CN105105104A - 耐热益生菌组合物及包含该组合物的健康食品 - Google Patents
耐热益生菌组合物及包含该组合物的健康食品 Download PDFInfo
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- CN105105104A CN105105104A CN201510242825.9A CN201510242825A CN105105104A CN 105105104 A CN105105104 A CN 105105104A CN 201510242825 A CN201510242825 A CN 201510242825A CN 105105104 A CN105105104 A CN 105105104A
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- microorganism
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- PHZLMBHDXVLRIX-UHFFFAOYSA-M potassium lactate Chemical compound [K+].CC(O)C([O-])=O PHZLMBHDXVLRIX-UHFFFAOYSA-M 0.000 description 1
- 235000011085 potassium lactate Nutrition 0.000 description 1
- 239000001521 potassium lactate Substances 0.000 description 1
- 229960001304 potassium lactate Drugs 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- AVTYONGGKAJVTE-UHFFFAOYSA-L potassium tartrate Chemical compound [K+].[K+].[O-]C(=O)C(O)C(O)C([O-])=O AVTYONGGKAJVTE-UHFFFAOYSA-L 0.000 description 1
- 239000001472 potassium tartrate Substances 0.000 description 1
- 229940111695 potassium tartrate Drugs 0.000 description 1
- 235000011005 potassium tartrates Nutrition 0.000 description 1
- CONVKSGEGAVTMB-RXSVEWSESA-M potassium-L-ascorbate Chemical compound [K+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] CONVKSGEGAVTMB-RXSVEWSESA-M 0.000 description 1
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- 235000010388 propyl gallate Nutrition 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
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- 235000019699 ravioli Nutrition 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 239000012176 shellac wax Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
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- 235000019980 sodium acid phosphate Nutrition 0.000 description 1
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- 229960005055 sodium ascorbate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000019279 sodium erythorbin Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- UFMBEBVGXVUTHP-UHFFFAOYSA-M sodium;acetic acid;2-carboxybenzoate Chemical compound [Na+].CC(O)=O.OC(=O)C1=CC=CC=C1C([O-])=O UFMBEBVGXVUTHP-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229910021654 trace metal Inorganic materials 0.000 description 1
- 150000003641 trioses Chemical class 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 235000019263 trisodium citrate Nutrition 0.000 description 1
- RULSWEULPANCDV-PIXUTMIVSA-N turanose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](C(=O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RULSWEULPANCDV-PIXUTMIVSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229960003487 xylose Drugs 0.000 description 1
- 235000020138 yakult Nutrition 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 1
- 235000007680 β-tocopherol Nutrition 0.000 description 1
- 239000011590 β-tocopherol Substances 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
- 239000002446 δ-tocopherol Substances 0.000 description 1
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Abstract
本发明提供了用于混合到健康食品中的益生菌微生物颗粒,其中微生物在食品的热处理中稳定存活。由本发明提供的健康食品包括面粉糕饼、面包、乳制品及其它。
Description
本申请是申请号为“201080035882.5”,申请日为“2010年7月8日”,发明名称为“耐热益生菌组合物及包含该组合物的健康食品”的申请的分案申请。
发明领域
本发明涉及健康食品制品,具体地涉及烘焙益生菌制品。提供了制备制品的方法,该制品在其制备的至少一个阶段中经受热处理,同时保持足够量的益生菌微生物存活。
发明背景
益生菌是活的微生物食品补充剂,其通过支持天然存在的肠道菌群、通过在胃肠道中竞争有害的微生物、通过帮助有用的代谢过程并通过加强寄助物对有毒物质的抵抗性而有利地影响宿主。许多生物体用于益生菌食品中,实例为微生物属乳杆菌属(Lactobacillus)或双岐杆菌(Bifidobacterium)。益生菌生物体应该在制品的使用期内存活以便是有效,且此外它们还应该在胃肠道至结肠的整个路径中存活。益生菌生物体通常加入奶制品诸如酸奶酪中。感受到了在其它食品类型中例如在烘焙制品中递送有益微生物的需求。然而,在制备烘焙的健康食品中主要问题是加工温度,通常该加工温度如此高(超过180℃)以致其几乎使制品无菌。WO94/00019描述了一种制备含有活微生物的烘焙制品的方法,该方法包括冷却烘焙制品并向其中注射活的悬浮液。与本发明为相同发明人的WO2009/069122描述了一种制备烘焙食品的方法,该方法包括封装益生菌颗粒,从而增强它们的稳定性。
发明概述
本发明的一个目的是提供一种用于制备包含益生菌微生物的营养上可接受的组合物的方法,该组合物耐高温。本发明的另一个目的是提供包含足够量的有生活力的微生物的烘焙制品。
本发明的另一个目的是提供一种用于制备益生菌烘焙制品且无需在烘焙过程之后向烘焙制品中注射有生活力的微生物的方法。
本发明的另外的目的是提供在烘焙的整个过程期间包含活的益生菌微生物的烘焙制品。
本发明的另外的目的是提供包含热稳定的益生菌组合物的烘焙制品。
本发明的目的还提供显示长保存期的益生菌烘焙制品。
本发明的其它目的和优点将随着描述进行而明显。
本发明提供了一种益生菌颗粒,其包括:i)芯,其包含益生菌微生物和所述微生物被吸收到其中的基质;ii)包覆所述芯的内部油层;和iii)第一外层和第二外层,所述外层包覆所述芯和所述内层,包含至少两种不同的聚合物。所述基质和所述两种不同的聚合物可包括三种营养上可接受的多糖。所述芯还可包括所述微生物的一种或多种补充剂。优选地,该剂支持所述微生物的生长,并可包括益生菌材料,诸如寡糖。所述内部油层可包括选自脂肪酸、蜡、脂肪、油和脂质的材料。所述第一外层向所述微生物给予在上胃肠道的条件下的稳定性,且所述第二外层提高所述微生物在增加的温度下在所述芯中的稳定性。所述基质包括选自糖类和另外的剂的一种或多种组分。所述剂选自稳定剂、螯合剂、增效剂、抗氧化剂和pH调节剂,且所述糖类优选包括益生菌寡糖。
本发明的颗粒中的所述两个外层包含两种不同的聚合物;聚合物可具有纤维性特征或具有凝胶状特征。在一个实施方案中,外层中的至少一层包含纤维性多糖,且外层中的至少一层包含凝胶状多糖。根据本发明的益生菌颗粒可包括另外的层,例如被定位在所述油层和所述第二外层之间的至少一层中间层。本发明的益生菌颗粒包括益生菌微生物;生物体优选为细菌的。所述微生物有利地包括选自乳杆菌属、双歧杆菌属、芽孢杆菌属(Bacillus)、埃希氏菌属(Escherichia)、链球菌属(Streptococcus)、二乙酰乳酸菌属(Diacetylactis)和酵母(Saccharomyces)或其混合物的属。在优选的实施方案中,微生物是益生菌细菌。
在一些实施方案中,所述外层中的一层可包含纤维性多糖。在另外的实施方案中,所述外层中的一层可包含凝胶状多糖。本发明提供了一种用于制造包含芯的益生菌颗粒的方法,芯含有益生菌微生物和吸收所述微生物的基质,被内部油层和两个外部聚合物层包围,该方法包括i)将益生菌微生物的悬浮液与基于纤维素的基质并与所述微生物的补充剂混合,从而获得芯混合物;ii)用油层包覆所述芯混合物的粒子,从而获得油包覆的粒子;iii)用第一聚合物层包覆所述油包覆的粒子,从而获得包覆两层的粒子,该第一聚合物层向所述微生物给予在上胃肠道的条件下的稳定性;和iv)用第二聚合物层包覆所述两层粒子,该第二聚合物层增加了微生物在烘焙的条件下在所述芯中的稳定性。所述微生物可包括一种或多种微生物菌株,并混合至微生物学相容的聚合物并吸收于微生物学相容的聚合物上,微生物学相容的聚合物也是营养上可接受的且可批准的,一个实例为多糖,诸如基于纤维素的材料。支持所述微生物的稳定性或生长的材料可加入到混合物中。优选包括的是被称为益生元的益生菌载体,例如麦芽糖糊精、海藻糖等等。包覆步骤可利用本领域已知的技术,包括流化床包覆、喷涂等等。在产生包覆层时,可使用溶液或悬浮液以及粉末等等。所述包覆步骤ii)至iv)导致相对于芯的质量,从10%至100%的质量增加,例如在15%至50%之间。在优选的实施方案中,用于制造益生菌颗粒的方法包括i)将包括选自乳杆菌属、双歧杆菌属、芽孢杆菌属、埃希氏菌属、链球菌属、二乙酰乳酸菌属和酵母或其混合物的至少一个属的益生菌微生物的水悬浮液与至少一种多糖和至少一种寡糖(一个实例是具有麦芽糖糊精和海藻糖的微晶纤维素)混合,从而获得芯混合物;ii)用油层包覆所述芯混合物的粒子,从而获得油包覆的粒子;iii)用第一聚合物层并用第二聚合物层包覆所述油包覆的粒子;iv)其中所述两层聚合物层是不同的并包括选自纤维素、改性纤维素、多糖和或合成聚合物及其混合物的至少两种材料。本发明还提供了包含益生菌颗粒的益生菌组合物,所述组合物展示高耐热性和长期存储稳定性,其中所述益生菌颗粒包括:i)芯,其包含益生菌微生物和所述微生物被吸收到其中的基质;ii)包覆所述芯的内部油层;和iii)第一外层和第二外层,所述外层包覆所述芯和所述内层,包含至少两种不同的聚合物。
重要地,本发明涉及包含具有芯的颗粒的益生菌组合物,芯含有益生菌微生物和吸收微生物的基质,被内部油层和两个外部聚合物层包围。根据本发明的益生菌组合物显示了对增加的温度的高抵抗性。当本文涉及对增加的温度的高抵抗性时,或当涉及高热稳定性时,预期的是与游离微生物相比,颗粒中的益生菌微生物的存活,且具体地与游离微生物相比,混合在食品制品中的颗粒中的益生菌微生物的存活。在本发明的一个方面中,在颗粒暴露于比环境温度高的温度时,三层颗粒的芯中的益生菌微生物存活。根据本发明的益生菌组合物的热稳定性足够高以保证混合在本发明的益生菌食品制品中的初始细菌接种量的一部分即使在所有必需的制造步骤之后仍然是有生活力的。这样的步骤可包括烘焙。
本发明提供了包含如上所述的益生菌组合物的健康食品制品或食品添加剂,益生菌组合物包含稳定的益生菌颗粒。所述制品可优选地包括烘焙制品,例如面粉糕饼或面包。所述制品还可包括金枪鱼、巧克力、果汁和乳制品。
本发明提供了包括面粉糕饼、面包、面粉、面粉制品、烘焙食品、冷冻的烘焙制品、酸奶酪、乳制品、巧克力、花蜜、果汁和金枪鱼的健康食品制品。根据本发明的包含益生菌颗粒的食品制品在生产过程期间可暴露于比环境温度高的温度。
本发明提供了包含益生菌颗粒的食品制品或食品添加剂,其中所述益生菌颗粒包括:i)芯,其包含益生菌微生物和所述微生物被吸收到其中的基质;ii)包覆所述芯的内部油层;和iii)第一外层和第二外层,所述外层包覆所述芯和所述内层,包含至少两种不同的聚合物。
在一些实施方案中,所述食品制品可选自由面粉糕饼、面包、面粉、面粉制品、烘焙食品、冷冻的烘焙制品、酸奶酪、乳制品、巧克力、花蜜、果汁和金枪鱼组成的组。优选地,所述食品制品在生产过程期间可暴露于比环境温度高的温度。
附图简述
通过以下实施例并参照附图,本发明的以上和其它特征及优点将更容易地明白,附图中:
图1显示了被包含在健康食品中的根据本发明的一个实施方案的多层囊的图解;封装被设计为提供在制造过程的加热步骤期间具有最大耐热性,且当提供所述食品时在完整地离开胃之后还在下胃肠道中具有高生物功效的益生菌微生物;白色芯包含益生菌微生物和吸收基质;邻近芯的第一深色层是油层;邻近油层的浅色层是耐酸层;邻近耐酸层的深色层是任选的中间层;且外部浅色层是耐热层。
发明详述
现已惊奇地发现,益生菌微生物可配制在具有至少三层的颗粒的芯中,从而即使在烘焙之后也提供有生活力的益生菌生物体的益生菌组合物,该组合物在存储时还是稳定的,且在口服施用后能够施用有生活力的微生物至结肠。
本发明提供了被用作健康食品添加剂的颗粒状益生菌。本发明具体地涉及一种用于制备烘焙食品诸如益生菌面粉糕饼的方法。混合益生菌微生物的悬浮液并用合适的载体材料造粒以形成待被包覆的粒子的芯部分。益生菌微生物可选自凝结芽胞杆菌(Bacilluscoagulans)GBI-30,6086;枯草芽孢杆菌(Bacillussubtilis)varnatt;双歧杆菌种(Bifidobacteriumsp)LAFTIB94;两岐双岐杆菌(Bifidobacteriumbifidum);两岐双岐杆菌rosell-71;短双岐杆菌(Bifidobacteriumbreve);短双岐杆菌Yakult;短双岐杆菌Rosell-70;婴儿双岐杆菌(Bifidobacteriuminfantis);婴儿双岐杆菌35624;乳双岐杆菌(Bifidobacteriumlactis);长双岐杆菌(Bifidobacteriumlongum);长双岐杆菌Rosell-175;长双岐杆菌BB536;动物双歧杆菌(Bifidobacteriumanimalis);动物双歧杆菌乳亚种(Bifidobacteriumanimalissubsp.lactis)BB-12;动物双歧杆菌乳亚种HN019;大肠埃希氏菌M-17;大肠埃希氏菌Nissle1917;嗜酸乳杆菌(Lactobacillusacidophilus);嗜酸乳杆菌DDS-1;嗜酸乳杆菌L10;嗜酸乳杆菌:LA-5;嗜酸乳杆菌NCFM;干酪乳杆菌(Lactobacilluscasei);干酪乳杆菌L26;干酪乳杆菌CRL431;干酪乳杆菌DN114-001(干酪乳杆菌免疫品种/防御);短乳杆菌(Lactobacillusbrevis);保加利亚乳杆菌(Lactobacillusbulgaricus);加氏乳杆菌(Lactobacillusgasseri);副干酪乳杆菌(Lactobacillusparacasei);干酪乳杆菌(Lactobacilluscasei)F19;干酪乳杆菌Shirota;副干酪乳杆菌St11(或NCC2461);植物乳杆菌(Lactobacillusplantarum);植物乳杆菌299V;罗伊乳杆菌(Lactobacillusreuteri)ATTC55730(罗伊乳杆菌SD2112);鼠李糖乳杆菌(Lactobacillusrhamnosus);唾液乳杆菌(Lactobacillussalivarius);德氏乳杆菌(Lactobacillusdelbrueckii);发酵乳杆菌(Lactobacillusfermentum);乳酸乳杆菌(Lactococcuslactis);乳酸乳杆菌L1A;乳酸乳杆菌亚种(Lactococcuslactissubsp);乳酸乳杆菌Rosell-1058;副干酪乳杆菌St11(或NCC24610);约氏乳杆菌(Lactobacillusjohnsonii)La1(=乳杆菌LC1);约氏乳杆菌La1(=乳杆菌LC1,约氏乳杆菌NCC533);鼠李糖乳杆菌Rosell-11;嗜酸乳杆菌Rosell-52;嗜热链球菌(Streptococcusthermophilus);二乙酰乳酸菌;鼠李糖乳杆菌ATCC53013(由Borbach&Goldin(=LGG)发现);鼠李糖乳杆菌LB21;鼠李糖乳杆菌GR-1&罗伊乳杆菌RC-14;嗜酸乳杆菌NCFM&两岐双岐杆菌BB-12;酿酒酵母(Saccharomycescerevisiae);酿酒酵母(鲍氏)lyo;及其混合物。
造粒过程可使用合适的造粒机,或可选择的流化床。干燥过程可包括冻干法。根据本发明的益生菌颗粒可具有大范围的尺寸。根据本发明的益生菌颗粒的非限制性实例是具有约从0.1微米至约1000微米的平均直径的基本上球形的粒子。不希望受任何理论限制,认为在待进一步用三层微生物学上可接受的材料包覆的粒子芯中将益生菌微生物与微生物学上可接受的聚合物诸如纤维素衍生物混合导致微生物的耐热性增加,其中增加的耐性可起因于降低的热导率和细胞稳定。根据本发明加工的益生菌微生物耐受预定的烘焙温度和烘焙时间的烘焙热。认为内部油层和第一外层(肠溶包覆层)在它们通过上胃肠道通道过程中还保护益生菌微生物,能够在小肠或结肠中或在两者中释放益生菌。本发明的颗粒状益生菌组合物的结构保证了在其用于制备食品制品之前存储时以及在食品制品存储时在食品制品内部相对高的稳定性(微生物生活力)。此外,所述结构保证了有生活力的微生物在食用健康食品例如健康烘焙制品的人的下胃肠道中的期望的释放。此外,当支持有益微生物的生长的寡糖(被称为益生菌)也包括在益生菌组合物中时,整个有益效果可被进一步增强。任选地,所述第一外层(胃肠道耐受包覆层,被称为肠溶包覆层)可通过中间惰性包覆层与所述第二外层(外部耐热包覆层)分离以便阻止它们之间的任何可能的反应。
所述内部油层可选自由蜂蜡、巴西棕榈蜡、日本蜡、骨蜡、石蜡、中国蜡、羊毛脂(羊毛蜡)、虫胶蜡、鲸蜡、蜡果杨梅脂、小烛树蜡、蓖麻蜡、梧牙草蜡、霍霍巴油、小冠巴西棕蜡、米糠蜡、大豆蜡、地蜡(ceresinwaxes)、褐煤蜡、地蜡(ozocerite)、泥煤蜡、微晶蜡、凡士林、聚乙烯蜡、费托蜡、化学改性蜡、取代酰胺蜡、聚合α-烯烃、植物油、氢化植物油、氢化蓖麻油、脂肪酸、脂肪酸酯、脂肪醇、酯化脂肪二醇、羟化脂肪酸、硬脂酸、硬脂酸钠、硬脂酸钙、硬脂酸镁、棕榈酸酯、棕榈油酸、羟基棕榈酸酯、长链油酸酯、脂肪醇、羟基二十八烷基羟基硬脂酸酯、磷脂、卵磷脂、磷脂酰胆碱组成的组。
根据常规程序,所述第一外层可包括一层或多层pH敏感涂层(在本领域中通常被称为“肠溶涂层”),以便延迟益生菌微生物的释放。合适的pH敏感聚合物包括在胃的pH下相对不溶且不可渗透但在小肠和结肠的pH下是更可溶的或易碎裂的或可渗透的那些。这样的pH敏感聚合物包括聚丙烯酰胺、邻苯二甲酸酯衍生物诸如碳水化合物的邻苯二甲酸酯、邻苯二甲酸醋酸直链淀粉、邻苯二甲酸醋酸纤维素(CAP)、其它邻苯二甲酸纤维素酯、邻苯二甲酸纤维素醚、邻苯二甲酸羟丙基纤维素(HPCP)、邻苯二甲酸羟丙基乙基纤维素(HPECP)、邻苯二甲酸羟丙基甲基纤维素(HPMCP)、HPMCAS、邻苯二甲酸甲基纤维素(MCP)、邻苯二甲酸聚乙烯乙酸酯(PVAcP)、邻苯二甲酸氢聚乙烯乙酸酯、邻苯二甲酸醋酸纤维素钠、淀粉酸邻苯二甲酸酯、乙酸-1,2,4-苯三酸纤维素(CAT)、苯乙烯顺丁烯二酸/邻苯二甲酸二丁酯共聚物、苯乙烯-顺丁烯二酸/聚邻苯二甲酸乙烯乙酸酯共聚物、苯乙烯和顺丁烯二酸共聚物、聚丙烯酸衍生物诸如丙烯酸和丙烯酸酯共聚物、聚甲基丙烯酸及其酯、聚丙烯酸和甲基丙烯酸共聚物、虫胶、以及乙酸乙烯酯和巴豆酸共聚物。优选的pH敏感聚合物包括虫胶、邻苯二甲酸酯衍生物、CAT、HPMCAS、聚丙烯酸衍生物,具体地包括丙烯酸和至少一种丙烯酸酯的共聚物、与丙烯酸和丙烯酸酯共聚物共混的聚甲基丙烯酸甲酯,以及乙酸乙烯酯、巴豆酸共聚物、海藻酸和海藻酸盐诸如海藻酸铵、海藻酸钠、海藻酸钾、海藻酸镁或海藻酸钙。pH敏感聚合物的特别优选的组包括CAP、PVAcP、HPMCP、HPMCAS、甲基丙烯酸和甲基丙烯酸甲酯的阴离子丙烯酸共聚物,以及包含丙烯酸和至少一种丙烯酸酯的渗透聚合物(osmopolymer)。邻苯二甲酸醋酸纤维素可被应用为本发明的封装益生菌组合物的肠溶涂层以提供益生菌微生物的延迟释放,直到剂型离开胃。CAP涂层溶液还可含有一种或多种增塑剂,诸如邻苯二甲酸二乙酯、聚乙二醇-400、三醋精、三醋精柠檬酸酯(triacetincitrate)、丙二醇以及其它本领域已知的。优选的增塑剂是邻苯二甲酸二乙酯和三醋精。CAP涂层制剂还可含有一种或多种乳化剂,诸如聚山梨醇酯-80。
甲基丙烯酸和甲基丙烯酸甲酯的阴离子丙烯酸共聚物也是用于延迟益生菌微生物的释放直到其运动至胃肠道中胃远端的位置的特别有用的肠溶涂层材料。这种类型的共聚物可以商品名EUDRAGIT-L和EUDRAGIT-S从RohmAmerica,Inc获得。EUDRAGIT-L和EUDRAGIT-S是甲基丙烯酸和甲基丙烯酸甲酯的阴离子共聚物。在EUDRAGIT-L中游离羧基与酯的比率为约1:1且在EUDRAGIT-S中为约1:2。还可使用EUDRAGIT-L和EUDRAGIT-S的混合物。为了包覆,这些丙烯酸涂层聚合物可溶解于有机溶剂或有机溶剂的混合物中或悬浮在水介质中。用于该目的的有用溶剂是丙酮、异丙醇和二氯甲烷。通常建议在丙烯酸共聚物的涂层制剂中包括5-20wt%增塑剂。有用的增塑剂包括聚乙二醇、丙二醇、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯、蓖麻油和三醋精。EUDRAGIT-L是优选的,因为其在肠的pH下相对迅速地溶解。除了以上所列的pH敏感聚合物以外,延迟释放涂层可由两种或更多种pH敏感聚合物的混合物或共混物组成,或可由一种或多种pH敏感聚合物和一种或多种非pH敏感聚合物的混合物组成。在调节延迟的持续时间或益生菌微生物从颗粒、珠或小球中释放的速率时,向pH敏感聚合物中加入非pH敏感聚合物是有用的。例如,可通过混合水不溶性聚合物与pH敏感聚合物来延长延迟,同时可通过混合水溶性聚合物与pH敏感聚合物来缩短延迟。优选的非pH敏感水不溶性聚合物包括纤维素酯、纤维素醚、聚丙烯酸酯、聚酰胺、聚酯和乙烯基聚合物。优选的非pH敏感水溶性聚合物包括羟烷基取代的纤维素制品诸如HPC、HEC和HPMC、PVA、PEG、PEO、PEG/PPG共聚物,和水溶性聚酰胺、多糖和聚丙烯酸酯。
在这样的涂层中可包括不同的添加剂,添加剂包括乳化剂、增塑剂、表面活性剂、填料和缓冲剂。最后,在剂型离开胃之后聚合物涂层保持基本完整,持续显著的一段时间(例如,大于一小时),之后成为充分益生菌微生物可渗透的以允许益生菌微生物通过经由涂层的扩散而逐步释放的意义上,聚合物涂层可以被描述为“准肠道的”。
任选地,根据本发明的制剂的特征为肠溶层和外部耐热层之间的中间层。根据本发明的组合物的中间包覆层基本上完全覆盖每个单独单元的肠溶涂层。提供中间层以便阻止肠溶层和外部耐热层之间的直接接触,从而阻止它们之间的任何相互作用。根据本发明的实施方案中的任何一个的中间包覆层任选地且优选地包括水溶性聚合物中的一种,水溶性聚合物包括但不限于乙烯类聚合物诸如聚维酮(PVP:聚乙烯吡咯烷酮)、聚乙烯醇、PVP和聚乙酸乙烯酯的共聚物、交联乙烯类聚合物、HPC(羟丙基纤维素)(更优选低分子量)、HPMC(羟丙基甲基纤维素)(更优选低分子量)、CMC(羧甲基纤维素)(更优选低分子量)、乙基纤维素、MEC(甲基乙基纤维素)、CMEC(羧甲基乙基纤维素)、HEC(羟乙基纤维素)、HEMC(羟甲基乙基纤维素)、聚氧化乙烯、阿拉伯胶、糊精、硅酸镁铝、淀粉、聚丙烯酸、聚甲基丙烯酸羟乙酯(PHEMA)、聚甲基丙烯酸酯及它们的共聚物、树胶、水溶性树胶、多糖、交联多糖、肽或交联肽、蛋白质或交联蛋白质、明胶或交联明胶、水解明胶或交联水解明胶、胶原或交联胶原、改性纤维素、聚丙烯酸或交联聚丙烯酸和/或其混合物。
所述第二外层(外部耐热涂层)可包括直链的、支链的或交联的聚合物。它们可以是均聚物或共聚物或接枝共聚物或嵌段共聚物,单一的或共混物。虽然它们可以是合成聚合物,优选地,这样的聚合物可以是天然存在的聚合物诸如多糖、交联多糖、树胶、改性多糖、改性淀粉和改性纤维素。多糖可选自由壳多糖、壳聚糖、右旋糖酐、支链淀粉、琼脂树胶、阿拉伯树胶、刺梧桐树胶、刺槐豆胶、黄蓍胶、角叉菜胶、印度胶、瓜尔胶、黄原胶和硬葡聚糖、淀粉、糊精和麦芽糖糊精、亲水胶体诸如果胶、高甲氧基果胶和低甲氧基果胶组成的组。磷脂诸如卵磷脂可应用于组合物中。交联多糖可选自由海藻酸盐、果胶、黄原胶、瓜尔胶、黄蓍胶和刺槐豆胶、角叉菜胶的不溶性金属盐或交联衍生物、其金属盐及其共价交联衍生物组成的组。改性纤维素可以选自由羟丙基纤维素、羟丙基甲基纤维素、羟乙基纤维素、甲基纤维素、羧甲基纤维素的交联衍生物和羧甲基纤维素的金属盐组成的组。更优选地,这样的聚合物可以是阳离子型聚合物。阳离子型聚合物的例子包括但不限于阳离子聚胺;阳离子聚丙烯酰胺;阳离子聚乙烯亚胺;阳离子聚乙烯醇,阳离子聚乙烯醇是聚丙烯酸二甲氨基乙酯/聚乙烯醇接枝共聚物的氯甲基季盐或聚丙烯酸二甲氨基乙酯/聚乙烯醇接枝共聚物的硫酸甲酯季盐;以名称QUAT.RTM.-188从DowChemicalCompany可获得的PVA与N-(3-氯-2-羟丙基)-N,N,N-三甲基氯化铵的一系列干燥共混物,含有不同量的水和NaOH;阳离子聚乙烯吡咯烷酮;明胶;聚乙烯吡咯烷酮;聚乙酸乙烯酯和聚乙烯吡咯烷酮的共聚物;聚乙烯醇和聚乙烯吡咯烷酮的共聚物;聚乙烯亚胺、聚烯丙胺及其盐、聚乙烯胺及其盐;双氰胺-聚亚烷基聚胺缩合物;聚亚烷基聚胺-双氰胺铵缩合物;双氰胺-福尔马林缩合物;表氯醇-二烃基胺的加成聚合物;二烯丙基二甲基氯化铵(“DADMAC”)的聚合物;以名称EudragitE可从RohmPharma(Degusa)获得的甲基丙烯酸二甲氨基乙酯和中性甲基丙烯酸酯的共聚物;二烯丙基二甲基氯化铵-SO2、聚乙烯咪唑、聚乙烯吡咯烷酮的共聚物;乙烯基咪唑、聚脒、壳聚糖、阳离子化淀粉、阳离子多糖诸如阳离子瓜尔胶和阳离子羟丙基瓜尔胶的共聚物;乙烯基苄基三甲基氯化铵、(2-甲基丙烯酰氧基乙基)三甲基氯化铵的聚合物;甲基丙烯酸二甲氨基乙酯、具有侧链季铵盐的聚乙烯醇、阳离子聚乙烯甲酰胺、阳离子聚乙烯乙酰胺、阳离子聚乙烯甲基甲酰胺、阳离子聚乙烯甲基乙酰胺、聚二甲氨基丙基甲基丙烯酰胺(DMAPMAM)、聚丙烯酸二甲氨基乙酯、聚丙烯酰乙基三甲基氯化铵、聚丙烯酰氨基丙基三甲基氯化铵(聚APTAC)、聚甲基丙烯酰氨基丙基三甲基氯化铵(聚MAPTAC)及其盐、聚乙烯基吡啶及其盐、聚二甲胺-共聚-表氯醇、聚二甲胺-共聚-表氯醇-共聚-乙二胺、聚酰氨基胺-表氯醇、阳离子淀粉的聚合物;含有聚合单元形式的且如果需要的话以分裂形式的N-乙烯基甲酰胺、烯丙胺、二烯丙基二甲基氯化铵、N-乙烯基乙酰胺、N-乙烯基吡咯烷酮、N-甲基-N-乙烯基甲酰胺、N-甲基-N-乙烯基乙酰胺、二甲氨基丙基甲基丙烯酰胺、丙烯酸二甲氨基乙酯、丙烯酸二乙氨基乙酯、丙烯酰乙基三甲基氯化铵或甲基丙烯酰基酰氨基丙基三甲基氯化铵的共聚物;以及其盐及其组合。壳聚糖可具有从80%至大于95%范围的脱乙酰度。壳聚糖还可任选地具有从50mpa至800mpa范围的粘度。壳聚糖可以任选地是三甲基壳聚糖或季铵化壳聚糖。聚合物还可以任选地是聚葡糖胺,聚葡糖胺是壳聚糖的组分之一。例如,聚合物可以任选地是D-葡糖胺的β-1,4-聚合物或D-葡糖胺和N-乙酰基-D-葡糖胺的β-1,4-聚合物。
根据本发明的优选的实施方案,将所述颗粒芯中的益生菌微生物与基质混合。所述基质可包括单糖,诸如包括酮丙糖(二羟基丙酮)和丙醛糖(甘油醛)的丙糖;丁糖,诸如酮丁糖(赤藓酮糖)、丁醛糖(赤藓糖、苏阿糖)和戊酮糖(核酮糖、木酮糖);戊糖,诸如戊醛糖(核糖、阿拉伯糖、木糖、来苏糖)、脱氧糖(脱氧核糖)和己酮醣(阿洛酮糖、果糖、山梨糖、塔格糖);己糖,诸如己醛醣(阿洛糖、阿卓糖、葡萄糖、甘露糖、古洛糖、艾杜糖、半乳糖、塔罗糖)、脱氧糖(海藻糖、墨角藻糖、鼠李糖);和庚糖,诸如(景天庚酮糖),以及辛糖和壬糖(神经氨酸)。基质可包括多种糖,诸如1)二糖诸如蔗糖、乳糖、麦芽糖、海藻糖、松二糖和纤维二糖,2)三糖诸如棉子糖、松三糖和麦芽三糖,3)四糖诸如阿卡波糖和水苏糖,4)其它寡糖诸如低聚果糖(FOS)、半乳寡聚糖(GOS)和甘露寡聚糖(MOS),5)多糖,诸如基于葡萄糖的多糖/葡聚糖,包括糖原、淀粉(直链淀粉、支链淀粉)、纤维素、糊精、右旋糖酐、β-葡聚糖(酵母聚糖、香菇多糖、西佐喃)和麦芽糖糊精;基于果糖的多糖/果聚糖,包括菊粉、果聚糖β2-6;基于甘露糖的多糖(甘露聚糖);基于半乳糖的多糖(半乳聚糖);和基于N-乙酰葡糖胺的多糖,包括壳多糖。可包括其它多糖,包括树胶诸如阿拉伯胶(阿拉伯树胶(gumacacia))。
根据本发明的优选的实施方案,所述内部芯中的益生菌微生物与还可包括另外的组分的基质混合。组分可选自螯合剂。优选地,螯合剂选自由抗氧化剂、依地酸二钾、依地酸二钠、依地酸钙二钠、依地酸、富马酸、苹果酸、麦芽醇、依地酸钠、依地酸三钠组成的组。
根据本发明的一些实施方案,芯还包括螯合剂和增效剂(多价螯合剂(sequestrate))两者。不希望受单一假设或理论限制,螯合剂和多价螯合剂可以任选地区分如下。螯合剂诸如柠檬酸意图帮助痕量金属的螯合,从而通过氧化帮助阻止活性成分诸如辛伐他汀的损失。多价螯合剂诸如抗坏血酸任选地且优选地具有若干羟基和/或羧酸基团,这些羟基和/或羧酸基团可提供氢供给以再生非活化的抗氧化剂自由基。因此多价螯合剂优选地作为氢的供应者以再生主抗氧化剂。根据本发明的优选的实施方案,芯还包括抗氧化剂。优选地,抗氧化剂选自由半胱氨酸盐酸盐、4,4-(2,3-二甲基四亚甲基二邻苯二酚)、富含生育酚的提取物(天然维生素E)、α-生育酚(合成维生素E)、β-生育酚、γ-生育酚、δ-生育酚、丁基氢醌(butylhydroxinon)、丁基羟基茴香醚(BHA)、丁基羟基甲苯(BHT)、没食子酸丙酯、没食子酸辛酯、没食子酸十二酯、叔丁基氢醌(TBHQ)、富马酸、苹果酸、抗坏血酸(维生素C)、抗坏血酸钠、抗坏血酸钙、抗坏血酸钾、抗坏血酸棕榈酸酯和抗坏血酸硬脂酸酯组成的组。包含在芯中的可以是柠檬酸、乳酸钠、乳酸钾、乳酸钙、乳酸镁、阿诺克索默、异抗坏血酸、异抗坏血酸钠、异抗坏血酸(erythorbinacid)、异抗坏血酸钠(sodiumerythorbin)、乙氧喹、甘氨酸、愈创树脂、柠檬酸钠(柠檬酸单钠、柠檬酸二钠、柠檬酸三钠)、柠檬酸钾(柠檬酸单钾、柠檬酸三钾)、卵磷脂、聚磷酸脂、酒石酸、酒石酸钠(酒石酸单钠、酒石酸二钠)、酒石酸钾(酒石酸单钾、酒石酸二钾)、酒石酸钠钾、磷酸、磷酸钠(磷酸单钠、磷酸二钠、磷酸三钠)、磷酸钾(磷酸单钾、磷酸二钾、磷酸三钾)、乙二胺四乙酸钙二钠(EDTA钙二钠)、乳酸、三羟基丁酰苯和硫代二丙酸。根据一个优选的实施方案,抗氧化剂是BHA。
根据本发明的优选的实施方案,芯还包括稳定剂。优选地,稳定剂可以是可使制剂的水溶液或分散体的pH升高到至少约6.8的碱性物质。这样的碱性物质的实例包括但不限于,抗酸剂诸如铝偏硅酸镁、铝硅酸镁、铝酸镁、干燥氢氧化铝、合成水滑石、合成硅酸铝、碳酸镁、沉淀碳酸钙、氧化镁、氢氧化铝和碳酸氢钠及其混合物;和pH调节剂诸如L-精氨酸、磷酸钠、磷酸氢二钠、磷酸二氢钠、磷酸钾、磷酸氢二钾、磷酸二氢钾、柠檬酸二钠、琥珀酸钠、氯化铵和苯甲酸钠及其混合物。碱性物质可选自由无机水溶性化合物或无机水不溶性化合物组成的组。无机水溶性碱性物质的实例包括但不限于,碳酸盐诸如碳酸钠或碳酸钾、碳酸氢钠、碳酸氢钾;磷酸盐,选自例如无水二碱式磷酸钠、无水二碱式磷酸钾、无水二碱式磷酸钙、磷酸三钠;碱金属氢氧化物,选自氢氧化钠、氢氧化钾或氢氧化锂;及其混合物。在存储过程中可吸附在组合物的粒子上的水分的存在下,碳酸氢钠有利地用来中和组合物中的酸基。碳酸钙在存储的组合物中发挥缓冲作用,而在摄食之后对材料释放没有明显的作用。还发现,碳酸盐充分地稳定组合物。无机水不溶性碱性物质的实例包括但不限于能够给予必要的碱度的合适的碱性化合物,包括通常应用于抗酸组合物中的某些药学上可接受的无机化合物,例如,氧化镁、氢氧化镁或碳酸镁、碳酸氢镁、氢氧化铝或氢氧化钙或碳酸铝或碳酸钙,复合的铝-镁化合物,诸如氢氧化镁铝、硅酸盐化合物诸如硅酸镁铝(VeegumF)、铝偏硅酸镁(NesulinFH2)、铝硅酸镁(NisulinA);以及药学上可接受的磷酸盐诸如三碱式磷酸钙;及其混合物。
本发明能够制造不同的健康食品制品而不分离混合加热步骤。能够例如制备含有益生菌颗粒的面包面团,避免现有技术方法的任何难处理的注射步骤。益生菌组合物和面团的其余部分之间的质量比可以是例如1:100。根据本发明的封装的益生菌微生物可并入面粉、面粉制品、烘焙食品、酸奶酪、金枪鱼、冷冻的烘焙制品、巧克力、热饮、花蜜和果汁及在处理和/或生产过程期间可暴露于比周围温度(室温)高的温度的其它制品中。
将在以下实施例中进一步描述和说明本发明。
实施例
实施例1
材料
材料: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
氢化植物油 | 第一包覆层剂 |
乙基纤维素E100 | 第二包覆层聚合物 |
海藻酸钠 | 第二包覆层聚合物和耐热聚合物 |
氯化钙 | 耐热组分(硬化剂) |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程。
2.利用氢化植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将氢化植物油喷涂到吸收了细菌的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
利用分别在6%(w/w)总固体浓度的乙醇中的85:15比率的乙基纤维素E100和海藻酸钠的溶液进行包覆。包覆过程的终点目标是通过包覆获得20%的重量增加。在40℃下利用流化床包覆机进行包覆过程。
4.第三包覆层-耐热涂层
海藻酸钙被用作第三包覆层的耐热聚合物。首先,单独制备海藻酸钠(3%w/w)和氯化钙(5%w/w)的水溶液。然后,将海藻酸钠和氯化钙溶液可选择地喷涂到得到的被包覆的微生物上,直到获得20%(w/w)的重量增加。
实施例2
材料
成分: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
氢化植物油 | 第一包覆层剂 |
高粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
盐酸(HCl) | pH调节剂 |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免微生物暴露于高温,且因此避免高温损害。
2.利用氢化植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将氢化植物油喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的微生物上,直到获得15%的的重量增加。
4.第三包覆层-耐热涂层
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得20%(w/w)的重量增加。
实施例3
材料
成分: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
氢化植物油 | 第一包覆层剂 |
低粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
盐酸(HCl) | pH调节剂 |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备细菌与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中细菌的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免细菌暴露于高温,且因此避免高温损害。
2.利用氢化植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将氢化植物油喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的细菌上,直到获得15%的的重量增加。
4.第三包覆层-耐热涂层,
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得20%(w/w)的重量增加。
实施例4
材料
成分: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
饱和植物油 | 第一包覆层剂 |
高粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
二氧化硅 | 助流剂 |
盐酸(HCl) | pH调节剂 |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免微生物暴露于高温,且因此避免高温损害。
2.利用饱和植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将饱和植物油喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的微生物上,直到获得15%的的重量增加。
4.第三包覆层-耐热涂层
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。然后,壳聚糖完全溶解之后,加入二氧化硅(1%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得25%(w/w)的重量增加。
实施例5
材料
成分: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
氢化植物油 | 第一包覆层剂 |
高粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
盐酸(HCl) | pH调节剂 |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免微生物暴露于高温,且因此避免高温损害。
2.利用氢化植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将氢化植物油喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的微生物上,直到获得15%的的重量增加。
4.第三包覆层-耐热涂层
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得30%(w/w)的重量增加。
实施例6
材料
成分: | 功能: |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
氢化植物油 | 第一包覆层剂 |
高粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
盐酸(HCl) | pH调节剂 |
方法
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免微生物暴露于高温,且因此避免高温损害。
2.利用氢化植物油的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将氢化植物油喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的微生物上,直到获得25%的的重量增加。
4.第三包覆层-耐热涂层
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得20%(w/w)的重量增加。
实施例7
测试封装的益生菌微生物颗粒的耐热性。因此,将来自实施例6的得到的封装的微生物颗粒暴露于85℃下45分钟。然后,利用如下描述的计数程序确定CFU/g。
嗜酸乳杆菌和双歧乳杆菌计数程序:
将10g样品悬浮于90ml磷酸盐缓冲液中并放置于胃托(Stomacher)中10分钟。然后,将得到的悬浮液摇动90分钟。然后将混合物连续地(十倍地)稀释,且最后倒入合适的板培养基中。含有半胱氨酸或麦芽糖的MRS生长介质分别用于嗜酸菌(acidophilus)和两叉菌(bifidus)。然后将得到的板在厌氧条件下温育3天。最后对微生物计数,并因此计算CFU/g。
结果:
*最终产品中两种微生物类型之间的重量比是1:1。
**微生物共混物构成最终产品的10%(w/w)。
***加热过程在80℃下进行45分钟。
实施例8
益生菌饼干
该益生菌饼干由0.3g填充物和30g饼干组成。填充物:将以下成分在室温下混合(百分比是基于总填充物重量的重量百分比):饼干配方:与1%益生菌粉末混合的1份糖、2份人造黄油、3份面粉。
微生物成活率
最高温度为约200℃,应用多达4.5分钟;其适合大多数工业饼干生产。烘焙后维持约50%活微生物。
实施例9
益生菌面包
该益生菌面包由0.3g填充物和30g面包组成。
微生物成活率
在模拟中获得的微生物成活率水平在50%至80%之间。以109微生物每克的起始点在200℃下烘焙10分钟后获得了多达83%活微生物。
实施例10
在干燥条件下根据本发明的封装的益生菌微生物的耐热性评估
目的
评估利用基于本发明的技术封装的益生菌微生物在干燥条件下与未包覆的益生菌微生物相比的耐热性和成活率。
总结
将封装的益生菌微生物和未封装的益生菌微生物(嗜酸乳杆菌和双歧杆菌)两者均放置于预热至80℃的烘箱中30分钟或45分钟。然后将益生菌取出并进行CFU测试以确定微封装的微生物与未封装的微生物对比的成活率。结果显示未封装的益生菌暴露于如此热的条件可能是灾难性的,其中不能计算CFU/g,这表明未封装的微生物发生全部破坏。相反,基于根据本发明的微囊化过程的封装的益生菌在这样的热处理条件之后在生活力测试中未显示显著的减少。基于这些结果,可推断,利用基于本发明的多层包覆的微囊化过程在以上所述的条件下对益生菌提供耐热性。
材料
2克根据本发明的被包覆的益生菌混合微生物(嗜酸乳杆菌和双歧杆菌)。表1中呈现了包覆层的组成。
2克未包覆的混合细菌(嗜酸乳杆菌和双歧杆菌)
方法
根据制造者加工记录批号RDEN904051和RDEN904051进行微囊化过程。
表1:微囊化过程的不同步骤的组分
成分 | 步骤 |
微晶纤维素(MCC) | 造粒内部芯 |
海藻糖脱水物 | 造粒内部芯 |
麦芽糖糊精DE15 | 造粒内部芯 |
嗜酸乳杆菌 | 造粒内部芯 |
双歧杆菌 | 造粒内部芯 |
氢化植物油(HVO) | 第一包覆层 |
高密度海藻酸钠 | 第二包覆层 |
壳聚糖 | 第三包覆层 |
加热测试
将微封装的和未封装的(对照)益生菌两者引入预热至80℃的烘箱中,持续30分钟或45分钟。
CFU测试
利用如下描述的方法在加热过程之前和之后对细菌进行CFU测试;
1)10g样品与90ml磷酸盐缓冲液。
2)胃托10分钟。
3)摇动样品90分钟。
4)十倍地稀释。
5)倾注培养法。
6)对于嗜酸菌,利用具有半胱氨酸的MRS。
7)对于两叉菌,利用具有麦芽糖而不是乳糖的MRS。
8)在厌氧条件下温育3天。
9)对细菌计数并计算CFU/g。该方法已在别处详细地描述(K.G.deC.Lima等人/LWT-FoodScienceandTechnology42(2009),491-494)。
对于封装的益生菌细菌,首先,在应用以上CFU方法之前利用研钵和杵破坏包围微生物的多层壳。
结果
表2.囊化过程对CFU的影响
*最终产品中两种微生物之间的重量比是1:1。
**微生物共混化合物构成最终产品的10%(w/w)。
表3.干燥条件下热处理对益生菌微生物的成活率的影响
结论
基于表3的结果,可推断,利用根据本发明的多层包覆过程的微囊化过程在干燥条件下对益生菌提供耐热性。
实施例11
在半烘焙条件下根据本发明的封装的益生菌微生物的耐热性评估
目的
评估利用根据本发明的技术封装的益生菌微生物在半烘焙条件下与未包覆的益生菌微生物相比的耐热性和成活率。
总结
将封装的益生菌微生物和未封装的益生菌微生物(嗜酸乳杆菌和双歧杆菌)两者均与白面包成分混合并在180℃、70%湿度下经受烘焙40分钟。为了能够从烘焙的面团中收集微生物,利用被称为“干酪包布(Cheesecloth)”和“馄饨(Ravioli)”的两种不同的方法将封装的微生物和未封装的微生物两者均放入面团中。因此,间接地通过利用干酪包布将微生物加入面团中以分离微生物与面团(干酪包布方法实验I),或直接地通过产生由预先含有微生物的相同面团构成的分离的袋(馄饨方法实验II)将微生物加入面团中。根据干酪包布方法,微生物被预先装入干酪包布中,然后在烘焙过程之前将干酪包布放入面团中(实验Ia),或将微生物放置于干酪包布薄片上,通过在面团块的中心产生小碗状物并由干酪包布薄片填充小碗状物而将干酪包布薄片预先放入面团中(实验Ib)。根据“馄饨”方法,首先由面团形成小袋样馄饨,在馄饨中放置2克被包覆的混合微生物并封闭馄饨。然后将袋放置在面团块的中心。通过这些方式,还可阻止烘焙过程之后面团粘附到微生物。阻止面团粘附到微生物是重要的,因为在这样的实验中,面团在压碎过程中作为“减震器”可构成对抗压碎力的机械屏障。通过这种方式,可确保在测试CFU之前涂层在压碎过程期间被完全破坏。烘焙后,分开微生物并确定每种微生物菌株以及封装的微生物和未封装的微生物的CFU/g。
CFU结果清楚地显示未包覆的微生物不能在烘焙条件下存活,而封装的微生物证明了在烘焙过程期间的耐热性及在烘焙过程后高成活率值。
材料
3杯面粉
10克酵母
2汤匙橄榄油
1/8茶匙盐
水
2克被包覆的益生菌混合微生物(嗜酸乳杆菌和双歧杆菌)
2克未包覆的混合细菌(嗜酸乳杆菌和双歧杆菌)
方法
烘焙过程
将面包成分混合在一起,且捏和几分钟后使面团发起。然后将面团分成单独的块。通过利用如以下所述的两种不同的“干酪包布”和“馄饨”方法(分别由实验I和实验II陈述)将微生物放入面团块中。
实验I-“干酪包布”方法
实验Ia-封装的微生物和未封装的微生物预先装入“干酪包布”中后,将封装的和未封装的微生物两者均放入面团中。将2g封装的微生物或未封装的微生物放置于每个面团块的中部。
实验Ib-将2g封装的微生物放置于干酪包布薄片的表面上,通过产生碗状物并用干酪包布薄片填充而将干酪包布薄片预先放入面团块的中部。然后用剩余的面团覆盖碗状物。
实验II-“馄饨”方法
首先由面团形成小袋样馄饨,在馄饨中放置2克封装的混合微生物并封闭馄饨。然后将袋放置在面团块的中心。
使面团发起另外的15分钟。
在180℃下进行烘焙40分钟。
在烘箱的底架上放置带有1/2升水的金属托盘以在将面包块放入烘箱中之前在烘箱内部产生湿度。在将面包块放入烘箱中之前测量烘箱内部产生的湿度。为了达到最佳的烘焙湿度标准,当湿度达到60%-70%之间时将面包块放入烘箱中。面团块被烘焙后将微生物容易地分出并送至CFU测试。
CFU测试
利用如下描述的方法在烘焙过程之前和之后对微生物进行CFU测试;
1.10g样品与90ml磷酸盐缓冲液。
2.胃托10分钟。
3.摇动样品90分钟。
4.十倍地稀释。
5.倾注培养法。
6.对于嗜酸菌,利用具有半胱氨酸的MRS。
7.对于两叉菌,利用具有麦芽糖而不是乳糖的MRS。
8.在厌氧条件下温育3天。
9.对微生物计数并计算CFU/g。
该方法已在别处详细地描述(K.G.deC.Lima等人/LWT-FoodScienceandTechnology42(2009),491-494)。
对于封装的益生菌细菌,首先,在应用以上CFU方法之前利用研钵和杵破坏包围微生物的多层壳。
结果
表4:在烘焙条件之前和之后封装和未封装的CFU/g
结论
以上获得的结果显示,利用根据本发明的技术的封装益生菌微生物在烘焙过程期间在暴露于面团中存在的湿度时是耐烘焙热的。
实施例12
在全烘焙条件下根据本发明的封装的益生菌微生物的耐热性评估
目的
利用商业程序,评估利用根据本发明的技术封装的益生菌微生物在全烘焙条件下的耐热性和成活率。该研究被设计为显示根据本发明的耐烘焙过程的封装益生菌的概念的可行性,在烘焙过程中封装益生菌经受剪切力、湿度和热。
摘要
该研究的目的是评估根据本发明的封装益生菌在商业使用的烘焙过程中的抵抗力。因此,封装益生菌直接加到面团中,面团首先遭受捏和的剪切力且随后遭受烘焙过程的热和湿度。设计该过程以便模拟商业程序中进行的烘焙过程。为了此目的,将根据本发明的封装益生菌直接加入面粉和其它成分中,然后在其上加入水(直接加入法),且随后捏和并烘焙。因此,将封装益生菌直接加入面团制作成分中,且然后通过捏和而均匀地分布在面团中,封装益生菌在面团中遭受在面团制作步骤期间的潮湿环境,随后遭受烘焙过程的加热。烘焙过程之后,进行CFU测试以确定封装微生物的成活率。CFU结果明显地显示,烘焙过程后封装的微生物证明了高成活率值。因此,可推断,根据本发明的封装益生菌在面团捏合过程中存在的高剪切下明确地耐受潮湿环境以及烘焙过程的热。
材料
面包成分:
白面粉:231克
橄榄油:18.7克
盐:2克
酵母:5克
封装益生菌:2克
烘焙前的面团:398.7克
烘焙后的面包:364.5克
烘焙过程的一般方法
将封装的益生菌微生物嗜酸乳杆菌和双歧杆菌与全部剩余的面包成分(白面包)均匀混合。加入水,且然后捏和面团。然后将得到的面团在180℃、70%湿度下烘焙40分钟。该过程如下:
装置
Kenwood混合器:5升碗状物。
面团制备
将面粉、酵母和封装的微生物放置在混合碗状物中。
将全部成分混合在一起。
加入油和盐。
逐渐加入水,直到面粉混合物形成结实的面团。
让混合器捏和面团10分钟。
关闭混合器并让面团留于碗状物盖中并发起30分钟。
开启混合器几秒钟以将面团“气体排除”。
烘焙程序
首先,在放入面团之前将烘箱预热至180℃。在180℃下进行烘焙40分钟。在烘箱的底架上放置含有1/2升水的金属托盘以在放入面团之前在烘箱内部产生合适的湿度(~70%RH)。在烘焙前测量烘箱内部产生的湿度。在烘焙盘中使面团成形并烘焙40分钟(180℃和70%RH)。在烘焙结束时再次检查湿度。
烘焙条件
烘焙前湿度:70%(RH)。
烘焙后湿度:70%(RH)。
烘焙温度:180℃。
烘焙持续时间:40分钟。
烘焙后取出烘焙面包样品以确定封装微生物的CFU/g。
CFU测试
利用如下描述的CFU方法对烘焙过程后的封装益生菌进行CFU测试:
1)取出20g样品(烘焙面包),向样品中加入90ml无菌磷酸盐缓冲液。
2)然后利用研钵和杵将混合物压碎几分钟。
3)向胃托一次性无菌包中加入另外的160ml无菌磷酸盐缓冲液。
然后利用胃托使混合物均化2分钟。
利用以下常规程序进行CFU/g测试:
1.十倍地稀释。
2.倾注培养法。
3.对于嗜酸菌,利用具有半胱氨酸的MRS。
4.对于两叉菌,利用具有麦芽糖而不是乳糖的MRS。
5.在厌氧条件下温育3天。
6.对微生物计数并计算CFU/g。
该方法已在别处详细地描述(K.G.deC.Lima等人/LWT-FoodScienceandTechnology42(2009),491-494)。
结果
表5中总结了烘焙前和烘焙后的CFU结果。CFU结果清楚地显示,封装微生物证明了在全烘焙过程期间的耐热性和在烘焙过程后高成活率值。
表5:在全烘焙条件下封装益生菌的CFU/g
结论
根据本发明的封装益生菌在商业制备过程中耐受烘焙热,在商业制备中将封装益生菌直接加到所有成分中,且然后在面团中存在的湿度下经受捏和过程,且随后经受烘焙过程的热。这些发现明显地表明,本发明的包覆层制剂提供了具有经得起烘焙产品制备的所有阶段的所需保护的益生菌,所有阶段包括捏和剪切力、相对高的湿度和烘焙热。
实施例13
材料:
成分 | 功能 |
嗜酸乳杆菌 | 益生菌微生物 |
双歧杆菌 | 益生菌微生物 |
微晶纤维素(MCC) | 芯基质 |
麦芽糖糊精 | 微生物的补充剂 |
海藻糖 | 微生物的补充剂 |
硬脂酸 | 第一包覆层油剂 |
高粘度海藻酸钠 | 第二包覆层聚合物 |
壳聚糖 | 耐热聚合物 |
盐酸(HCl) | pH调节剂 |
方法:
1.在微晶芯基质上吸收微生物
在MCC基质上分别地吸收基于38:62比率的嗜酸乳杆菌和双歧杆菌。为了此目的,制备微生物与麦芽糖糊精及海藻糖的30%的水基悬浮液。在该悬浮液中微生物的浓度为约15%(w/w)。在出口温度<35℃下进行吸收过程,以便避免微生物暴露于高温,且因此避免高温损害。
2.利用硬脂酸的第一包覆层
利用基于热熔法的流化床包覆机进行包覆。为了此目的,在40℃下将硬脂酸喷涂到吸收了微生物的MCC基质上以获得40%的重量增加。调低入口空气流量。
3.第二包覆层-肠溶涂层
海藻酸钠被用作肠溶聚合物。制备海藻酸钠的水溶液(2%w/w)。将海藻酸钠溶液喷涂到得到的被包覆的微生物上,直到获得15%的的重量增加。
4.第三包覆层-耐热涂层
壳聚糖被用作第三包覆层的耐热聚合物。首先,利用HCl制备pH5的壳聚糖水溶液(4%w/w)。将得到的溶液喷涂到得到的被包覆的微生物上,直到获得30%(w/w)的重量增加。
虽然已经依据一些具体的实施例描述了本发明,但是很多修改和变化形式是可能的。因此,应理解,在所附权利要求的范围内,本发明可不同于如具体描述的来实现。
Claims (11)
1.一种益生菌颗粒,包括:
i)芯,所述芯包括益生菌微生物和所述微生物被吸收到其中的基质,所述微生物包括选自乳杆菌属(Lactobacillius)、双歧杆菌属(Bifidobacterium)、芽孢杆菌属(Bacillus)、埃希氏菌属(Escherichia)、链球菌属(Streptococcus)、二乙酰乳酸菌属(Diacetylactis)和酵母(Saccharomyces)或其混合物的属;和
至少三个层,包括:
ii)内部油层,所述内部油层包覆所述芯;和
iii)第一外层和第二外层,其中所述第一外层和第二外层包覆所述芯和所述内层,其中所述第一外层是肠溶包覆层,所述肠溶包覆层包括选自包括下列的组的pH敏感性聚合物:海藻酸、海藻酸铵、海藻酸钠、海藻酸钾、海藻酸镁或海藻酸钙;且所述第二外层是外部耐热涂层,所述外部耐热涂层包含选自包括下列的组的至少一种聚合物:多糖、交联多糖、树胶、改性多糖、改性淀粉、改性纤维素、壳多糖、壳聚糖、右旋糖酐、支链淀粉、琼脂树胶、阿拉伯树胶、刺梧桐树胶、刺槐豆胶、黄蓍胶、角叉菜胶、印度胶、瓜尔胶、黄原胶、硬葡聚糖、糊精、麦芽糖糊精、果胶、高甲氧基果胶、低甲氧基果胶、卵磷脂;海藻酸盐、果胶、黄原胶、瓜尔胶、黄蓍胶、刺槐豆胶、角叉菜胶的不溶性金属盐和交联衍生物、其金属盐及其共价交联衍生物;羟丙基纤维素、羟丙基甲基纤维素、羟乙基纤维素、甲基纤维素、羧甲基纤维素的交联衍生物、羧甲基纤维素的金属盐;阳离子型聚合物、阳离子聚胺、阳离子聚丙烯酰胺、阳离子聚乙烯亚胺、阳离子聚乙烯醇、聚丙烯酸二甲氨基乙酯/聚乙烯醇接枝共聚物的氯甲基季盐或聚丙烯酸二甲氨基乙酯/聚乙烯醇接枝共聚物的硫酸甲酯季盐、PVA与N-(3-氯-2-羟丙基)-N,N,N-三甲基氯化铵的一系列干燥共混物、阳离子聚乙烯吡咯烷酮、明胶、聚乙烯吡咯烷酮、聚乙酸乙烯酯和聚乙烯吡咯烷酮的共聚物、聚乙烯醇和聚乙烯吡咯烷酮的共聚物、聚乙烯亚胺、聚烯丙胺及其盐、聚乙烯胺及其盐、双氰胺-聚亚烷基聚胺缩合物、聚亚烷基聚胺-双氰胺铵缩合物、双氰胺-福尔马林缩合物、表氯醇-二烃基胺的加成聚合物、二烯丙基二甲基氯化铵(“DADMAC”)的聚合物、甲基丙烯酸二甲氨基乙酯和中性甲基丙烯酸酯的共聚物;二烯丙基二甲基氯化铵-SO2、聚乙烯咪唑、聚乙烯吡咯烷酮的共聚物;乙烯基咪唑、聚脒、壳聚糖、阳离子化淀粉和阳离子多糖的共聚物;乙烯基苄基三甲基氯化铵、(2-甲基丙烯酰氧基乙基)三甲基氯化铵的聚合物、甲基丙烯酸二甲氨基乙酯、具有侧链季铵盐的聚乙烯醇、阳离子聚乙烯甲酰胺、阳离子聚乙烯乙酰胺、阳离子聚乙烯甲基甲酰胺、阳离子聚乙烯甲基乙酰胺、聚二甲氨基丙基甲基丙烯酰胺(DMAPMAM)、聚丙烯酸二甲氨基乙酯、聚丙烯酰乙基三甲基氯化铵、聚丙烯酰氨基丙基三甲基氯化铵(聚APTAC)、聚甲基丙烯酰氨基丙基三甲基氯化铵(聚MAPTAC)及其盐、聚乙烯基吡啶及其盐、聚二甲胺-共聚-表氯醇、聚二甲胺-共聚-表氯醇-共聚-乙二胺、聚酰氨基胺-表氯醇、阳离子淀粉的聚合物、含有聚合单元形式的和分裂形式的N-乙烯基甲酰胺、烯丙胺、二烯丙基二甲基氯化铵、N-乙烯基乙酰胺、N-乙烯基吡咯烷酮、N-甲基-N-乙烯基甲酰胺、N-甲基-N-乙烯基乙酰胺、二甲氨基丙基甲基丙烯酰胺、丙烯酸二甲氨基乙酯、丙烯酸二乙氨基乙酯、丙烯酰乙基三甲基氯化铵或甲基丙烯酰基酰氨基丙基三甲基氯化铵的共聚物及其盐或其组合、聚葡糖胺、D-葡糖胺的β-1,4-聚合物或D-葡糖胺和N-乙酰基-D-葡糖胺的β-1,4-聚合物。
2.根据权利要求1所述的益生菌颗粒,其中所述阳离子多糖是阳离子瓜尔胶或阳离子羟丙基瓜尔胶。
3.根据权利要求1或2所述的益生菌颗粒,其中三层颗粒的芯中的所述益生菌微生物经得住所述颗粒被暴露于高于环境温度的温度。
4.根据权利要求1-3中任一项所述的益生菌颗粒,其中所述益生菌微生物被吸收在基质中,所述基质包括选自糖类和另外的剂的一种或多种组分。
5.根据权利要求4所述的益生菌颗粒,其中所述剂选自稳定剂、螯合剂、增效剂、抗氧化剂和pH调节剂,且其中所述糖类包括益生菌寡糖。
6.根据任一项前述权利要求所述的益生菌颗粒,还包括被定位在所述油层和所述第二外层之间的至少一层中间层。
7.一种用于制造权利要求1所述的颗粒的方法,包括:
将益生菌微生物的悬浮液与基于纤维素的基质以及与所述微生物的补充剂混合,从而获得芯混合物;用油层包覆所述芯混合物的粒子,从而获得油包覆的粒子;用第一聚合物层包覆所述油包覆的粒子,其中所述第一聚合物层向所述微生物给予在上胃肠道的条件下的稳定性,从而获得包覆两层的粒子;和用第二聚合物层包覆所述两层粒子,其中所述第二聚合物层增加了所述微生物在烘焙的条件下在所述芯中的稳定性。
8.根据权利要求7所述的方法,其中所述包覆步骤中的每一个产生相对于所述芯的质量,从10%至100%的质量增加。
9.根据权利要求7所述的方法,包括:
i)将包含选自乳杆菌属、双歧杆菌属、芽孢杆菌属、埃希氏菌属、链球菌属、二乙酰乳酸菌属和酵母或其混合物的至少一个属的益生菌微生物的水悬浮液与至少一种多糖和至少一种寡糖混合,从而获得芯混合物;
ii)用油层包覆所述芯混合物的粒子,从而获得油包覆的粒子;
iii)用第一多糖层并用第二多糖层包覆所述油包覆的粒子;
其中所述两层多糖层是不同的,并包括纤维素、海藻酸盐、壳聚糖或其混合物中的至少两种。
10.一种包含根据权利要求1至6中任一项所述的益生菌颗粒的食品制品或食品添加剂。
11.根据权利要求10所述的食品制品,选自由面粉糕饼、面包、面粉、面粉制品、烘焙食品、冷冻的烘焙制品、酸奶酪、乳制品、巧克力、花蜜、果汁和金枪鱼组成的组。
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CN110432495A (zh) * | 2018-05-03 | 2019-11-12 | 内蒙古伊利实业集团股份有限公司 | 一种耐酸耐胆汁盐的益生菌制剂及其制备方法 |
CN111195267A (zh) * | 2018-11-16 | 2020-05-26 | 大汉酵素生物科技股份有限公司 | 具有促进肠干细胞增生、抗病毒、抗发炎和抗过敏功效的乳酸菌晶体组合物及其制备方法 |
CN111195267B (zh) * | 2018-11-16 | 2022-04-12 | 大汉酵素生物科技股份有限公司 | 具有促进肠干细胞增生、抗病毒、抗发炎和抗过敏功效的乳酸菌晶体组合物及其制备方法 |
CN109480038A (zh) * | 2018-12-21 | 2019-03-19 | 杭州远大生物制药有限公司 | 一种耐温益生菌巧克力制品及其制备方法 |
CN111035013A (zh) * | 2019-11-30 | 2020-04-21 | 江苏艾兰得营养品有限公司 | 一种益生菌微胶囊及其制备方法 |
CN111748477A (zh) * | 2020-07-28 | 2020-10-09 | 北部湾大学 | 一种提高益生菌耐受环丙沙星的方法 |
CN113455549A (zh) * | 2021-06-29 | 2021-10-01 | 黑龙江飞鹤乳业有限公司 | 一种奶酪产品及其制备方法和应用 |
CN113455549B (zh) * | 2021-06-29 | 2022-09-13 | 黑龙江飞鹤乳业有限公司 | 一种奶酪产品及其制备方法和应用 |
CN114209063A (zh) * | 2021-12-20 | 2022-03-22 | 广西大学 | 一种佛手多糖包埋副干酪乳杆菌微胶囊的制备方法 |
Also Published As
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ES2700879T3 (es) | 2019-02-19 |
US20130115334A1 (en) | 2013-05-09 |
US9961910B2 (en) | 2018-05-08 |
WO2011004375A1 (en) | 2011-01-13 |
CA2767602A1 (en) | 2011-01-13 |
NZ597992A (en) | 2013-11-29 |
AU2010269814A1 (en) | 2012-03-01 |
CN102595938A (zh) | 2012-07-18 |
AU2010269814A8 (en) | 2014-03-06 |
IL217449A0 (en) | 2012-02-29 |
RU2012104796A (ru) | 2013-08-20 |
EP2451300A4 (en) | 2013-07-31 |
AU2010269814B8 (en) | 2014-03-06 |
AU2010202518A1 (en) | 2010-07-08 |
US20100303962A1 (en) | 2010-12-02 |
RU2549098C2 (ru) | 2015-04-20 |
AU2010202518A8 (en) | 2010-07-22 |
AU2010269814B2 (en) | 2014-02-06 |
US20110008493A1 (en) | 2011-01-13 |
EP2451300A1 (en) | 2012-05-16 |
AU2010202518B2 (en) | 2014-10-23 |
CA2767602C (en) | 2019-04-02 |
EP2451300B2 (en) | 2023-07-19 |
EP2451300B1 (en) | 2018-09-05 |
IL199781A0 (en) | 2010-05-17 |
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