WO2023273254A1 - 软胶囊囊壳和软胶囊 - Google Patents

软胶囊囊壳和软胶囊 Download PDF

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Publication number
WO2023273254A1
WO2023273254A1 PCT/CN2021/142079 CN2021142079W WO2023273254A1 WO 2023273254 A1 WO2023273254 A1 WO 2023273254A1 CN 2021142079 W CN2021142079 W CN 2021142079W WO 2023273254 A1 WO2023273254 A1 WO 2023273254A1
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WIPO (PCT)
Prior art keywords
starch
gelling agent
soft capsule
gum
capsule shell
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PCT/CN2021/142079
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English (en)
French (fr)
Inventor
李绪发
陈洁伟
Original Assignee
仙乐健康科技股份有限公司
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Application filed by 仙乐健康科技股份有限公司 filed Critical 仙乐健康科技股份有限公司
Priority to EP21918102.1A priority Critical patent/EP4134072A4/en
Priority to CA3167605A priority patent/CA3167605A1/en
Priority to AU2021416461A priority patent/AU2021416461B2/en
Priority to JP2022532719A priority patent/JP7443521B2/ja
Publication of WO2023273254A1 publication Critical patent/WO2023273254A1/zh

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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
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • 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

Definitions

  • the application relates to the field of food or medicine, in particular to a soft capsule shell and a soft capsule.
  • Soft capsules are widely used in medicine, food, cosmetics and other fields. Because gelatin has excellent film-forming properties and mechanical strength, it is widely used as a traditional soft capsule material. However, due to the characteristics of gelatin itself, there are many quality defects in the application process. For example, gelatin molecules can produce a layer of toughness and elasticity on the surface of gelatin soft capsules through self-oxidation or cross-linking reactions with functional groups such as aldehyde groups.
  • the water-insoluble surface film of the film blocks the release of drugs, resulting in unqualified disintegration of soft capsules; coupled with religion, vegetarianism, and events such as mad cow disease, foot-and-mouth disease and poisonous capsules appearing in succession around the world, people have been trying to develop Research on substitutes of gelatin and its preparation for soft capsules.
  • Japanese Patent No. JP2007153851A proposes a film composition of non-animal source soft capsules obtained by mixing water, starch and natural gellan gum.
  • European Patent No. EP2815745A1 proposes a soft capsule comprising high acyl gellan gum, at least one starch and at least one plasticizer and a preparation method.
  • the gel formed by high acyl gellan gum is soft and elastic, and the rubber formed when it is combined with starch has weak strength, and the cracks are thinner when the pellets are formed, the cracking force is low, and oil leakage is easy.
  • Chinese Patent No. CN100528950C proposes a mixture of different acyl gellan gum and starch, comprising: a. high acyl gellan gum; b.
  • the produced film has high modulus, excellent strength and extensibility, and the produced soft capsule has good sealing performance.
  • High-acyl gellan gum and low-acyl gellan gum can be used as compound gelling agents, which can improve the strength and toughness of the rubber to a certain extent, but the viscosity of the glue is high, and it is easy to pre-gel during transportation, resulting in rubber defects or unevenness.
  • the prepared soft capsules The cracks are thin and easy to leak oil.
  • the present application is based in part on the inventors' discovery that starch compositions comprising a ratio of gellan gum to starch in a specific molecular weight range are superior to those not in this range in terms of the combined effect of forming soft capsule shells, disintegrating in water and gastric juices
  • the starch composition in it is found that the above-mentioned effects are related to the average particle size and content of the starch granules in the capsule shell, that is, the content of starch granules in the capsule shell of the soft capsule that realizes the effect of the present application is 9wt%-40wt%, and the starch granules are on average Starch granules with a particle size ⁇ 10 ⁇ m.
  • a soft capsule shell which is prepared from a film-forming composition comprising 2wt%-5wt% of a first gelling agent, 10wt%-35wt% of a plasticizer, 18wt% -35wt% easily gelatinizable starch, 4wt%-17wt% granular starch and 35wt%-55wt% water, wherein the first gelling agent is gellan gum, the gellan gum has 5.0 ⁇ 10 5 ⁇ 8.0 ⁇ 10 6 g/ The weight average molecular weight of mol and/or the molecular weight distribution coefficient of 1.0 ⁇ 6.0, the content of starch granules in the soft capsule shell is 9wt%-40wt%, and the starch granules are starch granules with an average particle size ⁇ 10 ⁇ m; the soft capsule
  • the capsule shell is a soft capsule shell that disintegrates in the stomach; easily gelatinized starch is selected from waxy corn starch, tapioca starch, hydroxypropy
  • gellan gum has a weight average molecular weight of 5.5 ⁇ 10 5 to 6.6 ⁇ 10 6 g/mol, preferably 5.5 ⁇ 10 5 to 4.7 ⁇ 10 6 g/mol, and/or gellan gum has a weight average molecular weight of 1.0 to Molecular weight distribution coefficient of 4.0.
  • the weight ratio of gellan gum to the total amount of starch is 0.05-0.2, preferably the weight ratio of gellan gum to the total amount of starch is 0.09-0.2; preferably, the content of gellan gum is 2.5wt% -5 wt%.
  • the content of plasticizer is 15wt% ⁇ 25wt%;
  • plasticizer is selected from glycerol, sorbitol, maltitol, erythritol, xylitol, crystalline fructose, trehalose Or one or a combination of glucose.
  • the film-forming composition further comprises 0.2wt%-10wt% of a second gelling agent, preferably, the second gelling agent is selected from carrageenan, agar, sodium alginate, pectin, One or a combination of pullulan, konjac gum, xanthan gum, locust bean gum, guar gum, flaxseed gum, curdlan gum, or tamarind gum.
  • the second gelling agent is selected from carrageenan, agar, sodium alginate, pectin, One or a combination of pullulan, konjac gum, xanthan gum, locust bean gum, guar gum, flaxseed gum, curdlan gum, or tamarind gum.
  • the easily gelatinized starch is selected from one or both of hydroxypropyl starch or oxidized hydroxypropyl starch
  • the granular starch is selected from acid-treated starch, acetate starch, hydroxypropyl distarch phosphate, One or a combination of starch phosphate, acetylated distarch phosphate, acetylated distarch adipate or acetylated oxidized starch.
  • the soft capsule shell is prepared by the following method, the method comprising a) adding the first gelling agent to the plasticizer, stirring evenly, then adding it to water, and heating the gelling agent at 60-98°C heating and stirring until the first gelling agent is dissolved; b) adding the starch, and heating and stirring at 60-98°C until the starch is dissolved; c) removing air bubbles to obtain the glue; and d) pelletizing and drying; preferably wherein The a) also includes adding a second gelling agent, and the a) is adding the first gelling agent and the second gelling agent to the plasticizer, stirring evenly, then adding it to water, and Heat and stir at 60-98° C. until the first gelling agent and the second gelling agent are dissolved.
  • the present application provides a soft capsule comprising the soft capsule shell of the present application and a filling.
  • the present application provides the application of the soft capsule shell or soft capsule of the present application in food, nutraceutical food and medicine.
  • the application provides the use of a film-forming composition to prepare soft capsules, wherein the film-forming composition comprises 2wt%-5wt% of the first gelling agent, 10wt%-35wt% plasticizer, 18wt%- 35wt% easily gelatinizable starch, 4wt%-17wt% granular starch and 35wt%-55wt% water, wherein the first gelling agent is gellan gum, and the gellan gum has 5.0 ⁇ 10 5 ⁇ 8.0 ⁇ 10 6 g/mol weight-average molecular weight and/or molecular weight distribution coefficient of 1.0 to 6.0, the content of starch granules in the soft capsule shell is 9wt%-40wt%, and the starch granules are starch granules with an average particle size ⁇ 10 ⁇ m; the soft capsule capsule
  • the shell is a soft capsule shell that disintegrates in the stomach; wherein the easily gelatinized starch is selected from waxy corn starch, tapioca starch,
  • granular starch selected from pea starch, corn starch, potato starch, acid-treated starch, acetate starch, hydroxypropyl distarch phosphate, starch phosphate, acetylated distarch phosphate, pregelatinized starch, acetylated One or a combination of distarch adipate or acetylated oxidized starch.
  • gellan gum has a weight average molecular weight of 5.5 ⁇ 10 5 to 6.6 ⁇ 10 6 g/mol, preferably 5.5 ⁇ 10 5 to 4.7 ⁇ 10 6 g/mol, and/or gellan gum has a weight average molecular weight of 1.0 to Molecular weight distribution coefficient of 4.0.
  • the weight ratio of gellan gum to the total amount of starch is 0.05-0.2, preferably the weight ratio of gellan gum to the total amount of starch is 0.09-0.2; preferably, the content of gellan gum is 2.5wt% -5 wt%.
  • the content of plasticizer is 15wt% ⁇ 25wt%;
  • plasticizer is selected from glycerol, sorbitol, maltitol, erythritol, xylitol, crystalline fructose, trehalose Or one or a combination of glucose.
  • the film-forming composition further comprises 0.2wt%-10wt% of a second gelling agent, preferably, the second gelling agent is selected from the group consisting of carrageenan, agar, sodium alginate, pectin, and propellant One or a combination of ranan gum, konjac gum, xanthan gum, locust bean gum, guar gum, flaxseed gum, curdlan gum, or tamarind gum.
  • the easily gelatinized starch is selected from one or both of hydroxypropyl starch or oxidized hydroxypropyl starch
  • the granular starch is selected from acid-treated starch, acetate starch, hydroxypropyl distarch phosphate, One or a combination of starch phosphate, acetylated distarch phosphate, acetylated distarch adipate or acetylated oxidized starch.
  • the soft capsule shell is prepared by the following method, the method comprising a) adding the first gelling agent to the plasticizer, stirring evenly, then adding it to water, and heating the gelling agent at 60-98°C heating and stirring until the first gelling agent dissolves; b) adding the starch, and heating and stirring at 60-98°C until the starch dissolves; c) removing air bubbles to obtain glue; and d) pelletizing and drying.
  • the a) also includes adding a second gelling agent, and the a) is adding the first gelling agent and the second gelling agent to the plasticizer, stirring evenly, Then add it into water, and heat and stir at 60-98° C. until the first gelling agent and the second gelling agent are dissolved.
  • the film-forming composition or soft capsule shell of the present application does not contain gelatin.
  • the film-forming composition, soft capsule shell or soft capsule of the present application in food, nutraceuticals, medicines and cosmetics.
  • the food, nutraceutical or pharmaceutical is gastric or gastric.
  • the effect of gastric disintegration can be verified in simulated gastric juice.
  • the present application provides a method of gastric delivery using the soft capsule shell or soft capsule of the present application.
  • the present application also provides the use of the soft capsule shell or soft capsule of the present application in preparing gastric medicine.
  • pectin should not be added to soft capsules that disintegrate in the stomach before this application, as indicated in Table 6.
  • the present application overcomes this cognitive bias by achieving excellent gastric disintegration in the presence of pectin through proper formulation and selection of gellan gum.
  • the present application provides a soft capsule shell, which is prepared from the film-forming composition of the present application.
  • the film-forming composition of the present application comprises a first gelling agent.
  • the content of the first gelling agent may be 2wt%-5wt%, such as 2wt%, 2.5wt%, 3wt%, 3.5wt%, 4wt%, 4.5wt%, 5wt%.
  • the first gelling agent may be gellan gum.
  • Gellan gum may have a weight average molecular weight of 5.0 ⁇ 10 5 to 8.0 ⁇ 10 6 g/mol, preferably 5.5 ⁇ 10 5 to 6.6 ⁇ 10 6 g/mol, preferably 5.5 ⁇ 10 5 to 4.7 ⁇ 10 6 , for example 6 ⁇ 10 5 g/mol, 9 ⁇ 10 5 g/mol, 1.5 ⁇ 10 6 g/mol, 2 ⁇ 10 6 g/mol, 2.5 ⁇ 10 6 g/mol, 3 ⁇ 10 6 g/mol, 4 ⁇ 10 6 g/mol, 5 ⁇ 10 6 g/mol or 6 ⁇ 10 6 g/mol.
  • Gellan gum may have a molecular weight distribution coefficient of 1.0-6.0, preferably 1.0-4.0, eg 2, 2.5 or 3.
  • the film-forming composition includes a plasticizer.
  • the content of plasticizer can be 10wt%-35wt%, such as 13wt%, 14wt%, 15wt%, 16wt%, 20wt%, 25wt% or 30wt%.
  • the plasticizer can be selected from one or a combination of glycerin, sorbitol, maltitol, erythritol, xylitol, crystalline fructose, trehalose or glucose.
  • the film forming composition comprises 18wt% - 35wt% readily gelatinizable starch and 4wt% - 17wt% granular starch.
  • the content of easily gelatinizable starch can be 20wt%-30wt%, such as 20wt%, 25wt% or 30wt%.
  • the content of granular starch may be 4wt% - 17wt%, such as 4wt%, 5wt%, 7wt%, 8wt%, 10wt%, 14wt% or 16wt%.
  • Easy-to-gelatinize starch refers to starch whose granules are broken or dissolved after starch gelatinization is complete; granular starch refers to starch whose granules are not broken after absorbing water and swelling.
  • the easily gelatinizable starch includes one or a combination of waxy corn starch, tapioca starch, hydroxypropyl starch, oxidized starch, oxidized hydroxypropyl starch, dextrin or maltodextrin.
  • Granular starches include pea starch, corn starch, potato starch, acid-treated starch, acetate starch, hydroxypropyl distarch phosphate, starch phosphate, acetylated distarch phosphate, pregelatinized starch, acetylated distarch phosphate One or a combination of acid ester or acetylated oxidized starch.
  • the weight ratio of gellan gum to the total amount of starch is 0.05-0.2. In one embodiment, the weight ratio of gellan gum to the total amount of starch is 0.07-0.2. For example, the weight ratio of gellan gum to the total amount of starch is 0.05, 0.07, 0.09, 0.1, 0.13, 0.16 or 0.2.
  • the film-forming composition contains water.
  • the content of water may be 35wt%-55wt%, such as 40wt%, 45wt%, 50wt% or 55wt%.
  • the film-forming composition may also comprise a second gelling agent.
  • the content of the second gelling agent can be 0.2wt%-10wt%, such as 0.25wt%, 1wt%, 2wt%, 3wt%, 4wt%, 5wt%, 6wt%, 7wt%, 8wt% or 9wt%.
  • the second gelling agent is selected from carrageenan, agar, sodium alginate, pectin, pullulan, konjac gum, xanthan gum, locust bean gum, guar gum, linseed gum, curdlan gum or tamarind One or a combination of glues.
  • the present application also provides a soft capsule shell made from the film-forming composition of the present application.
  • the state of starch in the soft capsule shell is granular starch (average size of starch granules ⁇ 10 ⁇ m), granulated starch (average size of starch granules ⁇ 10 ⁇ m) or fragments of broken starch granules, wherein the content of granular starch is 9wt%-40wt% of the total amount of the soft capsule shell, such as 10wt%, 15wt%, 20wt%, 25wt%, 30wt% or 35wt%.
  • the soft capsule shell of the present application is a soft capsule shell that disintegrates in the stomach. The inventors found that the starch granules in the soft capsule shell are related to the gastric disintegration effect of the soft capsule shell.
  • the present application provides a soft capsule, which comprises the soft capsule shell and filler of the present application.
  • Fillers can include various animal and vegetable oils, or suspensions, emulsions, semi-solids prepared from various solid functional ingredients and suitable auxiliary materials for soft capsules, or solid preparations (such as granules) made from solid functional ingredients and suitable auxiliary materials. , microcapsules, powder, plain tablets, capsules) or a combination.
  • the present application also provides a method for preparing the soft capsule shell of the present application, which includes a) adding the first gelling agent to the plasticizer, stirring evenly, then adding it to water, and heating and stirring at 60-98°C until the first gelling agent is dissolved; b) adding the starch, and heating and stirring at 60-98° C. until the starch dissolves; c) removing air bubbles to obtain the glue; and d) pelletizing and drying.
  • the a) also includes adding a second gelling agent, and the a) is adding the first gelling agent and the second gelling agent to the plasticizer, stirring evenly, Then add it into water, and heat and stir at 60-98° C. until the first gelling agent and the second gelling agent are dissolved.
  • Pill pressing can be carried out as follows: using a soft capsule production line, the glue is transported to the plastic box of the soft capsule filling machine, the glue is cooled on the surface of the drum to form a rubber skin, and the filling is compressed and molded, and can be further shaped in the tumbler . Drying can be carried out as follows: the shaped or shaped capsules are further dried, preferably until the water content of the capsule is 8-25%.
  • the application also provides the starch film-forming composition of the application, the soft capsule shell or the application of the soft capsule in food, nutraceuticals, medicine and cosmetics.
  • the film-forming composition of the present application through the use of gellan gum with specific molecular weight and distribution, is combined with starch within a certain range, and the film-forming has good mechanical strength and toughness. It is used for soft capsules in rubber strength, toughness and molding viscosity. In terms of combination, it is obviously superior to the existing technology, fully meets the requirements of industrial production of soft capsules, and can meet the requirements of disintegration and rupture in medium water and artificial gastric juice, and can be used as an alternative to soft capsule technology.
  • Starch granule content Dissolve 100 mg of dry film or dried soft capsule skin with 15 g of deionized water at 75°C for 30 minutes, stir several times during this period to completely dissolve the capsule skin, and then dissolve the dissolved soft capsule The turbid liquid of the capsule skin is centrifuged at 4000rpm for 15 minutes. After centrifugation under these conditions, the granular starch is deposited in the bottom sediment, and the upper liquid is removed. After the bottom sediment is fully dried, the content of the starch granules is represented by the sediment content. The proportion of mass in the cyst skin.
  • Rubber strength (F) and toughness index (T) use a physical property tester, select the spherical probe and puncture mode, test the speed of 1.0mm/s, record the rubber breaking force, the greater the breaking force, the better the rubber strength; the rubber is broken The corresponding rupture distance (mm), the larger the rupture distance, the better the toughness of the rubber.
  • Gap bonding index cut open the capsule on the non-crack, squeeze to empty the contents, then keep perpendicular to the gap and cut a ring with two gaps in the middle, place the ring on the glass slide, Make the two gaps perpendicular to the glass slide, measure the thickness of the two gaps and the thickness of the capsule shell under a microscope, and calculate the ratio P (%) of the thickness of the thinnest gap to the thickness of the capsule shell.
  • the two indicators of rubber strength and toughness are ⁇ 3 points respectively and the gap adhesion index is ⁇ 2 points, and the comprehensive evaluation must be ⁇ 2.4 to meet the industrial production of soft capsules.
  • Gellan gum is a microbial metabolic gum.
  • the molecular weight and distribution of gellan gum produced by different process conditions are different, which is reflected in the rheological properties and gel properties of gellan gum.
  • the weight-average molecular weight (Mw) and molecular weight dispersion coefficient (Mw/Mn) of gellan gum were studied by using SEC/MALLS (Size Exclusion Chromatography/Multi-angle Laser Scattering):
  • Gellan gum E weight average molecular weight (Mw): 4.672 ⁇ 10 6 ⁇ 4.515%, molecular weight distribution coefficient (Mw/Mn): 2.419 ⁇ 5.251%)
  • Gellan gum I weight average molecular weight (Mw): 1.503 ⁇ 10 6 ⁇ 4.915%, molecular weight distribution coefficient (Mw/Mn): 6.318 ⁇ 5.341%)
  • the method for preparing soft capsules from the film-forming composition comprises:
  • the soft capsule production line is used to transport the glue liquid to the plastic box of the soft capsule filling machine.
  • the glue liquid is cooled on the surface of the drum to form a rubber skin, which is pressed and bonded by the packaged filler, and can be further shaped by the tumbler. .
  • Soft capsules were prepared with ingredients and contents as described in Table 2, and tested and scored. The measurement results are shown in Table 2. According to Table 2, it can be seen that the combination of gellan gum and starch with specific molecular weight is used in Examples 1-6, and the formed rubber has better strength, toughness and molding adhesion, and the prepared soft capsule samples can be disintegrated with medium water and simulated gastric juice; While comparative example 1-2 adopts the same component content of the film-forming composition of the present application, when the gellan gum and starch with low weight-average molecular weight adopted in comparative example 1 are combined, the rubber strength formed is better, toughness is poor, and cannot be pressed Molding is made into soft capsule; when comparative example 2 adopts gellan gum and starch combination with high weight-average molecular weight, the strength and toughness of the formed rubber are general, and the molding adhesion is poor.
  • Comparative Example 3 uses a combination of gellan gum and starch whose molecular weight distribution is not within the scope of the present application. When it is made into a soft capsule, the molding adhesion is poor, and it can be disintegrated in medium water and simulated gastric juice.
  • Example 7-14 Combination of specific molecular weight gellan gum and starch As the proportion of gellan gum increases and the proportion of starch decreases, that is, when the proportion of gellan gum and starch gradually increases, the strength of the formed rubber increases and the toughness increases slightly, but soft Capsule forming adhesion weakened. It is unexpected that starch compositions comprising gellan gum to starch ratios in a particular molecular weight range have an overall advantage over starch compositions not within that range.
  • Examples 15-21 illustrate that gellan gum with specific molecular weight is combined with various types of starch to prepare soft capsules, and the technical effect is obviously better than that of the prior art.
  • Comparative example 4 and comparative example 5 illustrate that when the content of starch granules in the capsule shell is small, the soft capsule cannot disintegrate in simulated gastric juice.
  • Comparative Example 6 illustrates that the starch granules are relatively high, and the molding is poor when made into soft capsules.
  • Soft capsules were prepared according to the ingredients and contents described in Table 5 and Table 6, and tested and scored. The measurement results are shown in Table 5.
  • Examples 22-29 use specific molecular weight gellan gum and starch to combine with agar, locust bean gum, guar gum, konjac gum, low-ester pectin, carrageenan, and xanthan gum to prepare soft capsules. technology.

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Abstract

一种软胶囊囊壳，其由成膜组合物制备，所述成膜组合物包含2wt％-5wt％第一胶凝剂、10wt％-35wt％增塑剂、18wt％-35wt％易糊化淀粉、4wt％-17wt％颗粒淀粉和35wt％-55wt％水，其中第一胶凝剂是结冷胶，该结冷胶具有5.0×10 5～8.0×10 6g/mol的重均分子量和/或1.0～6.0的分子量分布系数。该成膜组合物具有良好的成膜机械强度、韧性和粘性，压制成软胶囊时缝合良好、可在介质水中和模拟胃液中崩解。该成膜组合物不包含动物来源成分，可应用于医药、食品、化妆品等领域。

Description

软胶囊囊壳和软胶囊
本申请要求2021年6月28日提交的申请号为202110721182.1，发明名称为“软胶囊囊壳和软胶囊”的中国发明专利申请的优先权。
技术领域
本申请涉及食品或药物领域，具体涉及一种软胶囊囊壳和软胶囊。
背景技术
软胶囊在医药、食品、化妆品等领域广泛应用，因明胶具有优异的成膜性能和机械强度，作为传统软胶囊材料广泛使用。但由于明胶本身的特性，在应用过程中表现出许多质量缺陷，如明胶分子可以通过自身氧化或与功能性基团如醛基发生交联反应，在明胶软胶囊表面产生一层坚韧而有弹性的水不溶性表膜，阻隔药物释放，导致软胶囊的崩解不合格；再加上宗教、素食主义者，以及随着世界各地相继出现疯牛病、口蹄疫和毒胶囊等事件，因此人们一直在试图开发明胶的替代品及其制备软胶囊的研究。
例如，日本专利号JP2007153851A提出了一种由非动物来源的软胶囊的薄膜组合物，通过混合水、淀粉和天然型结冷胶得到。欧洲专利号EP2815745A1提出了一种包含高酰基结冷胶、至少一种淀粉和至少一种增塑剂软胶囊及制备方法。高酰基结冷胶形成的凝胶质地柔软、富有弹性，与淀粉组合时形成的胶皮强度弱，压丸成型时夹缝较薄、破裂力低、易漏油。中国专利号CN100528950C提出了一种不同酰基结冷胶与淀粉的混合物，包含：a.高酰基结冷胶；b.低酰基结冷胶；c.淀粉；和d.增塑剂，使用该混合物制成的薄膜具有高模数以及优良强度和延伸性，制成的软胶囊具有良好密封性。高酰基结冷胶和低酰基结冷胶作为复配凝胶剂，可在一定程度改善胶皮强度和韧性，但胶液粘度高，输送时易预凝导致胶皮缺损或不平整，制备的软胶囊夹缝较薄、易漏油。
现有技术报道的以结冷胶为主要囊材的软胶囊制备过程中，存在胶液粘度高，输送时易凝胶导致胶皮缺损或不平整，压丸成型夹缝薄、易漏油等缺陷，较难实现软胶囊工业化生产。本领域中需要克服上述技术问题的植物软胶囊。
发明内容
本申请部分基于发明人的以下发现：包含特定分子量范围的结冷胶与淀粉比的淀粉组合物在形成软胶囊囊壳的综合效果、在水和胃液中崩解的效果上优于不在该范围内的淀粉组合物。进一步，发明人发现上述效果与囊壳中的淀粉颗粒的平均粒径大小和含量有关，即实现本申请效果的软胶囊囊壳中淀粉颗粒含量为9wt％-40wt％，所述淀粉颗粒是平均粒径大小≥10μm的淀粉颗粒。
此外，发明人先前的研究表明在成膜组合物中添加果胶会阻止制备的软胶囊囊壳在胃部崩解。出乎意料地，发明人发现在特定分子量范围内的结冷胶结合淀粉，即便存在果胶也可以在胃部崩解，如表5中显示的。
在一方面，提供了一种软胶囊囊壳，其由成膜组合物制备，所述成膜组合物包含2wt％-5wt％第一胶凝剂、10wt％-35wt％增塑剂、18wt％-35wt％易糊化淀粉、4wt％-17wt％颗粒淀粉和35wt％-55wt％水，其中第一胶凝剂是结冷胶，该结冷胶具有5.0×10 5～8.0×10 6g/mol的重均分子量和/或1.0～6.0的分子量分布系数，软胶囊囊壳中淀粉颗粒含量为9wt％-40wt％，所述淀粉颗粒是平均粒径大小≥10μm的淀粉颗粒；所述软胶囊囊壳是胃部崩解的软胶囊囊壳；易糊化淀粉选自蜡质玉米淀粉、木薯淀粉、羟丙基淀粉、氧化淀粉、氧化羟丙基淀粉、糊精、麦芽糊精中的一种或组合；颗粒淀粉选自豌豆淀粉、玉米淀粉、马铃薯淀粉、酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、预胶化淀粉、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉的一种或组合。
在一个实施方案中，结冷胶具有5.5×10 5～6.6×10 6g/mol，优选5.5×10 5～4.7×10 6g/mol的重均分子量，和/或结冷胶具有1.0～4.0的分子量分布系数。
在一个实施方案中，结冷胶与淀粉总量的重量比为0.05～0.2，优选结冷胶与淀粉总量的重量比为0.09-0.2；优选地，其中结冷胶的含量是2.5wt％-5wt％。
在一个实施方案中，增塑剂的含量是15wt％～25wt％；优选地，其中增塑剂选自甘油、山梨糖醇、麦芽糖醇、赤藓糖醇、木糖醇、结晶果糖、海藻糖或葡萄糖中的一种或组合。
在一个实施方案中，所述成膜组合物还包含0.2wt％-10wt％第二胶凝剂，优选地，所述第二胶凝剂选自卡拉胶、琼脂、海藻酸钠、果胶、普鲁兰多糖、魔芋胶、黄原胶、刺槐豆胶、瓜尔胶、亚麻籽胶、可得然胶或罗望子胶中的一种或组合。
在一个实施方案中，易糊化淀粉选自羟丙基淀粉或氧化羟丙基淀粉中的一种或两种，颗粒淀粉选自酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉的一种或组合。
在一个实施方案中，软胶囊囊壳通过如下的方法制备，所述方法包括a)将第一胶凝剂加入到增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至第一胶凝剂溶解；b)加入所述淀粉，并在60～98℃下加热搅拌至淀粉溶解；c)除去气泡即得胶液；和d)压丸和干燥中；优选地其中所述a)还包括加入第二胶凝剂，所述a)为将所述第一胶凝剂和第二胶凝剂加入到所述增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至所述第一胶凝剂和第二胶凝剂溶解。
在另一个方面，本申请提供了软胶囊，其包含本申请的软胶囊囊壳和填充物。
在另一个方面，本申请提供了本申请的软胶囊囊壳或软胶囊在食品、营养保健食品和药品中的应用。
在另一个方面，本申请提供了成膜组合物制备软胶囊的用途，其中所述成膜组合物包含2wt％-5wt％第一胶凝剂、10wt％-35wt％增塑剂、18wt％-35wt％易糊化淀粉、4wt％-17wt％颗粒淀粉和35wt％-55wt％水，其中第一胶凝剂是结冷胶，该结冷胶具有5.0×10 5～8.0×10 6g/mol的重均分子量和/或1.0～6.0的分子量分布系数，软胶囊囊壳中淀粉颗粒含量为9wt％-40wt％，所述淀粉颗粒是平均粒径大小≥10μm的淀粉颗粒；所述软胶囊囊壳是胃部崩解的软胶囊囊壳；其中易糊化淀粉选自蜡质玉米淀粉、木薯淀粉、羟丙基淀粉、氧化淀粉、氧化羟丙基淀粉、糊精、麦芽糊精中的一种或组合；颗粒淀粉选自豌豆淀粉、玉米淀粉、马铃薯淀粉、酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、预胶化淀粉、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉的一种或组合。
在一个实施方案中，结冷胶具有5.5×10 5～6.6×10 6g/mol，优选 5.5×10 5～4.7×10 6g/mol的重均分子量，和/或结冷胶具有1.0～4.0的分子量分布系数。
在一个实施方案中，结冷胶与淀粉总量的重量比为0.05～0.2，优选结冷胶与淀粉总量的重量比为0.09-0.2；优选地，其中结冷胶的含量是2.5wt％-5wt％。
在一个实施方案中，增塑剂的含量是15wt％～25wt％；优选地，其中增塑剂选自甘油、山梨糖醇、麦芽糖醇、赤藓糖醇、木糖醇、结晶果糖、海藻糖或葡萄糖中的一种或组合。
在一个实施方案中，成膜组合物还包含0.2wt％-10wt％第二胶凝剂，优选地，所述第二胶凝剂选自卡拉胶、琼脂、海藻酸钠、果胶、普鲁兰多糖、魔芋胶、黄原胶、刺槐豆胶、瓜尔胶、亚麻籽胶、可得然胶或罗望子胶中的一种或组合。
在一个实施方案中，易糊化淀粉选自羟丙基淀粉或氧化羟丙基淀粉中的一种或两种，颗粒淀粉选自酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉的一种或组合。
在一个实施方案中，软胶囊囊壳通过如下的方法制备，所述方法包括a)将第一胶凝剂加入到增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至第一胶凝剂溶解；b)加入所述淀粉，并在60～98℃下加热搅拌至淀粉溶解；c)除去气泡即得胶液；和d)压丸和干燥中。
在一个实施方案中，所述a)还包括加入第二胶凝剂，所述a)为将所述第一胶凝剂和第二胶凝剂加入到所述增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至所述第一胶凝剂和第二胶凝剂溶解。
在本文中，本申请的成膜组合物或软胶囊囊壳不包含明胶。
在一方面，提供了本申请的成膜组合物、软胶囊囊壳或软胶囊在食品、营养保健食品、药品和化妆品中的应用。在一个实施方案中，食品、营养保健食品或药品是胃部吸收的或胃用的。在本文中，胃部崩解效果可以通过在模拟胃液中验证。
在一个方面，本申请提供了使用本申请的软胶囊囊壳或软胶囊进行胃部递送的方法。本申请还提供了本申请的软胶囊囊壳或软胶囊在制备胃部用药中的用途。
本申请提供了如下的优点：
1.提供了具有优异的综合效果、在水和胃液中崩解的效果的软胶囊囊壳，丰富了软胶囊的配方；
2.本申请前认为胃部崩解的软胶囊不应添加果胶，如表6中表明。本申请通过适当的配方和结冷胶的选择，在存在果胶的情况下实现了优异的胃部崩解效果，克服了这种认知偏见。
具体实施方式
提供以下内容以进一步说明本申请。
本申请提供了软胶囊囊壳，其由本申请的成膜组合物制备。本申请的成膜组合物包含第一胶凝剂。第一胶凝剂的含量可以是2wt％-5wt％，例如2wt％、2.5wt％、3wt％、3.5wt％、4wt％、4.5wt％、5wt％。第一胶凝剂可以是结冷胶。结冷胶可以具有为5.0×10 5～8.0×10 6g/mol，优选5.5×10 5～6.6×10 6g/mol，优选5.5×10 5～4.7×10 6的重均分子量，例如6×10 5g/mol、9×10 5g/mol、1.5×10 6g/mol、2×10 6g/mol、2.5×10 6g/mol、3×10 6g/mol、4×10 6g/mol、5×10 6g/mol或6×10 6g/mol。结冷胶可以具有1.0～6.0的分子量分布系数，优选1.0～4.0，例如2、2.5或3的分子量分布系数。
成膜组合物包含增塑剂。增塑剂的含量可以是10wt％-35wt％，例如13wt％、14wt％、15wt％、16wt％、20wt％、25wt％或30wt％。增塑剂可以选自甘油、山梨糖醇、麦芽糖醇、赤藓糖醇、木糖醇、结晶果糖、海藻糖或葡萄糖中的一种或组合。
成膜组合物包含18wt％-35wt％易糊化淀粉和4wt％-17wt％颗粒淀粉。易糊化淀粉的含量可以是20wt％-30wt％，例如20wt％、25wt％或30wt％。颗粒淀粉的含量可以是4wt％-17wt％，例如4wt％、5wt％、7wt％、8wt％、10wt％、14wt％或16wt％。易糊化淀粉是指淀粉糊化完全后颗粒破碎或溶解的淀粉；颗粒淀粉是指淀粉不易完全糊化，吸水膨胀后颗粒未破碎的淀粉。易糊化淀粉包括蜡质玉米淀粉、木薯淀粉、羟丙基淀粉、氧化淀粉、氧化羟丙基淀粉、糊精或麦芽糊精的一种或组合。颗粒淀粉包括豌豆淀粉、玉米淀粉、马铃薯淀粉、酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、预胶化淀粉、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉的一种或组合。
在一个实施方案中，结冷胶与淀粉总量的重量比为0.05～0.2。在一个实施方案中，结冷胶与淀粉总量的重量比为0.07-0.2。例如，结冷胶与淀粉总量的重量比为0.05、0.07、0.09、0.1、0.13、0.16或0.2。
成膜组合物包含水。水的含量可以是35wt％-55wt％，例如40wt％、45wt％、50wt％或55wt％。
成膜组合物还可以包含第二胶凝剂。第二胶凝剂的含量可以是0.2wt％-10wt％，例如0.25wt％、1wt％、2wt％、3wt％、4wt％、5wt％、6wt％、7wt％、8wt％或9wt％。第二胶凝剂选自卡拉胶、琼脂、海藻酸钠、果胶、普鲁兰多糖、魔芋胶、黄原胶、刺槐豆胶、瓜尔胶、亚麻籽胶、可得然胶或罗望子胶中的一种或组合。
本申请还提供了由本申请的成膜组合物制成的软胶囊囊壳。淀粉在软胶囊囊壳中的状态是颗粒淀粉(淀粉颗粒平均粒径大小≥10μm)、颗粒破碎淀粉(淀粉颗粒平均粒径大小<10μm)或者淀粉颗粒破碎后的链段，其中颗粒淀粉含量为软胶囊囊壳总量的9wt％-40wt％，例如10wt％、15wt％、20wt％、25wt％、30wt％或35wt％。本申请的软胶囊囊壳是胃部崩解的软胶囊囊壳。发明人发现软胶囊囊壳中的淀粉颗粒与软胶囊囊壳的胃部崩解效果有关。
进一步，本申请提供了软胶囊，其包含本申请的软胶囊囊壳和填充物。填充物可包括各种动、植物油脂，或各种固体功效成分与软胶囊适宜辅料制备而成的混悬液、乳液、半固体，或固体功效成分与适宜辅料制成的固体制剂(如颗粒、微囊、粉末、素片、胶囊)中的一种或组合。
本申请还提供了制备本申请的软胶囊囊壳的方法，其包括a)将第一胶凝剂加入到增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至第一胶凝剂溶解；b)加入所述淀粉，并在60～98℃下加热搅拌至淀粉溶解；c)除去气泡即得胶液；和d)压丸和干燥。在一个实施方案中，所述a)还包括加入第二胶凝剂，所述a)为将所述第一胶凝剂和第二胶凝剂加入到所述增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至所述第一胶凝剂和第二胶凝剂溶解。压丸可以如下进行：采用软胶囊生产线，将胶液输送至软胶囊填充机的胶盒中，胶液在转鼓表面上冷却形成胶皮，经封装填充物压制成型，可进一步在转笼中定型。干燥可以如下进行：将成型或定型后胶丸进一步干燥，优选干燥至囊皮水分8-25％。
本申请还提供了本申请的淀粉成膜组合物、软胶囊囊壳或软胶囊在食 品、营养保健品、药品和化妆品中的应用。
本申请的成膜组合物，通过采用特定分子量及分布的结冷胶，与淀粉组合控制在一定范围内，成膜具有良好的机械强度和韧性，用于软胶囊在胶皮强度、韧性和成型粘合方面明显优于现有技术，完全满足软胶囊工业化生产要求，在介质水中和人工胃液中可满足崩解破裂要求，可以作为软胶囊技术的备选替代。
提供以下实施例以进一步说明本申请。应当理解，实施例仅仅是示例性的而非限制性的。本申请的范围由所附权利要求书限定。
实施例
为了表征成膜组合物形成的膜及软胶囊囊壳中的淀粉颗粒，采用以下的方法进行颗粒尺寸和含量的测定：
1)淀粉颗粒大小：成膜组合物通过混合加热制备的胶液放置在两个载玻片中间，通过加热加压使得胶液在95℃下形成薄膜，冷却后在此薄膜上滴加碘溶液进行染色。采用偏光显微镜，随机选取多个观察区域拍照，根据放大倍数校准标尺后，测量所拍摄区域内每颗淀粉颗粒的粒径，以其算术平均值表示淀粉颗粒大小。
2)淀粉颗粒含量：将100mg干膜或干燥后的软胶囊囊皮与15g去离子水在75℃的条件下溶解30分钟，期间多次搅拌使得囊皮完全溶解后，将溶解后的软胶囊囊皮浑浊液进行4000rpm离心15min，经过此等条件的离心，颗粒淀粉于底部沉淀中，去除上层液体，底层沉淀经过充分干燥后，以沉淀物含量表示淀粉颗粒含量，计算出颗粒淀粉在软胶囊囊皮中质量的占比。
为了更好说明本申请的效果，采用以下软胶囊性能指标进行评价说明：
(1)成型
1)胶皮强度(F)和韧性指标(T)：采用物性测试仪，选择球形探头与穿刺模式，测试速度1.0mm/s，记录胶皮破裂力，破裂力越大，胶皮强度越好；胶皮破裂时对应的破裂距离(mm)，破裂距离越大，胶皮的韧性越好。
2)夹缝粘合指标：从胶囊在非夹缝上剪开，挤压排空内容物，然后保持与夹缝垂直从中间剪取一个含有两条夹缝的环圈，使环圈置于载玻片上，并使两条夹缝垂直载玻片，在显微镜下测量两条夹缝处的厚度及囊壳的厚 度，计算最薄夹缝厚度占囊壳厚度的比值P(％)。
表1软胶囊胶皮强度、韧性和夹缝粘合指标评价标准
Figure PCTCN2021142079-appb-000001
软胶囊生产成型可行性以胶皮强度指标(F)、韧性指标(T)和夹缝粘合指标(P)进行综合评价，其中综合评价是由胶皮强度占比20％，韧性指标占比20％，成型粘合占比60％，三者相加得到，综合评价总分5分，分数越高表示综合性能越好。
胶皮强度、韧性两个指标分别≥3分且夹缝粘合指标≥2分，且综合评价必须≥2.4，才能满足软胶囊工业生产。
(2)崩解时限
参照美国药典USP<2040>有关崩解时限的规定，使用吊篮装置，将软胶囊分别在介质水中和模拟胃液中进行崩解测试，60分钟内崩解合格用符号“√”表示，崩解不合格用符号“×”表示。
本申请采用以下物料进行举例说明，但本申请并不限于以下物料，具体如下：
结冷胶是一种微生物代谢胶，不同的工艺条件生产出来的结冷胶分子量及分布不同，表现在结冷胶的流变性质和凝胶性质存在差异。通过采用SEC/MALLS(尺寸排阻色谱/多角激光散射)测试研究结冷胶的重均分子量(Mw)及分子量分散系数(Mw/Mn)：
结冷胶A(重均分子量(Mw)：5.98×10 5±4.682％，分子量分布系数 (Mw/Mn)：1.07±1.445％)
结冷胶B(重均分子量(Mw)：9.168×10 5±4.672％，分子量分布系数(Mw/Mn)：2.893±5.829％)
结冷胶C(重均分子量(Mw)：1.426×10 6±5.364％，分子量分布系数(Mw/Mn)：2.336±6.391％)
结冷胶D(重均分子量(Mw)：2.673×10 6±4.605％，分子量分布系数(Mw/Mn)：2.019±6.252％)
结冷胶E(重均分子量(Mw)：4.672×10 6±4.515％，分子量分布系数(Mw/Mn)：2.419±5.251％)
结冷胶F(重均分子量(Mw)：6.672×10 6±4.105％，分子量分布系数(Mw/Mn)：2.329±5.342％)
结冷胶G(重均分子量(Mw)：4.01×10 5±13.21％，分子量分布系数(Mw/Mn)：1.13±1.77％)
结冷胶H(重均分子量(Mw)：8.608×10 6±2.333％，分子量分布系数(Mw/Mn)：2.358±5.247％)
结冷胶I(重均分子量(Mw)：1.503×10 6±4.915％，分子量分布系数(Mw/Mn)：6.318±5.341％)
成膜组合物制备软胶囊的方法包括：
1)溶胶：A)先将结冷胶和增塑剂预混分散均匀，搅拌下加入到适量水中，在60～98℃下加热搅拌至结冷胶溶解；若含有除结冷胶外的食用胶，则先将结冷胶、食用胶和增塑剂预混并且分散均匀，搅拌下加入到水中，在60～98℃下加热搅拌至结冷胶和食品胶溶解；B)加入淀粉，继续在60～98℃下加热搅拌至淀粉溶解；C)除去气泡即得胶液；
2)压丸：采用软胶囊生产线，将胶液输送至软胶囊填充机的胶盒中，胶液在转鼓表面上冷却形成胶皮，经封装填充物压制粘合成型，可进一步通过转笼定型。
3)干燥：将成型或定型后胶丸进行干燥，直至胶皮水分为8-25％。
实施例1-6
如表2中所述的成分和含量制备软胶囊，并且进行测试和评分。测定结 果如表2中所示。根据表2可知，实施例1-6采用特定分子量的结冷胶与淀粉组合，形成的胶皮强度、韧性和成型粘合较好，制备的软胶囊样品用介质水和模拟胃液均可以崩解；而对照例1-2采用本申请的成膜组合物相同的组分含量，对照例1采用的重均分子量低的结冷胶和淀粉组合时，形成的胶皮强度较好、韧性差，无法压制成型制成软胶囊；对照例2采用重均分子量高的结冷胶和淀粉组合时，形成的胶皮强度和韧性一般，成型粘合差。对照例3采用分子量分布不在本申请范围的结冷胶和淀粉组合，制成软胶囊时成型粘合较差，在介质水和模拟胃液中均可以崩解。
实施例7-14
按照表3中所述的成分和含量制备软胶囊，并且进行测试和评分。测定结果如表3中所示。
实施例7-14特定分子量结冷胶与淀粉组合随着结冷胶比例增加、淀粉比例减少，即结冷胶与淀粉比例逐渐升高时，形成的胶皮强度增加，韧性稍有增加，但软胶囊成型粘合有减弱。包含特定分子量范围的结冷胶与淀粉比的淀粉组合物在综合效果上优于不在该范围内的淀粉组合物，这是意料不到的。
实施例15-21
按照表4中所述的成分和含量制备软胶囊，并且进行测试和评分。测定结果如表4中所示。
实施例15-21举例说明特定分子量的结冷胶与各类淀粉组合制备软胶囊，技术效果明显优于现有技术。对照例4、对照例5举例说明囊壳中淀粉颗粒含量较少时，软胶囊无法在模拟胃液中崩解。对照例6举例说明淀粉颗粒比较高，制成软胶囊时成型较差。
实施例22-29
按照表5和表6中所述的成分和含量制备软胶囊，并且进行测试和评分。测定结果如表5中所示。
实施例22-29采用特定分子量的结冷胶和淀粉分别与琼脂、刺槐豆胶、瓜尔胶、魔芋胶、低酯果胶、卡拉胶、黄原胶组合制备软胶囊技术效果优于 现有技术。
发明人先前的研究表明在成膜组合物中添加果胶会阻止制备的软胶囊囊壳在胃部崩解。出乎意料地，发明人发现在特定分子量范围内的结冷胶结合淀粉，即便存在果胶也可以在胃部崩解，如表5和表6中显示的。
上述实施例为本申请较佳的实施方式，但本申请的实施方式并不受上述实施例的限制，其他的任何未背离本申请的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本申请的保护范围之内。
Figure PCTCN2021142079-appb-000002
Figure PCTCN2021142079-appb-000003
Figure PCTCN2021142079-appb-000004
Figure PCTCN2021142079-appb-000005
Figure PCTCN2021142079-appb-000006
Figure PCTCN2021142079-appb-000007
Figure PCTCN2021142079-appb-000008

Claims (10)

  1. 软胶囊囊壳，其由成膜组合物制备，所述成膜组合物包含2wt％-5wt％第一胶凝剂、10wt％-35wt％增塑剂、18wt％-35wt％易糊化淀粉、4wt％-17wt％颗粒淀粉和35wt％-55wt％水，其中第一胶凝剂是结冷胶，该结冷胶具有5.0×10 5～8.0×10 6g/mol的重均分子量和/或1.0～6.0的分子量分布系数，软胶囊囊壳中淀粉颗粒含量为9wt％-40wt％，所述淀粉颗粒是平均粒径大小≥10μm的淀粉颗粒；所述软胶囊囊壳是胃部崩解的软胶囊囊壳；
    易糊化淀粉选自羟丙基淀粉、蜡质玉米淀粉、木薯淀粉、氧化淀粉、氧化羟丙基淀粉、糊精、或麦芽糊精中的一种或组合；且
    颗粒淀粉选自羟丙基二淀粉磷酸酯、豌豆淀粉、玉米淀粉、马铃薯淀粉、酸处理淀粉、醋酸酯淀粉、淀粉磷酸酯、乙酰化二淀粉磷酸酯、预胶化淀粉、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉中的一种或组合。
  2. 权利要求1的软胶囊囊壳，其中结冷胶具有5.5×10 5～6.6×10 6g/mol，优选5.5×10 5～4.7×10 6g/mol的重均分子量，和/或结冷胶具有1.0～4.0的分子量分布系数。
  3. 前述权利要求中任一项的软胶囊囊壳，其中结冷胶与淀粉总量的重量比为0.05～0.2，优选结冷胶与淀粉总量的重量比为0.09-0.2；优选地，其中结冷胶的含量是2.5wt％-5wt％。
  4. 前述权利要求中任一项的软胶囊囊壳，其中增塑剂的含量是15wt％～25wt％；优选地，其中增塑剂选自甘油、山梨糖醇、麦芽糖醇、赤藓糖醇、木糖醇、结晶果糖、海藻糖或葡萄糖中的一种或组合。
  5. 前述权利要求中任一项的软胶囊囊壳，其中所述成膜组合物还包含0.2wt％-10wt％第二胶凝剂，优选地，所述第二胶凝剂选自卡拉胶、琼脂、海藻酸钠、果胶、普鲁兰多糖、魔芋胶、黄原胶、刺槐豆胶、瓜尔胶、亚麻籽胶、可得然胶或罗望子胶中的一种或组合。
  6. 前述权利要求中任一项的软胶囊囊壳，其中易糊化淀粉选自羟丙基淀粉或氧化羟丙基淀粉中的一种或两种，颗粒淀粉选自酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉中的一种或组合。
  7. 前述权利要求中任一项的软胶囊囊壳，其通过如下的方法制备，所述方法包括a)将第一胶凝剂加入到增塑剂中，搅拌均匀，再加入到水中，并 在60～98℃下加热搅拌至第一胶凝剂溶解；b)加入所述淀粉，并在60～98℃下加热搅拌至淀粉溶解；c)除去气泡即得胶液；和d)压丸和干燥中；优选地其中所述a)还包括加入第二胶凝剂，所述a)为将所述第一胶凝剂和第二胶凝剂加入到所述增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至所述第一胶凝剂和第二胶凝剂溶解。
  8. 软胶囊，其包含权利要求1-7中任一项的软胶囊囊壳和填充物。
  9. 权利要求1-7中任一项的软胶囊囊壳或权利要求8的软胶囊在食品、营养保健品和药品中的应用。
  10. 成膜组合物制备软胶囊的用途，其中所述成膜组合物包含2wt％-5wt％第一胶凝剂、10wt％-35wt％增塑剂、18wt％-35wt％易糊化淀粉、4wt％-17wt％颗粒淀粉和35wt％-55wt％水，其中第一胶凝剂是结冷胶，该结冷胶具有5.0×10 5～8.0×10 6g/mol的重均分子量和/或1.0～6.0的分子量分布系数，软胶囊囊壳中淀粉颗粒含量为9wt％-40wt％，所述淀粉颗粒是平均粒径大小≥10μm的淀粉颗粒；所述软胶囊囊壳是胃部崩解的软胶囊囊壳；其中易糊化淀粉选自蜡质玉米淀粉、木薯淀粉、羟丙基淀粉、氧化淀粉、氧化羟丙基淀粉、糊精、麦芽糊精中的一种或组合；颗粒淀粉选自豌豆淀粉、玉米淀粉、马铃薯淀粉、酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、预胶化淀粉、乙酰化二淀粉己二酸酯或乙酰化氧化淀粉中的一种或组合；
    优选地，其中结冷胶具有5.5×10 5～6.6×10 6g/mol，优选5.5×10 5～4.7×10 6g/mol的重均分子量，和/或结冷胶具有1.0～4.0的分子量分布系数；
    优选地，其中结冷胶与淀粉总量的重量比为0.05～0.2，优选结冷胶与淀粉总量的重量比为0.09-0.2；优选地，其中结冷胶的含量是2.5wt％-5wt％；
    优选地，其中增塑剂的含量是15wt％～25wt％；优选地，其中增塑剂选自甘油、山梨糖醇、麦芽糖醇、赤藓糖醇、木糖醇、结晶果糖、海藻糖或葡萄糖中的一种或组合；
    优选地，其中所述成膜组合物还包含0.2wt％-10wt％第二胶凝剂，优选地，所述第二胶凝剂选自卡拉胶、琼脂、海藻酸钠、果胶、普鲁兰多糖、魔芋胶、黄原胶、刺槐豆胶、瓜尔胶、亚麻籽胶、可得然胶或罗望子胶中的一种或组合；
    优选地，其中易糊化淀粉选自羟丙基淀粉或氧化羟丙基淀粉中的一种或 两种，颗粒淀粉选自酸处理淀粉、醋酸酯淀粉、羟丙基二淀粉磷酸酯、淀粉磷酸酯、乙酰化二淀粉磷酸酯、乙酰化氧化淀粉或乙酰化二淀粉己二酸酯的一种或组合；
    优选地，其中软胶囊囊壳通过如下的方法制备，所述方法包括a)将第一胶凝剂加入到增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至第一胶凝剂溶解；b)加入所述淀粉，并在60～98℃下加热搅拌至淀粉溶解；c)除去气泡即得胶液；和d)压丸和干燥中；
    优选地，其中所述a)还包括加入第二胶凝剂，所述a)为将所述第一胶凝剂和第二胶凝剂加入到所述增塑剂中，搅拌均匀，再加入到水中，并在60～98℃下加热搅拌至所述第一胶凝剂和第二胶凝剂溶解。
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CN113332257A (zh) * 2021-06-28 2021-09-03 仙乐健康科技股份有限公司 软胶囊囊壳和软胶囊
CN113398088A (zh) * 2021-06-28 2021-09-17 仙乐健康科技股份有限公司 软胶囊囊壳及软胶囊

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