WO2021071102A1 - 액상결정 구조체를 형성하는 오메가-3-지방산 조성물 - Google Patents
액상결정 구조체를 형성하는 오메가-3-지방산 조성물 Download PDFInfo
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- WO2021071102A1 WO2021071102A1 PCT/KR2020/011962 KR2020011962W WO2021071102A1 WO 2021071102 A1 WO2021071102 A1 WO 2021071102A1 KR 2020011962 W KR2020011962 W KR 2020011962W WO 2021071102 A1 WO2021071102 A1 WO 2021071102A1
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- fatty acid
- acid composition
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- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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Definitions
- the present invention relates to an omega-3 fatty acid composition
- an omega-3 fatty acid composition comprising amphoteric lipids and omega-3 fatty acids or derivatives thereof that form a liquid crystal structure when exposed to an aqueous medium such as gastrointestinal fluid.
- Omega-3-fatty acids are polyunsaturated fatty acids having a double bond at the third carbon atom at the end of the carbon chain. They are mainly found in fish oil and are known to exist in plants such as sesame seeds.
- the main omega-3-fatty acids involved in human physiology are alpha-linoleic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and improve lipoprotein metabolism. It is known to have physiological activities such as (improving blood lipid levels), suppressing and improving cardiovascular diseases, improving hypertension, regulating the immune system, and acting on the development and function of the eye, genital and nervous systems.
- natural fish oil contains omega-3-fatty acids in the form of triglycerides of EPA and DHA.
- Natural fish oil is sold under various brand names such as Omacor, Lovaza, and Omtryg after processing, concentrating, and refining EPA and DHA in ethyl ester form due to problems such as low purity.
- omega-3-fatty acids In order for omega-3-fatty acids to pass through the biological membrane and be absorbed into the body, digestion under the action of bile acids and enzymes in the gastrointestinal tract, in particular, must be decomposed into fatty acids by emulsification and then absorbed into the gastrointestinal epithelial cells. It is absorbed into the systemic circulation through re-esterification and chylomicron formation with a glycerol group. At this time, there is a difference in absorption rate depending on the molecular structure of the omega-3-fatty acid.
- omega-3-acid ethyl esters which are commercially available as various products, have low bioavailability compared to triglycerides due to the low activity of enzymes involved in digestion and the absence of glycerol groups. .
- WO 2012/032417 describes omega-3- fatty acid ethyl esters and triglycerides comprising at least one free fatty acid; And lipids forming a self-nanoemulsifying drug delivery system (SNEDDS), a self-microemulsifying drug delivery system (SMEDDS), or a self-emulsifying drug delivery system (SEDDS) in an aqueous solution comprising at least one surfactant.
- SNEDDS self-nanoemulsifying drug delivery system
- SMEDDS self-microemulsifying drug delivery system
- SEDDS self-emulsifying drug delivery system
- a surfactant and co-surfactant of several times the composition ratio of the oil component must be contained. If the ratio of the surfactant is low, the self-emulsifying system Emulsifying emulsions are not well formed, and omega-3- fatty acids, which are oil components, are not emulsified in the gastrointestinal tract and separated, so absorption may not be achieved properly.
- emulsions are thermodynamically unstable and require a large amount of surfactant and co-surfactant to form. Therefore, in order to form such a self-emulsifying system, the total weight of the formulation is increased due to the oil component and many surfactants for emulsifying it, and the size of the formulation is increased, so that it is difficult for the patient to take the drug.
- eicosapentaenoic acid For effective drug delivery of omega-3-fatty acids, eicosapentaenoic acid; And it has been disclosed to prepare a liquid crystal composition comprising glyceryl monooleate and dissolving them in an organic solvent.
- a liquid crystal composition comprising glyceryl monooleate and dissolving them in an organic solvent.
- it is not a system in which liquid crystals are formed spontaneously when exposed to an aqueous solution, but after mixing under an organic solvent (chloroform) condition and volatilizing the organic solvent, a limited environment (pH 7.0 phosphate buffer) is added and strong external energy ( It was possible to form liquid crystal particles through ultrasonication).
- chloroform chloroform
- a limited environment pH 7.0 phosphate buffer
- omega-3-fatty acid compositions with improved ease of administration by minimizing the absorption effect of food intake and improving the absorption rate in the gastrointestinal tract to reduce the size of the formulation.
- the present invention provides a composition containing amphoteric lipids that form a liquid crystal structure, an auxiliary agent for forming a spontaneous liquid crystal structure, and an omega-3- fatty acid or a derivative thereof when exposed to an aqueous medium such as gastrointestinal fluid.
- a composition containing amphoteric lipids that form a liquid crystal structure, an auxiliary agent for forming a spontaneous liquid crystal structure, and an omega-3- fatty acid or a derivative thereof when exposed to an aqueous medium such as gastrointestinal fluid is intended to provide an omega-3-fatty acid formulation having a reduced size by improving the absorption rate of omega-3-fatty acids, thereby providing an omega-3-fatty acid composition with improved dosage.
- the present invention forms a liquid crystal consisting of an amphoteric lipid comprising a nonpolar tail group having 14 to 20 carbon atoms (C 14 to C 20 ) and a polar head group having a hydroxy (-OH) or carboxyl group (-COOH) My; And omega-3- fatty acids or derivatives thereof; And it provides an omega-3-fatty acid composition comprising a liquid crystal structure formation aid of the lipid component, and spontaneously forming liquid crystals in an aqueous medium.
- Liquid crystal forming agents (including liquid crystal structure formation aids) and omega-3- fatty acids or derivatives thereof comprising amphoteric lipids are in the range of 20 to 60 parts by weight and 40 to 80 parts by weight based on 100 parts by weight of the composition Each can exist as.
- the liquid crystal forming agent and the liquid crystal structure forming aid may be present in a weight ratio of 10:1 to 2:8.
- the present invention provides an omega-3- fatty acid oral formulation comprising the omega-3- fatty acid composition and a pharmaceutically acceptable carrier.
- the present invention provides an omega-3- fatty acid gelatin soft capsule comprising the omega-3- fatty acid composition.
- the liquid crystal forming agent composed of amphoteric lipids spontaneously formed a concentration-transition-type liquid crystal having a thermodynamically stable structure in the gastrointestinal tract irrespective of digestion, solubilizing omega-3-fatty acids, thereby remarkably improving elution.
- it is expected to be able to promote the absorption rate in the body.
- the absorption rate in the body is improved compared to the conventional formulation containing 1000 mg of omega-3 fatty acid, so that the same effect can be obtained even if a smaller dose of omega-3- fatty acid is administered than the conventional formulation.
- FIG. 1 is a dissolution test result of EPA ethyl esters in the test tubes of Examples 6, 8 and 68 and Comparative Examples 1 and 2.
- FIG. 1 is a dissolution test result of EPA ethyl esters in the test tubes of Examples 6, 8 and 68 and Comparative Examples 1 and 2.
- FIG. 2 is a result of dissolution test of DHA ethyl esters in the test tubes of Examples 6, 8 and 68 and Comparative Examples 1 and 2.
- FIG. 2 is a result of dissolution test of DHA ethyl esters in the test tubes of Examples 6, 8 and 68 and Comparative Examples 1 and 2.
- the present inventors have conducted various studies to develop a composition containing omega-3-fatty acid with improved patient compliance by improving the absorption rate, reducing the resulting dosage and reducing the size of the dosage form, and spontaneous in the gastrointestinal tract.
- a liquid crystal system composed of amphoteric lipids capable of forming a self-assembly lyotropic liquid crystal structure is formulated with omega-3- fatty acids or derivatives thereof, conventional omega-3- fatty acid formulations It was confirmed to have a higher absorption rate, and the present invention was completed.
- the present invention comprises two or more amphoteric lipids including a polar head group having a non-polar tail group having 14 to 20 carbon atoms (C 14 to C 20) and a hydroxy (-OH) or carboxyl group (-COOH)
- a liquid crystal forming agent consisting of; Omega-3- fatty acids or derivatives thereof; And it provides an omega-3-fatty acid composition comprising a liquid crystal structure formation aid of the lipid component, forming a liquid crystal in an aqueous medium.
- the omega-3- fatty acid composition may be included in an amount of 20 to 60 parts by weight of a liquid crystal forming agent and 40 to 80 parts by weight of an omega-3- fatty acid or derivative thereof based on 100 parts by weight of the composition.
- omega-3-fatty acid composition may have a weight ratio of the liquid crystal forming agent and the liquid crystal structure forming aid of 10:1 to 2:8.
- the omega-3 fatty acids are omega-3, omega-3-fatty acids, omega-3 derivatives (ethyl ester derivatives or carboxylic acid derivatives, omega-3 complexes), or omega-3 internal components DHA, EPA ( Eicosapentaenoic acid) and the like are possible, and these may be included in an amount of 40 parts by weight to 80 parts by weight based on a total of 100 parts by weight of the composition.
- the omega-3 fatty acid is contained in an amount of 40 parts by weight or less, the size of the dosage form increases or the amount of capsules per dose increases, making it difficult for the patient to take it. Due to the lack of this, the formation of the liquid crystal structure is difficult in vivo, so that the elution of omega-3-fatty acids in the body decreases and the absorption capacity in the body may not be improved.
- the liquid crystal forming agent is preferably 20 parts by weight to 60 parts by weight based on 100 parts by weight of the total composition.
- the liquid crystal forming agent is contained in an amount of less than 20 parts by weight, it may not be easy to form a liquid crystal structure in vivo, and thus the bioabsorption capacity may not be improved due to lower elution of omega-3-fatty acids in the body.
- the content of the main component omega-3-fatty acid is lowered, so that the size of the dosage form increases and the amount of one-time capsule is increased, so that it may not be easy for the patient to take medicine.
- the liquid crystal forming agent of the present invention has the form of a lipid solution, and when exposed to an excessive amount of aqueous medium including water and gastrointestinal fluid, liquid crystal structure particles of 1000 nm or less, preferably 500 nm or less are spontaneously formed. It refers to an amphoteric lipid formed by and a substance containing the same.
- the amphoteric lipid contains a polar head group and one to two non-polar tail groups in the molecular structure, and forms a nanometer-level liquid crystal in an aqueous medium.
- a reversed hexagonal phase, a reversed cubic phase, a multi-lamellar vesicle, etc. can be generated.
- the properties of the structure are not limited, and the structures have the advantage of being able to solubilize both a polar material and a non-polar material by forming a polar region and a non-polar region.
- the amphoteric lipid may be an amphoteric lipid consisting of 1 to 2 non-polar tail groups having 14 to 20 carbon atoms and at least one polar head group including a hydroxy or carboxyl group, and more preferably a neutral It may be one or a combination of two or more selected from the group consisting of acyl/diacyl glycerol, phytantriol, and phospholipids, but is not limited thereto.
- the neutral acyl/diacyl glycerol is glyceryl monooleate, glyceryl monolinoleate, glyceryl palmitate, glyceryl dioleate, glyceryl dioleate Tate (glyceryl dipalmitate), glyceryl phytanoate (glyceryl phytanoate), glyceryl palmitoleate (glyceryl palmitoleate), glyceryl distearate (glyceryl distearate), glyceryl dielaidiate (glyceryl dielaidiate) and glyceryl di It may be one or a combination of two or more selected from the group consisting of linoleate (glyceryl dilinoleate).
- the liquid crystal structure-forming aid is a lipid component that helps the liquid crystal former to form a liquid crystal structure spontaneously in a living body (for example, in the gastrointestinal tract). It includes a material having good miscibility with omega-3-fatty acids and excellent biocompatibility, and may be one or a combination of two or more from the group consisting of, for example, phospholipids, unsaturated fatty acids, tocopherol acetate, cholesterol and vegetable oils, It is not limited thereto.
- the phospholipid includes a polar head group and two nonpolar tail groups, and includes various derived or synthesized phospholipids including phospholipids derived from soybean or egg yolk. May, preferably phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerine, phosphatidylinositol and phosphatidylinositol, phosphatidylinositol, and phosphatidylinositol. It may be one or a combination of two or more selected from the group consisting of, but is not limited thereto.
- the unsaturated fatty acid is an unsaturated fatty acid in a liquid form at room temperature, has 1 to 3 double bonds, is a component derived from living organisms widely present in animals and plants, has excellent biocompatibility, and has an amphoteric lipid that forms liquid crystals.
- it serves to form a concentration transition type liquid crystal structure such as an inverted hexagonal structure, an inverted cubic structure, and a multilayered blister structure, and thus the solubilization and absorption promoting effect of omega-3-fatty acids is increased. It was confirmed through.
- the liquid unsaturated fatty acid may be one or a combination of two or more selected from the group consisting of oleic acid, linoleic acid, myristoleic acid, palmitoleic acid, and 11-eicosenoic acid, but is not limited thereto. .
- the omega-3- fatty acid may be selected from eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), and derivatives thereof are in the form of ethyl esters, triglycerides, free fatty acids and phospholipids of omega-3- fatty acids. It may be selected from the group consisting of, but is not limited thereto.
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- composition may further include one or more antioxidants selected from the group consisting of alpha-tocopherol acetate, butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT).
- antioxidants selected from the group consisting of alpha-tocopherol acetate, butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT).
- the composition may form a spontaneous concentration transition type liquid crystal structure in the gastrointestinal tract.
- the present invention provides an omega-3- fatty acid oral formulation comprising the omega-3- fatty acid composition and a pharmaceutically acceptable carrier.
- the present invention provides an omega-3- fatty acid soft capsule comprising the omega-3- fatty acid composition and a scientifically acceptable carrier.
- the soft capsule may be filled with 150 to 1500 mg of the omega-3- fatty acid composition, more preferably 600 to 800 mg of the omega-3- fatty acid composition, but is not limited thereto.
- Examples 1 to 20 including omega-3-fatty acid ethyl ester were prepared. Specifically, omega-3-fatty acid ethyl ester, liquid crystal forming agent (glyceryl monooleate, glyceryl diolate, phytantriol) and liquid crystal structure forming aid (phosphatidylcholine, oleic acid, tocopherol acetate, cholesterol) are added to a glass vial. After addition, it was mixed while stirring with a magnetic stirrer at room temperature. The total badge size was prepared at 20 g per formulation.
- omega-3-fatty acid ethyl ester liquid crystal forming agent
- liquid crystal structure forming aid phosphatidylcholine, oleic acid, tocopherol acetate, cholesterol
- Examples 21 to 40 containing omega-3-fatty acid triglyceride were prepared. Specifically, omega-3-fatty acid triglycerides, liquid crystal forming agents (glyceryl monooleate, glyceryl dioleate, phytantriol) and liquid crystal structure forming aids (phosphatidylcholine, oleic acid, tocopherol acetate, cholesterol) are added to the glass vial. After that, the mixture was mixed while stirring with a magnetic stirrer at room temperature. The total badge size was prepared at 20 g per formulation.
- Examples 41 to 60 containing omega-3-fatty acid phospholipid were prepared. Specifically, omega-3-fatty acid phospholipids, liquid crystal forming agents (glyceryl monooleate, glyceryl diolate, phytantriol) and liquid crystal structure forming aids (phosphatidylcholine, oleic acid, tocopherol acetate, cholesterol) in a glass vial After addition, the mixture was mixed while stirring with a magnetic stirrer at room temperature. The total badge size was prepared at 20 g per formulation.
- Examples 61 to 70 containing omega-3-fatty acid ethyl ester (Omega-3>90EE, K.D.Pharma) were prepared. Specifically, in a glass vial, omega-3-fatty acid ethyl ester, liquid crystal forming agent (glyceryl monooleate, liquid crystal structure forming aid (phosphatidylcholine, oleic acid) and antioxidant (tocopherol acetate, butylhydroxyanisole (BHA)), After butylhydroxytoluene (BHT) was added, the mixture was mixed while stirring with a magnetic stirrer at room temperature, and the total badge scale was prepared at 20 g per formulation.
- liquid crystal forming agent glyceryl monooleate, liquid crystal structure forming aid (phosphatidylcholine, oleic acid) and antioxidant (tocopherol acetate, butylhydroxyanisole (BHA)
- BHA butylhydroxyanisole
- Omako ® soft capsules and omega-3- fatty acid ethyl ester [Omega-3>90EE, KDPharma] were used as Comparative Example 1 and Comparative Example 2, respectively.
- the composition prepared in the examples was filled in a hard capsule (No. 00) to be 500 mg as an omega-3-fatty acid ethyl ester.
- the dissolution test was conducted in the device (paddle method) of method 2 of dissolution test method among general test methods of the Korean Pharmacopoeia.
- a pH 5.0 FeSSIf eluate containing 900 mL of 1.5% (w/v) Triton X-100 was maintained at 37.0 ⁇ 0.5°C, and the rotation speed of the paddle was 100 rpm. 5 mL of the sample was collected, and the eluate was not separately supplemented after collection.
- the collected sample was analyzed in a high-performance liquid chromatography (HPLC) apparatus, and the analysis conditions were as follows.
- HPLC high-performance liquid chromatography
- compositions according to Examples 6, 8 and 68 according to the present invention in artificial intestinal fluid as shown in FIGS. 1 and 2 were compared with Comparative Examples 1 and 2, which are conventional omega-3-fatty acid formulations, in artificial intestinal fluid. -It was confirmed that it promotes the absorption rate of fatty acids, and it can be predicted that the absorption rate in the body will increase.
- test solution of pH 5.0 containing 8.250 g of sodium taurocholine per 1 liter of purified water, 2.950 g of soybean-derived phosphatidyl choline, 8.650 g of acetic acid, 11.874 g of sodium chloride and 4.040 g of sodium hydroxide (artificial intestinal solution after meals, FeSSIF)
- test solution of pH 6.5 containing 1.700 g of sodium taurocholine, 0.600 g of soybean-derived phosphatidyl choline, 3.400 g of sodium dihydrogen phosphate, 6.200 g of sodium chloride, and 0.400 g of sodium hydroxide per 1 liter of purified water (artificial intestinal solution before meals, FaSSIF ) was prepared.
- composition prepared in the Example was filled in a soft capsule to be 500 mg as an omega-3-fatty acid ethyl ester, and then exposed to 900 ml of artificial intestinal solution before and after meals under the dissolution test conditions of Experimental Example 1 for 30 minutes. And, under the following conditions, a polarization microscope and dynamic light scattering particle size analysis were performed.
- composition of the embodiment according to the present invention in the artificial intestinal fluid forms liquid crystal particles in the artificial intestinal fluid as shown in FIGS. 3 and 4.
- a soft capsule filled with a composition containing omega-3-fatty acid a gelatin film was prepared, and then soft capsules of various sizes (5 oval, 12 oblong and 14 oval, etc.) were produced.
- a gelatin film containing 415 g of succinate gelatin, 130 g of concentrated glycerin, 305 g of purified water, and 150 g of amorphous sorbitol solution per 1 kg of the film was prepared, and after a one-day aging period, the film thickness was 0.080 mm.
- the composition containing -3-fatty acid was filled, and the preparation was completed by drying for about 2 days under 25°C/ventilating condition.
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Abstract
Description
(단위: mg) | 실시예 | |||||||||||||||||||
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | |
오메가-3-지방산에틸 에스테르 | 320 | 320 | 320 | 600 | 600 | 500 | 500 | 500 | 500 | 500 | 320 | 500 | 500 | 500 | 600 | 320 | 500 | 500 | 500 | 600 |
글리세릴 모노올레이트 | 390 | 129 | 215 | 110 | 75 | 200 | 125 | 240 | 125 | 60 | ||||||||||
글리세릴 디올레이트 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
피탄트리올 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
포스파티딜콜린 | 40 | 301 | 215 | 40 | 75 | 75 | 125 | 75 | 125 | |||||||||||
올레산 | 50 | 125 | 115 | 240 | 80 | 125 | 40 | 80 | 125 | 40 | ||||||||||
토코페롤 아세테이트 | 10 | 10 | ||||||||||||||||||
콜레스테롤 | 10 |
(단위: mg) | 실시예 | |||||||||||||||||||
21 | 22 | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | 40 | |
오메가-3-지방산트리글리세리드 | 320 | 320 | 320 | 600 | 600 | 500 | 500 | 500 | 500 | 500 | 320 | 500 | 500 | 500 | 600 | 320 | 500 | 500 | 500 | 600 |
글리세릴 모노올레이트 | 390 | 355 | 215 | 110 | 75 | 200 | 125 | 240 | 125 | 125 | ||||||||||
글리세릴 디올레이트 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
피탄트리올 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
포스파티딜콜린 | 40 | 75 | 215 | 40 | 75 | 75 | 125 | 75 | 125 | |||||||||||
올레산 | 50 | 125 | 115 | 115 | 80 | 125 | 40 | 80 | 125 | 40 | ||||||||||
토코페롤 아세테이트 | 10 | 10 | ||||||||||||||||||
콜레스테롤 | 10 |
(단위: mg) | 실시예 | |||||||||||||||||||
41 | 42 | 43 | 44 | 45 | 46 | 47 | 48 | 49 | 50 | 51 | 52 | 53 | 54 | 55 | 56 | 57 | 58 | 59 | 60 | |
오메가-3-지방산포스포리피드 | 320 | 320 | 320 | 600 | 600 | 500 | 500 | 500 | 500 | 500 | 320 | 500 | 500 | 500 | 600 | 320 | 500 | 500 | 500 | 600 |
글리세릴 모노올레이트 | 390 | 355 | 215 | 110 | 75 | 200 | 125 | 240 | 125 | 125 | ||||||||||
글리세릴 디올레이트 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
피탄트리올 | 355 | 125 | 170 | 125 | 110 | |||||||||||||||
포스파티딜콜린 | 40 | 75 | 215 | 40 | 75 | 75 | 125 | 75 | 125 | |||||||||||
올레산 | 50 | 125 | 115 | 115 | 80 | 125 | 40 | 80 | 125 | 40 | ||||||||||
토코페롤 아세테이트 | 10 | 10 | ||||||||||||||||||
콜레스테롤 | 10 |
(단위: mg) | 실시예 | |||||||||
61 | 62 | 63 | 64 | 65 | 66 | 67 | 68 | 69 | 70 | |
오메가-3-지방산에틸 에스테르 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 |
글리세릴 모노올레이트 | 163 | 163 | 163 | 163 | 110 | 110 | 110 | 125 | 125 | 125 |
포스파티딜콜린 | 82 | 90 | 90 | 90 | ||||||
올레산 | 82 | 82 | 82 | 45 | 45 | 45 | 120 | 120 | 120 | |
토코페롤 아세테이트 | 5 | 5 | 5 | 5 | ||||||
부틸히드록시아니솔 (BHA) | 5 | 5 | 5 | |||||||
부틸히드록시톨루엔 (BHT) | 5 | 5 | 5 |
Claims (15)
- 탄소수 14개 내지 20개(C14~C20)의 비극성 꼬리기와, 하이드록시(-OH) 또는 카르복실기(-COOH)를 갖는 극성 머리기를 포함하는 양쪽성 지질을 둘 이상 포함하여 이루어진 액상결정 형성제;오메가-3-지방산 또는 이의 유도체; 및지질 성분의 액상결정 구조 형성 보조제를 포함하며, 수성매질에서 액상결정을 형성하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 오메가-3-지방산 조성물은 조성물 100 중량부에 대하여, 액상결정 형성제 20 내지 60 중량부 및 오메가-3-지방산 또는 이의 유도체 40 내지 80 중량부를 포함하는 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 2에 있어서, 상기 오메가-3-지방산 조성물은 액상결정 형성제 및 액상결정 구조 형성보조제의 중량비가 10 : 1 내지 2 : 8인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 양쪽성 지질은 중성 아실/디아실 글리세롤, 피탄트리올 및 인지질로 이루어진 군에서 선택된 하나 또는 둘 이상의 조합인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 4에 있어서, 상기 중성 아실/디아실 글리세롤은 글리세릴 모노올레이트(glyceryl monooleate), 글리세릴 모노리놀레이트(glyceryl monolinoleate), 글리세릴 팔미테이트(glyceryl palmitate), 글리세릴 디올레이트(glyceryl dioleate), 글리세릴 디팔미테이트(glyceryl dipalmitate), 글리세릴 피타노에이트(glyceryl phytanoate), 글리세릴 팔미톨레이트(glyceryl palmitoleate), 글리세릴 디스테아레이트(glyceryl distearate), 글리세릴 디엘라이디에이트(glyceryl dielaidiate) 및 글리세릴 디리놀레이트(glyceryl dilinoleate)로 이루어진 군에서 선택된 하나 또는 둘 이상의 조합인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 액상결정 구조 형성 보조제는 인지질, 불포화지방산, 토코페롤 아세테이트, 콜레스테롤 및 식물성 오일로 이루어진 군에서 선택된 하나 또는 둘 이상의 조합인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 6에 있어서, 상기 인지질은 포스파티딜콜린(phosphatidylcholine), 포스파티딜에탄올아민phosphatidylethanolamine), 포스파티딜세린(phosphatidylserine), 포스파티딜글리세린(phosphatidylglycerine), 디팔미토일포스파티딜콜린(dipamitoyl phosphatidylcholine), 디스테아릴포스파티딜콜린(distearyl phosphatidylcholine), 포스파티딜이노시톨(phosphatidylinositol), 포스파티딘산(phosphatidic acid) 및 스핑고미엘린(sphingomyelin)으로 이루어진 군에서 선택되는 하나 또는 둘 이상의 조합인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 6에 있어서, 상기 불포화지방산은 올레산, 리놀레산, 미리스톨레산, 팔미톨레산 및 11-에이코센산(11-eicosenoic acid)으로 이루어진 군에서 선택된 하나 또는 둘 이상의 조합인 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 오메가-3-지방산은 에이코사펜타엔산(EPA) 또는 도코사헥사엔산(DHA)에서 선택된 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 이의 유도체는 오메가-3-지방산의 에틸 에스테르, 트리글리세리드, 유리 지방산 및 인지질 형태로 이루어진 군에서 선택된 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 조성물은 알파-토코페롤 아세테이트, 부틸히드록시아니솔 (BHA) 및 부틸히드록시톨루엔 (BHT)으로 이루어진 군에서 선택되는 하나 이상의 항산화제를 추가로 더 포함하는 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1에 있어서, 상기 조성물은 위장관 내에서 자발적 농도 전이형 액상결정(lyotropic liquid crystal) 구조를 형성하는 것을 특징으로 하는 오메가-3-지방산 조성물.
- 청구항 1 내지 청구항 12 중 어느 한 항의 오메가-3-지방산 조성물 및 약학적으로 허용 가능한 담체를 포함하는 오메가-3-지방산 경구제제.
- 청구항 1 내지 청구항 12 중 어느 한 항의 오메가-3-지방산 조성물 및 약학적으로 허용 가능한 담체를 포함하는 오메가-3-지방산 연질캡슐.
- 청구항 14에 있어서, 상기 연질캡슐은 오메가-3-지방산 조성물이 150 내지 1500 mg 충진된 것을 특징으로 하는 연질캡슐.
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US17/797,868 US20230083019A1 (en) | 2019-10-11 | 2020-09-04 | Liquid crystalline structure-forming omega-3-fatty acid composition |
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7008646B2 (en) * | 2001-02-20 | 2006-03-07 | Patrick Thomas Spicer | Cubic liquid crystalline compositions and methods for their preparation |
KR20070017447A (ko) * | 2005-04-06 | 2007-02-12 | 유효경 | 양쪽성 계면활성제와 폴리올을 함유하는 가용화용나노조성물 |
KR20110126746A (ko) * | 2009-03-09 | 2011-11-23 | 프로노바 바이오파마 너지 에이에스 | 지방산 오일 혼합물 및 계면활성제를 포함하는 조성물 및 이의 방법 및 사용 |
WO2012032417A2 (en) | 2010-09-08 | 2012-03-15 | Pronova Biopharma Norge As | Compositions comprising a fatty acid oil mixture, a free fatty acid, and a statin |
KR20140086722A (ko) * | 2012-12-28 | 2014-07-08 | 주식회사 종근당 | 양이온성 약리학적 활성물질의 서방성 지질 초기제제 및 이를 포함하는 약제학적 조성물 |
KR102096391B1 (ko) * | 2019-10-11 | 2020-04-06 | (주)아이엠디팜 | 액상결정 구조체를 형성하는 오메가-3-지방산 조성물 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR100797985B1 (ko) * | 2005-12-21 | 2008-01-28 | 주식회사 일신웰스 | 액정막 유화 조성물 및 그 제조방법 |
KR102108154B1 (ko) | 2017-02-08 | 2020-05-07 | (주)동구바이오제약 | 개선된 생체이용률을 갖는 오메가-3 지방산 및 HMG-CoA 환원효소 억제제를 포함하는 약제학적 복합제제 |
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7008646B2 (en) * | 2001-02-20 | 2006-03-07 | Patrick Thomas Spicer | Cubic liquid crystalline compositions and methods for their preparation |
KR20070017447A (ko) * | 2005-04-06 | 2007-02-12 | 유효경 | 양쪽성 계면활성제와 폴리올을 함유하는 가용화용나노조성물 |
KR20110126746A (ko) * | 2009-03-09 | 2011-11-23 | 프로노바 바이오파마 너지 에이에스 | 지방산 오일 혼합물 및 계면활성제를 포함하는 조성물 및 이의 방법 및 사용 |
WO2012032417A2 (en) | 2010-09-08 | 2012-03-15 | Pronova Biopharma Norge As | Compositions comprising a fatty acid oil mixture, a free fatty acid, and a statin |
KR20140086722A (ko) * | 2012-12-28 | 2014-07-08 | 주식회사 종근당 | 양이온성 약리학적 활성물질의 서방성 지질 초기제제 및 이를 포함하는 약제학적 조성물 |
KR102096391B1 (ko) * | 2019-10-11 | 2020-04-06 | (주)아이엠디팜 | 액상결정 구조체를 형성하는 오메가-3-지방산 조성물 |
Non-Patent Citations (2)
Title |
---|
See also references of EP4062904A4 |
YAGHMUR A, ET AL.: "Emulsified Microemulsions and Oil-Containing Liquid Crystalline Phases", LANGMUIR, AMERICAN CHEMICAL SOCIETY, US, vol. 21, no. 2, 1 January 2005 (2005-01-01), US, pages 569 - 577, XP002379478, ISSN: 0743-7463, DOI: 10.1021/la0482711 * |
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