WO2012150839A2 - Method for microencapsulating phosphatidylserine - Google Patents

Method for microencapsulating phosphatidylserine Download PDF

Info

Publication number
WO2012150839A2
WO2012150839A2 PCT/KR2012/003504 KR2012003504W WO2012150839A2 WO 2012150839 A2 WO2012150839 A2 WO 2012150839A2 KR 2012003504 W KR2012003504 W KR 2012003504W WO 2012150839 A2 WO2012150839 A2 WO 2012150839A2
Authority
WO
WIPO (PCT)
Prior art keywords
phosphatidylserine
oil
starch
lecithin
emulsion
Prior art date
Application number
PCT/KR2012/003504
Other languages
French (fr)
Korean (ko)
Other versions
WO2012150839A3 (en
Inventor
한지영
한정준
이관형
정국훈
황성기
Original Assignee
주식회사 두산
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 주식회사 두산 filed Critical 주식회사 두산
Priority to CN201280033216.7A priority Critical patent/CN103635181A/en
Publication of WO2012150839A2 publication Critical patent/WO2012150839A2/en
Publication of WO2012150839A3 publication Critical patent/WO2012150839A3/en

Links

Classifications

    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23J—PROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
    • A23J7/00—Phosphatide compositions for foodstuffs, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • PS phosphatidlyserine
  • Microencapsulation technology is a method to protect the core material from the external environment or to release it at a desired rate under certain conditions by forming a film using a coating material on the core material in a solid, liquid, or gas phase. It can be applied to a wide range of fields such as medicine, food, and cosmetics.It can protect unstable cores from external factors, reduce losses, isolate highly reactive cores, and conceal or solidify toxic, odor and taste. It is used for the purpose of simplifying, controlling the elution rate of the contents, and the like.
  • microencapsulation of highly reactive bioactive ingredients and food materials has the advantages of preventing oxidation and preservation, blocking unwanted flavors, controlling release, enhancing bioavailability, and improving handling and processability by changing physical properties.
  • the coating material of the capsule used in food must be edible, excellent in dissolution, high in emulsification, and easy to operate during microencapsulation. It should also be less reactive with the core material during processing and storage, protect the core material from the external environment, and be economical due to its low price.
  • Carbohydrates, gelatin, cellulose, fats, proteins, gums and the like are used as coating materials, and microencapsulation methods for coating with various coating materials have been studied to overcome disadvantages of highly reactive materials.
  • Phosphatidylserine is a kind of phospholipid (Phospholipid) existing in nature, and is composed of a serine group (hydrophilic moiety), a phosphate group, glycerol and two fatty acid groups (hydrophobic moiety).
  • lecithin In the human brain, lecithin accounts for almost half of the dry weight, and most of the lecithin is contained in the membranes of nerve cells. Lecithin, an important component of the cell membrane, contains phosphatidylserine, which is particularly present in the brain, and constitutes a neural cell membrane, releasing energy for life-sustaining activity, releasing neurotransmitters or synapses. It is known that he is deeply involved in the expression of neurons' function, such as information transmission. For this reason, phosphatidylserine is sometimes called the "nutrient of the brain.”
  • Phosphatidylserine has been subject to dozens of clinical trials since it was first isolated by Jordi Folch in 1942. As a result, phosphatidylserine has been shown to be effective in improving Alzheimer's dementia and in reducing brain function due to aging. have. In addition to the effects of improving brain function, it has been reported to show effects such as improvement in epilepsy, stress tolerance, and recovery of hormone secretion rhythm.
  • Phosphatidylserine has been reported to be effective only when ingested from 100 to 300 mg / day (day), but the supply through food is limited, and the supply through a variety of manufacturing is actively considered (Korea Patent Publication No. 2002-0085756 Reference).
  • Korean Patent Laid-Open Publication No. 2003-0058839 discloses a liquid composition in which medium chain fat is further added to a composition including phosphatidylserine and fats and oils. Such liquid compositions are described as being able to prevent phenomena of increasing viscosity or curing when phosphatidylserine is dissolved in an oil containing unsaturated fatty acids, and furthermore, it can be used in health foods and medicines in the form of soft capsules and the like.
  • the water dispersibility of phosphatidylserine is not good, and even when dispersed in an aqueous solution, the ester bond of phosphatidylserine is gradually hydrolyzed naturally in the aqueous phase, and also has a relatively low oxidation stability.
  • An object of the present invention is to provide a method for microencapsulating phosphatidylserine using starch as a coating material, to improve dispersibility, solubility, and stability in an aqueous solution of phosphatidylserine, and to prevent oxidation by oxygen in light or air. Can improve the long-term preservation and transport properties while maintaining the intrinsic function of phosphatidylserine.
  • Another object of the present invention is to provide a microcapsule preparation preparable by the above method.
  • the present invention comprises the steps of (a) dissolving phosphatidylserine in edible oil to prepare a phosphatidylserine liquid composition; (b) preparing a starch aqueous solution by mixing the processed starch modified with lipophilic and hydrophilicity with water before, after or simultaneously with step (a); (c) mixing and homogenizing the aqueous starch solution and the phosphatidylserine liquid composition to emulsify; And (d) provides a method for microencapsulation of phosphatidylserine, comprising the step of drying the obtained emulsion.
  • the present invention provides a microcapsule formulation comprising phosphatidylserine suitable for food or pharmaceutical use, which can be prepared by the above-described method.
  • the microencapsulation method of phosphatidylserine according to the present invention can prevent phosphatidylserine from being oxidized by oxygen in light or air, improve dispersibility, solubility, stability in water, and improve storage and transport characteristics.
  • phosphatidylserine can be effectively formulated into capsule formulations such as health functional foods (particularly beverages) and medicines while maintaining phosphatidylserine-specific functions such as preventing cognitive decline and reducing stress.
  • the present invention is a method for microencapsulating phosphatidylserine having a function such as improvement of memory, dementia improvement, improvement of epilepsy, stress resistance, recovery of hormonal secretion rhythm using starch which is a biodegradable polymer material.
  • phosphatidylserine having a function such as improvement of memory, dementia improvement, improvement of epilepsy, stress resistance, recovery of hormonal secretion rhythm using starch which is a biodegradable polymer material.
  • starch which is a biodegradable polymer material.
  • it provides a method of microencapsulating in powder form.
  • the phosphatidylserine liquid composition according to the present invention is prepared by dissolving phosphatidylserine in powder or granule form in an edible oil and fat.
  • Phosphatidylserine in the form of a powder is difficult to be incorporated into lipophilic modified starch because the powder particles do not dissolve well in water and have a hydrophilic part and a hydrophobic part together due to the nature of phospholipids. Therefore, it is important to dissolve phosphatidylserine using edible oils and oils to make the oil type closer to lipophilic.
  • the phosphatidylserine is a natural phosphatidylserine derived from animal tissues; Natural phosphatidylserine derived from plant tissues; A phosphatidylserine obtained by reacting lecithin selected from the group consisting of soybean lecithin, rapeseed lecithin, fish-derived lecithin, mollusk-derived lecithin and egg yolk lecithin with serine in the presence of phospholipase D, a saturated fatty acid having 6 to 30 carbon atoms, mono- Unsaturated fatty acids or polyunsaturated fatty acids, or phosphatidylserine, including sodium salts, potassium salts, magnesium salts, ammonium salts, phosphate salts, hydrochloride salts or sulfate salts thereof.
  • Edible oil and fat may be at least one selected from medium chain fat, soybean oil, sunflower oil, grape seed oil, rapeseed oil, olive oil, corn oil, pumpkin seed oil, safflower seed oil, palm oil and the like.
  • medium chain fat refers to an oil or fat consisting of fatty acids having 6 to 10 carbon atoms.
  • Medium chain fat can be absorbed without pancreatic lipase and bile, and has an advantage that the absorption rate is four times faster than long chain fat and does not become accumulated fat. It is also more polar than long chain fats and is well suited for solubilizing phosphatidylserine.
  • the phosphatidylserine liquid composition may further include one or more functional ingredients such as fish oil, saw palmetto fruit extract, vitamins, fragrances including DHA or EPA.
  • Powdered or granular phosphatidylserine and edible oils used in the present invention may be used by removing all organic solvents by concentration under reduced pressure after dissolving in an organic solvent.
  • the organic solvent may be used alone or in combination of two or more common organic solvents, such as ethanol, propanol, hexane, cyclohexane.
  • Phosphatidylserine may be included in 10 to 50% by weight based on the total weight of the composition, but is not limited thereto.
  • Starch is used as the outer wall material of the phosphatidylserine powder capsule of the present invention.
  • the use of starch makes the film constituting the surface rough, but has a firm and flexible elasticity and impact resistance, and a formulation having excellent properties of protecting internal materials from oxidation is obtained.
  • Processed starch used as coating material can be used to heat unmodified starch, enzymes (e.g. hydrolases, isomerases, oxidases, branching enzymes, etc.), acids (e.g. succinic acid, succinic acid, acetic acid).
  • (Modified) starch obtained by treatment with hydrochloric acid, etc.) unlike ordinary starch, it has both hydrophilic and lipophilic properties, and has stable emulsion formation and excellent film forming ability.
  • the starch may be used at about 5 to 30 times (w / w), preferably 5 to 15 times (w / w) of water at 50 to 90 ° C, preferably at 80 ° C.
  • Preparation of the starch aqueous solution may be carried out before, after or simultaneously with the step of preparing the phosphatidylserine liquid composition described above.
  • the starch aqueous solution may contain maltodextrin, arabic gum, guar gum, xanthan gum, sodium casein, gelatin, lecithin, sodium alginate, etc. to suppress elution of phosphatidylserine incorporated into starch and at the same time improve dispersibility in aqueous solution. It may further comprise one or more excipients.
  • the first starch aqueous solution and the phosphatidylserine liquid composition prepared above are mixed and homogenized at 1,000 to 10,000 rpm for 5 to 10 minutes to obtain a first emulsion, and then a high pressure homogenizer, an ultrasonic emulsifier, etc. is used to increase the composition stability.
  • the first emulsion may be further homogenized for 10 to 30 minutes at a pressure condition of 200 to 300 bar to obtain a secondary emulsion.
  • phosphatidylserine may be mixed in an amount of 20 to 50 parts by weight based on 100 parts by weight of starch.
  • Phosphatidylserine may be 1 to 30% by weight, preferably 3 to 20% by weight, based on the total weight of the mixture. If the phosphatidylserine content is less than 1% by weight, it is difficult to maintain the concentration that exerts the bioactive function in the final product, and if it exceeds 30% by weight, the emulsion stability may be deteriorated.
  • Secondary emulsification may be carried out one or more times to stabilize the composition.
  • Heat may be generated during the first and second emulsification, but the homogenization temperature may be generally 30 to 60 ° C, preferably 50 ° C. If the homogenization temperature exceeds 60 °C, the rancidity of phosphatidylserine can be promoted, if less than 30 °C the coating material can be hardened to reduce the stability of the capsule. At about 50 ° C., the degree of gelatinization of the internal and coating materials can be kept uniform, and is particularly effective in suppressing the rancidity of phosphatidylserine.
  • At least one of the primary emulsion and the secondary emulsion is maltodextrin, arabic gum, guar gum, xanthan gum, casein sodium, gelatin, lecithin to inhibit elution of phosphatidylserine incorporated into starch and at the same time improve dispersibility in aqueous solution.
  • excipients such as sodium alginate.
  • secondary encapsulation may be performed with another coating to improve acid resistance, shelf life, transportability, and the ability to protect the internals from oxidation.
  • Coating materials used for secondary encapsulation include, but are not limited to, whey protein, cyclodextrin, maltodextrin, sodium casein, gelatin, starch, and the like.
  • phosphatidylserine may be microencapsulated and powdered at the same time as it is dried.
  • Continuous powder drying or fluidized bed drying may be used to powder the final product.
  • spray drying is performed by using a nozzle having a size of 1 to 5 mm at a temperature of 150 to 200 ° C. of a hot air blower, a temperature of 100 to 150 ° C. of a nozzle part, and a temperature of 40 to 100 ° C. of a cyclone part. It can be carried out by spraying.
  • the average particle diameter of the microcapsules obtained after drying may range from approximately 400 to 700 nm.
  • the microcapsules prepared by the above method can improve dispersibility, solubility and stability in aqueous solution of phosphatidylserine, prevent oxidation by oxygen in light or air, and maintain the intrinsic function of phosphatidylserine for a long time. It is possible to improve the preservation and transport properties, and furthermore, to contain phosphatidylserine at high concentrations, thereby increasing the ability to be used as medicines, foods (health functional foods), etc., which are mainly composed of phosphatidylserine.
  • the present invention therefore also provides a microcapsule formulation comprising phosphatidylserine suitable for food or pharmaceutical use, which may be prepared by the methods described above.
  • phosphatidylserine suitable for food or pharmaceutical use, which may be prepared by the methods described above.
  • the content of phosphatidylserine may vary depending on the effective amount in the end use, but may be 1 to 25% by weight based on the total weight of the microcapsules.
  • phosphatidylserine powder PS40SW of Doosan Co., Ltd.
  • 60 g of soybean oil Welga Co., Ltd.
  • the mixture was stirred until completely clear and dried under reduced pressure to prepare a liquid composition containing 25% by weight of phosphatidylserine.
  • the processed starch substituted with 40 g of succinic acid was mixed with 540 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C.
  • An emulsion was prepared.
  • the primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. Then at 180 ° C Spray drying for 2 hours and powdered to prepare microcapsules (containing 10% by weight of phosphatidylserine) having an average particle diameter of 527 nm.
  • the average particle diameter of the microcapsules is a value measured after diluting the aqueous capsule solution with sterile tertiary distilled water using Zeta PALS.
  • the processed starch substituted with 60 g of succinic acid was mixed with 520 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C.
  • the primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying for 2 hours at 180 °C to powder to prepare a microcapsules (containing 6% by weight of phosphatidylserine) with an average particle diameter of 542 nm.
  • the processed starch substituted with 60 g of succinic acid was mixed with 520 g of an aqueous solution added with 3% by weight of arabic gum, gelatinized at 80 ° C, and then cooled to 50 ° C.
  • the primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying at 180 ° C for 2 hours to form a microcapsules (containing 6% by weight of phosphatidylserine) with an average particle diameter of 487 nm.
  • the processed starch substituted with 60 g of succinic acid was mixed with 520 g of an aqueous solution to which 1 wt% xanthan gum was added, gelatinized at 80 ° C, and then cooled to 50 ° C.
  • the primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying for 2 hours at 180 °C to powder to prepare a microcapsules (containing 6% by weight of phosphatidylserine) of an average particle diameter of 475 nm.
  • the processed starch substituted with 40 g of succinic acid was mixed with 520 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C.
  • Example 1 Example 2
  • Example 3 Example 4
  • Comparative Example 1 Comparative Example 2 0 days ⁇ ⁇ ⁇ ⁇ ⁇ X 30 days ⁇ ⁇ ⁇ ⁇ ⁇ X X 60 days ⁇ ⁇ ⁇ ⁇ ⁇ X X 90 days ⁇ ⁇ ⁇ ⁇ ⁇ X X
  • the phosphatidylserine-containing microcapsules prepared according to the method of the present invention can be seen that the water dispersibility and stability is very good because it is maintained at 4 °C for more than 3 months without precipitation and layer separation. . It can also be seen that microcapsule formulations in a very stable form are obtained for formulations which have been added with excipients or using additional coating materials other than starch.

Abstract

The present invention provides a method for microencapsulating phosphatidylserine, comprising the steps of: (a) producing a liquid phosphatidylserine composition by melting phosphatidylserine in edible oil and fat; (b) preparing an aqueous starch solution, before, after or at the same time as step (a) by mixing with water modified starch, which has been modified to be lipophilic and hydrophilic; (c) emulsifying by mixing and homogenizing the aqueous starch solution with the liquid phosphatidylserine composition; and (d) drying the resulting emulsified liquid.

Description

포스파티딜세린의 마이크로캡슐화 방법 Microencapsulation Method of Phosphatidylserine
본 발명은 뇌기능을 향상시키는 소재로 잘 알려진 포스파티딜세린(phosphatidlyserine, PS)을 마이크로캡슐형 제제로 제조하는 방법에 관한 것으로, 보다 구체적으로는 피막물질로 생분해성 고분자 물질인 전분을 사용하여 포스파티딜세린을 마이크로캡슐화하는 방법에 관한 것이다.The present invention relates to a method for preparing phosphatidlyserine (PS), which is well known as a material for improving brain function, as a microcapsule formulation, and more specifically, to a phosphatidylserine using starch, which is a biodegradable polymer material as a coating material. It relates to a method of microencapsulating
마이크로캡슐화(Microencapsulation) 기술은 고체, 액체, 기체상의 중심물질에 피복물질을 이용하여 막을 형성함으로써 중심물질을 외부 환경으로부터 보호하거나 특정 조건하에서 원하는 속도로 방출시키기 위한 방법이다. 의약품, 식품, 화장품 분야 등 광범위하게 응용될 수 있으며, 불안정한 중심물질을 외부요인으로부터 보호하여 손실을 줄이고, 반응성이 큰 중심물질을 격리할 수 있으며, 독성, 냄새, 맛을 은폐시키거나 고형화하여 취급을 간편하게 하고, 내용물의 용출 속도를 조절하는 등의 목적으로 이용되고 있다. Microencapsulation technology is a method to protect the core material from the external environment or to release it at a desired rate under certain conditions by forming a film using a coating material on the core material in a solid, liquid, or gas phase. It can be applied to a wide range of fields such as medicine, food, and cosmetics.It can protect unstable cores from external factors, reduce losses, isolate highly reactive cores, and conceal or solidify toxic, odor and taste. It is used for the purpose of simplifying, controlling the elution rate of the contents, and the like.
식품분야에서는 반응성이 높은 생리활성 성분 및 식품소재를 마이크로캡슐화함으로써 산화방지 및 보존성 향상, 원하지 않는 향미의 차단, 방출 제어, 생체 이용률 제고, 물성변화에 의한 취급 및 가공성 향상 등의 이점을 가진다. 식품에 이용되는 캡슐의 피복물질은 반드시 식용이 가능하며 용해가 뛰어나고 유화성이 높아야 하며 마이크로캡슐화 도중 조작이 용이해야 한다. 또한 가공과 저장 중 중심물질과 반응성이 적고 외부 환경으로부터 중심물질을 보호해야 하며, 가격이 낮아 경제적이여야 한다. 피복물질로는 탄수화물류, 젤라틴, 셀룰로오스, 유지, 단백질, 검(gum) 등이 사용되고 있으며, 반응성이 큰 물질의 단점을 극복하기 위하여 각종 피복물질을 사용하여 코팅시키는 마이크로캡슐화 방법이 연구되고 있다.In the food field, microencapsulation of highly reactive bioactive ingredients and food materials has the advantages of preventing oxidation and preservation, blocking unwanted flavors, controlling release, enhancing bioavailability, and improving handling and processability by changing physical properties. The coating material of the capsule used in food must be edible, excellent in dissolution, high in emulsification, and easy to operate during microencapsulation. It should also be less reactive with the core material during processing and storage, protect the core material from the external environment, and be economical due to its low price. Carbohydrates, gelatin, cellulose, fats, proteins, gums and the like are used as coating materials, and microencapsulation methods for coating with various coating materials have been studied to overcome disadvantages of highly reactive materials.
포스파티딜세린(Phosphatidylserine, PS)은 자연계에 존재하는 인지질(Phospholipid)의 일종으로써, 세린기(친수성 부분), 인산기, 글리세롤 및 2개의 지방산기(소수성 부분)로 구성된 물질이다. Phosphatidylserine (PS) is a kind of phospholipid (Phospholipid) existing in nature, and is composed of a serine group (hydrophilic moiety), a phosphate group, glycerol and two fatty acid groups (hydrophobic moiety).
인간의 뇌는 건조 중량 중 레시틴이 거의 절반을 차지하고, 그 레시틴 대부분이 신경 세포의 막에 포함되어 있다. 이와 같이 세포막의 중요한 성분인 레시틴에는 포스파티딜세린이 포함되어 있는데, 그 포스파티딜세린은 특히 뇌에 많이 존재하며 신경세포막을 구성하여, 생명 유지 활동을 위한 에너지의 출입, 신경전달물질의 방출이나 시냅스의 활동 등의 정보 전달 등 신경세포의 기능 발현에 깊게 관여하고 있는 것으로 알려져 있다. 이와 같은 이유로 인해 포스파티딜세린은 "뇌의 영양소"라 불리우기도 한다.In the human brain, lecithin accounts for almost half of the dry weight, and most of the lecithin is contained in the membranes of nerve cells. Lecithin, an important component of the cell membrane, contains phosphatidylserine, which is particularly present in the brain, and constitutes a neural cell membrane, releasing energy for life-sustaining activity, releasing neurotransmitters or synapses. It is known that he is deeply involved in the expression of neurons' function, such as information transmission. For this reason, phosphatidylserine is sometimes called the "nutrient of the brain."
포스파티딜세린은 1942년 조르디 폴크(Jordi Folch)에 의해 최초로 분리된 이후 현재까지 수십 건의 임상시험 대상이 되고 있으며, 그 결과 알츠하이머성 치매증의 개선 및 노화에 의한 뇌 기능 감퇴 개선에 있어 효과가 있는 것으로 알려져 있다. 뇌기능개선 효과 이외에도 간질에 대한 개선 효과, 스트레스 내성, 호르몬 분비 리듬의 회복 등의 기능도 나타내는 것으로 보고되고 있다.Phosphatidylserine has been subject to dozens of clinical trials since it was first isolated by Jordi Folch in 1942. As a result, phosphatidylserine has been shown to be effective in improving Alzheimer's dementia and in reducing brain function due to aging. have. In addition to the effects of improving brain function, it has been reported to show effects such as improvement in epilepsy, stress tolerance, and recovery of hormone secretion rhythm.
포스파티딜세린은 100 내지 300 mg/일(day)을 섭취하여야 효과가 있는 것으로 보고되고 있으나, 식품을 통한 공급에는 제약이 있어 다양한 제조를 통한 공급이 활발히 검토되고 있다(대한민국 공개특허공보 제2002-0085756호 참조).Phosphatidylserine has been reported to be effective only when ingested from 100 to 300 mg / day (day), but the supply through food is limited, and the supply through a variety of manufacturing is actively considered (Korea Patent Publication No. 2002-0085756 Reference).
포스파티딜세린은 최종 제품의 처리 과정에 따라 다르지만, 분말 및 과립 형태가 일반적이다. 이러한 분말 및 과립 형태는 유지(fat) 및 물에 대한 용해성이 좋지 못해 제품에 이용하기가 어려운 점이 있다. 유지에 대한 용해도를 높이기 위한 방안으로서, 대한민국 공개특허공보 제2003-0058839호는 포스파티딜세린과 유지를 포함하는 조성물에 중쇄지방이 더 첨가된 액상의 조성물을 개시하고 있다. 이러한 액상 조성물은 포스파티딜세린을 불포화지방산 함유 유지에 용해시키는 경우 점도가 높아지거나 경화되는 현상을 방지할 수 있고 나아가 연질캅셀 등의 형태로 건강식품 및 의약품에 이용될 수 있는 것으로 기재되어 있다. 그러나, 음료, 우유 등의 적용을 위해서는 포스파티딜세린의 수분산성이 좋지 못하고, 수용액에 분산되더라도 수상에서 포스파티딜세린의 에스터 결합이 서서히 자연 가수분해되며, 또한 상대적으로 산화안정성이 낮은 단점을 가진다.Phosphatidylserine depends on the processing of the final product, but powder and granular forms are common. These powder and granular forms are difficult to use in products due to poor solubility in fat and water. For maintenance As a method for increasing the solubility, Korean Patent Laid-Open Publication No. 2003-0058839 discloses a liquid composition in which medium chain fat is further added to a composition including phosphatidylserine and fats and oils. Such liquid compositions are described as being able to prevent phenomena of increasing viscosity or curing when phosphatidylserine is dissolved in an oil containing unsaturated fatty acids, and furthermore, it can be used in health foods and medicines in the form of soft capsules and the like. However, for the application of beverages, milk, etc., the water dispersibility of phosphatidylserine is not good, and even when dispersed in an aqueous solution, the ester bond of phosphatidylserine is gradually hydrolyzed naturally in the aqueous phase, and also has a relatively low oxidation stability.
본 발명의 목적은 전분을 피막물질로 사용하여 포스파티딜세린을 마이크로캡슐화하는 방법을 제공하는 것으로, 포스파티딜세린의 수용액에서의 분산성, 용해성, 안정성을 향상시키고, 빛이나 공기 중 산소에 의한 산화를 방지할 수 있으며, 포스파티딜세린의 고유의 기능을 유지하면서 장기 보존 및 운반 특성을 개선할 수 있다.SUMMARY OF THE INVENTION An object of the present invention is to provide a method for microencapsulating phosphatidylserine using starch as a coating material, to improve dispersibility, solubility, and stability in an aqueous solution of phosphatidylserine, and to prevent oxidation by oxygen in light or air. Can improve the long-term preservation and transport properties while maintaining the intrinsic function of phosphatidylserine.
본 발명의 다른 목적은 상기 방법으로 제조가능한 마이크로캡슐 제제를 제공하는 것이다.Another object of the present invention is to provide a microcapsule preparation preparable by the above method.
상기 목적을 달성하기 위하여 본 발명은 (a) 포스파티딜세린을 식용유지에 녹여 포스파티딜세린 액상 조성물을 제조하는 단계; (b) 단계 (a) 이전, 이후 또는 이와 동시에, 친유성 및 친수성을 갖도록 가공된(modified) 가공 전분을 물과 섞어 전분 수용액을 준비하는 단계; (c) 상기 전분 수용액과 포스파티딜세린 액상 조성물을 혼합 균질화하여 유화시키는 단계; 및 (d) 얻어진 유화액을 건조하는 단계를 포함하는, 포스파티딜세린의 마이크로캡슐화 방법을 제공한다.In order to achieve the above object, the present invention comprises the steps of (a) dissolving phosphatidylserine in edible oil to prepare a phosphatidylserine liquid composition; (b) preparing a starch aqueous solution by mixing the processed starch modified with lipophilic and hydrophilicity with water before, after or simultaneously with step (a); (c) mixing and homogenizing the aqueous starch solution and the phosphatidylserine liquid composition to emulsify; And (d) provides a method for microencapsulation of phosphatidylserine, comprising the step of drying the obtained emulsion.
상기 다른 목적을 달성하기 위하여 본 발명은 상술한 방법으로 제조가능한, 식품 또는 의약품 용도에 적합한 포스파티딜세린을 포함하는 마이크로캡슐 제제를 제공한다.In order to achieve the above another object, the present invention provides a microcapsule formulation comprising phosphatidylserine suitable for food or pharmaceutical use, which can be prepared by the above-described method.
본 발명에 따른 포스파티딜세린의 마이크로캡슐화 방법은 포스파티딜세린이 빛이나 공기 중 산소에 의하여 산화되는 것을 방지하고, 물에 대한 분산성, 용해성, 안정성을 향상시키며, 저장 및 운반 특성을 개선할 수 있다. 또한, 인지력 저하 예방, 스트레스 완화 등 포스파티딜세린 고유의 기능을 유지하면서 포스파티딜세린을 건강기능식품 (특히, 음료), 의약품 등의 캡슐 제형으로 효과적으로 제제화할 수 있다.The microencapsulation method of phosphatidylserine according to the present invention can prevent phosphatidylserine from being oxidized by oxygen in light or air, improve dispersibility, solubility, stability in water, and improve storage and transport characteristics. In addition, phosphatidylserine can be effectively formulated into capsule formulations such as health functional foods (particularly beverages) and medicines while maintaining phosphatidylserine-specific functions such as preventing cognitive decline and reducing stress.
본 발명은 기억력, 치매 개선 등의 뇌기능개선, 간질에 대한 개선 효과, 스트레스 내성, 호르몬 분비 리듬의 회복 등의 기능을 갖는 포스파티딜세린을 생분해성 고분자 물질인 전분을 피막물질로 하여 마이크로캡슐화하는 방법, 특히 분말형태로 마이크로캡슐화하는 방법을 제공한다.The present invention is a method for microencapsulating phosphatidylserine having a function such as improvement of memory, dementia improvement, improvement of epilepsy, stress resistance, recovery of hormonal secretion rhythm using starch which is a biodegradable polymer material. In particular, it provides a method of microencapsulating in powder form.
이하, 본 발명의 포스파티딜세린의 마이크로캡슐화 공정을 구체적으로 설명하면 다음과 같다.Hereinafter, the microencapsulation process of phosphatidylserine of the present invention will be described in detail.
(1) 포스파티딜세린을 식용유지에 녹여 포스파티딜세린 액상 조성물을 제조하는 단계(1) dissolving phosphatidylserine in edible oil and fat to prepare a phosphatidylserine liquid composition
본 발명에 따른 포스파티딜세린 액상 조성물은, 분말 또는 과립 형태의 포스파티딜세린을 식용유지에 녹여 제조된다. 분말 형태를 띠는 포스파티딜세린은 분말 입자가 물에 잘 녹지 않고 또한 인지질의 특성상 친수성 부분과 소수성 부분을 함께 가지고 있어서 친유성의 가공(modified) 전분 내로 혼입되기가 어렵다. 이에 포스파티딜세린을 식용유지를 이용하여 녹여서 유지 타입을 만들어 친유성에 더 가깝게 만드는 것이 중요하다. The phosphatidylserine liquid composition according to the present invention is prepared by dissolving phosphatidylserine in powder or granule form in an edible oil and fat. Phosphatidylserine in the form of a powder is difficult to be incorporated into lipophilic modified starch because the powder particles do not dissolve well in water and have a hydrophilic part and a hydrophobic part together due to the nature of phospholipids. Therefore, it is important to dissolve phosphatidylserine using edible oils and oils to make the oil type closer to lipophilic.
상기 포스파티딜세린은 동물조직 유래의 천연 포스파티딜세린; 식물조직 유래의 천연 포스파티딜세린; 대두 레시틴, 채종 레시틴, 어류 유래 레시틴, 연체동물 유래 레시틴 및 난황 레시틴으로 구성된 군으로부터 선택된 레시틴을 포스포리파제 D의 존재 하에서 세린과 반응시켜 얻어진 포스파티딜세린으로서, 탄소수 6 내지 30의 포화 지방산, 모노-불포화 지방산 또는 다가-불포화 지방산, 또는 이의 나트륨염, 칼륨염, 마그네슘염, 암모늄염, 인산염, 염산염 또는 황산염을 포함한 포스파티딜세린일 수 있다.The phosphatidylserine is a natural phosphatidylserine derived from animal tissues; Natural phosphatidylserine derived from plant tissues; A phosphatidylserine obtained by reacting lecithin selected from the group consisting of soybean lecithin, rapeseed lecithin, fish-derived lecithin, mollusk-derived lecithin and egg yolk lecithin with serine in the presence of phospholipase D, a saturated fatty acid having 6 to 30 carbon atoms, mono- Unsaturated fatty acids or polyunsaturated fatty acids, or phosphatidylserine, including sodium salts, potassium salts, magnesium salts, ammonium salts, phosphate salts, hydrochloride salts or sulfate salts thereof.
식용유지는 중쇄지방, 콩기름, 해바라기유, 포도씨유, 채종유, 올리브유, 옥수수유, 호박씨유, 홍화씨유, 팜유 등으로부터 선택된 1종 이상일 수 있다.Edible oil and fat may be at least one selected from medium chain fat, soybean oil, sunflower oil, grape seed oil, rapeseed oil, olive oil, corn oil, pumpkin seed oil, safflower seed oil, palm oil and the like.
본 명세서에서 사용된 "중쇄지방"이라 함은, 탄소 수 6 내지 10의 지방산으로 구성된 유지를 말한다. 중쇄지방은 췌장 리파제 및 담즙이 없이도 흡수될 수 있으며 장쇄지방에 비해 흡수속도가 무려 4배나 빠르고 축적지방이 되지 않는 장점이 있다. 또한, 장쇄지방에 비해 극성이 커서 포스파티딜세린을 가용화시키는데 매우 적합하다. As used herein, "medium chain fat" refers to an oil or fat consisting of fatty acids having 6 to 10 carbon atoms. Medium chain fat can be absorbed without pancreatic lipase and bile, and has an advantage that the absorption rate is four times faster than long chain fat and does not become accumulated fat. It is also more polar than long chain fats and is well suited for solubilizing phosphatidylserine.
상기 포스파티딜세린 액상 조성물은 DHA 또는 EPA가 포함된 어유, 쏘팔메토 열매 추출물, 비타민, 향료 등의 기능성 성분을 1종 이상 추가로 포함할 수도 있다.The phosphatidylserine liquid composition may further include one or more functional ingredients such as fish oil, saw palmetto fruit extract, vitamins, fragrances including DHA or EPA.
본 발명에서 사용되는 분말 또는 과립 형태의 포스파티딜세린과 식용유지는 유기용매에 녹인 후 감압농축하여 유기용매를 모두 제거하여 사용될 수 있다. 유기용매는 에탄올, 프로판올, 헥산, 사이클로헥산 등 일반적인 유기용매를 단독으로 또는 2종 이상 혼합하여 사용할 수 있다.Powdered or granular phosphatidylserine and edible oils used in the present invention may be used by removing all organic solvents by concentration under reduced pressure after dissolving in an organic solvent. The organic solvent may be used alone or in combination of two or more common organic solvents, such as ethanol, propanol, hexane, cyclohexane.
포스파티딜세린은 조성물 총 중량을 기준으로 10 내지 50 중량%로 포함될 수 있지만, 이에 한정되는 것은 아니다.Phosphatidylserine may be included in 10 to 50% by weight based on the total weight of the composition, but is not limited thereto.
(2) 친유성 및 친수성을 갖도록 가공된(modified) 가공 전분을 물과 섞어 전분 수용액을 준비하는 단계(2) preparing an aqueous solution of starch by mixing modified starch modified with water to be lipophilic and hydrophilic
본 발명의 포스파티딜세린 분말 캡슐의 외벽물질로는 전분이 사용된다. 전분을 사용하면 표면을 구성하는 막은 거칠어지지만, 견고하고 유연한 탄성과 내충격성을 갖게 되고, 산화로부터 내부 물질을 보호하는 특성이 뛰어난 제형이 얻어진다. Starch is used as the outer wall material of the phosphatidylserine powder capsule of the present invention. The use of starch makes the film constituting the surface rough, but has a firm and flexible elasticity and impact resistance, and a formulation having excellent properties of protecting internal materials from oxidation is obtained.
피복물질로 사용된 가공 전분은 미가공(unmodified) 전분을 열, 효소(예: 가수분해 효소, 이성질화 효소, 산화 효소, 가지화 효소(branching enzyme) 등), 산(예: 호박산, 숙신산, 초산, 염산 등) 등으로 처리하여 얻어진 가공(변성) 전분으로서, 일반 전분과는 달리 친수성 및 친유성 성질을 모두 지니고 있어 안정된 에멀젼 형성과 우수한 필름 형성능을 가지며 이로 인해 유지 성분을 함유하고 있는 식품 등에 여러 용도로 사용되는 전분이다. Processed starch used as coating material can be used to heat unmodified starch, enzymes (e.g. hydrolases, isomerases, oxidases, branching enzymes, etc.), acids (e.g. succinic acid, succinic acid, acetic acid). (Modified) starch obtained by treatment with hydrochloric acid, etc.), unlike ordinary starch, it has both hydrophilic and lipophilic properties, and has stable emulsion formation and excellent film forming ability. Starch used for purposes.
전분은 대략 5 내지 30배(w/w), 바람직하게는 5 내지 15배(w/w)의 물에서 50 내지 90℃, 바람직하게는 80℃에서 호화되어 사용될 수 있다. The starch may be used at about 5 to 30 times (w / w), preferably 5 to 15 times (w / w) of water at 50 to 90 ° C, preferably at 80 ° C.
전분 수용액의 준비는 상술한 포스파티딜세린 액상 조성물의 제조단계 이전, 이후 또는 이와 동시에 수행될 수 있다.Preparation of the starch aqueous solution may be carried out before, after or simultaneously with the step of preparing the phosphatidylserine liquid composition described above.
경우에 따라, 전분 수용액은 전분 내로 혼입되는 포스파티딜세린의 용출을 억제하고 동시에 수용액상에서 분산성을 향상시키기 위해 말토덱스트린, 아라빅검, 구아검, 잔탄검, 카제인 나트륨, 젤라틴, 레시틴, 알긴산 나트륨 등의 부형제를 1종 이상 추가로 포함할 수 있다.In some cases, the starch aqueous solution may contain maltodextrin, arabic gum, guar gum, xanthan gum, sodium casein, gelatin, lecithin, sodium alginate, etc. to suppress elution of phosphatidylserine incorporated into starch and at the same time improve dispersibility in aqueous solution. It may further comprise one or more excipients.
(3) 전분 수용액과 포스파티딜세린 액상 조성물을 혼합 균질화하여 유화시키는 단계(3) mixing and homogenizing the aqueous solution of starch and the phosphatidylserine liquid composition to emulsify
본 단계는, 앞서 준비한 전분 수용액과 포스파티딜세린 액상 조성물을 섞어 1,000 내지 10,000 rpm으로 5 내지 10 분간 균질화하여 1차 유화액을 얻은 다음, 조성 안정성을 높이기 위해 고압 균질기(homogenizer), 초음파 유화기 등을 이용하여 1차 유화액을 200 내지 300 bar의 압력조건에서 10 내지 30분간 추가로 균질화하여 2차 유화액을 얻는 단계로 구성될 수 있다.In this step, the first starch aqueous solution and the phosphatidylserine liquid composition prepared above are mixed and homogenized at 1,000 to 10,000 rpm for 5 to 10 minutes to obtain a first emulsion, and then a high pressure homogenizer, an ultrasonic emulsifier, etc. is used to increase the composition stability. The first emulsion may be further homogenized for 10 to 30 minutes at a pressure condition of 200 to 300 bar to obtain a secondary emulsion.
여기서, 포스파티딜세린은 전분 100 중량부에 대해 20 내지 50 중량부로 혼합될 수 있다.Here, phosphatidylserine may be mixed in an amount of 20 to 50 parts by weight based on 100 parts by weight of starch.
포스파티딜세린은 상기 혼합물 총 중량을 기준으로 1 내지 30 중량%, 바람직하게는 3 내지 20 중량%일 수 있다. 포스파티딜세린 함량이 1 중량% 미만이면, 최종 산물에서 생리활성기능을 발휘하는 농도를 유지하기 어렵고, 30 중량%를 초과하면 유화 안정성이 떨어질 수 있다.Phosphatidylserine may be 1 to 30% by weight, preferably 3 to 20% by weight, based on the total weight of the mixture. If the phosphatidylserine content is less than 1% by weight, it is difficult to maintain the concentration that exerts the bioactive function in the final product, and if it exceeds 30% by weight, the emulsion stability may be deteriorated.
2차 유화는 조성물을 보다 안정화시키기 위해서 1회 이상 수행될 수 있다.Secondary emulsification may be carried out one or more times to stabilize the composition.
1차 및 2차 유화과정에서는 열이 발생하기도 하는데 균질화 온도는 일반적으로 30 내지 60℃, 바람직하게는 50℃일 수 있다. 균질화 온도가 60℃를 초과하면, 포스파티딜세린의 산패가 촉진될 수 있고, 30℃ 미만이면 피복물질이 굳어져 캡슐의 안정성이 떨어질 수 있다. 대략 50℃일 때 내부물질과 피복물질의 호화 정도가 균일하게 유지될 수 있고, 특히 포스파티딜세린의 산패를 억제하는데 효과적이다.Heat may be generated during the first and second emulsification, but the homogenization temperature may be generally 30 to 60 ° C, preferably 50 ° C. If the homogenization temperature exceeds 60 ℃, the rancidity of phosphatidylserine can be promoted, if less than 30 ℃ the coating material can be hardened to reduce the stability of the capsule. At about 50 ° C., the degree of gelatinization of the internal and coating materials can be kept uniform, and is particularly effective in suppressing the rancidity of phosphatidylserine.
상기 1차 유화액 및 2차 유화액 중 적어도 하나는 전분 내로 혼입되는 포스파티딜세린의 용출을 억제하고 동시에 수용액상에서 분산성을 향상시키기 위해 말토덱스트린, 아라빅검, 구아검, 잔탄검, 카제인 나트륨, 젤라틴, 레시틴, 알긴산 나트륨 등의 부형제를 1종 이상 추가로 포함할 수 있다.At least one of the primary emulsion and the secondary emulsion is maltodextrin, arabic gum, guar gum, xanthan gum, casein sodium, gelatin, lecithin to inhibit elution of phosphatidylserine incorporated into starch and at the same time improve dispersibility in aqueous solution. And one or more excipients such as sodium alginate.
전분을 이용한 포스파티딜세린의 1차 캡슐화 후, 내산성, 저장성, 운반성, 내부물질을 산화로보터 보호하는 성능을 향상시키기 위해 또 다른 피복물질로 2차 캡슐화를 수행할 수 있다. 2차 캡슐화에 사용되는 피복물질로는 유청 단백질, 사이클로덱스트린, 말토덱스트린, 카제인나트륨, 젤라틴, 전분 등이 있으며, 이에 한정되는 것은 아니다.After primary encapsulation of phosphatidylserine with starch, secondary encapsulation may be performed with another coating to improve acid resistance, shelf life, transportability, and the ability to protect the internals from oxidation. Coating materials used for secondary encapsulation include, but are not limited to, whey protein, cyclodextrin, maltodextrin, sodium casein, gelatin, starch, and the like.
(4) 유화액의 건조단계(4) drying step of emulsion
앞서 얻어진 유화액은 슬러리 상에서 안정성이 다소 부족하여 내부물질이 밖으로 빠져나올 가능성이 있다. 이에 유화액을 건조하면 건조와 동시에 포스파티딜세린이 마이크로캡슐화되어 분말화될 수 있다.The previously obtained emulsion has a slight lack of stability on the slurry, and there is a possibility that the internal substance may come out. When the emulsion is dried, phosphatidylserine may be microencapsulated and powdered at the same time as it is dried.
최종제품의 형태를 분말화하기 위해서는 연속적인 분무 건조법 또는 유동층 건조법이 이용될 수 있다. Continuous powder drying or fluidized bed drying may be used to powder the final product.
예를 들어, 분무건조는, 열풍기의 온도 150∼200℃, 노즐부분의 온도 100∼150℃, 싸이클론(cyclone)부분의 온도 40∼100℃에서, 1∼5mm 크기의 노즐을 이용하여 유화액을 분사시켜 수행될 수 있다. For example, spray drying is performed by using a nozzle having a size of 1 to 5 mm at a temperature of 150 to 200 ° C. of a hot air blower, a temperature of 100 to 150 ° C. of a nozzle part, and a temperature of 40 to 100 ° C. of a cyclone part. It can be carried out by spraying.
건조 후 얻어진 마이크로캡슐의 평균 입경은 대략 400 내지 700 nm 범위일 수 있다.The average particle diameter of the microcapsules obtained after drying may range from approximately 400 to 700 nm.
상기 방법에 의해 제조된 마이크로캡슐은, 포스파티딜세린의 수용액에서의 분산성, 용해성, 안정성을 향상시키고, 빛이나 공기 중 산소에 의한 산화를 방지할 수 있으며, 포스파티딜세린의 고유의 기능을 유지하면서 장기 보존 및 운반 특성을 개선할 수 있고, 나아가 포스파티딜세린을 고농도로 포함할 수 있으므로, 포스파티딜세린을 주성분으로 하는 의약품, 식품(건강기능식품) 등으로의 활용 능력을 증대시킨다. The microcapsules prepared by the above method can improve dispersibility, solubility and stability in aqueous solution of phosphatidylserine, prevent oxidation by oxygen in light or air, and maintain the intrinsic function of phosphatidylserine for a long time. It is possible to improve the preservation and transport properties, and furthermore, to contain phosphatidylserine at high concentrations, thereby increasing the ability to be used as medicines, foods (health functional foods), etc., which are mainly composed of phosphatidylserine.
이에 본 발명은 또한 상술한 방법으로 제조가능한, 식품 또는 의약품 용도에 적합한 포스파티딜세린을 포함하는 마이크로캡슐 제제를 제공한다. 여기서 포스파티딜세린의 함량은 최종 용도에서의 효과량에 따라 달라질 수 있겠지만 마이크로캡슐 총 중량을 기준으로 1 내지 25 중량%일 수 있다. The present invention therefore also provides a microcapsule formulation comprising phosphatidylserine suitable for food or pharmaceutical use, which may be prepared by the methods described above. Wherein the content of phosphatidylserine may vary depending on the effective amount in the end use, but may be 1 to 25% by weight based on the total weight of the microcapsules.
이하 본 발명을 실시예를 통하여 상세히 설명하면 다음과 같다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명이 하기 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to the following Examples. However, the following examples are merely to illustrate the present invention and the present invention is not limited by the following examples.
제조예: 포스파티딜세린 액상 조성물의 제조Preparation Example: Preparation of Phosphatidylserine Liquid Composition
<제조예 1><Manufacture example 1>
포스파티딜세린 분말 (DS-PS60SW, ㈜두산) 100g에 헥산:에탄올 = 95:5 용액 500 ㎖를 첨가한 후 35℃에서 투명해질 때까지 혼합하였다. 이후 중쇄지방 66.7g (Medium Chain Triglycerides (MCTs), ㈜웰가)을 첨가한 후 혼합물이 완전히 투명해질 때까지 교반하고 감압건조하여 포스파티딜세린을 30 중량% 함유한 액상 조성물을 제조하였다.To 100 g of phosphatidylserine powder (DS-PS60SW, Doosan Co., Ltd.) was added 500 ml of a hexane: ethanol = 95: 5 solution, followed by mixing until it became clear at 35 ° C. After adding 66.7 g of medium chain fat (Medium Chain Triglycerides (MCTs), Welga Co., Ltd.), the mixture was stirred until completely clear and dried under reduced pressure to prepare a liquid composition containing 30 wt% of phosphatidylserine.
<제조예 2> <Manufacture example 2>
포스파티딜세린 분말 (㈜두산의 PS40SW) 100g에 헥산:에탄올 = 100:3 용액 500 ㎖를 첨가한 후 35℃에서 투명해질 때까지 혼합하였다. 이후 콩기름 60g (㈜웰가)을 첨가한 후 혼합물이 완전히 투명해질 때까지 교반하고 감압건조하여 포스파티딜세린을 25 중량% 함유한 액상 조성물을 제조하였다.To 100 g of phosphatidylserine powder (PS40SW of Doosan Co., Ltd.), 500 ml of a hexane: ethanol = 100: 3 solution was added and mixed at 35 ° C until it became clear. After adding 60 g of soybean oil (Welga Co., Ltd.), the mixture was stirred until completely clear and dried under reduced pressure to prepare a liquid composition containing 25% by weight of phosphatidylserine.
<제조예 3> <Manufacture example 3>
포스파티딜세린 분말 (㈜두산의 PS60SW) 100g에 헥산:에탄올 = 100:3 용액 500 ㎖를 첨가한 후 35℃에서 투명해질 때까지 혼합하였다. 이후 중쇄지방 90g (MCTs, ㈜웰가)과 참치 유래 어유(DHA 27 중량% 함유) 10g (㈜크로다)를 10:1(w/w)로 혼합한 혼합물을 첨가한 후 혼합물이 완전히 투명해질 때까지 교반하고 감압건조하여 포스파티딜세린을 25 중량% 함유한 액상 조성물을 제조하였다.To 100 g of phosphatidylserine powder (PS60SW of Doosan Co., Ltd.), 500 ml of a hexane: ethanol = 100: 3 solution was added and mixed at 35 ° C until it became clear. After adding a mixture of 90g of heavy chain fat (MCTs, Welga Co., Ltd.) and 10g (croda) of fish oil derived from tuna (containing 27% by weight of DHA) at 10: 1 (w / w), the mixture becomes completely transparent. After stirring to dryness under reduced pressure to prepare a liquid composition containing 25% by weight of phosphatidylserine.
실시예: 포스파티딜세린의 마이크로캡슐화Example Microencapsulation of Phosphatidylserine
<실시예 1><Example 1>
40g의 호박산으로 치환된 가공 전분을 540g의 멸균수에 혼합하여 80℃에서 호화시킨 다음 50℃까지 냉각하였다. 여기에 준비예 1에서 제조한 포스파티딜세린 액상 조성물 20g을 혼합(전분:포스파티딜세린 = 2:1(w/w))한 다음 균질기(homogenizer)를 이용하여 9000 rpm에서 9분 동안 균질화시켜 1차 유화액을 제조하였다. The processed starch substituted with 40 g of succinic acid was mixed with 540 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 1 was mixed therein (starch: phosphatidylserine = 2: 1 (w / w)), and then homogenized at 9000 rpm for 9 minutes using a homogenizer. An emulsion was prepared.
조성물의 안정성을 높이기 위해 상기 1차 유화액을 250 bar의 고압 균질기를 2회 통과시켜 추가로 균질화하였다. 이후 180℃에서 2시간 동안 분무건조하여 분말화시켜 평균입경 527 nm의 마이크로캡슐(포스파티딜세린 10 중량% 함유)을 제조하였다. 여기서, 마이크로캡슐의 평균입경은 Zeta PALS을 이용하여 캡슐 수용액을 멸균된 3차 증류수로 희석한 후 측정된 값이다.The primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. Then at 180 ° C Spray drying for 2 hours and powdered to prepare microcapsules (containing 10% by weight of phosphatidylserine) having an average particle diameter of 527 nm. Here, the average particle diameter of the microcapsules is a value measured after diluting the aqueous capsule solution with sterile tertiary distilled water using Zeta PALS.
<실시예 2><Example 2>
60g의 호박산으로 치환된 가공 전분을 520g의 멸균수에 혼합하여 80℃에서 호화시킨 다음 50℃까지 냉각하였다. 여기에 준비예 2에서 제조한 포스파티딜세린 액상 조성물 20 g을 혼합(전분:포스파티딜세린 = 3:1 (w/w))한 다음 균질기를 이용하여 9000 rpm으로 9분 동안 균질화시켜 1차 유화액을 제조하였다. The processed starch substituted with 60 g of succinic acid was mixed with 520 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C. 20 g of phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed therein (starch: phosphatidylserine = 3: 1 (w / w)), and then homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion. It was.
조성물의 안정성을 높이기 위해 상기 1차 유화액을 250 bar의 고압 균질기를 2회 통과시켜 추가로 균질화하였다. 이후 180℃에서 2시간 동안 분무건조하여 분말화시켜 평균입경 542 nm의 마이크로캡슐(포스파티딜세린 6 중량% 함유)을 제조하였다.The primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying for 2 hours at 180 ℃ to powder to prepare a microcapsules (containing 6% by weight of phosphatidylserine) with an average particle diameter of 542 nm.
<실시예 3><Example 3>
60g의 호박산으로 치환된 가공 전분을 3 중량% 아라빅검이 첨가된 520g의 수용액에 혼합하여 80℃에서 호화시킨 다음 50℃까지 냉각하였다. 여기에 준비예 2에서 제조한 포스파티딜세린 액상 조성물 20g을 혼합(전분:포스파티딜세린 = 3:1(w/w))한 다음 균질기를 이용하여 9000 rpm으로 9분 동안 균질화시켜 1차 유화액을 제조하였다. The processed starch substituted with 60 g of succinic acid was mixed with 520 g of an aqueous solution added with 3% by weight of arabic gum, gelatinized at 80 ° C, and then cooled to 50 ° C. 20 g of phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed therein (starch: phosphatidylserine = 3: 1 (w / w)), and then homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion. .
조성물의 안정성을 높이기 위해 상기 1차 유화액을 250 bar의 고압 균질기를 2회 통과시켜 추가로 균질화하였다. 이후 180℃에서 2시간 동안 분무건조하여 분말화시켜 평균입경 487 nm의 마이크로캡슐(포스파티딜세린 6 중량% 함유)을 제조하였다.The primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying at 180 ° C for 2 hours to form a microcapsules (containing 6% by weight of phosphatidylserine) with an average particle diameter of 487 nm.
<실시예 4><Example 4>
60g의 호박산으로 치환된 가공 전분을 1 중량% 잔탄검이 첨가된 520g의 수용액에 혼합하여 80℃에서 호화시킨 다음 50℃까지 냉각하였다. 여기에 준비예 2에서 제조한 포스파티딜세린 액상 조성물 20g을 혼합(전분:포스파티딜세린 = 3:1(w/w))한 다음 균질기를 이용하여 9000rpm에서 9분간 동안 균질화시켜 1차 유화액을 제조하였다. The processed starch substituted with 60 g of succinic acid was mixed with 520 g of an aqueous solution to which 1 wt% xanthan gum was added, gelatinized at 80 ° C, and then cooled to 50 ° C. 20 g of phosphatidylserine liquid composition prepared in Preparation Example 2 was mixed therein (starch: phosphatidylserine = 3: 1 (w / w)), and then homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion.
조성물의 안정성을 높이기 위해 상기 1차 유화액을 250 bar의 고압 균질기를 2회 통과시켜 추가로 균질화하였다. 이후 180℃에서 2시간 동안 분무건조하여 분말화시켜 평균입경 475 nm의 마이크로캡슐(포스파티딜세린 6 중량% 함유)을 제조하였다.The primary emulsion was further homogenized by two passes of a 250 bar high pressure homogenizer to increase the stability of the composition. After spray drying for 2 hours at 180 ℃ to powder to prepare a microcapsules (containing 6% by weight of phosphatidylserine) of an average particle diameter of 475 nm.
<실시예 5>Example 5
40g의 호박산으로 치환된 가공 전분을 520g의 멸균수에 혼합하여 80℃에서 호화시킨 다음 50℃까지 냉각하였다. 여기에 준비예 1에서 제조한 포스파티딜세린 액상 조성물 20g을 혼합(전분:포스파티딜세린 = 2:1(w/w))한 다음 균질기를 이용하여 9000rpm으로 9분간 균질화시켜 1차 유화액을 제조하였다. The processed starch substituted with 40 g of succinic acid was mixed with 520 g of sterile water, gelatinized at 80 ° C, and then cooled to 50 ° C. 20 g of the phosphatidylserine liquid composition prepared in Preparation Example 1 was mixed therein (starch: phosphatidylserine = 2: 1 (w / w)), and then homogenized at 9000 rpm for 9 minutes using a homogenizer to prepare a primary emulsion.
1차 유화액에 말토덱스트린 15g을 첨가하고 교반한 후, 조성물의 안정성을 높이기 위해 상기 1차 유화액을 250 bar의 고압 균질기를 2회 통과시켜 추가로 균질화하였다. 이후 180℃에서 2시간 동안 분무건조하여 분말화시켜 평균입경 463 nm의 마이크로캡슐(포스파티딜세린 6 중량% 함유)을 제조하였다.15 g of maltodextrin was added to the primary emulsion and stirred, and then further homogenized by passing the primary emulsion through a 250 bar high pressure homogenizer twice to increase the stability of the composition. After spray drying for 2 hours at 180 ℃ to powder to prepare a microcapsules (containing 6% by weight of phosphatidylserine) with an average particle diameter of 463 nm.
<시험예 1> 수분산성 및 저장 안정성 시험Test Example 1 Water Dispersibility and Storage Stability Test
실시예 1-5에서 제조한 포스파티딜세린 함유 마이크로캡슐, 비교예 1로서 포스파티딜세린 분말 (DS-PS60SW, ㈜두산), 및 비교예 2로서 준비예 1에서 제조한 포스파티딜세린 30 중량% 함유한 액상 조성물을, 포스파티딜세린 300mg/100㎖의 농도가 되도록 증류수에 가용화시킨 후 3개월 동안 4℃ 냉장 조건에서 보관하면서 분산성 및 유화 안정도를 육안으로 관찰하였다. 그 결과를 하기 표 1에 나타내고 있다. Microcapsules containing phosphatidylserine prepared in Example 1-5, phosphatidylserine powder (DS-PS60SW, Doosan Corporation) as Comparative Example 1, and a liquid composition containing 30% by weight of phosphatidylserine prepared in Preparation Example 1 as Comparative Example 2 of, After dissolving in distilled water to a concentration of 300mg / 100ml of phosphatidylserine, the dispersibility and emulsion stability were visually observed while being stored at 4 ℃ refrigerated conditions. The results are shown in Table 1 below.
◎ : 침전 현상 없이 안정함 ○ : 침전 현상이 매우 미세하게 있음◎: Stable without sedimentation ○: Very fine sedimentation
△ : 침전 현상이 조금 있음 X : 침전 현상 심함△: slight precipitation phenomenon X: severe precipitation phenomenon
표 1
실시예 1 실시예 2 실시예 3 실시예 4 실시예 5 비교예 1 비교예 2
0 일 ◎ ◎ ◎ ◎ ◎ ○ X
30일 ◎ ◎ ◎ ◎ ◎ X X
60일 ◎ ◎ ◎ ◎ ◎ X X
90일 ◎ ◎ ◎ ◎ ◎ X X
Table 1
Example 1 Example 2 Example 3 Example 4 Example 5 Comparative Example 1 Comparative Example 2
0 days ◎ ◎ ◎ ◎ ◎ ○ X
30 days ◎ ◎ ◎ ◎ ◎ X X
60 days ◎ ◎ ◎ ◎ ◎ X X
90 days ◎ ◎ ◎ ◎ ◎ X X
상기 표 1에서 보는 바와 같이, 본 발명의 방법에 따라 제조된 포스파티딜세린 함유 마이크로캡슐은 4℃에서 3개월 이상 동안 침전 및 층분리 없이 안정하게 유지되고 있으므로 수분산성 및 안정성이 매우 양호한 것을 알 수 있다. 또한, 부형제를 첨가하거나 전분 이외의 추가의 피복 물질을 사용한 제형의 경우도 매우 안정적인 형태의 마이크로캡슐 제형이 얻어지는 것을 알 수 있다. As shown in Table 1, the phosphatidylserine-containing microcapsules prepared according to the method of the present invention can be seen that the water dispersibility and stability is very good because it is maintained at 4 ℃ for more than 3 months without precipitation and layer separation. . It can also be seen that microcapsule formulations in a very stable form are obtained for formulations which have been added with excipients or using additional coating materials other than starch.
한편, 포스파티딜세린을 식용유지에 가용화시키지 않고 가공 전분으로 코팅처리하지 않은 비교예 1의 포스파티딜세린은 하루가 지난 후 곧바로 침전이 발생하였으며, 가공 전분으로 코팅하지 않은 비교예 2의 포스파티딜세린의 경우 곧바로 침전 및 층분리가 발생하였다.On the other hand, the phosphatidylserine of Comparative Example 1, which was not solubilized in edible oil and coated with processed starch, precipitated immediately after one day, and in the case of phosphatidylserine of Comparative Example 2 which was not coated with processed starch, Precipitation and delamination occurred.

Claims (10)

  1. (a) 포스파티딜세린을 식용유지에 녹여 포스파티딜세린 액상 조성물을 제조하는 단계;(a) dissolving phosphatidylserine in edible oil and fat to prepare a phosphatidylserine liquid composition;
    (b) 단계 (a) 이전, 이후 또는 이와 동시에, 친유성 및 친수성을 갖도록 가공된(modified) 가공 전분을 물과 섞어 전분 수용액을 준비하는 단계;(b) preparing a starch aqueous solution by mixing the processed starch modified with lipophilic and hydrophilicity with water before, after or simultaneously with step (a);
    (c) 상기 전분 수용액과 포스파티딜세린 액상 조성물을 혼합 균질화하여 유화시키는 단계; 및(c) mixing and homogenizing the aqueous starch solution and the phosphatidylserine liquid composition to emulsify; And
    (d) 얻어진 유화액을 건조하는 단계(d) drying the obtained emulsion
    를 포함하는, 포스파티딜세린의 마이크로캡슐화 방법.Comprising, phosphatidylserine microencapsulation method.
  2. 제1항에 있어서,The method of claim 1,
    상기 포스파티딜세린은 동물조직 유래의 천연 포스파티딜세린; 식물조직 유래의 천연 포스파티딜세린; 또는 대두 레시틴, 채종 레시틴, 어류 유래 레시틴, 연체동물 유래 레시틴 및 난황 레시틴으로 구성된 군으로부터 선택된 레시틴을 포스포리파제 D의 존재 하에서 세린과 반응시켜 얻어진 포스파티딜세린으로서, 탄소수 6 내지 30의 포화 지방산, 모노-불포화 지방산 또는 다가-불포화 지방산, 또는 이의 나트륨염, 칼륨염, 마그네슘염, 암모늄염, 인산염, 염산염 또는 황산염을 포함하는 포스파티딜세린인 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.The phosphatidylserine is a natural phosphatidylserine derived from animal tissues; Natural phosphatidylserine derived from plant tissues; Or phosphatidylserine obtained by reacting a lecithin selected from the group consisting of soybean lecithin, rapeseed lecithin, fish-derived lecithin, mollusk-derived lecithin and egg yolk lecithin with serine in the presence of phospholipase D, having a saturated fatty acid having 6 to 30 carbon atoms, mono A method of microencapsulating phosphatidylserine, characterized in that it is a phosphatidylserine comprising an unsaturated fatty acid or a polyvalent-unsaturated fatty acid, or a sodium salt, potassium salt, magnesium salt, ammonium salt, phosphate salt, hydrochloride salt or sulfate salt thereof.
  3. 제1항에 있어서,The method of claim 1,
    상기 단계 (a)에서, 식용유지는 탄소수 6 내지 10의 지방산으로 구성된 유지, 콩기름, 해바라기유, 포도씨유, 채종유, 올리브유, 옥수수유, 호박씨유, 홍화씨유 및 팜유로 구성된 군으로부터 선택된 1종 이상인 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.In the step (a), the edible oil is one or more selected from the group consisting of fats and oils, soybean oil, sunflower oil, grape seed oil, rapeseed oil, olive oil, corn oil, pumpkin seed oil, safflower oil and palm oil consisting of 6 to 10 carbon atoms. Characterized in that, microencapsulation method of phosphatidylserine.
  4. 제1항에 있어서,The method of claim 1,
    상기 단계 (a)에서, 상기 포스파티딜세린 액상 조성물은 DHA 또는 EPA가 포함된 어유, 쏘팔메토 열매 추출물, 비타민 및 향료로 구성된 군으로부터 선택된 1종 이상을 추가로 포함하는 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.In the step (a), the phosphatidylserine liquid composition further comprises at least one selected from the group consisting of fish oil, saw palmetto fruit extract, vitamins and flavors containing DHA or EPA, phosphatidylserine Microencapsulation method.
  5. 제1항에 있어서,The method of claim 1,
    상기 단계 (b)에서, 가공 전분은 열, 효소 및 산(acid)으로 구성된 군으로부터 선택된 1종 이상으로 처리된 전분인 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.In the step (b), the processed starch is treated with one or more selected from the group consisting of heat, enzyme and acid. A method of microencapsulating phosphatidylserine, characterized in that it is starch.
  6. 제1항에 있어서,The method of claim 1,
    상기 단계 (b)에서, 가공 전분은 5 내지 30배(w/w)의 물에서 50 내지 90℃의 온도에서 호화되는 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.In the step (b), the processed starch is characterized in that the gelatinization at a temperature of 50 to 90 ℃ in water of 5 to 30 times (w / w), microcapsule method of phosphatidylserine.
  7. 제1항에 있어서,The method of claim 1,
    상기 단계 (b)의 전분 수용액 및 단계 (c)의 유화액 중 적어도 하나는 말토덱스트린, 아라빅검, 구아검, 잔탄검, 카제인 나트륨, 젤라틴, 레시틴 및 알긴산 나트륨으로 구성된 군으로부터 선택된 1종 이상의 부형제를 추가로 포함하는 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.At least one of the aqueous solution of starch of step (b) and the emulsion of step (c) is maltodextrin, arabic gum, guar gum, xanthan gum, casein sodium, gelatin, lecithin and sodium alginate A method for microencapsulating phosphatidylserine, further comprising at least one excipient selected from the group consisting of:
  8. 제1항에 있어서,The method of claim 1,
    상기 단계 (c)는Step (c) is
    (c1) 상기 전분 수용액과 포스파티딜세린 액상 조성물의 혼합물을 30 내지 60℃에서 1,000 내지 10,000 rpm으로 균질화하여 1차 유화액을 얻는 단계; 및(c1) homogenizing the mixture of the starch aqueous solution and the phosphatidylserine liquid composition at 1,000 to 10,000 rpm at 30 to 60 ° C. to obtain a primary emulsion; And
    (c2) 상기 1차 유화액을 200 내지 300 bar의 압력조건에서 30 내지 60℃에서 균질화하여 2차 유화액을 얻는 단계(c2) homogenizing the primary emulsion at 30 to 60 ° C. under a pressure condition of 200 to 300 bar to obtain a secondary emulsion.
    를 포함하는 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.Characterized in that it comprises a, phosphatidylserine microencapsulation method.
  9. 제1항에 있어서,The method of claim 1,
    상기 단계 (d)에서, 건조는 분무건조 또는 유동층 건조인 것을 특징으로 하는, 포스파티딜세린의 마이크로캡슐화 방법.In the step (d), the drying is spray drying or fluidized bed drying, microencapsulation method of phosphatidylserine.
  10. 제1항 내지 제9항 중 어느 한 항의 방법으로 제조가능한, 식품 또는 의약품 용도에 적합한 포스파티딜세린을 포함하는 마이크로캡슐 제제.A microcapsule formulation comprising phosphatidylserine, which is suitable for food or pharmaceutical use, which is preparable by the method of claim 1.
PCT/KR2012/003504 2011-05-04 2012-05-04 Method for microencapsulating phosphatidylserine WO2012150839A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201280033216.7A CN103635181A (en) 2011-05-04 2012-05-04 Method for microencapsulating phosphatidylserine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020110042580A KR101763947B1 (en) 2011-05-04 2011-05-04 Method of microcapsulating phosphatidylserine
KR10-2011-0042580 2011-05-04

Publications (2)

Publication Number Publication Date
WO2012150839A2 true WO2012150839A2 (en) 2012-11-08
WO2012150839A3 WO2012150839A3 (en) 2013-01-03

Family

ID=47108156

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2012/003504 WO2012150839A2 (en) 2011-05-04 2012-05-04 Method for microencapsulating phosphatidylserine

Country Status (3)

Country Link
KR (1) KR101763947B1 (en)
CN (1) CN103635181A (en)
WO (1) WO2012150839A2 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110583801A (en) * 2019-10-17 2019-12-20 东北农业大学 Method for preparing powdered oil by compounding octenyl succinic anhydride modified starch and xanthan gum
CN111363767A (en) * 2020-04-22 2020-07-03 山东惠仕莱生物科技有限公司 Preparation method of phosphatidylserine for food
CN116570018A (en) * 2023-04-19 2023-08-11 广东萃怪香料有限公司 Perfume slow-release nanoparticle and preparation method and application thereof

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103892281B (en) * 2014-04-11 2016-04-06 内蒙古伊利实业集团股份有限公司 Containing alimentation composition and preparation method thereof and the application of phosphatidylserine
CN109222109A (en) * 2017-12-15 2019-01-18 理星（天津）生物科技有限公司 A kind of phosphatidylserine pellet and its preparation method and application
CN108142950A (en) * 2017-12-27 2018-06-12 浙江健智元生物科技有限公司 A kind of acer truncatum seed oil composite Nano microcapsule powder for improving brain neuroblastoma and preparation method thereof
CN109568292A (en) * 2018-12-29 2019-04-05 中山百灵生物技术有限公司 A kind of microgel and preparation method thereof containing GPC
CN110368362B (en) * 2019-08-01 2022-10-04 聊城大学 Preparation method of phosphatidylserine emulsion
CN110692893A (en) * 2019-11-12 2020-01-17 南通厚元生物科技有限公司 Preparation method of solid beverage containing phosphatidylserine and omega-3 fatty acid
CN111418846A (en) * 2020-04-27 2020-07-17 南通厚元生物科技有限公司 Microcapsule powder containing industrial cannabis protein and phosphatidylserine and preparation method thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991011178A1 (en) * 1990-01-26 1991-08-08 Fluntera Ag Encapsulation of active substances in starch
KR20020091492A (en) * 2001-05-30 2002-12-06 문장조 Microencapsulation Using Porous Dextrin with Matrix Inside and Manufacturing Method the Same
KR20030058839A (en) * 2002-01-02 2003-07-07 주식회사 두산 Liquid Composition Comprising Phosphatidylserine and Method for the preparation
KR20030070798A (en) * 2002-02-26 2003-09-02 주식회사 국순당 Method for preparation of micoencapsulated lipid soluble antioxidant coated by polysaccharides and proteins
KR20080014379A (en) * 2006-08-11 2008-02-14 주식회사 두산 Solid lipid nanoparticle composition containing phosphatidylserine and method for preparing the same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991011178A1 (en) * 1990-01-26 1991-08-08 Fluntera Ag Encapsulation of active substances in starch
KR20020091492A (en) * 2001-05-30 2002-12-06 문장조 Microencapsulation Using Porous Dextrin with Matrix Inside and Manufacturing Method the Same
KR20030058839A (en) * 2002-01-02 2003-07-07 주식회사 두산 Liquid Composition Comprising Phosphatidylserine and Method for the preparation
KR20030070798A (en) * 2002-02-26 2003-09-02 주식회사 국순당 Method for preparation of micoencapsulated lipid soluble antioxidant coated by polysaccharides and proteins
KR20080014379A (en) * 2006-08-11 2008-02-14 주식회사 두산 Solid lipid nanoparticle composition containing phosphatidylserine and method for preparing the same

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110583801A (en) * 2019-10-17 2019-12-20 东北农业大学 Method for preparing powdered oil by compounding octenyl succinic anhydride modified starch and xanthan gum
CN111363767A (en) * 2020-04-22 2020-07-03 山东惠仕莱生物科技有限公司 Preparation method of phosphatidylserine for food
CN116570018A (en) * 2023-04-19 2023-08-11 广东萃怪香料有限公司 Perfume slow-release nanoparticle and preparation method and application thereof
CN116570018B (en) * 2023-04-19 2024-01-02 广东萃怪香料有限公司 Perfume slow-release nanoparticle and preparation method and application thereof

Also Published As

Publication number Publication date
KR101763947B1 (en) 2017-08-01
KR20120124745A (en) 2012-11-14
WO2012150839A3 (en) 2013-01-03
CN103635181A (en) 2014-03-12

Similar Documents

Publication Publication Date Title
WO2012150839A2 (en) Method for microencapsulating phosphatidylserine
US6444242B1 (en) Microencapsulated oil or fat product
KR101156789B1 (en) Composition for gelatin film, gelatin film, and capsule made with the same
WO2016117621A1 (en) Ω-3 fatty acid self-emulsifying composition
CN107362154A (en) With the microcapsules for improving shell
JPH02103289A (en) Microencapsulation of fish oil
US10898442B2 (en) Microencapsulates containing stabilised lipid, and methods for the production thereof
US20060128665A1 (en) Marine lipid compositions
CN102724972A (en) Coated capsules and tablets of a fatty acid oil mixture
KR102180667B1 (en) Ph dependent carriers for targeted release of pharmaceuticals along the gastrointestinal tract, compositions therefrom, and making and using same
TW200534864A (en) S/O type pharmaceutical preparation and process for producing the same
US20230248808A1 (en) Joint Health Composition and Use Thereof in Healthy Mammals
Zeng et al. A nanoencapsulation suspension biomimetic of milk structure for enhanced maternal and fetal absorptions of DHA to improve early brain development
US20050220857A1 (en) Physiologically compatible, phospholipid-containing, stable and hard matrix
KR20180128025A (en) Nano-capsules containing lipid-soluble active ingredients, method for their preparation and uses thereof
US10806742B2 (en) Liquid phospholipid-containing compositions for the preparation of pharmaceuticals
JP2007504197A (en) Physiologically active composition of phosphatidylserine base
JP2023518822A (en) Pharmaceutical carrier capable of pH-dependent reconstitution, method of production and method of use thereof
MX2011006978A (en) Compositions and applications of carotenoids of improved absorption and bioavailability.
JP4913340B2 (en) Capsule
CN1802102A (en) Enteral composition for the prevention and/or treatment of sepsis
US20050232996A1 (en) Matrix comprising a bioactive component containing phospholipid
CN106456783B (en) Oral homogeneous preparation containing omega-3 polyunsaturated fatty acid and resveratrol
JP2009079011A (en) Liquid composition for filling soft capsule
CN113845677A (en) Emulsion film and preparation method thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12780042

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205A DATED 26.02.2014)

122 Ep: pct application non-entry in european phase

Ref document number: 12780042

Country of ref document: EP

Kind code of ref document: A2