CN107072958B - Soft botanical capsule composition without chemical metal salts - Google Patents
Soft botanical capsule composition without chemical metal salts Download PDFInfo
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- CN107072958B CN107072958B CN201480082150.XA CN201480082150A CN107072958B CN 107072958 B CN107072958 B CN 107072958B CN 201480082150 A CN201480082150 A CN 201480082150A CN 107072958 B CN107072958 B CN 107072958B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Abstract
The present invention relates to a soft capsule composition of vegetal origin containing no chemical metal salt, more specifically to a soft capsule composition of vegetal origin containing iota-carrageenan as a high-valent vegetal gelling agent in a small amount of less than 6% by weight, which has no problem of disintegration of the capsule even without using chemical metal salts such as sodium or potassium salts, and which can bond soft capsules by pressure alone without heating. According to the present invention, the amount of carrageenan which is 10 to 20 times more expensive than starch (starch or modified starch) is minimized to save the production cost of soft capsules, and since sodium (salt), which is a chemical synthetic product causing adult diseases such as hypertension and heart disease, is not used and is not heated in the binding (sealing) step, thermal denaturation of active ingredients contained in the contents of soft capsules can be prevented.
Description
Technical Field
The present invention relates to a soft capsule composition of vegetal origin containing no chemical metal salt, more specifically to a soft capsule composition of vegetal origin containing iota-carrageenan as a high-valent vegetal gelling agent in a small amount of less than 6% by weight, which has no problem of disintegration of the capsule even without using chemical metal salts such as sodium or potassium salts, and which can bond soft capsules by pressure alone without heating.
Background
The preparation method of the common soft capsule (soft Gelatin capsule) comprises the following steps: a coating solution is prepared by mixing predetermined amounts of gelatin, glycerin and water, and then heating and dissolving at 70-80 ℃. The film-coating solution is characterized by forming a semi-solid gel-like film at a temperature of less than about 35 ℃. A Spreader box (spinner box) attached to the soft capsule molding machine flows the film coating solution into a Casting Drum (Casting Drum), and the Casting Drum is rotated to form a film coating. At this time, the temperature of the casting drum is 15 ℃ or less, and when the film-coated solution is brought into contact with the casting drum, a film (representing a tape) having elasticity is rapidly formed. The formed indicator tape passes over the transfer rolls of the forming machine and over the Die rolls (Die Roll) and wedges (Wedge, heat transfer device). The soft capsule forming machine is provided with a casting drum and a spreader case at both sides thereof so that the respective indication tapes formed at both sides are overlapped to pass between two mold rollers, and at a time point of passing through the mold rollers, the indication tapes receive heat of 35 to 45 ℃ through wedges to have a property of being adhesive, whereby the soft capsules are adhered by using a die (Pocket) formed in the mold rollers by using such a principle. Before bonding the soft capsule, a predetermined amount of the contents of the wedge is injected (Injection) into the soft capsule whose lower end is sealed, and the upper end is immediately sealed to complete the molding of the soft capsule.
Gelatin used in general soft capsules is mostly prepared by processing cow leather (cat Hide), cow Bone (cat Bone), Pig skin (Pig skin), and the like. In the case of dissolving gelatin in a predetermined amount of water, such a solution has Thermoreversible (thermoleversible) characteristics according to a change in temperature. The thermoreversible nature of an aqueous gelatin solution refers to the property of existing in the form of a viscous liquid colloid (Sol) at high temperatures and becoming semi-solid (Gel) at low temperatures. Gelatin is used in most of the conventional soft capsules because of its characteristics.
Recently, due to diseases of cattle or pigs such as mad cow disease and foot and mouth disease, social consciousness of animal raw materials is deteriorated, and studies on plant raw materials are continuously conducted. In the case of gelatin, the process is troublesome and many unsanitary parts are present, and thus it is frequently reported as a medium. Gelatin is obtained by hydrolyzing collagen, and has a structure in which amino acids are linked by Peptide bonds (Peptide bonds) and are entangled in a linear or complex branched form. Due to such characteristics, in the case of soft capsules made of gelatin, a Network (Network) is formed between molecules by components such as aldehyde, tannin, and limonene contained in the capsule contents, resulting in delayed disintegration, and when the pH of the contents is high, a phenomenon occurs in which the capsule film is hardened and broken, and when the pH of the contents is low to 1.2 or less, a problem occurs in which the film is hydrolyzed and liquid leakage (content leakage phenomenon) occurs. Thus, the following studies have been conducted since decades ago: instead of using gelatin as an animal protein, soft capsules were prepared as a carbohydrate raw material derived from nature.
In order to overcome the disadvantages of the conventional animal soft capsule materials, and to replace the gelatin, various gums, starches, carrageenan, and the like have been developed as plant soft capsule materials. Among them, carrageenans are classified into iota-carrageenan, kappa-carrageenan and lambda-carrageenan, and particularly, it is known that in the case of iota-carrageenan, calcium ion (Ca) is required to form a gel network2+) If one wants to disintegrate at 20 ℃, sodium ions (Na) are required+)(WJ Reilly,2002,Garrageenan)。
Korean international application No. PCT/US2000/018420 (a film-forming composition comprising modified starch and Iota (Iota) -carrageenan and a method for preparing a soft capsule using the same) is characterized in that the modified starch and Iota-carrageenan are used as film-forming agents, sodium salt or potassium salt is used as a buffer, the film bonding temperature is 25 to 80 ℃, and a wet film has a melting point 4 to 20 ℃ higher than the bonding temperature. Since the amount of the modified starch blended with iota-carrageenan is large, the amount of carrageenan having a high viscosity and being relatively expensive is large, and thus much cost is required. In order to prepare the coating solution, the coating solution is heated at a temperature of 75 ℃ or higher, and the prepared wet film has a melting point of 65 ℃ or higher, so that the bonding temperature is actually 45 ℃ or higher. In this case, the Injection wedge (Injection wedge) needs to be heated, and the contents passing through the wedge are affected by the heat.
Korean application No. 10-2009-.
Korean application No. 10-2011-.
Korean application No. 10-2012-7015423 (film-forming composition for soft capsules) is characterized by using an acid-hydrolyzed waxy corn starch (acid-hydrolyzed waxy corn starch) having a specific viscosity at a specific temperature, and does not mention the characteristics of carrageenan.
In most vegetable soft capsules, metal salts are used as buffers, and sodium salt forms are mostly used. Soft capsules of pharmaceuticals or health foods ingested for health contain sodium, which is not advantageous for improving the health of korea. In addition, since the binding (sealing) temperature is very high with respect to the binding temperature, the contents filled in the soft capsule may be thermally denatured. The more expensive carrageenan is used than modified starch, the more the product cost increases, and thus it is preferable to reduce the amount thereof. Further, if it is desired to approach the plant-derived soft capsules on the market, it is not preferable to use a chemical synthetic product such as a salt or a buffer.
In this regard, the present inventors have intensively studied and endeavored to overcome the problems of the prior art described above, and finally confirmed that the following non-animal derived soft capsules can be prepared to complete the present invention: in the case of using a small amount of iota-carrageenan, the production cost of the soft capsule is reduced, sodium (salt) which has an adverse effect on the human body is not used, and the binding (sealing) temperature is low, so that thermal denaturation of the contents is not caused.
Disclosure of Invention
Technical problem
Accordingly, an object of the present invention is to provide a plant-based soft capsule composition, which is capable of bonding soft capsules by pressure without heating, without using a modified starch for forming a film and a small amount of high-purity carrageenan for gelation, and which is capable of bonding soft capsules by using only pressure without using a metal salt such as a sodium salt or a potassium salt, and which is economical because the amount of carrageenan used is small compared to conventional ones, when preparing soft capsules of non-animal origin.
Technical scheme
According to an embodiment of the present invention, there is provided a wet film composition for soft capsules comprising modified starch and iota-carrageenan, the wet film composition for soft capsules being characterized in that the weight ratio of the modified starch to the iota-carrageenan is from 4.1:1 to 6.5:1, the wet film composition for soft capsules not comprising a buffering agent as a chemical metal salt.
In contrast to the conventional wet film composition for soft capsules comprising iota-carrageenan (korean patent No. 10-0541722) which is characterized in that the weight ratio of modified starch to iota-carrageenan is 1.5:1 to 4.0:1 and which comprises a buffering agent as a chemical metal salt, the wet film composition for soft capsules of the present invention is characterized in that the weight ratio of modified starch to iota-carrageenan is 4.1:1 to 6.5:1 and which does not comprise a buffering agent as a chemical metal salt. According to the experimental example of the present invention, in the case where the buffer agent as a chemical metal salt is not included, if the weight ratio of the modified starch to the iota-carrageenan is 4.0:1 or less, the disintegration time is more than 20 minutes, but according to the present invention, in the case where the content of the high-valent iota-carrageenan is reduced so that the weight ratio of the modified starch to the iota-carrageenan is 4.1:1 or more, the buffer agent as a chemical metal salt is not included, and the disintegration time can be reduced to 20 minutes or less.
In the present invention, any conventionally known modified starch that can form a soft capsule together with iota-carrageenan can be used as the modified starch, and preferably, a wet film composition for soft capsules, which is characterized by being hydroxypropylated corn starch or hydroxypropylated tapioca starch, is provided.
In the present invention, iota-carrageenan having any average molecular weight range known in the art can be used as the iota-carrageenan, and preferably, a wet film composition for soft capsules characterized by having an average molecular weight of 40 to 60 million DT is provided. Iota-carrageenan used in examples of the present invention was analyzed by Gel Permeation Chromatography (GPC), and according to the analysis results, the average molecular weight was about 49 million DT, the low molecular morphology having a molecular weight of 50000DT or less was less than 15%, and the high molecular morphology having a molecular weight exceeding 50000DT was 85% or more.
In the present invention, there is provided a wet film composition for soft capsules, wherein the iota-carrageenan is preferably contained in a concentration of 4 to 5.9% by weight based on the total weight of the wet film composition for soft capsules.
In contrast to conventional wet film compositions for soft capsules comprising iota-carrageenan (korean patent No. 10-0541722), which comprise iota-carrageenan in an amount of 6 to 12% by weight of the composition, the wet film compositions for soft capsules of the present invention are characterized by comprising iota-carrageenan in an amount of 4 to 5.9% by weight of the composition. According to the experimental examples of the present invention, in the case where a buffer agent as a chemical metal salt is not included, if the content of iota-carrageenan is 6% by weight or more, the disintegration time is more than 20 minutes, but according to the present invention, in the case where the content of high-valent iota-carrageenan is reduced to make the content of iota-carrageenan 5.9% by weight or less, the disintegration time can be reduced to within 20 minutes without including a buffer agent as a chemical metal salt. In addition, according to the experimental examples of the present invention, when the iota-carrageenan content was 4% or more, it was confirmed that gelation was good in the aqueous solution.
In the present invention, there is provided a wet film composition for soft capsules, characterized in that the above-mentioned chemical metal salt is a sodium salt or a potassium salt. It has been known that iota-carrageenan requires calcium ion (Ca) in order to form a gel network2+) If one wants to disintegrate at 20 ℃, sodium ions (Na) are required+) (WJ Reilly,2002, Garrageenan). However, in the present invention, the following is initially found: in the case of reducing the content of high-valence iota-carrageenan, no sodium salt or potassium salt is containedThe chemical metal salt (2) is rather excellent in gelation, and can shorten the disintegration time to within 20 minutes.
In the present invention, there is provided a wet film composition for soft capsules, which is characterized in that the disintegration time of the capsule at a temperature of 37 ℃ is within 20 minutes even without using the above-mentioned chemical metal salt. In the examples of the present invention, the following are demonstrated: in the case of reducing the content of high-valent iota-carrageenan, the disintegration time of the capsule at a temperature of 37 ℃ can be shortened to within 20 minutes without the presence of a chemical metal salt such as a sodium salt or a potassium salt. The disintegration time is a time when a solid preparation such as a tablet or a capsule disappears in a test solution or disperses in a predetermined particle state or less, that is, a time when the solid preparation is dissolved or dispersed in the gastrointestinal tract when the tablet or capsule is ingested, and is defined in the korean pharmacopoeia and the health food dictionary, which are announced by the food and drug safety agency, and in the case of the capsule, the solid preparation should be disintegrated in purified water at 37 ℃ within 20 minutes.
In the present invention, there is provided a wet film composition for soft capsules, characterized in that when bonding the above soft capsules, bonding can be performed under room temperature conditions only by means of pressure without heating the wedge. In the examples of the present invention, if a chemical metal salt is used in order to shorten the disintegration time, it is necessary to heat the wedge temperature for bonding the soft capsule to 50 ℃ or more, but according to the present invention, the following cases are demonstrated: with a reduced content of high-valent iota-carrageenan, the bonding can be carried out under room temperature (below 25 ℃) conditions with the aid of pressure alone without heating the wedge. The wedge pressure during the bonding is in the range of 200kPa to 500 kPa.
The present invention provides a wet film composition for soft capsules, which is characterized by preferably comprising 24.2 to 26% by weight of modified starch, 4 to 5.9% by weight of iota-carrageenan, 15 to 25% by weight of a plasticizer, and 45 to 55% by weight of purified water, based on the total weight of the wet film composition for soft capsules. The wet film composition for soft capsules of the present invention may further contain a preservative, a colorant, and the like, which are used in ordinary soft capsules, as necessary.
In the present invention, any plasticizer used in conventional soft capsules can be used as the plasticizer, but the present invention preferably provides a wet film composition for soft capsules, which is characterized by being at least one selected from the group consisting of glycerin, D-sorbitol, sugar alcohols and polyols.
According to another embodiment of the present invention, there is provided a dry film composition for soft capsules comprising modified starch and iota-carrageenan, the dry film composition for soft capsules characterized by a weight ratio of modified starch to iota-carrageenan of 4.1:1 to 6.5:1, the dry film composition for soft capsules not comprising a buffering agent as a chemical metal salt.
The present invention provides a dry film composition for soft capsules, which is characterized by preferably comprising 48.4 to 52 wt% of modified starch, 8 to 11.8 wt% of iota-carrageenan and 30 to 50 wt% of a plasticizer, based on the total weight of the dry film composition for soft capsules. The dry film composition for soft capsules of the present invention may further contain a preservative, a colorant, and the like, which are used in ordinary soft capsules, as necessary.
In the present specification, the "wet film composition for soft capsules" refers to a wet film composition supplied to a casting drum by mixing and dissolving film materials, particularly for the purpose of producing soft capsules by a rotary-die encapsulation apparatus, and the "dry film composition for soft capsules" refers to a dry film composition finally obtained in a drying step after forming filled capsules from the wet film composition through a rotary die. The wet film composition was subjected to the above-described drying process to remove water, so that the content of the components in the composition was doubled as shown in the following table 1.
TABLE 1
The present invention will be described in more detail below.
The present invention aims to make it possible to prepare soft capsules from plant-derived components such as starch and carrageenan.
In order to solve the problems as described above, first, a plant-derived polymer that can be formed into a film should be selected. Therefore, raw materials effective for film formation have been selected by examining the characteristics of various cereals, potatoes, cellulose and processed products thereof (modification treatment, decomposition and the like).
Most of the non-processed raw materials (starch, cellulose, etc.) were confirmed to be incapable of forming a film or to form a physically very weak film. The following was found: processed starches tend to form films, and in particular, modified starches derived from corn have high viscosity when dissolved and form films satisfactorily. In this regard, the present inventors continued the study of grafting a gelator having thermoreversible characteristics as basic properties when preparing a soft capsule.
Carrageenan is known as a polymer extracted from plants, having similar thermoreversible properties to gelatin. The type of carrageenan effective for film formation and an appropriate blending amount that does not cause problems in film formation and disintegration are set.
Starch (Starch) is utilized as a human energy source and is contained in grains, corn, potatoes, sweet potatoes, and the like. The structure of starch is classified into amylose (amylose) and amylopectin (amylopectin), and starch derived from grains is generally formed from approximately 15 to 30% of amylose and approximately 70 to 85% of amylopectin, but in the case of glutinous rice or waxy corn, most of the amylopectin is present.
When the starch is heated by pouring hot water into the starch or suspending the starch in water, the starch particles expand to form a liquid with a strong viscosity, i.e., a paste state. This phenomenon is called gelatinization and is generally seen in a predetermined temperature range depending on the kind of starch. In amylose, glucose molecules are bound in a linear form, so that they are easily gelatinized if suspended in water to be heated, and form a film when dried after gelatinization.
In the case where starch is subjected to hydrolysis or oxidative degradation, modified starch is produced by degrading high molecules and repolymerizing the degraded product during the reaction. Typical modified starches are classified as acid-modified starches, oxidized starches, starch derivatives, alpha-starches, Ether (Ether) starches, Ester (Ester) starches, soluble starches, crosslinked starches, grafted starches, and the like. Among these modified starches, ether starch has high stability to pH, is easily gelatinized, and has good film-forming ability. In particular, hydroxypropyl starches having hydroxypropyl groups with ether bonds have a low gelatinization starting concentration, are nonionic, have excellent aging stability, and can form strong and elastic films, and thus are used as film-forming agents for soft capsules of non-animal origin.
According to the investigation results of hydroxypropylated modified starches of starches derived from various grains, modified starches derived from corn having suitable amylose and amylopectin structures are selected as coating forming agents for soft capsules. Hydroxypropyl corn starch is readily available for use from starch processing companies.
In order to produce a wet film for molding in a soft capsule process, the film solution must be gelled at a low temperature, and therefore must have thermoreversible properties. As is known, the only substances having thermoreversible properties among vegetable raw materials are carrageenans. The carrageenan is prepared by extracting red seaweed such as Eucheuma cottonii (Eucheuma cottonii), Eucheuma spinosum (Eucheuma spinosum), and Chondrus crispus (Chondrus crispus) with water or alkali. Carrageenan is classified into Iota (Iota) -carrageenan, Kappa (Kappa) -carrageenan and Lambda (Lambda) -carrageenan according to structural characteristics, and the structures of the three types of carrageenan are different depending on the kind of seaweed to be processed. The structural characteristics of carrageenan are divided into the degree of ester bond of Sulfate (Sulfate) in Galactose (Galactose) Sugar molecules (Sugar units) and the composition ratio of 3,6-anhydrogalactose (3, 6-anhydroglucose). Iota-carrageenan consists of 32% sulphate esters (Sulfate ester) and 30% 3,6-anhydrogalactose, kappa-carrageenan consists of 25% sulphate esters and 34% 3,6-anhydrogalactose, lambda-carrageenan has only 35% sulphate esters, 3,6-anhydrogalactose is excluded. Due to this structural characteristic, the physical and chemical characteristics of each carrageenan are different.
In the presence of potassium ions (K)+) In the case of kappa-carrageenan, a Thermoreversible gel (thermoleversible gel) may be formed in aqueous solution, iota-carrageenan, a Thermoreversible gel in aqueous solution, in the presence of potassium ions (K)+) Or calcium ion (Ca)++) In the case of (3), a gel having high elasticity or strength can be formed. In the case of lambda carrageenan, a thermally reversible gel cannot be formed. In the case of kappa carrageenan, hard and brittle gels are formed, and in the case of iota carrageenan, clear and elastic gels are formed, which is characteristic of them. The gel formed by these iota-carrageenan and kappa-carrageenan has the property of dissolving in water at temperatures above 70 ℃, and therefore a Salt (Salt) containing sodium has to be dosed. In the case of adding sodium salt, the carrageenan-containing coating formulation had the property of dissolving in water at a temperature of 20 ℃.
Gels using iota-Carrageenan have excellent clarity and elasticity and can therefore be considered as Carrageenan having properties most suitable for soft capsules of non-animal origin (Gelatin Free) (Gelatine Hand book, Theory and Industrial Practice-Reinhard Schrieber, eds., 2007, 3.Practical applications, 3.1.1.2 Carrageenans; Handbook of Pharmaceutical Excipients, Fourth Edition, Raymond C Rowes eds., 2003, Carrageenan).
The carrageenan is prepared by mixing iota-carrageenan, kappa-carrageenan and lambda-carrageenan according to the species and extraction method of the marine algae. Recently, as separation and purification techniques have been developed, products having improved purity of specific carrageenan are being sold. In the case of iota-carrageenan, gelation properties also vary depending on purity, and gelation characteristics vary depending on molecular weight distribution. The inventors of the present invention confirmed that a firm gel can be formed in a concentration less than high-purity iota carrageenan from the results of tests on the gelation properties of standardized iota carrageenan, non-standardized iota carrageenan, and high-purity iota carrageenan. Typical iota carrageenan is very wide and has an average molecular weight of about 100,000 to 10,000,000DT, but iota carrageenan used in the present invention is extracted from eucheuma isophyton or carrageenan, has an average molecular weight of 400,000DT to 600,000DT, and is iota carrageenan having a low molecular morphology of less than 50,000DT of less than 15% and a high molecular morphology of 50,000DT or more of 85% or more. The iota-carrageenan of the present invention is pure iota-carrageenan having a purity of 100% and containing no sugars (sugar, glucose, maltodextrin, and lactose) or metal salts (calcium and sodium) for adjusting viscosity or gel strength. In order to confirm the molecular weight distribution of iota-carrageenan of the present invention, the molecular weight distribution was confirmed by a korean high molecular test institute (Korea polymer testing & research institute), which is an internationally recognized testing organization.
Fig. 1 is a graph showing the molecular weight analysis of iota-carrageenan used in examples of the present invention. From the above analysis chart, it was confirmed that the average molecular weight (Mw) was 489,265 DT. From the above experimental results, the distribution of the respective molecular weights can be confirmed, and the molecular weight 50,000DT or less can be confirmed to be less than 15%.
In the examples of the present invention, the amount of iota-carrageenan used for gelation was set and dissolved at a certain concentration, and then the viscosity and the gelation state were confirmed, and as a result, it was confirmed that gelation was achieved in an aqueous solution of 4% or more. When the concentration is less than 4%, even if the temperature is cooled to 15 ℃ or less, the Sol (Sol) state is maintained, and the Sol exists as a liquid having viscosity and fluidity, and thus the concentration is such that a wet film cannot be produced by gelation. On the contrary, the viscosity of the aqueous solution of 10% or more is very high (80 ℃, 10,000cp or more), so that excessive heating is required in the process of preparing the soft capsule, and the process of dissolving the coating, transferring and Spreading (Spreading) for film formation is very difficult, so that it is not preferable.
In order to confirm the property of dissolving the capsule in water after the preparation of the soft capsule, that is, the influence on disintegration, the disintegration time of iota-carrageenan gel was confirmed by concentration, and as a result, it was confirmed that the dissolution time increased as the concentration increased. Further, it was confirmed that the disintegration state was confirmed by preparing a wet film from iota-carrageenan and modified starch at predetermined concentrations and then drying the film, and as a result, it was confirmed that the disintegration standard (within 20 minutes at 37 ℃) could not be satisfied when carrageenan was blended in an amount of 6% or more. Further, it was confirmed that the disintegration time was shortened in the case of adding a sodium salt (disodium hydrogenphosphate), whereas the disintegration time was delayed in the case of adding a potassium salt (potassium chloride). This demonstrates that in the case of iota-carrageenan, as in the above-mentioned document, cold water is not readily soluble except in the sodium salt form. Also, it was confirmed that a sodium salt generally used for a soft capsule of a buffered vegetable is used as an aid for disintegration. In some patents it is mentioned that potassium salts can also be used for buffering, but this causes disintegration delay problems and is therefore not preferred.
The gel-forming properties by concentration and the effect on disintegration of iota-carrageenan were tested and as a result, it was confirmed that the film was formed under the condition that the film solution was less than 6%, preferably 4.0% to 5.9%, and there was no problem of disintegration even without the sodium salt.
In order to confirm the relationship between the amount of iota-carrageenan and the soft capsule sealing temperature, the heating temperature (bonding temperature) of the wedge was confirmed by blending the film solution at a concentration, and as a result, it was confirmed that a wet film prepared at a concentration of less than 6% can be bonded only by the pressure of the molding die (mold) even without being heated. This is because the bonding can be performed without the influence of carrageenan gel due to the partially sticky nature of the modified starch. In the case of soft capsules of plant origin, since the amount of carrageenan blended is large and the melting point of the wet film is high, the temperature of the adhesive wedge should be set high. In this case, the capsule contents are passed through the wedge and filled into the capsule (Injection) and a portion of the contents are returned to the contents canister, thereby allowing the contents to continue to be heated. In general, in the case where the contents are heated, there is a possibility that the content of heat-sensitive ingredients (saponin, partially water-soluble vitamins, etc.) may be reduced. In the case of a content prepared from a suspension agent of beeswax or polyethylene glycol (PEG), layer separation occurs, and there is a possibility that an unfavorable state may occur after filling a capsule. Further, since heating is not performed, it is also very preferable in terms of energy saving.
Thus, the present inventors have used the iota-carrageenan content to the minimum, and thus have solved the disintegration problem, prevented the contents from deteriorating, and completed a plant-derived soft capsule having great economic advantages, even without using the sodium salt.
Advantageous effects
The amount of carrageenan 10 to 20 times higher than that of starch (starch and modified starch) is minimized to save the cost for producing soft capsules, and since sodium (salt), which is a chemical synthetic product causing adult diseases such as hypertension and heart diseases, is not used and heating is not performed in a binding (sealing) step, thermal denaturation of active ingredients contained in the contents of the soft capsules can be prevented.
Drawings
Fig. 1 is a gel permeation chromatogram for analyzing the molecular weight of iota-carrageenan used in the examples of the present invention.
Fig. 2a is a photograph showing the gelled state according to the iota-carrageenan concentration in the example of the present invention.
Fig. 2b is a graph showing the viscosity change and gellable region according to the iota-carrageenan concentration in the example of the present invention.
Fig. 3 is a graph comparing disintegration times according to iota-carrageenan concentration and presence or absence of salt addition in examples of the present invention.
Fig. 4 is a photograph showing the capsule shape when molding is performed using room temperature as the bonding (wedge) temperature in the example of the present invention.
FIG. 5 is a photograph showing a state 20 minutes after the start of disintegration of the capsule in the example of the present invention.
Detailed Description
The present invention will be described in more detail below with reference to examples. These examples are merely illustrative of the present invention and thus should not be construed as limiting the scope of the present invention thereto.
Experimental example 1
In order to set the amount of high purity iota-carrageenan required for gelation for preparing a wet film, viscosity and a gelled state were confirmed after dissolution by concentration.
1) The blending method comprises the following steps: after 0.5g of carrageenan was put into a 250ml beaker, 100g of carrageenan was prepared by filling purified water, and the mixture was stirred and the temperature was raised to 80 ℃ to complete hydration. The viscosity and the gelled state were confirmed after mixing to 0.5 to 13 wt% at 0.5 wt% intervals by the same method.
2) Viscosity measuring method
(1) Viscometer: boleffet (Brookfield) DV-II +
(2) Conditions are as follows: LV3, LV4(Spindle), 80 ℃,20 rpm
3) Method for confirming gelation state: about 3g of the hydrated solution was dropped onto a stainless steel plate at a temperature of about 10 ℃. After 10 minutes of curing, when pressing about 2mm with a reagent spoon and releasing the press, the gel should not be applied to the spoon and the gel should not crack.
Table 2: confirmation of viscosity and gelled state by iota-carrageenan concentration
Fig. 2a is a photograph showing a gelled state according to the iota-carrageenan concentration. As shown in the photograph of fig. 2a, when the iota-carrageenan concentration was 4% or more, a gel having no deformation or no crack was formed.
Fig. 2b is a graph showing the viscosity change and gellable region according to the iota-carrageenan concentration.
From the above experimental results, it was confirmed that gelation was achieved in an aqueous solution of iota-carrageenan in an amount of 4% or more. In the case of less than 4%, even if cooling is performed, the solvent exists in a sol state in a viscous and brittle form, and thus is a concentration at which a wet film cannot be produced. On the other hand, an aqueous solution of 8% or more has a viscosity of 5000cp or more and is very high, so that it is necessary to heat excessively in the process of producing soft capsules, and the coating film dissolution process, transfer and spreading process for the film are very difficult, so that the concentration is not preferable.
Experimental example 2
In order to confirm the water-soluble property of the capsule after the preparation of the soft capsule, the disintegration state was confirmed by preparing a wet film by changing the iota-carrageenan concentration and then drying the film. In the case of a general gelatin soft capsule, the amount of the powder component (gelatin) is about 40%, but the carrageenan of the present invention shows a sharp viscosity due to the low-temperature purified water, and thus the appropriate amount of the powder component is about 30% when considering the load of the stirring motor of the capsule dissolving tank. After drying, the plasticizer for imparting elasticity to the film is set to 15 to 25% by weight, which is an amount generally used, using glycerin, as in the case of the gelatin soft capsule. As the solvent, purified water is set to about 45 to 55 wt%. In order to confirm the influence of the potassium salt and the sodium salt, experiments were carried out by adding 1 wt% of each of potassium chloride and disodium hydrogen phosphate to a comparative example in which iota-carrageenan was 7.5 wt%.
1) The preparation method of the membrane comprises the following steps: after weighing purified water, iota-carrageenan (corresponding weight%), hydroxypropyl corn starch, glycerin were placed in a 250ml sterilized glass bottle, and stirred with a spoon for 5 minutes. After stoppering and dipping in a 80 ℃ water bath, the film solution was prepared by heating for 30 minutes. The film solution was thinly spread on a flat stainless steel plate at a thickness of about 0.8 mm. The dried product is transferred to a drying chamber (20 to 25 ℃, humidity 20 to 25%) and dried for 1 day, and then stored at room temperature for 10 days.
2) Disintegration test method: after cutting the dried film at 10mm in the transverse direction and 10mm in the longitudinal direction, the disintegration tube was put into a reciprocating motion in purified water at 37 deg.C, thereby measuring the disintegration time.
Table 3: disintegration state according to iota-carrageenan concentration and influence of potassium and sodium salts
Fig. 3 is a graph comparing disintegration time according to carrageenan concentration and presence or absence of salt addition.
From the above results, it was confirmed that the disintegration time of the film increased as the compounding ratio of iota-carrageenan increased. Further, it was confirmed that when the amount of the compound is 6% or more, the disintegration standard (37 ℃ C., within 20 minutes) cannot be satisfied. Further, it was confirmed that the disintegration time was shortened in the case of comparative example 5 in which a sodium salt was added, whereas the disintegration time was delayed in the case of comparative example 4 in which a potassium salt was added. This demonstrates that iota-carrageenan, as in the case of the above-mentioned documents, is not readily soluble in cold water, except in the sodium salt form. Also, it was confirmed that a sodium salt generally used for a soft capsule of a buffered vegetable is used as an aid for disintegration. In some patents it is mentioned that potassium salts may also be used for buffering, but this creates a disintegration delay problem and is therefore not preferred.
When the disintegration results as described above are considered, the concentration of high-purity iota-carrageenan without disintegration problems is less than 6% (4 to 5.9 wt%), preferably 8 to 11.8 wt% in the case of dry film, without using sodium salt.
Experimental example 3
In order to confirm the amount of iota-carrageenan and the sealing temperature of the soft capsules, the composition of the present invention (example 3), the composition containing 6% or more of carrageenan (comparative example 1), and the composition using a sodium salt (comparative example 5) were blended, and soft capsules were prepared using a general soft capsule molding machine of a rotary mold system, and the preparation process (dissolution time, adhesion temperature) and the quality of the soft capsules (disintegration, adhesion rate, and breaking strength) were compared.
1) Composition of coating solution
(1) Example 3: 5 percent by weight of iota-carrageenan, 25 percent by weight of propyl corn starch, 20 percent by weight of glycerin and 50 percent by weight of purified water
(2) Comparative example 1: 6 percent by weight of iota-carrageenan, 24 percent by weight of hydroxypropyl corn starch, 20 percent by weight of glycerin and 50 percent by weight of purified water
(3) Comparative example 5: 7.5 percent by weight of iota-carrageenan, 22.5 percent by weight of hydroxypropyl corn starch, 19.5 percent by weight of glycerin, 49.5 percent by weight of purified water and 1 percent by weight of disodium hydrogen phosphate
2) Preparation method
(1) The total film dissolved matter was weighed in each weight% corresponding to 100 kg.
(2) Purified water and glycerin were put into a 400L capsule dissolving tank.
(3) After the iota-carrageenan and hydroxypropyl corn starch were charged, the mixture was stirred at 10RPM for 10 minutes (in comparative example 5, disodium hydrogen phosphate was added).
(4) Stirring is continued, and the temperature is raised to 80-90 ℃ for dissolution.
(5) The vacuum degree was adjusted to 640mmHg or more, and the mixture was degassed for about 10 minutes.
(6) The molded product is transferred to a heat-insulating container (receiver) to wait for molding.
(7) The film formulation and the content (soybean oil) were molded in a predetermined amount by a soft capsule molding machine (Changsu, Jumbo) molding machine).
(8) After drying for 3 days, the sample was stored at room temperature for 20 days, and then the test was carried out.
Table 4: according to the production condition of carrageenan concentration and sealing temperature of soft capsule
Fig. 4 is a photograph showing the capsule shape when molding is performed with room temperature as the bonding (wedge) temperature. As a result, it was confirmed that the capsule was not sealed in the case of comparative example 5 in which the iota-carrageenan content was large and the sodium salt was used.
Fig. 5 is a photograph showing a state 20 minutes after the start of disintegration. As shown in the photographs, in the case of example 3 of the present invention and comparative example 5 using a sodium salt, the remaining amount of the capsule was not present in the disintegration auxiliary plate. However, in the case of comparative example 1 in which the sodium salt was not used, much residue remained undissolved in the disintegration auxiliary plate even after 20 minutes had elapsed.
As a result, in example 3 which is the composition of the present invention, the molding can be performed without heating at the time of bonding. It was confirmed that in the case of comparative example 5 containing 7.5% carrageenan, molding could be performed only by setting the bonding temperature to be extremely high (52 ℃). In the case of soft capsules derived from plants in most cases, the amount of carrageenan blended is large, and the melting point of the wet film is high, and therefore, it is necessary to set the temperature of the adhesive wedge to be high. In the case of comparative example 1 containing 6% iota-carrageenan, heating was not necessary when bonding was performed, but the disintegration time was 23 minutes (within 20 minutes on the basis), which is not preferable. As described above, it was confirmed that when the amount of iota-carrageenan blended is less than 6%, the wet film can be bonded by only the pressure of the molding die (mold) without being heated, and there is no problem in the disintegration stability even without using the sodium salt.
Industrial applicability
As described above, according to the present invention, when preparing a soft capsule of non-animal origin, modified starch for film formation and a small amount of high-purity carrageenan for gelation are used, so that there is no problem of capsule disintegration even without using a metal salt such as a sodium salt or a potassium salt, the soft capsule can be bonded by only pressure without heating, and the amount of carrageenan used is small compared to the conventional ones, so that a vegetable soft capsule excellent in economy can be prepared. Further, the amount of carrageenan 10 to 20 times higher than that of starch (starch and modified starch) is minimized to save the production cost of the soft capsule, and since sodium (salt), which is a chemical synthetic product causing adult diseases such as hypertension and heart disease, is not used and is not heated in the binding (sealing) step, thermal denaturation of the active ingredient contained in the contents of the soft capsule can be prevented.
Claims (6)
1. The wet film composition for the soft capsules comprises modified starch and iota-carrageenan, wherein the modified starch is hydroxypropylated corn starch, the weight ratio of the modified starch to the iota-carrageenan is 4.1:1 to 6.5:1, the wet film composition for the soft capsules does not contain a buffering agent serving as a chemical metal salt, and the wet film composition for the soft capsules comprises 24.2 to 26 wt% of the modified starch, 4 to 5.9 wt% of the iota-carrageenan, 15 to 25 wt% of a plasticizer and 45 to 55 wt% of purified water in the total weight of the wet film composition for the soft capsules.
2. The wet film composition for soft capsules according to claim 1, wherein the iota-carrageenan has an average molecular weight of 40 to 60 million DT.
3. The wet film composition for soft capsules according to claim 1, wherein said chemical metal salt is a sodium salt or a potassium salt.
4. The wet film composition for soft capsules according to claim 1, wherein the disintegration time of the capsule at a temperature of 37 ℃ is within 20 minutes even without using the chemical metal salt.
5. The wet film composition for soft capsules according to claim 1, wherein when bonding said soft capsules, bonding is performed only by means of pressure at room temperature without heating of wedges.
6. The wet film composition for soft capsules according to claim 1, wherein said plasticizer is one or more selected from the group consisting of glycerin and D-sorbitol.
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/KR2014/008969 WO2016047825A1 (en) | 2014-09-25 | 2014-09-25 | Vegetable soft capsule composition not comprising chemical metal salts |
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| US10711119B2 (en) | 2018-01-10 | 2020-07-14 | Cp Kelco Aps | Carrageenan-based compositions for films and capsules |
| CN110075081A (en) * | 2019-06-12 | 2019-08-02 | 江苏艾兰得营养品有限公司 | A kind of soft capsule and preparation method thereof and purposes |
| CN112586587A (en) * | 2020-12-10 | 2021-04-02 | 浙江艾兰得生物科技有限公司 | Anti-sticking chewable plant gel candy gel rubber |
| CN113337015B (en) * | 2021-06-17 | 2022-12-06 | 四川农业大学 | Preparation method of composite edible film |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649572A (en) * | 2002-01-18 | 2005-08-03 | 贝纳制药公司 | Non-gelatin capsule shell formulation comprising iota-carrageenan and kappa-carrageenan |
| CN101606919A (en) * | 2008-06-21 | 2009-12-23 | 方家淇 | Produce the method for medical capsule shells with carrageenan |
| WO2012070577A1 (en) * | 2010-11-22 | 2012-05-31 | 富士カプセル株式会社 | Soft capsule coating |
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| US6340473B1 (en) * | 1999-07-07 | 2002-01-22 | R.P. Scherer Technologies, Inc. | Film forming compositions comprising modified starches and iota-carrageenan and methods for manufacturing soft capsules using same |
| KR101411364B1 (en) * | 2012-03-16 | 2014-06-30 | 주식회사 서흥 | Soft capsule film composition using starch as main base material |
| KR101212320B1 (en) * | 2012-04-13 | 2012-12-13 | 김규조 | Vegetable soft capsule shell including modified starch and soft capsule having the same |
| KR101445334B1 (en) * | 2013-06-05 | 2014-10-01 | 코스맥스바이오 주식회사 | Vegetable Soft Capsule Composition without Chemical Metal Salts |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1649572A (en) * | 2002-01-18 | 2005-08-03 | 贝纳制药公司 | Non-gelatin capsule shell formulation comprising iota-carrageenan and kappa-carrageenan |
| CN101606919A (en) * | 2008-06-21 | 2009-12-23 | 方家淇 | Produce the method for medical capsule shells with carrageenan |
| WO2012070577A1 (en) * | 2010-11-22 | 2012-05-31 | 富士カプセル株式会社 | Soft capsule coating |
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