Three-layer seamless soft capsules, process for their preparation and use

Abstract

Provided are three-layer seamless soft capsules, including a core, an intermediate protective layer wrapping the core, and a film layer wrapping the intermediate protective layer, wherein the intermediate protective layer contains 279-294 parts by weight of a first oily substance and 6-21 parts by weight of phospholipids; the phospholipids contain 10-60 wt% of phosphatidylcholine; and the first oily substance is a hardened oil or a hardened oil composition in a solid state at room temperature and having a melting point of 40-60℃. The present application solves the problem of capsule easy to break and leak oil caused by large oil droplets in the film layer during the manufacturing process of seamless soft capsules.

Description

Technical Field

[0001] This invention relates to the field of soft capsules, and more specifically to a three-layer seamless soft capsule, its preparation method, and its uses. Background Technology

[0002] Seamless soft capsules are formed using a drop-forming method, creating spherical capsules with stable filler weights under varying liquid flow rates and specific frequencies. However, the membranes of seamless capsules still commonly suffer from uneven thickness and oil droplets. To reduce these issues, components such as interfacial tension modifiers and gelation promoters can be added to the membrane composition or capsule contents.

[0003] Seamless soft capsules can comprise multi-layered seamless soft capsules, such as two-layer seamless capsules and three-layer two-layer seamless capsules. JP2015199698A provides a two-layer seamless capsule containing phospholipids. Since capsules cannot be formed when manufacturing seamless capsules with a single-layer film containing phospholipid oil, the capsule contents are further compounded with an emulsifier of HLB 3 or lower. JP2022026425A provides a two-layer seamless soft capsule containing phospholipids of 85% or more by weight of phosphatidylcholine in the capsule contents, which reduces thickness unevenness and oil droplet problems in seamless capsules. Therefore, the prior art has solved the oil droplet problem in two-layer seamless soft capsules by adding phospholipids containing 85% phosphatidylcholine, or by compounding phospholipids with an HLB < 3 emulsifier, to the contents.

[0004] However, for three-layer and two-layer seamless capsules, technical solutions are still needed to address issues such as uneven thickness and oil droplets. Summary of the Invention

[0005] Through long-term research, the inventors discovered that during the molding process of three-layer seamless soft capsules, due to the concentric nozzles, air bubbles and oil droplets from the core and middle layers inevitably remain in the outer membrane layer, forming small oil droplets. When these droplets exceed one-third of the cross-sectional diameter of the rubber, the product cannot be molded or is prone to rupture and leakage at the oil droplet locations. Because the structure of three-layer seamless soft capsules differs from that of two-layer seamless soft capsules, and the formulations used are also different, there are currently no reported solutions to the oil droplet problem in three-layer seamless soft capsules.

[0006] This invention provides a three-layer seamless soft capsule that solves the problem of excessive oil droplets in the membrane causing poor forming or easy rupture and oil leakage. Through in-depth research, the inventors discovered that the three-layer seamless soft capsule contains phospholipids in the middle protective layer, and by limiting the ratio of phospholipids to oily substances, the invention can solve the problem of excessive oil droplets in the membrane causing easy rupture and oil leakage during the manufacturing process of seamless soft capsules, thus completing this invention.

[0007] In one aspect, the present invention provides a three-layer seamless soft capsule comprising a core, an intermediate protective layer enclosing the core, and a membrane layer enclosing the intermediate protective layer. In one embodiment, the intermediate protective layer comprises 279-294 parts by weight of a first oily substance and 6-21 parts by weight of phospholipids. In one embodiment, the phospholipids contain 10-60 wt% phosphatidylcholine. In one embodiment, the first oily substance is a hardened oil or a composition of hardened oils that is solidified at room temperature and has a melting point of 40-60°C.

[0008] In one embodiment, the core comprises 0.5-100 parts by weight of an active substance and 400-500 parts by weight of a second oily substance. In one embodiment, the second oily substance is a hardened oil or a compound hardened oil that solidifies at room temperature and has a melting point of 24-64°C.

[0009] In one embodiment, the film layer comprises 80-320 parts by weight of a water-soluble gelling agent and 10-125 parts by weight of a plasticizer.

[0010] In one embodiment, the first oily substance is selected from one or a combination of palm oil, shortening, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, extractive palm stearate, palm oil extract, palm super oil extract, palm double oil extract, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter or cocoa butter substitute.

[0011] In one embodiment, the first oily substance is shortening or a combination of shortening and palm oil in a ratio of 4:6 to 9:1.

[0012] In one embodiment, the active substance is a substance that is unstable in water and / or acid.

[0013] In one embodiment, the substance that is unstable in water and / or acid is in powder form. In one embodiment, the average particle size of the powder is 10-250 micrometers.

[0014] In one embodiment, the substance that is unstable in water and / or acid includes one or more of probiotics, vitamins, lactoferrin, and enzymes.

[0015] In one embodiment, the probiotics include Bifidobacteria and / or Lactobacilli.

[0016] In one embodiment, the vitamins include one or more of vitamin B1, vitamin B2, vitamin B12, and vitamin C.

[0017] In one embodiment, the water-soluble gelling agent comprises one or more of gelatin, carrageenan, agar, gellan gum, pectin, and starch.

[0018] In one embodiment, the water-soluble gelling agent comprises gelatin and pectin, wherein the weight ratio of pectin to gelatin is 1:10 to 3:10. In one embodiment, the pectin is selected from low-ester pectin and / or amide pectin. In one embodiment, the degree of esterification (DE) of the pectin is <50%. In one embodiment, the degree of amidation (DA) of the pectin is 0-25%.

[0019] In one embodiment, the plasticizer is selected from one or more of glycerol, sorbitol, erythritol, and maltitol.

[0020] In one embodiment, the phospholipid is selected from one or more of soybean phospholipids, sunflower phospholipids, and egg yolk phospholipids.

[0021] In one embodiment, the second oily substance is selected from one or more of palm oil, shortening, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, fractionated palm stearate, palm oil extract, palm super oil extract, palm double oil extract, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter, and cocoa butter substitute.

[0022] In one embodiment, the melting point of the intermediate protective layer is 0-10°C higher than that of the core. In one embodiment, the rubber layer has a moisture content of 2-10 wt%.

[0023] In another aspect, the present invention provides a method for preparing the three-layer seamless soft capsule described herein, comprising: completely dissolving a first oily substance at 60–85°C, adding phospholipids, stirring evenly, and then cooling to 40–60°C to obtain an intermediate layer solution.

[0024] In one implementation, the method includes:

[0025] (1) Sol: The water-soluble gelling agent and plasticizer are premixed and dispersed evenly, and then added to water under stirring. The mixture is heated and stirred at 55-85°C until the colloid is dissolved and the air bubbles are removed.

[0026] (2) Ingredients: A) Inner layer solution preparation method: Melt the second oily substance completely at 60-85℃, cool down to 40-50℃ and add the substance that is unstable in water and / or acid, stir thoroughly and remove air bubbles to obtain the inner layer solution; B) Middle layer solution preparation method: Melt the first oily substance completely at 60-85℃, add phospholipid, stir thoroughly and cool down to 40-60℃;

[0027] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer dripper for drip preparation;

[0028] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 2-10%.

[0029] In another aspect, the present invention provides the use of the three-layer seamless soft capsules described herein in food, health products or pharmaceuticals.

[0030] The beneficial effects of this invention include:

[0031] The three-layer seamless soft capsule provided by this invention can reduce the thickness unevenness and oil droplet ratio in the seamless capsule, ensuring that the product is not easily broken or leaked during production, storage and transportation. In addition, the middle protective layer can protect the core from moisture, ensuring the stability of probiotic activity or vitamins and other functional ingredients. It can be applied to food, health nutrition products and pharmaceuticals. Detailed Implementation

[0032] As used herein, the term "comprising" is synonymous with "including" or "containing" and is inclusive of endpoints or open-ended concepts, and does not exclude additional unstated elements or method steps. "Comprising" is a technical term used in the language of claims, meaning that the stated element is present, but other elements may be added and still form a construction or method within the scope of the claims. Unless otherwise indicated, "%" as used herein refers to weight percentage.

[0033] This document provides a three-layer seamless soft capsule or a formulation composition thereof, comprising a core, an intermediate protective layer enclosing the core, and a membrane layer enclosing the intermediate protective layer. Preferably, the melting point of the intermediate protective layer is 0-10°C higher than that of the core, for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9°C. The intermediate protective layer may not contain emulsifiers other than phospholipids.

[0034] The intermediate protective layer may comprise a first oily substance and phospholipids. The intermediate protective layer may comprise 279-294 parts by weight of the first oily substance and 6-21 parts by weight of phospholipids. The intermediate protective layer may comprise 279-294 parts by weight of the first oily substance, for example, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, or 290 parts by weight of the first oily substance. The intermediate protective layer may comprise 6-21 parts by weight of phospholipids, for example, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 parts by weight of phospholipids.

[0035] Phospholipids may contain phosphatidylcholine. Phosphatidylcholine may comprise 10-60 wt% of the phospholipids, for example, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, or 59 wt%.

[0036] The first oily substance can be a hardened oil or a combination of hardened oils that is solidified at room temperature (e.g., 20℃±5℃) and has a melting point of 40-60℃. The first oily substance can be selected from one or more of palm oil, shortening, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, fractionated palm stearate, palm oil extract, palm super oil extract, palm double oil extract, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter, and cocoa butter substitute. The weight ratio of phospholipids to the first oily substance in the intermediate protective layer can be 2:98-7:93. Preferably, the first oily substance is shortening and palm oil. More preferably, the ratio of shortening to palm oil is 4:6 to 9:1, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, or 8:1.

[0037] The core may contain an active substance and a second oily substance. The core may contain 0.5-100 parts by weight of the active substance, such as 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 parts by weight. The core may contain 400-500 parts by weight of the second oily substance, such as 410, 420, 430, 440, 450, 460, 470, 480, or 490 parts by weight. The second oily substance may be a hardened oil or a compound hardened oil that is solidified at room temperature (e.g., 20℃±5℃) and has a melting point of 24-64℃. The second oily substance may be selected from one or more of palm oil, shortening, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, fractionated palm stearate, palm oil extract, palm super oil extract, palm double oil extract, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter, and cocoa butter substitute. Preferably, the second oily substance is shortening: palm oil in a ratio of 4:6 to 9:1, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, or 8:1.

[0038] In this document, the active substance may be a substance that is unstable in water and / or acid. For example, a substance that is unstable in water and / or acid may be in powder form with an average particle size of 10-250 micrometers. There are no particular limitations on the types of substances that are unstable in water and / or acid, including but not limited to one or more of probiotics, vitamins, lactoferrin, and enzymes. Probiotics may include Bifidobacteria and / or lactic acid bacteria. Vitamins may include one or more of vitamin B1, vitamin B2, vitamin B12, and vitamin C.

[0039] The film layer may contain water-soluble gelling agents and plasticizers. The film layer may contain 80-320 parts by weight of water-soluble gelling agent, such as 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, or 310 parts by weight. The film layer may contain 10-125 parts by weight of plasticizer, such as 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, or 120 parts by weight. There are no particular limitations on the type of water-soluble gelling agent, including but not limited to one or more of gelatin, carrageenan, agar, gellan gum, pectin, and starch.

[0040] Water-soluble gelling agents may contain gelatin and pectin. The weight ratio of pectin to gelatin may be 1:10 to 3:10, for example, 2:10. Pectin may be selected from low-ester pectin and / or amide pectin. For example, the degree of esterification (DE) of pectin is <50%, and / or the degree of amidation (DA) of pectin is 0-25%, for example, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, or 24%.

[0041] There are no particular restrictions on the types of plasticizers, including but not limited to one or more of glycerol, sorbitol, erythritol, and maltitol. Phospholipids may be selected from one or more of soybean phospholipids, sunflower phospholipids, and egg yolk phospholipids.

[0042] There are no particular restrictions on the types of the second oily substance, including but not limited to palm oil, shortening, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, extractive palm stearate, palm oil extract, palm super oil extract, palm double oil extract, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter and cocoa butter substitute.

[0043] The formulation composition of the present invention may contain a certain amount of water to prepare the adhesive. Those skilled in the art can conventionally determine the amount of water used to prepare the adhesive, for example, the amount of water mentioned in the examples and the range of its composition.

[0044] This invention also provides a method for preparing a three-layer seamless soft capsule according to the present invention, comprising: completely dissolving a first oily substance at 60–85°C, adding phospholipids, stirring until homogeneous, and then cooling to 40–60°C to obtain an intermediate layer solution. The method may include one or more of the following:

[0045] (1) Sol: The water-soluble gelling agent and plasticizer are premixed and dispersed evenly, and then added to water under stirring. The mixture is heated and stirred at 55-85°C until the colloid is dissolved and the air bubbles are removed.

[0046] (2) Ingredients: A) Inner layer solution preparation method: Melt the second oily substance completely at 60-85℃, cool down to 40-50℃ and add the substance that is unstable in water and / or acid, stir thoroughly and remove air bubbles to obtain the inner layer solution; B) Middle layer solution preparation method: Melt the first oily substance completely at 60-85℃, add phospholipid, stir thoroughly and cool down to 40-60℃;

[0047] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer dripper for drip preparation;

[0048] (4) Drying: Dry using a rotary drum until the rubber moisture content is 2-10%, for example 3%, 4%, 5%, 6%, 7%, 8% or 9%.

[0049] Example

[0050] The embodiments of this application will be described in detail below with reference to examples. Those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products. Unless otherwise specified, all listed quantities are based on total weight and described in parts by weight. This application should not be construed as being limited to the specific embodiments described.

[0051] 1. Materials

[0052] Probiotic powder, shortening (melting point 41℃), palm oil (melting point 52℃), phospholipids, gelatin, pectin, and glycerin are all commercially available substances.

[0053] 2. Preparation method:

[0054] (1) Sol: The water-soluble gelling agent and plasticizer are premixed and dispersed evenly, and then added to water under stirring. The mixture is heated and stirred at 55-85°C until the colloid is dissolved and the air bubbles are removed.

[0055] (2) Ingredients: A) Inner layer solution preparation method: Melt the first oily substance completely at 60-85℃, cool down to 40-50℃ and add the substance that is unstable in water and / or acid, stir thoroughly and remove air bubbles to obtain the inner layer solution; B) Middle layer solution preparation method: Melt the second oily substance completely at 60-85℃, add phospholipid, stir thoroughly and then cool down to 40-60℃;

[0056] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer dripper for drip preparation;

[0057] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 2-10%.

[0058] 3. Evaluation Indicators

[0059] (1) Oil droplet diameter ratio: Observation was performed using an optical microscope at 4*10x magnification, and measurements were taken using LISSCAPTURE software. The oil droplet diameter and the thickness of the rubber at the location of the oil droplet were recorded. The formula for calculating the oil droplet diameter ratio is as follows:

[0060] Oil droplet diameter percentage (X) = Oil droplet diameter (A) / Rubber thickness at the location of the oil droplet (B)

[0061] (2) Number of oil droplets: The number of oil droplets on the capsule skin was recorded by observing with an optical microscope at 4*10x magnification and measuring with LISSCAPTURE software.

[0062] (3) Determination of appearance deformation pass rate: The optical microscope was used to observe the capsules at 4*10x magnification, and the shortest and longest diameters of the capsules were measured using LISSCAPTURE software.

[0063] Capsule deformation (Y) = Shortest diameter of capsule (C) / Longest diameter of capsule (D)

[0064] Five random sampling points (top, middle, bottom, left, and right) were taken from the capsule pile, with 100 capsules sampled at each point. The proportion of capsules with a deformation greater than 0.9 was observed and recorded, and the average value of the five batches of samples was taken.

[0065] The appearance pass rate (P) of the capsules = the number of capsules with a deformation greater than 0.9 mm / the total number of capsules sampled.

[0066] (4) Rupture force of seamless soft capsule: Using a physical property tester, the rupture force mode was selected, and the force (g) generated when the 3-layer seamless soft capsule ruptured was recorded.

[0067] To better illustrate the effects of the present invention, the following performance indicators are used for evaluation:

[0068] Table 1: Oil droplet percentage, bursting force, and appearance pass rate of seamless soft capsules

[0069]

[0070]

[0071] Examples 1-6: Preparation and testing of three-layer seamless soft capsules 1-6

[0072] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in Tables 2-4 below, and then tested and scored. The test results are shown in Table 4.

[0073] Element:

[0074] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0075] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0076] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0077] Preparation method:

[0078] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0079] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0080] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0081] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0082] Table 2: Formulations of the film layer in Examples 1-6 and Comparative Examples 1-4

[0083] Coating layer formulation composition Weight in grams (g) gelatin 160 glycerin 24 pectin 24 water 592

[0084] Table 3: Core formulations of Examples 1-6 and Comparative Examples 1-4

[0085] Core Formula Composition Grams Probiotic powder 50 Compound hardening oil A 450

[0086] Table 4: Formulations of the intermediate protective layer in Examples 1-6 and Comparative Examples 1-4 (In the formulation of the intermediate protective layer, the phospholipid contains 40 wt% phosphatidylcholine).

[0087]

[0088] As shown in Table 4, in Examples 1-6, with a suitable ratio of phospholipid to hardened oil, the oil droplet ratio, breaking force, and capsule appearance qualification rate of the product were significantly improved, resulting in a higher overall score and a significant improvement in the overall product condition. Comparative Example 1 shows the overall capsule condition when the phospholipid to hardened oil ratio was 0:300, characterized by a high oil droplet ratio and, under low breaking force, the capsules were essentially broken. Comparative Examples 2-4 are outside the scope of this invention in terms of phospholipid to hardened oil ratios, specifically reflected in the generally lower oil droplet ratio, breaking force, and capsule appearance qualification rate scores in Comparative Example 2. In Comparative Examples 3-4, although the oil droplet ratio and breaking force were better, the capsule appearance qualification rate was significantly lower.

[0089] Examples 7-12: Preparation and Testing of Three-Layer Seamless Soft Capsules 7-12

[0090] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in Tables 5-7 below, and then tested and scored. The test results are shown in Table 8.

[0091] Element:

[0092] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0093] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0094] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0095] Preparation method:

[0096] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0097] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0098] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0099] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0100] Table 5: Formulations of the film layer in Examples 7-12 and Comparative Examples 5-7

[0101] Coating layer formulation composition Grams gelatin 160 glycerin 24 pectin 24 water 592

[0102] Table 6: Intermediate Layer Formulations of Examples 7-12 and Comparative Examples 5-7

[0103] Intermediate protective layer formulation composition Grams Compound hardened oil B 288 Phospholipids 12

[0104] Table 7: Formulations of the film layer in Examples 7-12 and Comparative Examples 5-7

[0105] Core Formula Composition Grams Probiotic powder 50 Compound hardening oil A 450

[0106] Table 8: Overall Evaluation of Examples 7-12 and Comparative Examples 5-7

[0107]

[0108]

[0109] As shown in Examples 7-12, when the content of phosphatidylcholine is in the range of 10-60 wt%, the proportion of oil droplets, the number of oil droplets, and the breaking force of the capsules are significantly improved. Comparative Examples 5-7 are not within the phosphatidylcholine ratio range of the present invention, which is reflected in the higher proportion of oil droplet diameter and the greater number of oil droplets. Comparative Examples 6 and 7 are reflected in the reduced breaking force and poor appearance qualification rate.

[0110] Compare with Example 8-11

[0111] Seamless soft capsules were prepared using the ingredients and contents listed in Tables 9-11 below, following the preparation method described below. The capsules were then tested and scored. The results are shown in Table 11.

[0112] Element:

[0113] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0114] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0115] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0116] Preparation method:

[0117] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0118] (2) Ingredients: A) Inner layer solution preparation method: melt the compound hardened oil A completely at 85°C, add the formula amount of phospholipid, stir evenly, cool down to 45°C, add bacterial powder, stir evenly, and remove air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: melt the hardened oil completely at 85°C, cool to 45°C for later use.

[0119] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0120] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0121] Table 9: Coatings of Comparative Examples 8-11

[0122]

[0123]

[0124] Table 10: Formulation of intermediate protective layer in Comparative Examples 8-11

[0125] Intermediate protective layer formulation composition Grams Compound hardened oil B 300

[0126] Table 11: Core formulation of Comparative Examples 8-11 (The core formulation contains 40 wt% phosphatidylcholine in the phospholipids)

[0127]

[0128] Although adding phospholipids can theoretically emulsify the contents and improve their uniformity, as shown in the control example, adding phospholipids to the core, regardless of the proportion, fails to improve the capsule's formation. This confirms that adding phospholipids to the intermediate protective layer can provide a stabilizing balance between the inner and outer layers, thus improving capsule quality. Adding phospholipids to the core only maintains the core's stability but cannot guarantee the stability of both the core and the intermediate layer. Adding phospholipids to the intermediate layer ensures its stability and simultaneously stabilizes both the core and the intermediate layer.

[0129] Compare with Examples 12-15

[0130] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in Tables 12-14 below, and then tested and scored. The test results are shown in Table 14.

[0131] Element:

[0132] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0133] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0134] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0135] Preparation method:

[0136] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0137] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0138] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0139] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0140] Table 12: Coatings of Comparative Examples 12-15

[0141] Coating layer formulation composition Grams gelatin 160 glycerin 24 pectin 24 water 592

[0142] Table 13: Core formulations of Comparative Examples 12-15

[0143] Core Formula Composition Grams Probiotic powder 50 Compound hardening oil A 450

[0144] The formulation and preparation process of the intermediate protective layer are modified as follows: the compound hardened oil B is completely melted at 85°C, the formula amount of caprylic / capric glyceride or monoglyceride is added, and after stirring evenly, the temperature is lowered to 45°C for later use.

[0145] Table 14: Formulation of intermediate protective layer in Comparative Examples 12-15

[0146]

[0147] As shown in Table 14 (Comparative Examples 12-15), when other substances with emulsifying properties were added to replace phospholipids, although the physical properties of the intermediate layer could be significantly changed, none of them could positively improve the quality of the capsules. As shown in Comparative Examples 12-13, with the increase of caprylic / capric triglyceride content, the percentage of oil droplet diameter and the number of oil droplets in the capsules were significantly lower. In Comparative Examples 14-15, with the increase of monoglyceride content, the bursting force and the appearance qualification rate of the capsules were significantly lower.

[0148] Examples 13-14: Preparation and Testing of Three-Layer Seamless Soft Capsules 13-14

[0149] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in the table below, and then tested and scored. The results are shown in Table 17.

[0150] Element:

[0151] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0152] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0153] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0154] Preparation method:

[0155] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0156] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0157] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0158] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0159] Table 15: Formulation of the film layer in Examples 13-14

[0160] Coating layer formulation composition Grams gelatin 160 glycerin 24 pectin 24 water 592

[0161] Table 16: Intermediate Protective Layer Formulations for Examples 13-14 (In the intermediate protective layer formulations, the phosphatidylcholine content in the phospholipids is 40 wt%)

[0162]

[0163]

[0164] Table 17: Core formulations of Examples 13-14

[0165] Core Formula Composition and Overall Evaluation Example 13 Example 14 Probiotics (grams) 0.5 100 Compound hardened oil A (grams) 499.5 400 Oil droplet diameter percentage 5 5 Number of oil droplets 5 4 Fracture force 5 4 Capsule appearance pass rate 5 4 Overall evaluation 5 4.3

[0166] As shown in Table 17 Examples 13-14, in addition to the probiotic powder in the above examples, other probiotics, vitamins (such as vitamin B1, vitamin B2, vitamin B12 or vitamin C), lactoferrin and enzymes that are unstable in water and / or acid are also applicable within the addition range of the above examples.

[0167] Examples 15-18: Preparation and Testing of Three-Layer Seamless Soft Capsules 15-18

[0168] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in the table below, and then tested and scored. The results are shown in Table 20.

[0169] Element:

[0170] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0171] Intermediate protective layer: compound hardened oil B (shortening: palm oil = 1:1), phospholipids;

[0172] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0173] Preparation method:

[0174] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0175] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0176] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0177] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0178] Table 18: Formulation of intermediate protective layer in Examples 15-18

[0179] Intermediate protective layer formulation composition Grams Compound hardened oil B 288 Phospholipids 12

[0180] Table 19: Core formulations of Examples 15-18

[0181] Core Formula Composition Grams Probiotic powder 50 Compound hardening oil A 450

[0182] Table 20: Formulation of the film layer in Examples 15-18

[0183] Coating layer formulation composition and overall evaluation Example 15 Example 16 Example 17 Example 18 Gelatin (grams) 240 240 80 80 Pectin (in grams) 24 72 8 24 Glycerin (in grams) 26.4 124.8 35.2 10.4 Water (grams) 509.6 363.2 676.8 685.6 Oil droplet diameter percentage 5 5 5 5 Number of oil droplets 5 5 5 5 Fracture force 5 5 4 4 Capsule appearance pass rate 4 4 5 5 Overall evaluation 4.8 4.8 4.75 4.75

[0184] As shown in Examples 15-18, when the weight parts of gelatin are 80-240, the weight parts of pectin are 8-72, and the plasticizer is 10-125, the prepared capsules all have high molding quality.

[0185] In the three-layer structure of the capsule of the present invention, by using phospholipids with a specific phosphatidylcholine content, a specific combination of phospholipid hardening oil, and specifying the compounding positions of phospholipids and hardening oils, and preferably the compounding ratio of the first oily substance, the resulting capsule has good mechanical strength and good appearance quality. It is significantly superior to the prior art in terms of oil droplet ratio, rupture force, and capsule appearance qualification rate, and fully meets the requirements for the industrialization of three-layer seamless soft capsules. It can be used as an alternative to seamless soft capsule technology.

[0186] Examples 19-24, Comparative Examples 16-20: Preparation and Testing of Three-Layer Seamless Soft Capsules

[0187] Seamless soft capsules were prepared according to the following preparation method using the ingredients and contents listed in the table below, and then tested and scored. The results are shown in Table 23.

[0188] Element:

[0189] Core ingredients: Probiotic powder and compound hardened oil A (shortening: palm oil = 1:1);

[0190] Intermediate protective layer: compounded hardened oil B (shortening: palm oil = different proportions, see the examples and comparative examples below for details), phospholipids;

[0191] The outer membrane consists of gelatin, pectin, glycerin, and water.

[0192] Preparation method:

[0193] (1) Sol: A) First, premix and disperse pectin, gelatin and plasticizer (glycerin) evenly, add an appropriate amount of water while stirring, and heat and stir at 70°C until the colloid is dissolved; B) Remove the air bubbles to obtain the gel solution of the film layer.

[0194] (2) Ingredients: A) Inner layer solution preparation method: Melt the compound hardened oil A completely at 85℃, cool it down to 45℃, add the bacterial powder, stir thoroughly and remove the air bubbles to obtain the inner layer solution; B) Intermediate layer solution preparation method: Melt the compound hardened oil B completely at 85℃, add the formula amount of phospholipid, stir thoroughly, and then cool it down to 45℃ for later use.

[0195] (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer drip head for drip preparation.

[0196] (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 5%.

[0197] Table 21: Formulations of the film layer in Examples 19-24 and Comparative Examples 16-20

[0198] Coating composition Grams gelatin 160 glycerin 24 pectin 24 water 592

[0199] Table 22: Core formulations of Examples 19-24 and Comparative Examples 16-20

[0200] Core Formula Composition Grams Probiotic powder 50 Compound hardening oil A 450

[0201] Table 23: Overall Evaluation of Examples 19-24 and Control Examples 16-20

[0202]

[0203]

[0204] As shown in Examples 19-24 and Comparative Examples 16-20, when the first oily substance is shortening or the ratio of shortening to palm oil is within the range of 4:6 to 9:1, which is within the scope of protection of this invention, the overall evaluation score of the capsules is higher, and the overall quality of the capsules is better. Comparative Examples 16-20 are not within the scope of protection of this invention, mainly manifested in poor capsule appearance qualification rate and low breaking strength.

[0205] Although the invention has been described with reference to illustrative embodiments, those skilled in the art will understand that various other changes, omissions, and / or additions can be made without departing from the spirit and scope of the invention, and that elements of the described embodiments can be substituted with substantially equivalents. Furthermore, many modifications can be made without departing from the scope of the invention to adapt particular situations or materials to the teachings of the invention. Therefore, this invention is not intended to be limited to the specific embodiments disclosed for carrying out the invention, but rather is intended to encompass all embodiments falling within the scope of the appended claims.

Claims

1. A three-layer seamless soft capsule, characterized in that... It includes a core, an intermediate protective layer surrounding the core, and a membrane layer surrounding the intermediate protective layer. The intermediate protective layer contains 279-294 parts by weight of a first oily substance and 6-21 parts by weight of phospholipids. The phospholipids contain 10-60 wt% phosphatidylcholine. The first oily substance is a hardened oil or a combination of hardened oils that is solidified at room temperature and has a melting point of 40-60°C. The first oily substance is a combination of shortening and palm oil in a ratio of 4:6 to 9:

1. The core contains 0.5-100 parts by weight of active substance and 400-500 parts by weight of second oily substance. The second oily substance is a hardened oil or compound hardened oil that is solidified at room temperature and has a melting point of 24-64℃. and The film layer contains 80-320 parts by weight of water-soluble gelling agent and 10-125 parts by weight of plasticizer.

2. The three-layer seamless soft capsule according to claim 1, characterized in that... Active substances are substances that are unstable in the presence of water and acid.

3. The three-layer seamless soft capsule according to claim 2, characterized in that... Substances that are unstable in water and acid are in powder form, with an average particle size of 10-250 micrometers.

4. The three-layer seamless soft capsule according to claim 2, characterized in that... The substance that is unstable in water and acid is one or more of the following: probiotics, vitamins, lactoferrin, and enzymes.

5. The three-layer seamless soft capsule according to claim 4, characterized in that... The probiotics are Bifidobacteria and / or lactic acid bacteria.

6. The three-layer seamless soft capsule according to claim 4, characterized in that... The vitamins mentioned are one or more of vitamin B1, vitamin B2, vitamin B12, and vitamin C.

7. The three-layer seamless soft capsule according to claim 1, characterized in that... The water-soluble gelling agent is one or more of gelatin, carrageenan, agar, gellan gum, pectin, and starch.

8. The three-layer seamless soft capsule according to claim 7, characterized in that... The water-soluble gelling agents are gelatin and pectin, with the weight ratio of pectin to gelatin being 1:10 to 3:

10.

9. The three-layer seamless soft capsule according to claim 8, characterized in that... The pectin is selected from low-ester pectin and / or amide pectin.

10. The three-layer seamless soft capsule according to claim 8, characterized in that... The degree of esterification (DE) of pectin is less than 50%.

11. The three-layer seamless soft capsule according to claim 8, characterized in that... The degree of amidation (DA) of pectin is 0-25%.

12. The three-layer seamless soft capsule according to claim 1, characterized in that... The plasticizer is selected from one or more of glycerol, sorbitol, erythritol, and maltitol.

13. The three-layer seamless soft capsule according to any one of claims 1-12, characterized in that... Phospholipids are selected from one or more of soybean phospholipids, sunflower phospholipids, and egg yolk phospholipids.

14. The three-layer seamless soft capsule according to claim 1, characterized in that... The second oily substance is selected from one or more of the following: palm oil, coconut oil, hydrogenated soybean oil, hydrogenated palm oil, highly hydrogenated palm oil, hydrogenated coconut oil, extractive palm stearate, palm oil essence, palm super oil essence, palm double oil essence, palm middle fraction, palm oil transesterified fat, palm oil transesterified fat, cocoa butter, and cocoa butter substitute.

15. The three-layer seamless soft capsule according to claim 1, characterized in that... The second oily substance is shortening.

16. The three-layer seamless soft capsule according to claim 1, characterized in that... The second oily substance is shortening or a combination of shortening and palm oil in a ratio of 4:6 to 9:

1.

17. The three-layer seamless soft capsule according to any one of claims 1-12 and 14-16, characterized in that... The melting point of the intermediate protective layer is 0-10°C higher than that of the core, and / or the moisture content of the rubber is 2-10wt%.

18. The three-layer seamless soft capsule according to claim 14, characterized in that... The melting point of the intermediate protective layer is 0-10°C higher than that of the core, and / or the moisture content of the rubber is 2-10wt%.

19. A method for preparing a three-layer seamless soft capsule according to any one of claims 1-18, characterized in that... include: The first oily substance is completely dissolved at 60~85℃, phospholipids are added, and after stirring evenly, the temperature is lowered to 40~60℃ to obtain the intermediate layer solution.

20. The method according to claim 19, characterized in that... The method includes: (1) Sol: The water-soluble gelling agent and plasticizer are premixed and dispersed evenly, and then added to water under stirring. The mixture is heated and stirred at 55~85℃ until the colloid is dissolved and the air bubbles are removed. (2) Ingredients: A) Inner layer solution preparation method: Melt the second oily substance completely at 60~85℃, cool down to 40~50℃, add the substance that is unstable in water and acid, stir thoroughly and remove air bubbles to obtain the inner layer solution; B) Middle layer solution preparation method: Melt the first oily substance completely at 60~85℃, add phospholipid, stir thoroughly and cool down to 40~60℃; (3) Drip preparation: Use a seamless soft capsule drip preparation device and select a 3-layer dripper for drip preparation; (4) Drying: Use a rotary drum to dry until the rubber moisture content is reduced to 2-10%.

21. Use of the three-layer seamless soft capsule according to any one of claims 1-18 in the preparation of food.

22. Use of the three-layer seamless soft capsule according to any one of claims 1-18 in the preparation of health products.

23. Use of the three-layer seamless soft capsule according to any one of claims 1-18 in the preparation of a pharmaceutical product.

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