolloid films obtained by the present invention produce less waste and provide easier processing than gelatin based films.

Example 6

Kappa-2-carrageenan is obtained in the form of an alkali-treated, clarified, low divalent extract of a mixture of Gigartina skottsbergii and Sarcothalia crispata, respectively, using mainly haploid (gametophytic) plants. Such an extract is commonly known as kappa-2-carrageenan. The total amount of lambda and theta carrageenans from diploid (tetrasporophytic) plants is approximately 0 to 5% for Gigartina skottsbergii compared to 5 to 10% for Sarcothalia crispata . The extract is recovered and subsequently subjected to ion exchange to obtain kappa-2-carrageenans with low divalency. The properties of kappa-2-carrageenans are presented in Table (XIV) and are considered to be covered by the scope of the invention.

Table XIV
Properties of sodium and potassium kappa-2-carrageenans Kgn Na K2-S Kgn K 2-S Kgn Na K2-N Kgn K K2-N Source algae Gigartina skottsbergii Gigartina skottsbergii Sarcothalia crispata Sarcothalia crispata Mg,% 0.00 0.12 0,03 0.12 Ca,% 0.04 0.34 0.11 0.43 K,% 1.24 9.27 1.35 8.63 Na,% 6.53 0.68 7.23 1.34 Viscosity, MPa · s 45.5 39.5 62.5 31.5 pH 7.46 8.51 7.1 7.91 2% water gel Ur (g) Initial 38 17 102 Permeability (cm) 7.46 6.9 21 12.1 2% aqueous gel (KCl) Ur (g) 10 134 thirty 179 Permeability (cm) 5.7 1.9 5,0 2.7 2% aqueous gel (KCl + CaCl ₂ ) Ur (g) 112 279 114 263 Permeability (cm) 2.1 2.7 2.7 2.0

K2 = kappa-2-carrageenan

The composition of the films for kappa-2-carrageenans and the corresponding properties of the films are presented in Table XV. These films are formed using the expansion box method. The compositions use a 50/50 mixture of kappa-2-carrageenans from Gigartina skottsbergii and Sarcothalia crispata , and they have a variable content of potassium cations. It is believed that all of the compositions below are within the scope of the present invention, although some may be more preferred for a particular application than others.

Table XV
Films of kappa-2-carrageenans from various source algae and cation content. Note one Note 2 Note 3 Note four Ingredients (g) Na K2-S * 162.6 162.6 195.1 0,0 Na K2S-N * 162.6 0,0 195.1 0,0 K-K2S-S * 0,0 0,0 0,0 162.6 K-K2-N * 0,0 162.6 0,0 162.6 Water 1851.5 1851.5 1851.5 1851.5 B790 starch 858.5 858.5 858.5 858.5 Glycerol 1300.8 1300.8 1300.8 1300.8 In the form of a film for molding Note one Note 2 Note 3 Note four Gel, ^o C 35-40 63 fifty 58 Melt, ^about With 58-60 83-85 69 93-95 pH 5.3 5,6 6.6 5,6 Cast film Solids, mouth. 57.3% 57.3% 57.3% 57.3% Ur (g) 214.3 610.5 459.1 901.4 Dried film (16 hours 40 ^about C) Solids, mouth. 95 91 86 93 Ur (g) 5132 6902 8914 4517 Permeable. cm 2,3 1.8 1.8 1,6

* = kappa-2-carrageenan

All of the above compositions according to the invention show sufficient dry film strength for use in the manufacture of soft capsules, although some show greater strength values than others. The sodium form of kappa-2-carrageenan (Examples -1 and -3) provides the greatest elasticity, while all the potassium forms of kappa-2-carrageenan (Example-4) give films that are more rigid, although applicable. Processing a composition containing potassium kappa-2-carrageenan is also difficult because the mixture begins to form a gel when it is transferred from a Ross mixer to a film-forming machine. The generated films in Example 4 have lower strength, most likely due to premature gelation during transfer and / or the film formation process. Accurate temperature control is necessary when it is desirable to maximize the strength of the film and to avoid a quick transition from the molten mass to a rubbery state and then to a glassy state (glass transition temperature). The film obtained using Kappa-2-carrageenan with "mixed cations" (Example-2) provides melt and cast film properties that are intermediate between films containing all sodium and all potassium Kappa-2-carrageenans, with an increased gelation temperature and a decrease in elasticity (as shown by permeability) compared to all sodium kappa-2-carrageenans.

Example 7

Soft capsule example

Soft gel capsules (7.5 oval) containing mineral oil (Formula A below) are prepared using a Technopar SGM1010 soft capsule machine with 7.25-inch and 4-inch heads. The molten mass used to form the capsule shell is prepared as follows: 11.35 pounds of kappa-2-carrageenan (defined as Kappa-2-carrageenan A in Example 5) are added to a charge of 33.89 pounds of glycerol in a Ross DS40 vacuum mixer, jacketed, and dispersed at maximum speed for 5 minutes. An additional 11.35 pounds of kappa-2-carrageenan (defined in Example 5 as kappa-2-carrageenan A) was added to the mixture and dispersed for an additional 5 minutes. The pre-mixed mixture of 50 pounds of modified PureCote B790 starch in 94.1 pounds of deionized water is then loaded into the mixer. The mixer lid is closed and evacuated at 26 inches to remove air. The contents are mixed for 30 minutes using a planetary mixer and dispersant at a speed equal to 1/3 of the maximum. Vacuum overlap and the contents of the mixer was further stirred while heating to 90 C by means ^of steam at low pressure (<10 psi) in the jacket of the mixer. After reaching a temperature of 90 ^C. disperser speed was gradually increased to 2/3 of the maximum speed while maintaining the molten mass at a temperature of at least 90 ^{° C} for 45 minutes. The molten mass was partitioned using a sealed plate to cause the molten mass to flow as needed from the Ross mixer through a flexible hose with temperature control and an electric heating (~ 125 ° ^C) to a closed distributor box. Cast films formed in the dispenser box are continuous and even. Films are transported by means of rollers to heads forming capsules, where capsules are formed, filled with mineral oil and sealed. The sealing temperature of the capsule is 62 ^° C, and the sealing pressure is ~ 2 bar. Sealing ability improves as the tape thickness decreases from 0.28 inches to 0.16 inches. The capsules were dried in a tunnel drier for 72 hours at ⁸⁰ F and 19% RH (relative humidity). The integrity of the sealed capsule remains good after drying. The cast film obtained from this composition is dark amber and cloudy with a slight odor of algae. The tensile strength of the film (0.3 mm thick) is 310 g at 58% solids content. Film breaking load after drying overnight ^at 40 ° C and 40% RH (~ 80% solids) is equal to 3309 g See. Table A below.

Additional soft capsules (Formula B below) encapsulating mineral oil are prepared according to the above method and equipment using a second composition containing 39.7 pounds of Sorbitol SP, 59.5 pounds of glycerin, 19.6 pounds of sodium ion exchange kappa-2- carrageenan (a mixture of 50/50 carrageenans J and I, above), 44.6 pounds of PureCote B760 starch and 92.6 pounds of water. Sorbitol SP is added to the preformed starch / water mixture. The film immediately after casting has a thickness of 0.6 mm and a tear force of 263 g at a 55% solids content. The film sample, which was dried overnight ^at 40 ° C and 40% RH (~ 80% solids) has a thickness of 0.7 mm and a breaking load equal to 6463, the film immediately after casting is more elastic and stretched over the rollers when submitting into capsule heads. Capsules formed using capsules sealing temperature of 42 ^{° C} and sealing pressure of 0.5 bar.

The weight of the capsules, the film thickness for each half of the capsule, and the bursting force are evaluated. The breaking force is measured by squeezing the capsule to failure. The compression sensor has a speed of 1 mm / s. Ten capsules are tested for each condition. It is reported that the strength of the shell is the tensile strength of the capsule with a horizontal seam. The strength of the seam is measured for 10 capsules with a vertically located seam. The results are shown in Table XVI. Both kappa-2-carrageenan films are flexible, as shown by the tearing distance, and produce a strong capsule seam, which is indicated by the capsule rupture force and the capsule does not collapse along the seam, but along the top of the seam (away from the point of pressure application).

Table XVI
Capsule properties Capsule formula Capsule weight (mg) Film Weight / Fill Weight (mg) Thickness film1 / film2, mm Shell rupture distance, mm Shell Strength, Newtons Seam gap distance Seam Strength, Newtons Formula A 471 151/320 357/312 6.3 206 6.3 210 Formula B 499 187/312 420/370 5.3 124 5.1 105

Example 8

Kappa-2-carrageenan is obtained from Sarcothalia crispata , with a final composition of approximately 74% unmodified kappa-2-carrageenan and 26% lambda-carrageenan. Kappa-2-Carrageenan has a viscosity of 340 cps and a pH of 9.4 when tested in a 1.5% aqueous solution at 75 ^C. The content of the ions is approximately 4.4% Potassium 4% sodium, 0.2 % calcium and 0.4% magnesium. The composition is prepared by adding 2% Kappa-2-Carrageenan to a mixture of 20% glycerol and 78% deionized water by mixing while heating to 85 ^{° C,} keeping the temperature during mixing at 85 ^{° C} for 15 minutes, adjusting any loss of water deionized water at 85 ^about C, then pouring into a Petri dish and drying overnight at 45 ^about C to a film with approximately 80% solids content. The dried film has a breaking force of 469 grams and a permeability of 3.3 cm.

Example 9

To obtain samples with 2.25% kappa-2-carrageenan with a varying molecular weight according to viscosity, when measuring viscosity at 75 ^about C for an aqueous solution with a 1.5% solids content, the following methodology is used: 105 grams of water and 147 a gram of corn syrup is mixed in a glass. The dry pre-mixture was obtained Kappa-2-Carrageenan, granulated sugar, and salt (as indicated in Table XVII) is added to the liquid with stirring and heated to 95 ^C. The hot liquid was poured into 2 cups for gel and 2 vials (fill 1/2 ) The plates for the gel and one tube (located to receive the gel surface at an angle of 45 degrees to be used for measurement of the melting temperature) were placed in a water bath at ¹⁰ ° C for an hour. A second tube is used to measure the temperature of the gel. The solids content for casting is approximately 62%. And a melting temperature of the gel for samples 1b, 2b and 3b, which contain added calcium and potassium cations, greater than 50 ^{° C} and are relatively constant with increasing molecular weight. It was observed that all of the gel melting temperature and the samples 1a, 2a and 3a, which contain ion exchange kappa carrageenans 2 are below 50 ^C. The temperatures of the gel and melting drop with decreasing molecular weight (measured by viscosity). In particular, the sample 1a, which comprises kappa-carrageenan 2 with a viscosity of 9 mPa · s, a gel film provides a reduced gel temperature of 25 ^{° C} and a melting point of 36 ° ^C.

Table XVII
Kappa-2-carrageenan compositions and their properties 1a 2a 3a 1b 2b 3b Ingredient (g) K2 (9 MPa · s)
CNN N 7.88 0 0 7.88 0 0 K2 (20 MPa · s)
Kgn I 0 7.88 0 0 7.88 0 K2 (41 MPa · s)
Kgn J 0 0 7.88 0 0 7.88 Sugar 90.13 90.13 90.13 88.78 88.78 88.78 CaCl ₂ 0 0 0,0 0.58 0.58 0.58 Kcl 0 0 0,0 0.76 0.76 0.76 For casting Ur (g) No break No break No break 819 964 1178 Permeable., Cm 5,0 13.0 7.5 Pace. pl., ^about With 36 39.5 42 75 76-77 77 Gel temp., ^About With 25 35.5 34-36 57 58.5-60 58-59

K2 = kappa-2-carrageenan

Although the invention has been described in detail with reference to its specific embodiments, it will be obvious to a person skilled in the art that various changes and modifications can be made without departing from its essence and scope of claims.

Claims (44)

1. A homogeneous thermo-reversible gel film comprising a film-forming amount of kappa-2-carrageenan and optionally at least one component of a plasticizer, a second film former, a filler, and a pH adjuster. 2. The film according to claim 1, further comprising at least one cation of potassium or ammonium cations in an amount of less than 50% of the dry weight of kappa-2-carrageenan in the gel film. 3. The film according to claim 1, in which the specified Kappa-2-carrageenan is present in an amount equal to at least 0.5% of the dry weight of the gel film. 4. The film according to claim 1, wherein said kappa-2-carrageenan is present in an amount of 0.5% -25% of the dry weight of the gel film. 5. The film according to claim 1, wherein said kappa-2-carrageenan is present in an amount of 1.5% -25% of the dry weight of the gel film. 6. The film according to claim 1, in which the specified kappa-2-carrageenan is present in an amount equal to at least 10% of the total dry weight of the film-forming agents in the gel film. 7. The film according to claim 1, in which the specified kappa-2-carrageenan is present in an amount equal to at least 20% of the total dry weight of the film-forming agents in the gel film. 8. The film according to claim 1, in which the specified kappa-2-carrageenan is present in an amount equal to at least 50% of the total dry weight of the film-forming agents in the gel film. 9. The film according to claim 1, in which the specified kappa-2-carrageenan is present in an amount equal to at least 80% of the total dry weight of the film-forming agents in the gel film. 10. The film according to claim 1, in which the specified Kappa-2-carrageenan is the only film former that is present in the gel film. 11. The film according to claim 1, wherein said second film former is selected from the group consisting of starch, a starch derivative, a starch hydrolyzate, cellulose gums, kappa-carrageenan; iota carrageenan; alginates, propylene glycol alginate, polymannan gums, dextran, pectin, gellan, pullulan, alkyl cellulose ethers and modified alkyl cellulose ethers. 12. The film according to claim 1, in which the specified plasticizer is at least one component selected from the group consisting of glycerol, sorbitol, polydextrose, maltitol, lactitol and polyalkylene glycols; said second film former is at least one component selected from the group consisting of starch, a starch derivative, a starch hydrolyzate, cellulose gum, a hydrocolloid, an alkyl cellulose ether, and a modified alkyl cellulose ether; and said filler is at least one component selected from the group consisting of microcrystalline cellulose, microcrystalline starch, starch, derivatives of starch, inulin, starch hydrolysates and polydextrose. 13. The film according to claim 1, having a tensile strength at break equal to at least 1500 g 14. The film according to claim 1, having a tensile strength at break equal to at least 4000 g. 15. The film according to claim 1, having a tensile strength at break equal to at least 5000 g 16. The film according to claim 1, having a tensile strength at break equal to at least 6000 g 17. The film according to claim 1, having a solids content equal to at least 50% by weight of the gel film. 18. The film according to claim 1, having a solids content equal to at least 60% by weight of the gel film. 19. The film according to claim 1, having a solids content equal to at least 80% by weight of the gel film. 20. The film according to claim 1, having a solids content equal to at least 90% by weight of the gel film. 21. The method of producing gel films according to claims 1 to 20, which includes stages (i) heating, hydrating, mixing, solubilizing and, optionally, deaerating the composition of said kappa-2-carrageenan and, optionally, at least one component of said plasticizer, said second film former, said filler, and said pH adjuster in the device, providing sufficient shear, temperature and residence time for the formation of their homogeneous thermoreversible molten composition, where the specified temperature is equal to the solubilization temperature of the molten comp zitsii or exceeds it; and (ii) cooling said molten composition to a temperature equal to or below the gelation temperature to form a gel film. 22. The method according to item 21, in which the specified molten composition is supplied directly to at least one device from among the mixer, pump or device for removing volatile components. 23. The method according to item 21, in which the specified device is a Ross mixer, a Stefan processing device, an extruder, an inkjet cooking chamber or a device for mixing fluids. 24. Soft capsules comprising capsule walls and an encapsulated substance, wherein said capsule walls contain films according to any one of claims 1 to 20. 25. The soft capsules of claim 24, wherein said encapsulated substance is at least one component selected from the group consisting of pharmaceuticals, vitamins, nutritional supplements, dye, dye beads, pigments, agricultural products, cosmetics, antioxidants, flavors, or food. 26. The method of obtaining soft capsules according to paragraph 24, which includes stages (i) heating, hydrating, mixing, solubilizing and, optionally, deaerating the composition of said kappa-2-carrageenan and, optionally, at least one component of said plasticizer, said second film former, said filler, and said pH adjuster in the device, providing sufficient shear, temperature and residence time for the formation of their homogeneous molten composition, where the specified temperature is equal to the solubilization temperature of the molten composition or exceed Shakes her; and (ii) preparing soft capsules directly from said molten composition or allowing said molten composition to cool to its gelation temperature or lower and, further, obtaining soft capsules from it. 27. The method of claim 26, wherein said device is a Ross mixer, a Stefan processing device, an extruder, an inkjet cooking chamber, or a device for mixing fluids. 28. The method according to p. 26, in which the specified molten composition is supplied directly to at least one device from among the mixer, pump or device for removing volatile components before obtaining soft capsules. 29. The method according to p, in which the specified molten composition has a solids content equal to at least 50% before receiving soft capsules. 30. The method according to p, in which the specified gel film has a solids content equal to at least 60% before receiving soft capsules. 31. A solid form containing a filler material encapsulated by a homogeneous thermally reversible gel film according to any one of claims 1 to 20. 32. The solid form according to p, in which the filler is a powder, tablet, tablet, capsule, microcapsule or capsule. 33. The solid form of claim 31, wherein said solid form is a hard capsule. 34. The film according to claim 1, including from 0.5 to 25 wt.% Kappa-2-carrageenan, from 10 to 50 wt.% Of the second film former, from 5 to 40 wt.% Plasticizer and having a solids content of 50 to 90%, by weight of the gel film and, optionally, a means for adjusting the pH. 35. A soft capsule comprising a film according to clause 34, encapsulating a filling substance. 36. The film according to claim 1, having a solids content of at least 50% and wherein said Kappa-2-carrageenan has a viscosity of less than 10 cPs at 75 ° C. at 1.5% concentration of Kappa-2- solids carrageenan in a 0.10 molar solution of sodium chloride. 37. A soft capsule comprising a film according to clause 36, encapsulating a filling substance. 38. The gel film according to claim 1, further comprising a flavoring agent and having a solids content of at least 50%. 39. A soft capsule comprising a film of claim 38, encapsulating a filler material. 40. The gel film of claim 38, wherein said flavoring is sugar. 41. The film according to claim 1, in which the specified film does not contain a plasticizer. 42. The film according to claim 1, consisting of the specified Kappa-2-carrageenan, flavoring and water. 43. The film according to § 42, in which the specified flavoring is a corn syrup. 44. A soft capsule containing a film according to claim 42, encapsulating a filling substance.

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