RU2341290C2 - Homogeneous, thermally reversible gel containing carragenan of underviscosity, and products made thereof - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: this invention is intended for homogeneous, thermally reversible gel containing Carragenan where specified Carragenan has viscosity less than 10 centipoise at 75°C when measured in 0.10 molar aqueous solution of sodium chloride containing 1.5 wt % Carragenan in relation to total mass of all components in solution, and optionally one agent selected from plasticizer, the second filming agent, bulking agent and pH regulating agent, where gel contains at least 40% of solid products. This invention is also intended for methods of gel production, as well as for various products containing gel, including food, soft capsules, solid capsules and solid encapsulated powders, tablets, tablet-capsule.

EFFECT: provides gelling temperature reduction of Carragenan gels and gel films.

45 cl, 5 dwg, 5 tbl, 2 ex

Description

This application claims the benefits of provisional patent applications US No. 60/462785; 60/462721; 60/462758; 60/462617; 60/462793; 60/462783; 60/462792; 60/462794; all registered April 14, 2003.

The present invention is directed to a homogeneous, thermally reversible gel containing carrageenan, where carrageenan has a viscosity of less than 10 cP at 75 ° C, when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% Carrageenan relative to the total the mass of all components in solution, and optionally at least one agent selected from a plasticizer, a second film-forming agent, a filler, and a pH adjusting agent, where the gel contains at least 40% solids. The present invention is also directed to and methods for their preparation, as well as a variety of products containing gel, including food products, soft capsules, hard capsules and solid forms of encapsulated powders, tablets, tablet capsules and the like.

Carrageenan is a commercially significant galactan polysaccharide found in red algae. All carrageenans contain repeating units of galactose, connected by alternating α1 → 3 and β1 → 4 glycosidic bonds, and are sulfated to very different degrees. Types of carrageenan can be different, in part, by their degree and position of sulfation, as well as by the seaweeds from which they are derived. Various types of carrageenan include kappa, kappa-2, iota, lambda, mu and nude. Since carrageenans differ in their composition and structure, they are known to differ in properties and applications. Carrageenans also differ in molecular weight, content and type of cations.

In systems with a high solids content, for example, with more than 40% solid products, carrageenan-based gelling compositions are known to form very viscous systems that cause processing problems when a gel is obtained, for example, such processing requires significant heat, shear, manipulations to prevent premature gelation or the formation of gels and gel films that are less than completely homogeneous (which leads to gels with less strength). Important industrial applications, such as the production of soft capsules, hard capsules, food products (chewing gum, sweets and the like), hard forms of encapsulated powders, tablets and the like, would benefit from the use of specific carrageenan gels, where gelation occurs at low temperatures. For a long time it was believed that the gelation temperature of carrageenan does not depend on its molecular weight. Unexpectedly for the inventors of the present invention, for high solids carrageenan gels, for example at least 40% solids, gels and gel films containing low molecular weight carrageenans, as mentioned here, result in a very desirable temperature reduction gelation.

The present invention is directed to a homogeneous, thermally reversible gel containing carrageenan, where carrageenan has a viscosity of less than 10 cP at 75 ° C, when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% Carrageenan relative to the total the mass of all components in solution, and optionally at least one agent selected from a plasticizer, a second film-forming agent, a filler and a pH adjusting agent, where the gel contains at least 40% solids. The present invention is also directed to methods for their preparation, as well as to a variety of products containing gel, including food products (e.g., chewing gums, sweets), soft capsules, hard capsules and hard forms of encapsulated powders, tablets, capsule tablets and the like. The present invention is also directed to a method for lowering the gelation temperature of carrageenan gels and gel films, comprising using the reduced molecular weight carrageenan described herein.

Figure 1 is a flowchart of the method of the present invention for the manufacture of films and soft capsules using a Stefan processor together with an extruder.

FIG. 2 is a flow diagram of a method of the present invention for the manufacture of films and soft capsules using the fluid mixing device of FIG. 3 and an extruder. The block diagram shows the film exiting the extruder entering the encapsulation device.

Figure 3 is a partially torn side view of a fluid mixing apparatus for mixing first and second fluids with steam to be used in the method of the present invention.

FIG. 4 is another version of the block diagram of FIG. 2 showing a film exiting the extruder entering the encapsulation apparatus.

FIG. 5 is a flow diagram of a method of the present invention for the manufacture of films and soft capsules using the fluid mixing device of FIG. 3, a cooling drum, and an encapsulation device.

As noted above, carrageenan is a commercially significant galactan polysaccharide found in red algae. Preferred types of carrageenan that can be used in the present invention are kappa, kappa-2 and iota carrageenan. These types of carrageenan may vary, in part, in their degree and position of sulfation, as well as in the algae 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 about 25 to 34%. Iota carrageenan can be obtained, for example, from Eucheuma denticulatum (also referred to as "Spinosum"). Kappa carrageenan has a repeating unit of D-galactose-4-sulfate-3,6-anhydro-D-galactose and is obtained, for example, from Kappaphycus alvarezii (also known as "Eucheuma cottonii"). In contrast, kappa-2 carrageenan is reported by R. Falshaw, HJBixler and K.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 performance of commercial extracts II, Food Hydrocolloids 15 (2001) 619-630, are copolymers containing a certain number of repeating units of kappa (3: 6-anhydrogalactose (3: 6-AG)) and repeating iota units (3: 6-anhydrogalactose-2-sulfate (3: 6-AG-2-S)) covalently linked to the copolymer chain and derived from certain Gigartinaceae algae. The above links state that such kappa-2 carrageenans have properties that are significantly different compared to simple mixtures of kappa and iota carrageenans. Other references discussing kappa-2 carrageenan are discussed in these publications. Although there is significant historical disagreement regarding the physical nature of kappa-2 carrageenans, recent studies, such as those directly discussed above, confirm that kappa-2 carrageenans are copolymers containing repeating units of kappa and iota, covalently linked (at certain kappa ratios and iota residues) in the main chain of the copolymer, with a clear difference from the physical mixtures of kappa and iota polymers.

As used here, in kappa-2 carrageenan, the molar ratio of the content of 3: 6AG-2S to 3: 6AG is from 25 to 50%, in iota carrageenan the molar ratio of the content of 3: 6AG-2S to 3: 6AG is from 80 to 100%, and kappa carrageenan has a molar ratio of 3: 6AG-2S to 3: 6AG, less than kappa-2 carrageenan. For example, in kappa carrageenan from Eucheuma cortonii, a well-known and used seaweed source for kappa carrageenan, the molar ratio of 3: 6AG2S to 3: 6AG is less than about 10%; and for iota carrageenan from Spinosum, a well-known and used seaweed source for iota carrageenan, the molar ratio of 3: 6AG2S to 3: 6AG is more than about 85%. This means that for kappa-2 carrageenan, the ratio of kappa (3: 6-AG) repeating units to iota (3: 6-AG-2-S) repeating units is between 1.0 and 3.0: 1, more specifically, from 1.5 to 3.0: 1 (more specifically, depending on the desired application). The molar ratios of the 3: 6AG-2S to 3: 6AG content defined here are found for iota, kappa and kappa-2 carrageenans, regardless of the degree of their modification and the content of the precursor (e.g., repeating mu and nu units). Thus, any carrageenans with reduced molecular weight that satisfy the descriptions given here, regardless of their degree of modification (from alkaline treatment), are within the scope of the present invention.

The kappa-2 carrageenan to be used in the present invention can be contained in a number of seaweed species, or purified or isolated from them, within the class of, for example, Gigartinaceae algae, such as Gigartina radula, Gigartina corymbifera, Gigartina skottsbergii, Iridaea cordata, Sarcothalia crispata and Mazzaella laminarioides. The seaweed source for kappa-2 carrageenan to be used in the present invention is any source that produces kappa-2 carrageenan having a molar ratio of 3: 6AG-2S to 3: 6AG described herein.

Methods for extracting carrageenans from their sources include the optional complete or partial filtering of insoluble products from the starting material or the use of unfiltered material, as well as extruded algae. It is understood that small or microscopic amounts of other carrageenans (e.g., lambda carrageenans) may be present during the process of extracting carrageenan from the above algae and can be used together with carrageenan in the present invention.

The gel carrageenan of the present invention is a reduced molecular weight carrageenan having a viscosity of less than 10 cP, more specifically 5 to 8 cP at 75 ° C, when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% carrageenan with a reduced molecular weight relative to the weight of all components in solution. These viscosity studies can be performed using a Brookfield LVF viscometer (Brookfield Engineering Laboratories, Inc.), using a # 1 spindle at 60 rpm and determining viscosity after six revolutions.

In the gels of the present invention, the solids content is at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, and at least 90 wt.% Of all components in the gel.

The reduced molecular weight carrageenans used in the gel of the present invention typically contain a cation, which may be at least one cation selected from cations of calcium, potassium, magnesium, ammonium or sodium. Sodium and potassium are preferred for kappa and kappa-2 carrageenan, while sodium, potassium and calcium are preferred for iota carrageenan. The sodium and potassium content or a mixture thereof for kappa and kappa-2 carrageenan may be at least 75%, 80%, 85%, 90%, 95% or 98% by weight of the total cation in them; and the content of sodium, potassium and calcium for iota carrageenan, or a mixture thereof, may be at least 75%, 80%, 85%, 90%, 95% or 98 wt.% of the total cation content in them.

The gels of the present invention based on low molecular weight carrageenans described herein are found to reduce the gelation temperature of the resulting gel, compared to carrageenans of a similar type and content having a higher molecular weight. For example, the authors found that iota low molecular weight carrageenans described here reduce the gelation temperature from about 81 ° C (iota carrageenan having 3.37% potassium and 1.3% calcium by weight carrageenan and a viscosity of 23 cP when measured using the studies presented here) to about 34 ° C (iota carrageenan of the present invention having 3.37% potassium and 1.3% calcium by weight of carrageenan and a viscosity of 6 cP when measured using the studies given here) and from about 60 ° C (iota carrageenan having 7.8% sodium from the mass of carrageenan (0% potassium and calcium) and a viscosity of 23 cP when measured using the studies given here) to about 30 ° C (iota carrageenan of the present invention having 7.5% sodium and 0.5% potassium by weight carrageenan and a viscosity of 6 cP when measured using the studies presented here). In addition, the authors found that the low molecular weight kappa carrageenans described here reduce the gelation temperature from about 28 ° C (kappa carrageenan having 5.4% sodium, 0.09% calcium, 0% potassium by weight carrageenan and viscosity 129 cP when measured using the studies given here) to about 21 ° C (the kappa carrageenan of the present invention having a predominantly sodium cation and a viscosity of 8 cP when measured using the studies given here). In addition, the authors found that the low molecular weight kappa-2 carrageenans described herein reduce the gelation temperature from about 35 ° C (kappa-2 carrageenan having 7.4% sodium, 0.15% calcium, 0.67% potassium by weight of carrageenan and a viscosity of 41 cP when measured using the studies provided here) to about 25 ° C (kappa-2 carrageenan of the present invention having 7.7% sodium, 0.01% calcium, 1.0% potassium from carrageenan mass and 9 cP viscosity when measured using the studies given here). The gelation temperature of the gels and gel films of the present invention containing reduced molecular weight carrageenan may vary depending on other materials and combinations of reduced molecular weight carrageenans contained in the gel and gel film (e.g., plasticizers, second film-forming agents, fillers, and the like) like that.). Thus, for example, but not limited to, the gels of the present invention can have a gelation temperature of about 60 ° C or less, 50 ° C or less, 45 ° C or less, 40 ° C or less, 35 ° C or less ( at least 80%, 85%, 90%, 95 wt.% iota of carrageenan in relation to the total mass of carrageenan in the gel, and contain at least 50% of a cation of sodium, calcium and / or potassium); 60 ° C or less, 50 ° C or less, 40 ° C or less, 30 ° C or less, 28 ° C or less, 25 ° C or less, 21 ° C or less (at least 80%, 85 %, 90%, 95 wt.% Kappa carrageenan in relation to the total mass of carrageenan in the gel, and contain at least 50% sodium cation); and 60 ° C or less, 50 ° C or less, 35 ° C or less, 30 ° C or less, 25 ° C or less (at least 80%, 85%, 90%, 95 wt.% kappa - 2 carrageenan in relation to the total mass of carrageenan in the gel, and contain at least 50% sodium cation). Sodium cation may be present in an amount of at least 75%, 85%, 90%, 95% by weight relative to the total weight of the cation.

The low molecular weight carrageenan used in the present invention is typically present in a gelling amount. This amount is mainly from 0.5% to 25%, more specifically from 0.5% to 15%, more specifically from 3.0% to 15 wt.% Of all components in the gel, depending on use of gel.

The gels and gel films of the present invention are generally regarded as homogeneous and thermally reversible.

As used here, the term “homogeneous” defines gels and gel films that are visually homogeneous to the naked eye and free from defects such as lumps, cracks, undissolved particles that were supposed to dissolve, inhomogeneous distribution of insoluble particles, and the like. “Fish eyes” (mixed liquid and solid states) or “gel balls” (heterogeneous gel structure) would not meet the definition of “homogeneous” as used here.

The gels and gel films of the present invention can be obtained and used in a wide variety of applications as films obtained by filling or in further processing.

As used here, the term "thermally reversible" defines a gel and a gel film that have a melting point. As used here, the melting temperature is the temperature or temperature range in which the gel film softens or flows.

As used here, the phrase “gel films” refers to a thin membrane or three-dimensional network formed from structured carrageenan. The gelling composition is characterized by a gelling temperature, a temperature below which the molten mass of the gel composition must be cooled to form a self-supporting structure.

Optionally, the molten mass can be poured hot and allowed to cool, and also dried to further concentrate solid products (controlled removal of moisture) until the gel composition forms a gel film. The melting point of a thermally reversible gel film is higher than its gelation temperature.

The homogeneous, thermally reversible gel and gel film of the present invention may optionally contain at least one agent selected from a plasticizer, a second film-forming agent, a filler, and a pH adjusting agent. The components to be added to the gel and gel film, and their amounts may vary depending on the desired use of the gel and gel film.

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

Examples of a second film-forming agent that can be used in the present invention include at least one starch, starch hydrosylate, starch derivative, cellulosic resin, hydrocolloid, cellulose alkyl ether or modified cellulose alkyl ether. Examples of the hydrocolloid include at least one of kappa, kappa-2 and iota carrageenans having a higher molecular weight than that used here (for example, having a viscosity of 10 cP or more at 75 ° C, as measured in A 0.10 molar solution of sodium chloride containing 1.5 wt.% Carrageenan with a higher molecular weight), and their incompletely modified versions; alginates, including potassium alginate, sodium alginate, ammonium alginate and propylene glycol alginate; polymannan resins (for example, in the new one, with a viscosity of less than about 1000 mP, as measured at 1 wt.% in water at 25 ° C), such as a low viscosity guar gum; pullulan; gellan (including higher and lower acyl gellan); dextran; pectin and combinations thereof. An example of an alkyl cellulose ether that can be used in the present invention is hydroxyethyl cellulose. Examples of modified cellulose alkyl ethers that can be used in the present invention include hydroxypropyl cellulose and hydroxypropyl methyl cellulose. Carrageenan used in the present invention can be only a gelling agent and a film-forming agent in the gel and gel film. When the gels of the present invention contain second film-forming agents, the carrageenan of the present invention may be present in an amount of at least 10%, at least 20%, at least 50%, or at least 80 wt.% the total number of film-forming agents in a dry gel film.

Examples of filler include non-colloidal (from a plant source) cellulose, microcrystalline (from a plant source) cellulose, microcrystalline starch, modified and unmodified starch, derivatives and fractions of starch, inulin, starch hydrosylates, sugar, corn syrup and polydextrose. As used here and in the claims, the term "modified starch" includes starches such as hydroxypropylated starches, starches diluted with acids, and the like. Examples of modified starches that may be used in the present invention include Pure Cote ™ B760, B790, B793, B795, M250 and M180, Pure-Dent ™ B890 and Pure-Set ™ B965, all available from Grain Processing Corporation of Muscatine , Iowa, and CAraTex ™ 75701, available from Cerestar, Inc. Examples of starch hydrosylates include maltodextrin, also known as dextrin. Unmodified starches, such as potato starch, can also affect film strength when combined with hydrocolloids, within the scope of the present invention. As a rule, modified starches are products obtained by chemical treatment of starches, for example, acid treatment of starches, enzymatic treatment of starches, oxidation of starches, cross-linking of starches, and other derivatives of starches. Preferred modified starches are derivatives of starches in which the side chains are modified with hydrophilic or hydrophobic groups to thereby form a more complex structure with strong interaction between the side chains.

The amount of filler to be used in the present invention is generally in the range of 0 to 20% by weight of the dry gel, but may be used more if desired, for example at least 20%, more preferably at least at least 30 wt.% of the dry gel. It should be noted that starch, starch derivatives and starch hydrosylates can be multifunctional. That is, in addition to being used as fillers, they can be used as second film-forming agents. When used as fillers and second film-forming agents, they are usually used in an amount of at least 10%, preferably at least 20%, more preferably at least 30 wt.% Of the dry gel, depending on 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 adding beneficial cations, such as potassium or sodium. For some compositions, a pH adjusting agent can be used to improve the stability of the gel and gel film. The amount of pH adjusting agent is generally in the range of 0 to 4%, preferably 0 to 2%.

The gels of the present invention may also contain colorants and perfumes, such as sugar, corn syrup, fructose, sucrose, aspartame, sucrolose, sorbitol, mannitol, maltitol and the like, whether other components such as plasticizers, fillers, second film-forming agents are present and the like or not. In one embodiment, the gel and gel film of the present invention comprise carrageenan of the present invention, perfume and water in a high solids system; for example, with more than 40%, 50%, 60%, 65%, 75%, 80%, 85%, 90% of solid products.

The thicknesses of the dry gel film typically used for soft capsules are in the range of 0.5 to 3.0 mm, more preferably 0.8 to 1.2 mm.

It is possible that the gels and gel films of the present invention may contain thermally irreversible resins. However, in order not to adversely affect the homogeneous and thermally reversible nature of the gel and gel films of the present invention, such thermally irreversible resins should be present in an amount of less than 50 wt.% Of low molecular weight carrageenan, preferably less than 40%, more preferably less than 30%. Examples of such thermally irreversible resins include crosslinked resins, such as calcium precipitated (e.g., crosslinked) pectins and / or alginates. Alginates and pectins that react with calcium, as well as their less purified forms, are considered as thermally reversible resins in the absence of divalent cations. Other thermally irreversible resins, such as tragacanth gum, affect the thermal reversibility of carrageenan by absorbing water in their structure, creating the same effect as increasing the amount of carrageenan without secondary film-forming agents. Additional film-forming agents, such as polymannanes, can form continuous networks, either alone or synergistically with other components, during the activation and loading process.

The reduced molecular weight carrageenan gels of the present invention are mainly prepared by a method using a device that provides a sufficiently high shear, temperature (above the gelation temperature) and residence time so as to provide a homogeneous molten mass of the composition and gel formation upon cooling. Such devices include, but are not limited to, Ross mixers, Stefan processors, conventional inkjet boilers, extruders, and fluid mixing devices, as shown in FIG. 3. Ross mixers, Stefan processors, extruders and conventional jet boilers are readily available commercially. Before cooling, the molten mass can be supplied to at least one of the devices, such as a pump, mixer or device that prevents the volatilization of components. An example of a device that performs any of these functions is an extruder. The extruded molten mass can also be sent to a film forming or molding device (for example, a distribution hopper, as used in a capsule molding machine), which facilitates the uniform filling of a continuous film, or through a die that directly forms a film or a molded extrudate from equipment for molten mass delivery. Precautions must be taken to maintain the molten mass at a temperature above the onset of a limited yield / gel structure. Insulated and pre-heated (to maintain an appropriate temperature) transport flexible pipes can be used to maintain the flow of molten mass until the desired gel and gel film formation begins on the bulk rolls or at other film formation points, such as an extruder (device for forming flow restriction films) or die. Additional processing methods (such as preheating the outlet / piston-shaped head, as seen in the Ross method system) can pump (under pressure) the molten mass through the flexible transport pipes discussed above. Additional insulation can help maintain the temperature of the molten mass through the use of a Teflon disk, originally placed below the surface of the molten mass, immediately after removal of the mixing device. In addition, the inlet flexible pipes can be introduced into the heated inlet (bulk) bins for molten mass located on the encapsulation machine, either directly in the bins or by optionally modifying the inlet bins, which introduces the casing / cover in the upper half, which helps maintain the temperature of the molten mass in the inlet hopper, reduces moisture loss and maintains a uniform (central) filling of the hopper during the long process of film formation for upsul. It is understood that other methods of maintaining the temperature of the molten mass can be used to form films for capsules. These include, but are not limited to, extruding the molten mass through film-shaped dies / openings that can be directly fed to the capsule forming apparatus, stored at temperatures that maintain the appropriate conditions for the films (to form capsules) until required , or dried to the desired moisture levels, solids content, and texture until required. Such dried films have the property of re-absorption of water (water is introduced by any means) in the gel film matrix and can be rehydrated as needed, for example, for the manufacture of soft capsules or other solid forms. The film is saturated with moisture until the desired moisture content and strength / texture are achieved, which will make it possible to introduce the film into an encapsulation machine for making soft capsules.

As used herein, a “fluid mixing device” refers to the device of FIG. Figure 3 illustrates a device 10 for mixing fluids. The fluid mixing device 10 is for mixing steam 2 with a first fluid or suspension 4 and a second fluid or suspension 6 to form a molten mass or mixture of 8 suspensions.

The fluid mixing device 10 comprises a first body 20 having a first inlet 22 through which steam 2 enters the body 22, an nozzle end 24 from which steam 2 leaves the body 20, and a nozzle valve or rod 26 located at the end 24 of the nozzle. The drive means 30 are connected to the first casing 20 to control the outlet velocity or outlet pressure of the first fluid 2 at the end 24 of the nozzle. Drive means 30 may be of a type manufactured by Fisher Controls U.S.A.

In addition, the fluid mixing device 10 comprises a second mixing housing 40 connected to a first housing 20 at an end 24 of the nozzle 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 a third inlet 44, through which the second fluid 6 enters the second housing 40. The inlets 42 and 44 are located after the first inlet 22. As shown in FIG. 3, the second inlet 42 and the third inlet 44 are located in a common plane and are separated by some radial distance from a friend, the most e is preferably arranged directly opposite each other (i.e., under 180 °) around the central axis Y of the device 10 for mixing. The second housing 40 defines a generally cylindrical mixing chamber 52, which in turn defines a flow passage extending along the axis along the axis of the mixing chamber 52 from the input end 54 of the mixing chamber 52 to the output end 56 of the chamber 52. The nozzle valve 26 in motion by the actuator 30, between closed and unclosed positions at the inlet end 54 to control the flow rate of steam 2 in the mixing chamber 52.

The end of the nozzle 24 of the first housing 20 directs the steam 2 to the inlet end 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, into the mixing chamber 52. Steam 2, the first fluid 4 and the second fluid 6 are mixed in the mixing chamber 52 to form a molten mass or mixture 8, which leaves the mixing chamber 52. Then, the molten mass 8 can be molded into a molded product or formed into a film, for example, by pouring mixture 8 onto a cooling drum or passing mixture 8 through an extruder.

Referring to FIG. 4, a film and capsule making system 100 with a fluid mixing device 10 includes a film making unit 60, for making and supplying a film 9, and an encapsulation machine 80 for forming capsules 89. The film making unit 60 comprises : device 10 for mixing fluids; first fluid supply means 62 for supplying the first fluid 4 to the fluid mixing device 10; second fluid supply means 64 for supplying a second fluid 6 to the fluid mixing device 10; a suspension mixture supply path 70 for supplying a molten mass or a mixture of 8 suspensions from the fluid mixing device 10 to the molding device; an optional extruder 73 communicating fluids with a feed path 70 that extrudes the blend 8 in the form of a film 9; encapsulation machine 80 for capsule formation 89; and a conveyor belt 90 for transporting the filled capsules 90 to the next process, such as drying or packaging. Extruder 73 may be of the type manufactured by Wenger or Clextrel.

The encapsulation machine 80 may be a conventional encapsulation machine with a rotational die type manufactured by R.P. Scherer Technologies of Paradise Valley, Nevada. As shown in FIG. 4, the encapsulation machine 80 includes an encapsulated product storage tank 82 that contains an encapsulated product 81, which is to be encapsulated. The encapsulation product 81 may include liquid, semi-liquid or powder pharmaceutical preparations, vitamins, food additives, coloring balls, pigments, agricultural active agents and pre-measured feed additives. The encapsulation machine 80 may be connected to one or more rolls 77, 77 'and 78, 78', so that the films 9, 9 'can be guided to the encapsulation machine 80. The film 9 is introduced between the heater block 86 and the rotary die 88. Parts of the film 9 fall under the action of vacuum into the protrusions formed on the surfaces of the rotary die 88. A certain amount of encapsulation product 81 is delivered to the compartments formed in the film 9 under the action of vacuum. Further rotational movement of the dies 88, 88 ′ hermetically connects the films 9, 9 ′ together in the space between the rotational dies 88, 88 ′. The filled capsules 89 fall into boxes 87, 87 'and fall onto a conveyor 90 for drying and packaging.

With reference to FIG. 5, a capsule manufacturing system 100a is similar to that shown in FIG. 4, where like symbols refer to like elements. In FIG. 5, however, the film manufacturing unit 60a includes an optional distribution hopper 72 and an optional cooling drum or bulk drum 74 instead of the extruder 73 of the system of FIG. 4. System 100a includes a fluid mixing device 10 and a mixture supply path 70 for guiding a mixture of 8 suspensions from the fluid mixing device and to the distribution hopper 72. The distribution hopper 72 distributes the mixture 8 on the bulk drum 74. A film 9 is formed on the bulk drum 74, when mixture 8 cools. After that, the film 9 is introduced into the machine 80 for encapsulation. The film 9 'is preferably formed in the same manner as the film 9, by means of a second film production unit (not shown).

The fluid mixing device 10 is adapted to produce a mixture for forming a film, more specifically a food film for the manufacture of food capsules or strips. Incompatible film components are typically placed in different fluid inlet streams, such that such incompatible components are encountered together for the first time at the vapor injection boundary in the mixing chamber 52 of the fluid mixing device. While FIG. 3 shows one inlet for steam and the first and second fluids, one or more additional inlets for one or more additional fluids may be provided. Preferably, the casings 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 is not necessary to achieve homogeneity in step (i). That is, the homogeneity of the molten mass can be obtained before or after introducing the molten composition into at least one of the devices, such as a mixer, pump or anti-volatility device, provided that the molten mass reaches homogeneity before gelation.

The gels and gel films of the present invention, as shown by the strength of their gels, are very suitable for use in the manufacture of soft capsules. Thus, the present invention is also directed to soft capsules made from the carrageenan gels and gel films of the present invention, as well as to methods for making such soft capsules.

A method of manufacturing soft carrageenan-based gel capsules of reduced molecular weight of the present invention includes the use of any conventional encapsulation device, for example, a conventional device with a rotational die or a concave matrix. For example, after receiving the molten mass of the present invention, it can be poured onto drums, cooled, and then introduced between rotational dies for encapsulation, where the films are again heated, filled, sealed and cut. For a good description of this conventional method, see International Patent Application WO 98/42294. Alternatively, and as an advantage of the present invention compared to conventional soft capsule manufacturing methods, the use of the high shear device described above makes it possible to sufficiently hydrate the molten mass, apply it to the drums when it is cooled, and then introduce it into conventional encapsulating devices for filling, sealing and cutting. This continuous type method can be used to eliminate the step of re-heating fully gelled and cooled films. The above method can be used to make the soft capsules of the present invention having any desired shape.

Soft capsule filling materials can be any materials widely used in the above methods with rotational dies, including pharmaceutical ingredients, agricultural ingredients, health food ingredients, veterinary ingredients, food products, cosmetics, personal care products, industrial products, and the like, and may be a liquid (including emulsions), solid products, suspension, dispersion and the like.

The present invention is also directed to a solid form containing a filling material encapsulated by a homogeneous, thermally reversible gel film of the present invention. One type of such solid form is hard capsules. Hard capsules, as used here, refer to those solid forms that are commonly used, for example, in the pharmaceutical industry, when two shell halves are formed, filling material, usually a powder, is placed in the shell, and the two halves are combined with the formation of a hard capsule. One way of making such hard capsules typically involves immersing the metal rods or bars in the molten composition of the present invention and allowing the gel film to form around the rods. The gel films are 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. In general, the filling materials may be liquids (including emulsions) or solid products such as powders. The filling materials may be a pharmaceutical ingredient, an agricultural ingredient, a health food ingredient, a veterinary ingredient, a food product, a cosmetic ingredient, and the like.

In solid form, a powder, tablet, tablet capsule, microcapsule or capsule may also be encapsulated in accordance with known techniques. For example, encapsulating a hard capsule with a gel film of the present invention would provide the ability to provide reliable sealing / environmental resistance.

The present invention is also directed to a delivery system comprising a homogeneous, thermally reversible gel film, where the gel film contains: (i) a film-forming amount of low molecular weight carrageenans of the present invention and, optionally, at least one agent selected from a plasticizer, a second a film-forming agent, a filler, and a pH adjusting agent; and (ii) an active substance. The present invention is also directed to a method for its production. Examples of active substances that may be contained in a gel film are at least one agent selected from an oral care agent, a breath freshening agent, an antimicrobial agent, a cooling agent, a pharmaceutical agent, a nutritional treatment agent, an agent to stimulate the salivary glands, vitamin, mineral, coloring agent, cosmetic ingredient, agricultural active substance, sweetener, flavoring, perfume or food product. Examples of flavoring agents include sugar, corn syrup, fructose, sucrose, aspartame, sucrose, sorbitol, mannitol, maltitol and the like, whether other components such as plasticizers, fillers, second film-forming agents and the like are present or not. One embodiment of the delivery system of the present invention comprises carrageenan as described herein, flavoring and water in a high solids system; for example, with more than 40%, 50%, 60%, 65%, 75%, 80%, 85%, 90% of solid products.

A gel film can also be used to modify the dissolution profile of dosage forms. For example, the gel films of the present invention may contain added components that can create solid dosage forms having the ability to directly release, controlled, enteral or sustained release, or can be released upon activation by a known event, condition or process. The definitions of “direct release,” “delayed release,” and “enteric” can be found in the US Pharmacopeia and are incorporated herein by reference.

Further, the present invention is described in more detail with reference to the following examples, but it should be understood that the present invention is not considered to be limited by them. Unless otherwise indicated herein, all fractions, percentages, ratios and the like are massive.

EXAMPLES

Example 1

Iota, kappa and kappa-2 carrageenans with different viscosity values are measured at 75 ° C using a Brookfield LVF viscometer and a test sample prepared at 1.5 wt.% Carrageenan in a 0.10 molar aqueous solution of sodium chloride. The measurements are in table 1.

Table 1
Carrageenan Properties Iota Iota Kappa Kappa-2 Kappa-2 Kappa-2 Viscosity, cP 6 23 7.5 9 twenty 41 pH 8.9 8.9 9.2 8.7 9.6 10.1 Sodium,% 7.47 7.82 4.80 7.70 6.90 7.40 Potassium,% 0.5 0.00 1.40 1,0 0.00 0.67 Calcium% 0.00 0.00 0.00 0.01 0.16 0.15 Magnesium% 0.00 0.02 0,03 0.00 0,03 0.05

The following procedure is used to prepare 2.25% samples of kappa-2 carrageenan with different molecular weights, as shown by viscosity, where viscosity is measured at 75 ° C for an aqueous solution with 1.5% solids: 105 grams of water and 147 grams of corn syrup mixed in a beaker. A dry mixture of kappa-2 carrageenan, granulated sugar and salts (as indicated in table 2) is added to the liquid and heated with stirring to 95 ° C. The hot liquid is poured into 2 cups for gel and 2 tubes (1/2 volume). The gel cups and one tube (placed to give the gel surface at 45 degrees for use in measuring the melting temperature) are placed in a water bath at 10 ° C for one hour. A second tube is used to measure the temperature of the gel. Solid products after pouring account for approximately 62%. The tensile strength (at maximum force) and penetration (piston stroke distance at maximum force) are measured on gels using the Texture Analyzer. The gelation and melting points decrease when the molecular weight decreases (as measured by viscosity). In particular, sample 1a, which contains Kappa-2 carrageenan with a viscosity of 9 cP, gives a gel film with a reduced gelation temperature of 25 ° C and a melting point of 36 ° C.

table 2
Kappa 2 (K2) carrageenan preparations and their properties 1a 2a 3a Ingredient (g) K2 (9 cP) 7.88 0 0 K2 (20 cP) 0 7.88 0 K2 (41 cP) 0 0 7.88 Sugar 90.13 90.13 90.13 CaCl ₂ 0 0 0,0 Kcl 0 0 0,0 After loading Bf (g) 36 613 90 Penetration 32 33 41 Pace. melting ° C 36 39.5 42 Pace. gelation ° C 25 35.5 34-36

The same technique is used to prepare 2.25% iota carrageenan or kappa carrageenan samples.

Table 3
Preparations iota carrageenan and kappa carrageenan and their properties 3a S1 3b S2 3c S-3 Ingredient (g) Iota (6 cP) 7.88 0 7.88 0 0 0 Iota (23 cp) 0 7.88 0 7.88 0 0 Comp. example Kappa (8 cP) 0 0 0 0 7.88 0 Kappa (129 cP) 0 0 0 0 0 7.88 Comp. example Sugar 90.13 90.13 89.25 89.25 90.13 90.13 CaCl ₂ 0 0 0.38 0.38 0 0 3a S1 3b S2 3c S-3 Kcl 0 0 0.50 0.50 0 0 After loading Bf (g) 41 478 39 560 22.1 68 Penetration mm 35.1 38 34.5 32 33.8 43.8 Pace. melted ° C 42-43 66-67.5 58-59 86-88 23.5 47 Pace. gelation ° C 30-31 59-61 34-36 80-82 20-21 27-28

Example 2

The following techniques are used to prepare and evaluate materials and films in this example. The Stefan UMC5 processor is a laboratory mixing device that provides appropriate high shear mixing, heating and deaeration of drugs that are poured like films in the laboratory. The corresponding download size used with 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.

The mixture is prepared in a Stefan UMC5 processor by pre-mixing the plasticizers to obtain uniformity and adding the dry carrageenans of the present invention in parts, while stirring for about 30 seconds at 200 rpm. 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 anhydrous carrageenan mixture and stirred at 300 rpm for 5 minutes. The mechanical stirring is increased to 2100 rpm and the mixture is heated to 85 ° C-95 ° C with stirring. When the target temperature is reached, the mixture is stirred for 30 minutes, then the sample is kept in vacuum (50-60 bar), while stirring, for an additional 45 minutes.

When the retention time in vacuum at a given temperature ends, the sample is poured into a preheated two-pin wide-necked ceramic jar. Temperature and pH are recorded. Viscosity is measured on a hot sample using a Brookfield LVF viscometer.

A small portion of the sample is kept separately and cooled, usually overnight, before measuring the gelation / melting properties and solids using an Atago E handheld refractometer (Gardco, Pompano Beach, FL). The melting point is determined by placing a small lump of chilled gel on a wire string held upright in a test tube so that the lump does not come into contact with the wall of the test tube. The tube is coated with aluminum foil with a small hole to enable temperature measurement of the gel using a Tempermeter digital probe. The tube is placed in a heated bath, so that the lump is below the surface of the hot water bath, at approximately 100 ° C. The melting point is recorded when the gel-like sample becomes wet in appearance, softens and can mix (register the temperature range). When the sample melts, the tube is transferred to a second beaker containing cold tap water (15 ° C). A temperature sensor is used to record the temperature when the sample has cooled and to probe the surface of the sample to determine if the sample has begun to gel. The gelation temperature is the temperature when cooled, when the sample no longer flows, filling the cavity made by the probe.

The hot sample is then poured using a draw bar with a gap set to obtain a clearance of 3 mm onto metal plates of 177 mm × 177 mm × 5 mm, which are previously pollinated with lecithin to facilitate easy removal of the film material. The gel-coated plates are closed from above to prevent moisture loss from the poured film. Poured films are generally cooled (to less than 8 ° C) for at least half an hour before removal of the film for examination. Cooling is not necessary for film formation. Strips of dried film are made by drying the coated plates in a forced air / ventilation oven at 40 ° C. Films that are dried for 2 hours at 40 ° C give an intermediate solids content of about 60%, while films that are dried overnight at 40 ° C produce 80% or more of solid products. Test properties are measured at room temperature (approximately 20 ° C) unless otherwise indicated. The percentage of solid products of the dried film is determined between the poured film during its formation of solid products and the dried film according to the mass difference. Tear strength (BF) is measured on strips of poured and dried film using the Texture Analyzer TA-108S Mini Film Test Rig.

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 quality).

Table 4
Properties of kappa-2 carrageenans used for the manufacture of films Carrageenan X Carrageenan Y Carrageenan Z Mg,% 0,03 0.02 0,07 Ca,% 0.16 0.01 0.06 K,% 0.00 1.00 2.19 Na,% 6.90 7.70 5.12 Viscosity, cP 45 eighteen 6 pH 9.6 8.7 8.1 2% water gel Bf (g) 0 0 0 2% water gel (KCl) Bf (g) 29th 13 0 2% water gel (KCl + CaCl ₂ ) Bf (g) 112 93 thirty

Table 5
Kappa-2 carrageenan films Comp. pr. X1 Comp. Ave. Y1 An example of the present invention Z1 Ingredients (g) Water 834.7 834.7 825 Carrageenan X 75.0 0 0 Carrageenan Y 0 61,4 0 Carrageenan Z 0 0 90 Calcium Sulphate Dihydrate 0 1.7 0 Potassium chloride 15.0 0 0 Starch B760 0 0 225 M-100 227.3 227.3 0 Sorbitol SP 272.2 275.4 272.2 Glycerol 90.8 91.9 90.8 Temp. ° C * 88 82 75 Viscosity, cP * 16,150 6,500 18,250 Solid Products Priced 42 39 40 Melting point, ° C 85 74-77 62-65 Temp gelation, ° C 60-65 56 42 pH 6.9 5.8 6.9 Film film BF (g) at ~ 40% 302 338 117 Dried 2 hours at 40 ° C BF (g) at ~ 60% NT 766 536 Dry overnight 16 hours at 40 ° C Average film thickness (mm) 0.62 BF (g) at ~ 80% 4470 3227 6073 NT = don't research * Temperature and viscosity of the molten mass before filling

Although the present invention has been described in detail with reference to its specific embodiments, one skilled in the art will appreciate that numerous changes and modifications can be made without departing from its spirit and scope.

Claims (45)

1. A homogeneous, thermally reversible gel containing carrageenan, where the specified carrageenan has a viscosity of from 5 to less than 10 cP at 75 ° C, when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% The specified carrageenan relative to the weight of all components in the specified solution, and optionally at least one agent selected from a plasticizer, a second film-forming agent, a filler and a pH adjusting agent, wherein said gel contains at least 40% solids, and carrageenan presence at least 70% of all carrageenans present in said gel. 2. The gel according to claim 1, wherein said carrageenan is at least one of carrageenans selected from iota carrageenan, kappa carrageenan or kappa-2 carrageenan. 3. The gel according to claim 2, wherein said carrageenan is at least 80% by weight iota of carrageenan with respect to the total weight of all carrageenan in the gel, and the gel has a gelation temperature of 60 ° C. or less. 4. The gel according to claim 2, wherein said carrageenan is at least 80 wt.% Kappa carrageenan with respect to the total weight of all carrageenan in the gel, and the gel has a gelation temperature of 30 ° C. or less. 5. The gel according to claim 2, wherein said carrageenan is at least 80 wt.% Kappa-2 carrageenan with respect to the total weight of all carrageenan in the gel, and the gel has a gelation temperature of 35 ° C. or less. 6. The gel according to claim 1, in which the specified viscosity is from 5 to 8 SP. 7. The gel according to claim 1, wherein said carrageenan is the only carrageenan in the gel. 8. The gel according to claim 1, wherein said gel contains a plasticizer. 9. The gel according to claim 1, wherein said carrageenan contains at least one cation selected from cations of calcium, potassium, magnesium, ammonium or sodium. 10. The gel according to claim 9, in which the specified cation is at least 75 wt.% Sodium with respect to the total content of cations. 11. The gel according to claim 9, in which the specified cation represents at least 85 wt.% Sodium in relation to the total content of cations. 12. The gel according to claim 9, in which the specified cation represents at least 90 wt.% Sodium with respect to the total content of cations. 13. The gel according to claim 9, in which the specified cation is at least 95 wt.% Sodium in relation to the total content of cations. 14. The gel according to claim 9, in which said cation is at least 98 wt.% Sodium or potassium, or combinations thereof with respect to the total content of cations. 15. The gel according to claim 1, in which the specified carrageenan is present in an amount of from 0.5 to 25 wt.% The gel. 16. The gel according to claim 1, in which the specified carrageenan is present in an amount of from 0.5 to 15 wt.% The gel. 17. The gel according to claim 1, in which the content of these solid products is at least 50%. 18. The gel according to claim 1, in which the content of these solid products is at least 60%. 19. The gel according to claim 1, in which the content of these solid products is at least 70%. 20. The gel according to claim 1, in which the content of these solid products is at least 80%. 21. The gel according to claim 1, in which the content of these solid products is at least 90%. 22. The gel according to claim 1, wherein said carrageenan is present in an amount of at least 40% of the total dry weight of the film-forming agents in the gel. 23. The gel according to claim 1, wherein said carrageenan is present in an amount of at least 80% of the total dry weight of the film-forming agents in the gel. 24. The gel according to claim 1, wherein said carrageenan is the only film-forming agent present in the gel. 25. The gel according to claim 1, wherein said second film-forming agent is selected from the group consisting of starch, a starch derivative, starch hydrosylate, cellulose resins, alginates, propylene glycol alginate, polymannan resins, dextran, pectin, gellan, pullulan, ethers cellulose, alkyl ethers of modified cellulose and at least one carrageenan having a viscosity of 10 cP or more at 75 ° C. when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5% by weight of said carrageenan of the total weight of all components in said solution. 26. The gel according to claim 1, a film in which said plasticizer is at least one element selected from the group consisting of glycerol, sorbitol, polydextrose, maltitol, lactitol and polyalkylene glycols; said second film-forming agent is at least one element selected from the group consisting of starch, a starch derivative, starch hydrosylate, cellulose resin, hydrocolloid, cellulose alkyl ether or modified cellulose alkyl ether; and said filler is at least one element selected from the group consisting of microcrystalline cellulose, microcrystalline starch, starch, derivatives of starch, inulin, starch hydrosylates and polydextrose. 27. The gel according to any one of claims 1 to 26, wherein said gel is a gel film. 28. A food product containing a gel according to any one of claims 1 to 26. 29. Soft capsules containing filling material encapsulated by a gel according to any one of claims 1 to 26, wherein said gel is a gel film. 30. Soft capsules according to clause 29, in which the specified encapsulated substance is at least one element selected from the group consisting of pharmaceutical preparations, vitamins, food additives, paints, coloring balls, pigments, agricultural agents, cosmetics, antioxidants, flavors and foods. 31. A solid form containing a filler material encapsulated by a gel according to any one of claims 1 to 26. 32. The solid form according to p, in which the specified filling material is a powder, tablet, tablet capsule, microcapsule or capsule. 33. Hard capsules containing filling material encapsulated by a gel according to any one of claims 1 to 26, wherein said gel is a gel film. 34. The hard capsules of claim 33, wherein said encapsulated substance is at least one element selected from the group consisting of pharmaceuticals, vitamins, nutritional supplements, paints, coloring balls, pigments, agricultural agents, cosmetics, antioxidants, flavorings and foods. 35. The method of producing a gel according to any one of claims 1 to 26, comprising the steps of: (i) heating, hydrating, mixing, solubilizing and optionally deaerating a composition of said carrageenan and optionally at least one agent selected from said plasticizer, said second film-forming agent, said filler, and said pH adjusting agent in a device, providing sufficient shear, temperature and residence time to form from it a homogeneous, thermally reversible, molten composition, where the specified temperature is equal to or higher than the temperature s solubilize the molten composition; and (ii) cooling said molten composition at a gel temperature or below to form a gel. 36. The method according to clause 35, in which the specified molten composition is introduced directly into at least one of the devices, such as a mixer, pump or device that prevents the volatilization of the components, before cooling. 37. The method according to clause 35, wherein said device is a Ross mixer, a Stefan processor, an extruder, a jet boiler, or a device for mixing fluids. 38. A method of manufacturing a soft capsule according to clause 29, which includes the stages: (i) heating, hydrating, mixing, solubilizing and optionally deaerating a composition of said carrageenan and optionally at least one agent selected from said plasticizer, said second film-forming agent, said filler, and said pH adjusting agent in a device, providing sufficient shear, temperature and residence time to form from it a homogeneous, molten composition, where the specified temperature is equal to or higher than the solubilization temperature of the spread avlennoy composition; and (ii) making soft capsules directly from said molten composition or allowing said molten composition to cool to its gelation temperature or lower, and then making soft capsules from it. 39. The method of claim 38, wherein said device is a Ross mixer, a Stefan processor, an extruder, an inkjet boiler, or a fluid mixing device. 40. The method according to § 38, in which the specified molten composition is injected directly into at least one of the devices, such as a mixer, pump or device that prevents the volatilization of the components, before making soft capsules. 41. The method according to § 38, wherein said molten composition comprises at least 50% solid products before making soft capsules. 42. The method according to § 38, in which the specified molten gel film contains at least 60% of solid products before the manufacture of soft capsules. 43. A method of lowering the gelation temperature of a composition having at least 40% solids and containing carrageenan and optionally at least one agent selected from a plasticizer, a second film-forming agent, a filler, and a pH adjusting agent, including the step of using at least one low molecular weight carrageenan having a viscosity of 5 to less than 10 cP at 75 ° C when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% of said carrageenan with by lower molecular weight relative to the weight of all components in the specified solution. 44. A delivery system comprising a homogeneous, thermally reversible gel film, wherein said gel film contains: (i) a film-forming amount of carrageenan and optionally at least one agent selected from a plasticizer, a second film-forming agent, a filler, and a regulatory agent pH and (ii) an active substance; in which carrageenan contains at least one low molecular weight carrageenan having a viscosity of from 5 to less than 10 cP at 75 ° C, when measured in a 0.10 molar aqueous solution of sodium chloride containing 1.5 wt.% specified carrageenan with a reduced molecular weight relative to the weight of all components in the specified solution. 45. The delivery system of claim 44, wherein said active substance is at least one element selected from the group consisting of an oral care agent, a breath freshening agent, an antimicrobial agent, a cooling agent, a pharmaceutical agent , a therapeutic nutritional agent, an agent for stimulating the salivary glands, vitamin, mineral, coloring agent, cosmetic ingredient, agricultural active agent, sweetener, flavoring, fragrance and food product.

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