Use in the manufacture of gelatin compositions and gelatin capsules

Abstract

The present invention relates to the field of gelatin capsules, and more particularly to providing gelatin compositions for use in the manufacture of gelatin capsules, especially soft gelatin capsules. The compositions of the present invention are particularly useful in reducing crosslinking in capsules over time and improving the stability of the capsules.

Description

Technical Field

[0001] The present invention relates to the field of gelatin capsules, and more particularly to the provision of gelatin compositions for use in the manufacture of gelatin capsules, especially soft gelatin capsules. The compositions of the present invention are particularly useful for providing stable soft capsules by reducing cross-linking in the capsules.

Background Art

[0002] Capsules are a dosage form widely used in pharmaceutical and nutritional applications. A capsule includes an outer portion, i.e., a capsule shell surrounding an inner portion, i.e., a capsule filling. The capsule shell is typically manufactured using gelatin to which a certain amount of plasticizer and water are added. Two types of capsules are commercially available, hard capsules (i.e., hard shell capsules) and soft capsules (i.e., soft shell capsules). The shell of a hard capsule is typically made of two parts, a cap and a body, while the shell of a soft capsule is typically made of a single part. Hard capsules and soft capsules are well known in the art and are also referred to as hard gelatin capsules and soft gelatin capsules.

[0003]

[0004] The gelatin in a capsule shell dissolves upon ingestion, allowing the capsule to release its filling, which becomes available for absorption by the body. Good capsule performance depends on the dissolution of its shell. However, with certain fillings, particularly soft capsules, the proper dissolution of the capsule shell can decrease over the capsule's lifespan, thereby reducing the capsule's storage stability. One of the main reasons for this decrease in dissolution over time is due to cross-linking reactions. Cross-linking can occur between the free functional groups of the gelatin in the capsule shell and certain components of the capsule filling. Cross-linking can also occur between gelatin molecules in the capsule shell. In either case, the gelatin molecules become less soluble, resulting in the capsule shell taking longer to dissolve, dissolving only partially, or in extreme cases not dissolving at all. This is unacceptable, especially when the pharmaceutical composition needs to be delivered to the patient.

[0005] The method for manufacturing soft gelatin capsules is well known. A gel mass is formed from a gelatin composition, and then the gel mass is formed into a so-called gelatin ribbon or film. Two gelatin ribbons are sealed with the assistance of a die roll to form a capsule shell. As soon as the ribbon is sealed, the filler can be enclosed, and a filled capsule is manufactured. The capsule is then dried. For efficient and smooth manufacturing, the gel mass should form easily and have appropriate viscosity and tackiness for ribbon formation. It is also important that it has appropriate rheological properties during the drying step. If the capsule shell is too tacky, problems will occur during drying.

[0006] Chinese Patent No. 103800912 provides a stable soft capsule shell containing 20-32% by weight of hydrolyzed protein, 24-36% by weight of gelatin, 5-9% by weight of water, 17-27% by weight of plasticizer, 7-18% by weight of disintegrant, and 0.2-2.5% by weight of antioxidant. The hydrolyzed protein may be hydrolyzed soy protein, hydrolyzed rice protein, hydrolyzed wheat protein, hydrolyzed collagen, or a mixture thereof, with hydrolyzed soy protein being more preferably used. However, hydrolyzed soy protein is not very soluble, making it difficult to form gel clumps. Furthermore, soy can be an allergen. In addition, the use of hydrolyzed soy protein negatively affects the color and turbidity of the capsule, resulting in an opaque capsule. Regarding collagen hydrolysates, the inventors have found that using such a large amount of collagen hydrolysate in combination with such a small amount of gelatin in the manufacture of capsules can be very problematic due to the stickiness of the gel clumps and the gelatin ribbons made from such gel clumps, which can also lead to improper sealing and leakage of the capsule filling. Furthermore, drying may have a negative impact on the excessive stickiness of the capsule shell. In addition, the use of large amounts of disintegrant results in opaque capsules, which makes them less appealing to consumers.

[0007] U.S. Patent No. 7,485,323 provides a gelatin composition comprising 5-10% by weight of a low molecular weight gelatin hydrolysate having a high primary amine content and 90-95% by weight of gelatin, wherein the gelatin composition has an average viscosity of about 15-50 cP.

[0008] U.S. Patent Application Publication No. 2020377924 relates to a process for producing a low-crosslinking gelatin mixture obtained by selecting a specific gelatin extract during the gelatin manufacturing process.

[0009] The gelatin composition of the present invention aims to solve one or more of the above problems, such as enabling the manufacture of gelatin capsules with reduced crosslinking, improved dissolution and improved storage stability, improving the manufacturing process of gelatin capsules, and enabling the manufacture of capsules that are properly sealed and have a reduced risk of leakage. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] Chinese Patent No. 103800912 Specification [Patent Document 2] U.S. Patent No. 7485323 [Patent Document 3] U.S. Patent Application Publication No. 2020377924 [Overview of the project]

[0011] The present invention a. 50% to 80% by weight (based on the weight of the gelatin composition) of gelatin and b. 20% to 50% by weight of collagen hydrolysate (based on the weight of the gelatin composition) This relates to a gelatin composition, including the following:

[0012] The gelatin composition of the present invention exhibits improved rheological properties, such as reduced tackiness during gel mass formation, and simplifies the formation and manufacture (including drying) of gelatin capsules. Furthermore, the gelatin composition of the present invention is useful in improving the shelf life of soft capsules after manufacture by reducing crosslinking of gelatin from the capsule shell, thereby maintaining good dissolution of the capsule shell over time.

[0013] In a preferred embodiment, the gelatin composition is produced by co-drying gelatin and collagen hydrolysate. The co-dried gelatin and collagen hydrolysate have improved powder properties, dissolve more easily, and as a result, gel clumps form more readily.

[0014] The present invention further relates to the use of the gelatin composition of the present invention in the manufacture of gelatin capsules, preferably soft gelatin capsules.

[0015] The present invention further comprises a soft capsule shell, a. Gelatin in an amount of 37% to 62% by weight (based on the weight of the capsule shell), b. 12% to 31% by weight of collagen hydrolysate (based on the weight of the capsule shell) c. 17% to 30% by weight of plasticizer (based on the weight of the capsule shell), and This relates to soft capsule shells, including having a moisture content of 5-10% by weight (based on the weight of the capsule shell).

[0016] In a further embodiment, the present invention relates to a method for producing a composition of co-dried gelatin and collagen hydrolysate. [Modes for carrying out the invention]

[0017] The present invention a. 50% to 80% by weight (based on the weight of the gelatin composition) of gelatin and b. 20% to 50% by weight of collagen hydrolysate (based on the weight of the gelatin composition) This relates to a gelatin composition, including the following:

[0018] Preferably, the gelatin composition of the present invention contains gelatin in the following proportions by total weight of the gelatin composition: 51% to 80% by weight, 52% to 80 wt, 53% to 80% by weight, 54% to 80% by weight, 55% to 80% by weight, 56% to 80% by weight, 57% to 80% by weight, 58% to 80% by weight, 59% to 80% by weight, 60% to 80% by weight, 61% to 80% by weight, 62% to 80% by weight, 63% to 80% by weight, 64% to 80% by weight, and 65% to 80% by weight.

[0019] Preferably, the gelatin composition of the present invention further contains, based on the total weight of the gelatin composition, 20% to 49% by weight, 20% to 48% by weight, 20% to 47% by weight, 20% to 46% by weight, 20% to 45% by weight, 20% to 44% by weight, 20% to 43% by weight, 20% to 42% by weight, 20% to 41% by weight, 20% to 40% by weight, 20% to 39% by weight, 20% to 38% by weight, 20% to 37% by weight, 20% to 36% by weight, 20% to 35% by weight of a collagen hydrolyzate.

[0020] In a preferred embodiment, the gelatin composition of the present invention contains 60% to 80% by weight of gelatin (based on the weight of the gelatin composition) and 20% to 40% by weight of a collagen hydrolyzate (based on the weight of the gelatin composition).

[0021] In another preferred embodiment, the gelatin composition of the present invention contains 65% to 80% by weight of gelatin (based on the weight of the gelatin composition) and 20% to 35% by weight of a collagen hydrolyzate (based on the weight of the gelatin composition).

[0022] Preferably, the composition has a moisture content of 5% to 15% by weight, preferably 8% to 12% by weight, more preferably 5% to 10% by weight.

[0023] The composition may contain one or more additives. The additives can be any suitable type of additives such as vitamins, minerals, plasticizers, colorants, stabilizers, flavorings, etc.

[0024] Collagen is the main component of animal and human connective tissue. Collagen consists of amino acid chains wound together to form a triple helix, which in turn forms elongated profibrils. It is mainly found in fibrous tissues such as tendons, ligaments, and skin. It is also found in bones, teeth, corneas, cartilage, intervertebral discs, and blood vessels. Collagen for industrial processing is mainly derived from animal skin and / or bone. Collagen can be processed to produce gelatin, which is obtained by the irreversible partial hydrolysis of collagen. According to the Food Chemistry Regulations, gelatin is defined as a product obtained from the hydrolysis of collagen with acid, alkali, or enzymes, which is the main protein component of animal skin, bone, and connective tissue. A typical gelatin manufacturing method involves several key steps for producing gelatin from raw materials:

[0025] Pre-processing step: Before processing, the raw materials are washed to remove dirt, metal fragments, and other foreign matter.

[0026] Treatment of raw materials with acids, alkalis, or enzymes leads to the hydrolysis of collagen.

[0027] Extraction step: The raw materials are treated with hot water, during which the gelatin is extracted from the raw material matrix and solubilized in an aqueous medium.

[0028] After the extraction step, the gelatin is recovered through further steps of purification, concentration, and drying.

[0029] In the collagen hydrolysate production process, the gelatin after the extraction step is further hydrolyzed to obtain collagen hydrolysate, which is then recovered through further steps such as purification, sterilization, concentration, and drying.

[0030] Gelatin is typically characterized by its gel strength (bloom) and, in warm solutions, by a certain viscosity. This gelatin can be further hydrolyzed into shorter protein chains to produce collagen hydrolysates or collagen peptides, losing its gel-forming ability and even becoming soluble in water at ambient temperature. Hydrolysis can be carried out, for example, by enzymatic treatment with endoproteases, or a combination of endoproteases and exoproteases. Chemical hydrolysis can also occur.

[0031] Therefore, gelatin can be obtained by typical industrial processes from collagen-containing materials such as animal skin, preferably cowhide and / or pigskin and / or fish skin, more preferably cowhide and / or pigskin; or animal bone, preferably pig bone and / or cow bone and / or fish scales / bones and / or poultry bone, more preferably pig bone and / or fish scales / bones.

[0032] Gelatin is further characterized by its viscosity. This viscosity can range from 1.5 mPa.s to 7 mPa.s. Preferably, the viscosity is 2.5 mPa.s to 5.5 mPa.s, more preferably 4.0 mPa.s to 5.5 mPa.s, and even more preferably 4.5 mPa.s to 5.5 mPa.s. Viscosity is a well-known gelatin parameter in the art and is measured according to the method detailed below.

[0033] Gelatin is further characterized by its bloom value. The bloom value can range from 45g bloom to 325g bloom, preferably 90g bloom to 300g bloom, more preferably 100g bloom to 300g bloom, even more preferably 150g bloom to 300g bloom, and even more preferably 200g bloom to 300g bloom. Bloom is a well-known parameter of gelatin in the art and is measured according to the method detailed below.

[0034] Preferably, the gelatin has an average molecular weight (Mw) of 20kDa to 220kDa, preferably 30kDa to 150kDa, more preferably 40kDa to 120kDa, even more preferably 40kDa to 110kDa, even more preferably 50kDa to 100kDa, and even more preferably 60kDa to 90kDa. The average molecular weight is, as used herein, the weight-average molecular weight.

[0035] Preferably, the collagen hydrolysate has an average molecular weight (Mw) of 300 to 5000 Da, preferably 500 to 3000 Da, and more preferably 1000 to 3000 Da (average molecular weight (Mw) measured by gel permeation chromatography (size exclusion chromatography using linear polymers such as polystyrene sulfonate or collagen chain fragments of different molecular weights as calibration vehicles). In this specification, the average molecular weight is the weight-average molecular weight.

[0036] The composition of the present invention preferably has a transmittance of at least 50% at 450 nm (T%450nm) and / or at least 60% at 620 nm (T%620). More preferably, the transmittance at 450 nm is 60% or more, and even more preferably, 65% or more. More preferably, the transmittance at 620 nm is 70% or more, and even more preferably, 75% or more. High transmittance indicates low opacity of the final product, which is preferable for consumers.

[0037] Preferably, the composition is a free-flowing composition in the form of a particulate solid. As used herein, the expression “particulate solid” is not particularly limited to the properties of a particulate solid, and particularly includes granules, folds, pellets, lozenges, powders, strips, and flakes. Preferably, the composition is a powder.

[0038] Preferably, the compositions of the present invention are characterized by having a substantially unimodal particle size distribution. As used herein, a substantially unimodal particle size distribution means that the largest peak in the particle size distribution has an area at least nine times that of the next largest peak.

[0039] Such a substantially unimodal particle size distribution is advantageous in that the composition remains homogeneous during storage, transport, or handling of large bags. Such a particle size distribution can be obtained, for example, when the collagen hydrolysate and the gelatin of the composition are co-dried, i.e., when they are mixed together before the start of the drying step. After drying, the composition is ground to obtain the particle size defined above. Such a particle size distribution is also advantageous for use in soft capsule manufacturing processes. In fact, such a particle size distribution is very uniform and contains very little fine material. The presence of such fine material is typically undesirable for capsule manufacturers, as it can lead to the formation of foam if foam formation is not properly controlled or removed during the capsule manufacturing process, ultimately resulting in a capsule shell with bubbles, improper sealing, and / or a risk of leakage.

[0040] The particle size distribution can be determined using the mesh size. Such particle sizes can be measured with 8 mesh (2.36 mm opening), 10 mesh (2 mm opening), 14 mesh (1.40 mm opening), 20 mesh (0.85 mm opening), 40 mesh (0.425 mm opening), 60 mesh (0.250 mm opening), 100 mesh (0.150 mm opening), 200 mesh (0.075 mm opening), and 400 mesh (0.038 mm opening). Preferably, at least 50% by weight of the composition, preferably at least 55% by weight, more preferably at least 60% by weight, even more preferably at least 65% by weight, even more preferably at least 70% by weight, even more preferably at least 75% by weight, even more preferably at least 80% by weight, even more preferably at least 85% by weight, and even more preferably at least 90% by weight has the same particle size as measured using the previous mesh size.

[0041] In one preferred embodiment, the composition of the present invention is delivered in the form of a particulate solid having a particle size distribution where the main peak is measured at a 14-mesh (1,40 mm opening). Therefore, preferably, at least 50% by weight, preferably at least 55% by weight, more preferably at least 60% by weight, even more preferably at least 65% by weight, and even more preferably at least 70% by weight, and even more preferably at least 75% by weight of the composition have a particle size greater than 1,40 mm and up to 2 mm. Even more preferably, up to 1% by weight, more preferably up to 0.5% by weight of the composition have a particle size of 0.425 mm or less.

[0042] In another preferred embodiment, the composition of the present invention is delivered in the form of a particulate solid having a particle size distribution with the main peak measured at 400 mesh (opening of 0.038 mm). Therefore, preferably, at least 50% by weight, preferably at least 55% by weight, more preferably at least 60% by weight, even more preferably at least 65% by weight, and even more preferably at least 70% by weight, and even more preferably at least 75% by weight of the composition has a particle size measured at 400 mesh, i.e., a particle size greater than 0.038 mm and up to 0.075 mm. Even more preferably, up to 5% by weight, more preferably up to 3% by weight, and even more preferably up to 2% by weight of the composition has a particle size measured at 100 mesh, i.e., a particle size greater than 0.150 mm. Even more preferably, up to 1% by weight, more preferably up to 0.5% by weight of the composition has a particle size measured at 60 mesh, i.e., a particle size greater than 0.250 mm. Such particle sizes can be obtained by co-drying or by an aggregation process in which at least a portion of the collagen hydrolysate is used as a binder.

[0043] The composition of the present invention can be produced by dry-mixing a desired amount of gelatin and a desired amount of collagen hydrolysate. Alternatively, according to a preferred embodiment of the present invention, the composition of the present invention is produced by co-drying a desired amount of gelatin with a desired amount of collagen hydrolysate. Co-drying is advantageous in that the composition remains homogeneous during storage, transport, or handling in a large bag. Conversely, if the components are dry-mixed, separation may occur during storage, handling, or transport due to differences in density and particle size distribution between the components. Since collagen hydrolysate powder tends to have smaller particle sizes and may be present in greater quantities at the top of a large bag, while gelatin powder may be present at the bottom, separation can result in an irregular composition. In that case, it is necessary to include a mixing step before using the composition in, for example, a capsule manufacturing process. This additional mixing step may be disadvantageous to capsule manufacturers because it requires additional mixing equipment, storage tanks, and handling of the components.

[0044] Therefore, in a further aspect of the present invention, a method for producing a gelatin composition, (i) to provide an aqueous composition containing collagen hydrolysate and gelatin, and (ii) The step of drying the aqueous composition, Preferably, the gelatin composition is a. Gelatin in an amount of 50% to 80% by weight (based on the weight of the gelatin composition), and b. A method is provided which comprises 20% to 50% by weight (based on the weight of the gelatin composition) of collagen hydrolysate.

[0045] Preferably, a grinding step is performed after drying to obtain a composition having a desired particle size distribution. Alternatively, an agglomeration step is performed after drying to obtain a composition having a desired particle size distribution.

[0046] In the method of the present invention, the gelatin composition is preferably the gelatin composition described herein. The preferred embodiments described herein for the gelatin composition (e.g., the concentration and properties of gelatin, the concentration and properties of collagen hydrolysate, the particle size distribution, etc.) are applied to the method for producing the gelatin composition described herein, with necessary modifications.

[0047] Such a method is referred to herein as co-drying. Drying can be carried out by any suitable technique known in the art, such as spray drying, rotary drum drying, hot air flow drying, belt drying, or tunnel drying. Drying is preferably carried out using a tunnel dryer. Drying is continued until the composition has a moisture content of 5% to 15% by weight, preferably 8% to 12% by weight, and more preferably 5% to 10% by weight.

[0048] The present invention preferably further relates to a gelatin composition obtained by the co-drying method described herein. The gelatin composition obtained by the co-drying method described herein is preferably, and particularly, a gelling composition previously described herein according to a preferred embodiment of the present invention.

[0049] The aqueous composition of step (i) can be obtained by different methods.

[0050] A hydrolyzed collagen product and gelatin in powder form can be dissolved in water to obtain an aqueous composition, which can then be dried.

[0051] Collagen hydrolysates can be produced in situ during the gelatin production step, after the gelatin extraction step. Gelatin can then be dissolved in an extraction medium (typically water), and a portion of it can be further hydrolyzed, thereby producing an aqueous mixture of gelatin and collagen hydrolysates. The mixture can then be dried in an appropriate manner.

[0052] Preferably, the aqueous composition of step (i) is obtained during the gelatin manufacturing process, in which a collagen hydrolysate in powder or liquid form is added to the gelatin and solubilized in an extraction medium after the gelatin extraction step. The mixture is then dried in an appropriate manner.

[0053] Therefore, preferably, a method for producing a gelatin composition, (i) To provide raw materials containing collagen, (ii) Hydrolyzing collagen into gelatin by treating raw materials containing collagen with alkali, acid, or enzymes. (iii) Extracting gelatin into an aqueous medium at a temperature of 40°C to 90°C. (iv) Adding a collagen hydrolysate and / or hydrolyzing a portion of the gelatin to obtain an aqueous composition containing gelatin and a collagen hydrolysate. (v) Dry the composition obtained in step (iv) (vi) The step of grinding if applicable, preferably the gelatin composition a. Gelatin in an amount of 50% to 80% by weight (based on the weight of the gelatin composition), and b. A method is provided that contains 20% to 50% by weight (based on the weight of the gelatin composition) of collagen hydrolysate.

[0054] Alternatively, gelatin can be completely hydrolyzed to produce collagen hydrolysate, to which gelatin (in powder or liquid form) is added before drying.

[0055] Preferably, the aqueous composition of step (i) has a water content of 20% to 80% by weight, more preferably 30% to 70% by weight, and even more preferably 40% to 60% by weight.

[0056] The present invention further relates to a soft capsule shell comprising the composition and plasticizer of the present invention.

[0057] The present invention further comprises a soft capsule shell, a. Gelatin, 37% to 62% by weight (based on the weight of the capsule shell) b. 12% to 31% by weight of collagen hydrolysate (based on the weight of the capsule shell) c. 17% to 30% by weight of plasticizer (based on the weight of the capsule shell), and This relates to soft capsule shells, including having a moisture content of 5-10% by weight (based on the weight of the capsule shell).

[0058] Gelatin and collagen hydrolysates are as defined herein.

[0059] Preferably, the capsule shell of the present invention contains 35% to 55% by weight, more preferably 37% to 55% by weight, even more preferably 40% to 55% by weight, and even more preferably 40% to 50% by weight of gelatin, based on the weight of the capsule shell. In a further preferred embodiment, the capsule shell of the present invention contains 35% to 60% by weight, more preferably 37% to 60% by weight, and even more preferably 40% to 60% by weight of gelatin, based on the weight of the capsule shell. In a further preferred embodiment, the capsule shell of the present invention contains 35% to 40% by weight of gelatin.

[0060] Preferably, the capsule shell of the present invention further contains 18% to 30% by weight, more preferably 18% to 25% by weight, and even more preferably 20% to 25% by weight of collagen hydrolysate, based on the weight of the capsule shell.

[0061] In a more preferred embodiment, the capsule shell of the present invention comprises, by weight of the capsule shell, 20 to 31% by weight of collagen hydrolysate, more preferably between 25 to 31% by weight of collagen hydrolysate, and even more preferably between 25 to 30% by weight of collagen hydrolysate.

[0062] Preferably, the capsule shell of the present invention contains 17% to 37% by weight, more preferably 25% to 37% by weight, even more preferably 27% to 37% by weight, and even more preferably 27% to 35% by weight of the capsule shell as a plasticizer. In further embodiments, the capsule shell of the present invention contains 20% to 35% by weight, more preferably 20% to 30% by weight of the plasticizer.

[0063] A suitable plasticizer may be glycerin, sorbitol, or propylene glycol, and preferably the plasticizer is glycerin.

[0064] Preferably, the capsule shell of the present invention has a moisture content of 5% to 10% by weight, more preferably 8% to 10% by weight.

[0065] In a preferred embodiment, the capsule shell comprises 40% to 55% by weight of gelatin (based on the weight of the capsule shell), 18% to 25% by weight of collagen hydrolysate (based on the weight of the capsule shell), 27% to 35% by weight of plasticizer (based on the weight of the capsule shell), and 5% to 10% by weight of water (based on the weight of the capsule shell). In a more preferred embodiment, the capsule shell of the present invention comprises, in addition to the preferred ranges of gelatin, plasticizer and water described in this paragraph, 20% to 31% by weight of collagen hydrolysate, more preferably between 25% and 31% by weight of collagen hydrolysate, based on the weight of the capsule shell.

[0066] In a more preferred embodiment, the soft capsule shell of the present invention comprises 37-55% by weight of gelatin and / or 20-31% by weight of collagen hydrolysate, more preferably 25-31% by weight of collagen hydrolysate.

[0067] The combined weight percentage does not exceed 100%.

[0068] Preferably, the capsule shell of the present invention contains 10% by weight or less, preferably 7% by weight or less, more preferably 5% by weight or less, and even more preferably 3% by weight or less of a disintegrant, based on the weight of the capsule shell, and more preferably it contains substantially no disintegrant. The disintegrant may be any suitable disintegrant that is typically used in solid dosage forms such as capsules and tablets, and may be one or more of the following: starch, sodium carboxymethyl starch or hydroxypropyl starch, maltodextrin, etc. Reducing the amount of disintegrant can increase the transparency of the capsule.

[0069] Preferably, the capsule shell of the present invention further contains less than 0.5% by weight, preferably less than 0.2% by weight, of the antioxidant, and preferably is substantially free of antioxidants. The antioxidant may be any suitable antioxidant typically used in solid dosage forms such as capsules and tablets, and may be one or more of the following: fumaric acid, cysteine, glycine, ethylenediaminetetraacetic acid, sodium bisulfite, sodium metabisulfite, sodium thiosulfate, vitamin C, etc.

[0070] The capsule shell of the present invention is a soft capsule shell.

[0071] Preferably, the capsule shell has a thickness of 0.60 to 1.5 mm, more preferably 0.70 to 1 mm, and even more preferably 0.75 to 0.95 mm.

[0072] Furthermore, the present invention relates to a capsule comprising the capsule shell and capsule filling of the present invention, preferably a soft capsule.

[0073] Capsule fillers can be pharmaceutically active fillers, or any suitable filler for soft capsules such as dietary supplements. Fillers can be solids, semi-solids, pastes, emulsions, liquids, etc.

[0074] The capsule shells and capsules of the present invention have been found to have good solubility and remain stable during storage, i.e., they have good solubility during manufacturing and storage. The capsule shells and capsules of the present invention can maintain good solubility during storage for more than one year after manufacturing, preferably more than 18 months, and more preferably more than 24 months. The storage conditions are the usual storage conditions for capsules known in the art. The capsule shells and capsules of the present invention are further characterized in that more than 70% by weight dissolves after 15 minutes when placed in water at 37°C with stirring. Preferably, more than 80% by weight dissolves after 15 minutes. The capsule shells and capsules of the present invention, at 40°C, 75% relative humidity, and more than 70% by weight, dissolve after 15 minutes with stirring in water at 37°C. Preferably, more than 80% by weight dissolves after 15 minutes. The solubility properties can also be seen in films manufactured using the composition of the present invention. The films are similar to capsules, except that they are not formed into capsules but have a sheet shape, and can have circular, square, or any other suitable geometric shape. Capsules and films manufactured using a given gelatin composition have similar dissolution properties. Therefore, similar conclusions can be drawn regarding the dissolution properties of the film and the dissolution properties of capsules manufactured using a given gelatin composition.

[0075] The capsule shells and capsules of the present invention can be manufactured according to methods known in the art, such as plate processes, rotary die processes, reciprocating die processes, Acogel processes, and seamless processes.

[0076] The present invention further relates to the use of the compositions of the present invention in the manufacture of capsule shells, more preferably soft capsule shells.

[0077] The present invention further relates to the use of the composition of the present invention in the manufacture of capsules, more preferably soft capsules.

[0078] The present invention further relates to the use of the composition of the present invention as a component of a capsule shell, preferably a component of a soft capsule shell.

[0079] The composition may be used as a mixture, or the gelatin and collagen of the present invention may be added separately during the manufacture of the capsule shell or capsule, preferably the composition is used as a mixture as described herein.

[0080] The use of the composition of the present invention in the manufacture of soft capsule shells and soft capsules has been found to be advantageous in reducing crosslinking and, therefore, improving the storage stability of the capsule shells and capsules.

[0081] Measurement method The parameters of the products outlined herein are determined using the following measurement methods.

[0082] The moisture content is measured by placing 5g of the product in an oven at 105°C for 18 hours. The difference in weight before and after drying is calculated as the moisture content.

[0083] The bloom value is the mass in grams required to press a standard plunger 4 mm into a 6.67% gel and allow it to mature at 10.0°C for 17 hours. A 6.67% solution of the gelatin sample is prepared in a wide-mouthed test bottle at 60°C, cooled to 10°C, and allowed to mature at this temperature for 17 hours. The resulting gel is tested using a gelmeter according to the GME Monograph Standardised Methods for the Testing of Edible Gelatine (version 12, May 2017).

[0084] Viscosity is measured at 6.66% at 60°C according to British standards and expressed in mPa.s. This is measured as described in the GME Monograph Standardised Methods for the Testing of Edible Gelatine (version 12, May 2017).

[0085] Transmittance is %T=(I / I o It is defined as ) × 100, where I is transmitted light, and I o is the incident light. The transmittance of the composition was measured according to spectrophotometric method, in which a solution of 6.67 wt% of the composition at 60°C was measured at 450 nm and 620 nm with a spectrophotometer.

[0086] Dissolution Capsule or film stability testing involves measuring dissolution over time.

[0087] Dissolution test: Fill the container with 900 ml of water while stirring at 37°C and 50 rpm. Place the capsule / film in the sinker at the bottom of the container at time 0.

[0088] At time t (e.g., 3 minutes, 9 minutes, 15 minutes, and 45 minutes): 5 ml of liquid is removed from the container and its transmittance is measured at 214 nm. Before placing the capsules in the container, the reference transmittance (0% dissolution) is measured in pure water. The dissolution rate at time t is calculated by comparing the transmittance measured at time t with the reference transmittance. The particle size distribution is measured according to the standard method ASTM E11.

[0089] The particle size was measured by passing the composition through a series of vibrating sheaves stacked on top of each other, with the bottom sheave having the best mesh size: 8 mesh (2.36 mm), 10 mesh (2 mm), 14 mesh (1.40 mm), 20 mesh (0.85 mm), 40 mesh (0.425 mm), 60 mesh (0.250 mm), 100 mesh (0.150 mm), 200 mesh (0.075 mm), and 400 mesh (0.038 mm).

[0090] The present invention will be further described by non-limiting embodiments. [Examples]

[0091] Example 1: Manufacturing of capsules according to the present invention A gel mass is prepared at 60°C according to Table 1. The gelatin is type A or type B gelatin with an average molecular weight of 40kDa to 100kDa, a bloom strength of 150g bloom to 300g bloom, and a viscosity of 2.5mPa.s to 5.5mPa.s. The average molecular weight of the collagen hydrolysate is 1000 to 3000Da. The components in Table 1 are mixed in a receptor placed in a water bath at 60°C to form a gel mass.

[0092] Next, the gel mass was formed into capsules using a soft gelatin capsule manufacturing machine, and no filler was used in this test. The thickness of the capsule shell was approximately 0.75–1 mm.

[0093] As comparative experiment A, capsules are being manufactured according to Table 1. [Table 1]

[0094] Solubility is measured after capsule production according to the method described above (Reference Method USP 711) for Example 1 and Comparative Experiment A (T0 in Figure 1).

[0095] The capsules from Example 1 and Comparative Experiment A were subjected to accelerated aging in a chamber with a climate of 40°C and 75% relative humidity for 6 months. After accelerated aging, dissolution was measured (6M in Figure 1).

[0096] Figure 1 shows the time course of the capsules from Example 1 and Comparative Experiment A before (T0) and after (6M) accelerated aging. It can be seen that the composition according to the present invention showed improved dissolution both before and after accelerated aging. Furthermore, where the comparative experiment showed a delay in dissolution after accelerated aging, this was not observed in the composition according to the present invention. This indicates that there was little to no crosslinking in the capsule according to the present invention. [Table 2]

[0097] Example 2: Production of a film using the composition according to the present invention. The gel mass is prepared at 60°C according to Table 2 below. The gelatin is type A or type B gelatin with an average molecular weight of 40kDa to 100kDa, a bloom strength of 150g bloom to 300g bloom, and a viscosity of 2.5mPa.s to 5.5mPa.s. The average molecular weight of the collagen hydrolysate is 300 to 5000Da. The components in Table 2 are mixed together in a receiver placed in a 60°C water bath to produce a gel mass. The mixture is degassed and the gelatin film is cast onto a glass plate to a thickness of approximately 0.75mm to 1mm. The film is placed in a climate chamber and stored under temperature and relative humidity conditions until the film has a moisture content of 10% by weight.

[0098] As comparative experiment B, the films shown in Table 2 below will be prepared. [Table 3]

[0099] The transmittance, set time / temperature, G', and melting time / temperature results at 450nm and 620nm are shown below. [Table 4]

Claims

1. A gelatin composition, a. 50% to 80% by weight of gelatin, based on the weight of the composition, b. A gelatin composition characterized by containing 20% ​​to 50% by weight of collagen hydrolysate, based on the weight of the composition.

2. The composition according to claim 1, further characterized in that the collagen hydrolysate has an average molecular weight of 300 to 5000 Da, preferably 500 to 3000 Da, and more preferably 1000 to 3000 Da.

3. The composition according to claim 1 or 2, further characterized in that the gelatin has an average molecular weight of 40 kDa to 110 kDa.

4. The composition according to any prior claim, further characterized in that the gelatin has a bloom strength of 45 g bloom to 325 g bloom and / or a viscosity of 2.5 mPa.s to 5.5 mPa.s.

5. The composition according to any one of the preceding claims, characterized in that it has a substantially unimodal particle size distribution.

6. The composition according to any prior claim, further characterized by having a transmittance of at least 50%, preferably 60% or more, more preferably 65% ​​or more at 450 nm, and / or a transmittance of at least 60%, preferably 70% or more, more preferably 75% or more at 620 nm.

7. A composition according to any of the preceding claims, for use in the manufacture of gelatin capsules.

8. It is a soft capsule shell, a. 37% to 62% by weight of gelatin, based on the weight of the capsule shell. b. 12% to 31% by weight of collagen hydrolysate, based on the weight of the capsule shell. c. 17% to 30% by weight of a plasticizer, based on the weight of the capsule shell, and d. A soft capsule shell containing 5-10% by weight of moisture.

9. The soft capsule shell according to claim 8, comprising 20 to 31% by weight of collagen hydrolysate.

10. The soft capsule shell according to claim 8 or 9, further characterized by comprising 37 to 55% by weight of gelatin and / or 18 to 30% by weight of collagen hydrolysate.

11. (i) To provide an aqueous composition containing collagen hydrolysate and gelatin, (ii) drying the aqueous composition, and (iii) A method for producing the composition according to claim 5, comprising the step of optionally grinding or agglomerating, preferably grinding.

12. The method described above is (i) To provide raw materials containing collagen, (ii) Hydrolyzing the collagen into gelatin by treating the raw materials containing collagen with alkali, acid, or enzyme, (iii) Extracting gelatin into an aqueous medium at a temperature of 40°C to 90°C. (iv) Adding a collagen hydrolysate and / or hydrolyzing a portion of the gelatin to obtain an aqueous composition containing gelatin and a collagen hydrolysate. (v) drying the composition obtained in step (iv), and (vi) The method according to claim 11, further comprising the step of optionally grinding or agglomerating, preferably grinding.

13. The method according to claim 11, wherein the aqueous composition of step (i) is obtained by dissolving gelatin and collagen hydrolysate in water.

14. Use of the composition according to any one of claims 1 to 7 in the manufacture of a soft gelatin capsule shell and a soft gelatin capsule.

15. A capsule comprising a shell according to any one of claims 8 to 10 and a filler enclosed by the shell.

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