CN111374946A - Liposome, composition, and method for producing liposome - Google Patents

Liposome, composition, and method for producing liposome Download PDF

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CN111374946A
CN111374946A CN201911248435.7A CN201911248435A CN111374946A CN 111374946 A CN111374946 A CN 111374946A CN 201911248435 A CN201911248435 A CN 201911248435A CN 111374946 A CN111374946 A CN 111374946A
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liposome
oil
composition
ethylene oxide
component
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木下雅崇
福永丈朗
后藤昌史
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Sunstar Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • 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
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Abstract

The invention provides a liposome, a composition and a liposome manufacturing method, wherein the liposome is a liposome containing an oil component, and the transparency and the liposome particle size uniformity are maintained as much as possible in the composition containing the liposome. The liposome comprises a hydrogenated phospholipid and at least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil with an average addition mole number of ethylene oxide of 40-95, PPG-6 decyl tetradecyl alcohol polyether-30 and PEG-20phytosterol, and contains an oil component.

Description

Liposome, composition, and method for producing liposome
Technical Field
The present invention relates to a liposome (liposome) encapsulating an oil and fat component, a composition, a method for producing a liposome, and the like.
Background
Liposomes are artificial capsules (capsules) composed of phospholipids and the like, which are main components of biological membranes. Phospholipids are amphiphilic structures and form lipid bilayers (in other words, bilayer membranes). Can absorb oil soluble substances in the bimolecular film, and can absorb water soluble substances in the inner water phase according to the preparation method.
[ Prior art documents ]
[ patent document ]
[ patent document 1] Japanese patent laid-open No. 2015-174860
[ patent document 2] International publication No. 2008/093848
Disclosure of Invention
[ problems to be solved by the invention ]
As described above, liposomes can absorb oil-soluble substances inside the bilayer membrane, and therefore the following possibilities are considered: can be used for stably containing an oil or fat component in an aqueous composition. In addition, in recent years, the function of vegetable oil and fat components has been attracting attention, and particularly, there is an increasing demand for blending vegetable oil and fat components in external compositions (particularly, external aqueous compositions) such as cosmetics.
In addition, when such an aqueous composition is used in cosmetics, in particular, the appearance (transparency) is often regarded as important, and it is particularly important that the transparency is maintained. The reason for this is that: consumers tend to avoid compositions that become cloudy over time, especially cosmetic compositions. In general, the smaller the liposome particle size, the more transparent the aqueous composition, and therefore, from the viewpoint of the above, the liposome particle size is preferably relatively small. Further, the smaller the liposome particle size, the more percutaneous absorbability tends to be high, and therefore, this is also preferable from the viewpoint described above.
Further, the more uniform the size of each liposome particle (i.e., the more uniform), the less likely the liposome is to be incorporated or disintegrated, and the dispersion stability over time tends to be high. From the viewpoint, the size of each liposome particle is preferably as uniform as possible.
Accordingly, an object of the present invention is to provide a liposome in which an oil or fat component is encapsulated, and which can maintain transparency and liposome particle size uniformity as much as possible in a composition containing the liposome.
[ means for solving problems ]
The present inventors have found that a liposome-containing composition maintaining transparency and liposome particle size uniformity can be prepared by using a specific surfactant in liposome preparation, and further improvements have been repeated, thereby completing the present invention.
The present invention includes, for example, the subject matters described in the following items.
Item 1.
A liposome, comprising: a hydrogenated phospholipid, and
at least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil with an average addition mole number of ethylene oxide of 40-95, PPG-6 decyltetradecyltetradecylpolyether-30 (PPG-6-Decyltrabeceth-30), and PEG-20Phytosterol (PEG-20Phytosterol), and
oil and fat components are contained.
Item 2.
The liposome according to item 1, wherein the lipid component is at least one selected from the group consisting of rice oil, soybean oil, olive oil, meadowfoam oil, sunflower oil, hazelnut oil, and tocopherol (tocophenol).
Item 3.
The liposome according to item 1 or 2, wherein the hydrogenated phospholipid is hydrogenated lecithin.
Item 4.
A liposome, comprising: hydrogenated lecithin, and
polyoxyethylene hardened castor oil having an average addition mole number of ethylene oxide of 55 to 65, and
contains rice bran oil.
Item 5.
The liposome according to any one of claims 1 to 4, wherein the average particle diameter is 82nm or less.
Item 6.
The liposome according to any one of items 1 to 5, wherein the polydispersity index (PdI) is 0.26 or less.
Item 7.
A composition comprising a liposome according to any one of claims 1 to 6.
Item 8.
The composition according to item 7, which is an external pharmaceutical composition, an oral composition, or a cosmetic composition.
Item 9.
The liposome according to any one of claims 1 to 6, or the composition according to claim 7 or 8, wherein the pH is 6-7.5.
Item 10.
A method of making liposomes, comprising: stirring the composition, and
treating the stirred composition at a pressure of 100MPa to 400MPa, said composition comprising:
hydrogenation treatment of phospholipids,
At least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil with an average addition mole number of ethylene oxide of 40-95, PPG-6 decyl tetradecyl polyether-30 and PEG-20phytosterol,
An oil component, and
and (3) water.
Item 11.
The method of item 10, wherein the composition has a pH of 6 to 7.5.
[ Effect of the invention ]
The invention provides a composition containing liposome, liposome contained in the composition and a manufacturing method thereof, which maintain transparency and liposome particle size uniformity. The liposome-containing composition is particularly advantageously utilized as a cosmetic composition.
Drawings
Fig. 1A and 1B show the state of liposome suspensions prepared using different surfactants immediately after preparation and after 3 months of storage.
Fig. 2A and 2B show the state of liposome suspensions prepared using different oil and fat components (particularly, vegetable oil and fat components) in appropriate compositions immediately after preparation.
Detailed Description
Hereinafter, each embodiment included in the present invention will be described in further detail. The present invention preferably comprises: the present invention is not limited to the above-described compositions containing liposomes, liposomes contained in the compositions, and methods for producing the same, and the present invention includes all the contents disclosed in the present specification and understood by those skilled in the art.
The liposome contained in the present invention comprises (A) a hydrogenated phospholipid and (B) at least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil having an average molar number of addition of ethylene oxide of 40 to 95, PPG-6 decyltetradecanol polyether-30, and PEG-20phytosterol, and contains (C) an oil component. Hereinafter, the liposome included in the present invention may be referred to as "liposome of the present invention". Although not particularly limited, the liposome of the present invention preferably further contains (D) cholesterol (cholestrol).
The phospholipid to be hydrogenated is preferably exemplified by: glycerophospholipids such as phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and phosphatidylacid, or sphingophospholipids such as sphingomyelin (sphingomyelin). In addition, lecithin (lecithin) (e.g., soybean lecithin, corn lecithin, cottonseed oil lecithin, egg yolk lecithin, egg white lecithin, etc.) may also be used. The lecithin is preferably lecithin having a phosphatidylcholine content of 60 mass% or more, and more preferably 65 mass% or more, 70 mass% or more, 75 mass% or more, 80 mass% or more, 85 mass% or more, or 90 mass% or more. Further, phospholipid derivatives into which polyethylene glycol or an amino polysaccharide has been introduced, and phosphatidylcholine hydroxide, lysophosphatidylcholine, and the like are also included in the phospholipids herein.
The hydrogenated phospholipid is preferably a phospholipid obtained by hydrogenating the phospholipid. Among them, for example, hydrogenated glycerophospholipids are preferable, and hydrogenated phosphatidylethanolamine, hydrogenated phosphatidylserine, hydrogenated phosphatidylinositol, hydrogenated phosphatidylcholine, and the like are particularly preferable. In addition, hydrogenated lecithin (e.g., hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, hydrogenated corn lecithin, hydrogenated cottonseed oil lecithin, etc.) may also be used.
The hydrogenated phospholipids may be used singly or in combination of two or more.
In the liposome of the present invention, polyoxyethylene hardened castor oil having an average addition mole number of ethylene oxide of 40 to 95, PPG-6 decyltetradecanol polyether-30, and PEG-20phytosterol can be used as the surfactant. These components may be used singly or in combination of two or more.
The polyoxyethylene hardened castor oil used in the present invention has an average number of moles of ethylene oxide added of 40 to 95(40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, or 95). Preferably about 45 to 90, more preferably about 50 to 80, further preferably about 55 to 70, and further preferably about 55 to 65.
PPG-6 decyltetradecanol polyether-30 has a structure in which ethylene oxide and propylene oxide are addition-polymerized to decyltetradecanol, and the average number of moles of ethylene oxide added is 6 and the average number of moles of propylene oxide added is 30.
PEG-20 Phytosterols are polyethylene glycol ethers of Phytosterols (Phytosterols) and are compounds with an average molar number of addition of ethylene oxide of 20.
The oil and fat component includes, in particular, animal oil and fat components and plant oil and fat components. The animal fat and oil component herein includes not only an animal-derived fat and oil component but also a component known as an animal-derived fat and oil component even if it is a synthetic fat and oil component. Similarly, the vegetable oil and fat component herein includes not only a vegetable-derived oil and fat component but also a component known as a vegetable-derived oil and fat component even if it is a synthetic oil and fat component. For example, since tocopherol is a component contained in a large amount of vegetable oil, even if it is synthesized, it is contained in the vegetable oil component. The oil and fat component is particularly preferably a vegetable oil and fat component.
Examples of the plant oil and fat component include rice oil, soybean oil, olive oil, meadowfoam seed oil, sunflower seed oil, hazelnut oil, and tocopherol (preferably α -tocopherol, including D- α -tocopherol, dl- α -tocopherol, and dl- α -tocopherol acetate, for example). furthermore, the rice oil is preferably rice bran oil.
(A) The content ratio of the hydrogenated phospholipid to the surfactant (B) may be appropriately set within a range of the liposome capable of obtaining the effect of the present invention, and for example, the ratio of (B): (A) preferably 1: about 1 to 10, more preferably 1: about 2 to 8 or 1: about 2.5 to 6, and more preferably 1: about 3 to 5. When the liposome of the present invention contains (D) cholesterol, the content ratio of the total amount of (a + D) and (B) of (a) and (D) may be appropriately set, for example, in terms of a mass ratio of (B): (A + D) is preferably 1: about 1 to 10, more preferably 1: about 2 to 8 or 1: about 2.5 to 6, and more preferably 1: about 3 to 5 or 1: about 4-5.
The form in which (a), (B), and (D) are contained in the liposome is not particularly limited, and for example, the form may include the form in which they are present in a hydrophilic region or a hydrophobic region formed inside the liposome, the form in which they are present on the membrane surface of the outermost membrane of the liposome constituent, and the like, and the form in which they are present together with the membrane constituent of the liposome (particularly, the form in which they are contained in the liposome as a membrane constituent component of the liposome) is preferable.
The amount of the (C) fat or oil component encapsulated in the liposome of the present invention can be suitably set, for example, in terms of mass ratio, (C): (A) preferably 1: about 1 to 10, more preferably 1: about 2 to 8 or 1: about 2.5 to 6, and more preferably 1: about 3 to 5. When (D) is contained, the mass ratio of (C) to (a) is preferably (C): more preferably, (a + D) is 1: about 1 to 10, preferably 1: about 2 to 8 or 1: about 2.5 to 6, and more preferably 1: about 3 to 5 or 1: about 4-5.
Furthermore, liposomes are classified into both Multilamellar Liposomes (MLV) and unilamellar liposomes based on the number of lipid bilayers. Unilamellar liposomes are further classified by their size into small unilamellar liposomes (SUV), large unilamellar Liposomes (LUV), giant unilamellar liposomes (GUV), and the like. Any of these can be suitably used as the liposome of the present invention. In addition, regarding the size (particle size) of the liposome of the present invention, the average particle diameter (average outer diameter in the case of particles having no spherical shape) is preferably 82nm or less, and more preferably 81nm or less, 80nm or less, 79nm or less, 78nm or less, 77nm or less, 76nm or less, 75nm or less, 74nm or less, or 73nm or less, for example. The lower limit of the average particle diameter is not particularly limited. For example, it may be 10nm or more, 15nm or more, or 20nm or more.
The Polydispersity Index (PdI) of the liposome of the present invention is preferably 0.26 or less, more preferably 0.25 or less, 0.24 or less, 0.23 or less, 0.22 or less, 0.21 or less, or 0.20 or less, and still more preferably 0.19 or less, 0.18 or less, or 0.17 or less. The polydispersity index (PDI) is an index for evaluating the width of the particle size distribution, and is a value in the range of 0 to 1. The closer to 0, the more uniform the dispersion.
The average particle diameter and PdI are values measured by a dynamic light scattering method. For example, it can be determined using a particle size distribution meter based on dynamic light scattering.
In addition, the preferable pH value of the liposome is about 6-7.5. Liposomes having such a pH range are preferable because the dispersion stability with time is further improved. Liposomes of this pH range can be prepared, for example, by: the pH of the composition used in liposome preparation is pre-adjusted to the pH range. The pH adjustment may be carried out using a pH adjuster. Examples of the pH adjuster include sodium hydroxide and potassium hydroxide.
The invention also encompasses liposome compositions comprising the liposomes of the invention. The liposome composition is preferably an aqueous composition. The composition is preferably used as, for example, a pharmaceutical composition for external use, an oral composition, and a cosmetic composition.
The liposome and the composition containing the liposome of the present invention can be prepared, for example, as follows: the composition containing the liposome-containing raw material and water is stirred and further subjected to high-pressure treatment.
As a raw material of the liposome, the contents can be directly preferably applied. For example, a composition obtained by mixing the component (a), the component (B), and the component (C), and further, if necessary, the component (D) or another component (for example, a polyhydric alcohol, preferably propylene glycol) with water can be prepared and used. The above-described materials for liposome can be preferably applied to various conditions such as the amount of each component used. Further, it is also preferable that the pH of the composition is adjusted to about 6 to 7.5 in advance. As described above, a pH adjuster (e.g., sodium hydroxide, potassium hydroxide, etc.) can be used for pH adjustment.
The agitation treatment may preferably be a well-known agitation treatment used in the field of liposome preparation. For example, the material may be stirred for about 2 minutes to 10 minutes at a rotation speed of 3000rpm to 10000rpm, preferably about 4000rpm to 6000rpm, using a homomixer. By the agitation treatment, liposomes can be generally prepared.
In addition, the high pressure treatment may preferably use a well-known high pressure treatment used in the liposome preparation field. For example, a method of subjecting the stirred composition to high-pressure treatment using a wet micronizing apparatus can be mentioned. An example of such a wet type micronizing apparatus is starburst mini (starburst minini) (Sugino machine). The high-pressure treatment may be carried out, for example, at a pressure of 100MPa to 400MPa (preferably 150MPa to 300 MPa). By high pressure processing, the particle size of the liposomes can generally be reduced and made more uniform.
Further, the liposome suspension thus obtained can be used as it is as a liposome composition containing the liposome of the present invention.
The liposome and the liposome composition of the present invention may contain other components than the above-mentioned components within a range not to impair the effects of the present invention. Examples thereof include: oily component, lipid, water-soluble substance, physiologically active substance, etc. Known components used in external pharmaceuticals or cosmetics can be particularly preferably used. For example, there may be mentioned: a bactericide (particularly, a phenol bactericide such as isopropyl methylphenol); antioxidants such as ascorbic acid; organic acids such as lactic acid and citric acid; basic compounds such as potassium hydroxide and sodium hydroxide; lipids such as phosphatidylglycerol and phosphatidylethanolamine; natural polymers such as chitosan (chitosan), fucoidan (fucoidan), and hyaluronic acid (hyaluronic acid); synthetic polymers such as polyethylene glycol and carboxyvinyl polymers; saccharides such as trehalose (trehalase), lactulose (lactulose), and maltitol (maltotol); and polyols such as glycerin (glycerol).
The liposome and the liposome composition of the present invention are known components, and commercially available products, for example, can be used.
In addition, in this specification, The term "comprising" includes "consisting essentially of … …" and "consisting of … …" (The term "comprising" includes "and" connecting "). The present invention includes any combination of all the constituent elements described in the present specification.
In addition, various features (such as properties, structures, and functions) described in the embodiments of the present invention can be arbitrarily combined when the subject included in the present invention is specifically designated. That is, the present invention includes all of the subjects composed of all combinations of the features described in the present specification which can be combined.
[ examples ]
The present invention will be described more specifically below, but the present invention is not limited to the following examples.
Liposome suspensions of examples 1 to 3 and comparative examples 1 to 8 were prepared according to the compositions shown in tables 1 and 2. More specifically, according to the composition shown in table 1, hydrogenated lecithin (hydrogenated lecithin), rice oil (san blan (Sunbran) rice oil (pressed rice bran oil): san and oil & fat company ltd., inc.), various surfactants (see table 2), cholesterol, and methyl paraben were dissolved (heated at 80 ℃) in propylene glycol, water (in which potassium hydroxide was dissolved) heated to 80 ℃ was added thereto, the pH was adjusted to about 7, the mixture was stirred at 5000rpm for 5 minutes, and further, high-pressure treatment was performed at 200MPa, thereby preparing liposome suspensions of examples and comparative examples. Furthermore, the stirring treatment was carried out using a homomixer (homomixer Mark II: Primex corporation). The high-pressure treatment was carried out using a wet micronizing apparatus (starburst mini (starburst) sequoia machinery). In the preparation of the liposome suspension of comparative example 8, a surfactant and potassium hydroxide were not used. In comparative example 8, the amount of ion-exchanged water was increased in accordance with the absence of the surfactant and potassium hydroxide. The average number of moles of ethylene oxide added to the polyoxyethylene hardened castor oil used in comparative example 3, example 2, and comparative example 6 was 30, 60, and 100, respectively.
[ Table 1]
Figure BDA0002308342150000091
PC denotes phosphatidylcholine.
Figure BDA0002308342150000101
In addition, the mean particle diameter and the polydispersity index (PdI) of the liposomes contained in the obtained liposome suspensions of the respective examples (except for comparative example 8) were measured using a particle size distribution analyzer (nano-particle size potentiometer (Zetasizer nano): marvin (Malvern)) based on dynamic light scattering. After the preparation, the mixture was left standing in the dark at normal temperature (25 ℃) for 3 months, and then the same measurement was performed. The measurement results are shown in table 2. Further, photographs of liposome suspensions of each example immediately after preparation (initial stage) and after standing for 3 months (3M) are shown in fig. 1A and 1B.
According to the result, the following results are obtained: in the case of preparing a liposome containing a hydrogenated phospholipid and a surfactant and encapsulating an oil component (particularly, a vegetable oil component: rice oil in this example), it is considered that when a polyoxyethylene-hardened castor oil having an average molar number of addition of ethylene oxide of 40 to 95, PPG-6 decyltetradecanol polyether-30, and PEG-20phytosterol are used as the surfactant, the average particle diameter is small in both cases immediately after the preparation and after the long-term storage (3 months in this example), the transparency of the composition is maintained, PdI is small, and the stability is high.
In addition, liposome suspensions were prepared in the same manner as in example 2 or comparative example 8, except that the amount of ion exchange water was increased accordingly without using potassium hydroxide, and the vegetable oil and fat component was soybean oil, olive oil, meadowfoam seed oil, sunflower oil, hazelnut oil, or tocopherol instead of rice oil, and the mean particle diameter and polydispersity index (PdI) of the liposomes were measured immediately after preparation. The measurement results are shown in tables 3 and 4. Photographs of liposome suspensions of respective examples immediately after preparation (initial stage) are shown in fig. 2A and 2B (fig. 2A: examples a to F, and fig. 2B: comparative examples a to F).
Figure BDA0002308342150000121
It is known that: in any case of using any of the vegetable oil and fat components, the average particle size of the liposome of the obtained liposome suspension is small, and the transparency of the composition is maintained, and PdI is small and the stability is high. From the above results, it is considered that the case of using rice oil as the vegetable oil component is particularly preferable.

Claims (11)

1. A liposome, comprising:
hydrogenating phospholipids; and
at least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil with an average addition mole number of ethylene oxide of 40-95, PPG-6 decyl tetradecyl polyether-30, and PEG-20phytosterol, and
oil and fat components are contained.
2. The liposome of claim 1, wherein the lipid component is at least one selected from the group consisting of rice oil, soybean oil, olive oil, meadowfoam seed oil, sunflower seed oil, hazelnut oil, and tocopherol.
3. The liposome according to claim 1 or 2, wherein the hydrotreated phospholipid is hydrogenated lecithin.
4. A liposome, comprising:
hydrogenated lecithin; and
polyoxyethylene hardened castor oil having an average addition mole number of ethylene oxide of 55 to 65, and
contains rice bran oil.
5. The liposome according to any one of claims 1 to 4, wherein the average particle diameter is 82nm or less.
6. The liposome according to any of claims 1 to 5, wherein the polydispersity index is 0.26 or less.
7. A composition comprising a liposome of any one of claims 1 to 6.
8. The composition according to claim 7, which is an external pharmaceutical composition, an oral composition, or a cosmetic composition.
9. The liposome according to any one of claims 1 to 6, or the composition according to claim 7 or 8, wherein the pH is 6-7.5.
10. A method of making liposomes, comprising:
stirring the composition; and
treating the stirred composition at a pressure of 100MPa to 400MPa, the composition comprising:
hydrogenating phospholipids;
at least one surfactant selected from the group consisting of polyoxyethylene hardened castor oil with an average addition mole number of ethylene oxide of 40-95, PPG-6 decyl tetradecyl polyether-30, and PEG-20 phytosterol;
a fat component; and
and (3) water.
11. The method for producing liposomes according to claim 10, wherein the pH of the composition is 6 to 7.5.
CN201911248435.7A 2018-12-11 2019-12-09 Liposome, composition, and method for producing liposome Pending CN111374946A (en)

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JP2017171649A (en) * 2016-03-18 2017-09-28 日光ケミカルズ株式会社 Having liposome compositions with high percutaneous absorption properties, and cosmetics or skin external preparations containing the same

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