Transdermal phosphatidylcholine preparation
阅读说明:本技术 磷脂酰胆碱经皮吸收制剂 (Transdermal phosphatidylcholine preparation ) 是由 中西博文 于 2018-04-27 设计创作,主要内容包括:本发明提供一种在粘合剂层中含有磷脂酰胆碱的磷脂酰胆碱经皮吸收制剂。本发明涉及的磷脂酰胆碱经皮吸收制剂(1),构成为在支撑体(2)的至少一个面上形成的粘合剂层(3)包含磷脂酰胆碱、粘合成分和亲油性成分,所以能将制剂固定在患处,将所谓与液体等的制剂相比具有更好处理性的剂型作为贴剂,除了上述优点之外,由于磷脂酰胆碱可以稳定地存在于粘合剂层(3)中,所以通过贴附在人体等的皮肤等,利用磷脂酰胆碱的经皮吸收可以使皮下脂肪等局部肥胖溶解,能发挥使脂肪减少等效果,从而可以成为作为含有磷脂酰胆碱的减脂剂起作用的贴剂型的经皮吸收制剂(1)。(The present invention provides a phosphatidylcholine percutaneous absorption preparation containing phosphatidylcholine in an adhesive layer. The phosphatidylcholine percutaneous absorption preparation (1) according to the present invention is configured such that the adhesive layer (3) formed on at least one surface of the support (2) contains phosphatidylcholine, an adhesive component and a lipophilic component, and therefore, the preparation can be fixed to an affected area, and a dosage form having better handling properties than a preparation such as a liquid is used as a patch, and in addition to the above-described advantages, phosphatidylcholine can be stably present in the adhesive layer (3), so that when the preparation is attached to the skin or the like of a human body or the like, local obesity such as subcutaneous fat can be dissolved by percutaneous absorption of phosphatidylcholine, and effects such as fat reduction can be exerted, and thus, the transdermal absorption preparation (1) can be a patch type transdermal absorption preparation that functions as a fat reducing agent containing phosphatidylcholine.)
1. A transdermal preparation comprising a support and an adhesive layer formed on at least one surface of the support,
the binder layer comprises phosphatidylcholine, a binding component, and a lipophilic component.
2. The percutaneous absorption preparation according to claim 1,
the adhesive component is a styrenic based thermoplastic elastomer.
3. The percutaneous absorption preparation according to claim 1 or 2,
further comprises carnitine.
4. The percutaneous absorption preparation according to any one of claims 1 to 3,
the content of phosphatidylcholine is 2.5-8.0 mass% relative to the entire adhesive layer.
5. The percutaneous absorption preparation according to any one of claims 1 to 4,
the lipophilic component comprises mineral oil.
6. The percutaneous absorption preparation according to any one of claims 1 to 5,
further comprising a polyolefin having a branched structure.
7. The percutaneous absorption preparation according to claim 6,
the polyolefin with a branched structure is a hydrogenated C6-14 olefin polymer.
Technical Field
The present invention relates to a phosphatidylcholine percutaneous absorption preparation. More specifically, the present invention relates to a patch-type transdermal absorption preparation comprising phosphatidylcholine in an adhesive layer.
Background
Phosphatidylcholine is a main component of soybean lecithin obtained from oil extracted from soybean seeds, and is used as a surfactant (emulsifier, etc.), a skin conditioner, etc. in cosmetics, pharmaceuticals, etc. The phosphatidylcholine including both hydrophilic and lipophilic ones can penetrate fat cells, and phosphatidic acid such as phosphatidylcholine participates in activation of a fatty acid release pathway that reduces local obesity such as subcutaneous fat, and therefore, the effect of dissolving subcutaneous fat can be expected to be exerted.
As a means for reducing obesity including subcutaneous fat accumulation and excess fat (having a fat layer) in obesity, for example, a method of directly injecting a composition for removing subcutaneous fat accumulation subcutaneously is employed, and a phosphatidylcholine preparation or the like is used as the composition (for example, see patent document 1). However, this subcutaneous injection of phosphatidylcholine preparations is accompanied by pain during the treatment. Since this is problematic in terms of safety and the like, development of a percutaneous absorption type preparation (percutaneous absorption preparation, also referred to as a transdermal preparation) that can achieve self-administration without direct subcutaneous injection is desired. Thus, a transdermal composition containing natural phosphatidylcholine, L-carnitine, propylene glycol, glycerol, and water, but not including a lipophilic base, is provided (for example, see patent document 2).
Disclosure of Invention
Problems to be solved by the invention
In addition, it is desired to provide a percutaneously absorbable preparation which contains phosphatidylcholine in an adhesive layer and which is made into a patch. The transdermal drug delivery system in which the adhesive layer contains phosphatidylcholine and the dosage form is a patch can provide a transdermal drug delivery system of a type that is not applied to the skin or the like, and the transdermal drug delivery system can be attached to an affected area in consideration of fat reduction or the like to fix the drug to the affected area or the like, and has an advantage that the dosage form is a patch, and in addition, has a better handling property than a liquid or gel preparation. However, in the configuration of the preparation provided so far such as the configuration disclosed in the above-mentioned
The present invention has been made in view of the above problems, and provides a transdermal phosphatidylcholine absorption preparation in the form of a patch containing phosphatidylcholine in an adhesive layer.
Means for solving the problems
In order to solve the above problems, the present invention provides a transdermal drug delivery system comprising a support and an adhesive layer formed on at least one surface of the support, wherein the adhesive layer contains phosphatidylcholine, an adhesive component and a lipophilic component.
The transdermal preparation according to the present invention is characterized in that the adhesive component is a styrene-based thermoplastic elastomer in the present invention.
The transdermal preparation according to the present invention is characterized in that carnitine is further contained in the present invention.
The transdermal preparation according to the present invention is characterized in that, in the present invention, the content of phosphatidylcholine is 2.5 to 8.0 mass% with respect to the entire adhesive layer.
The transdermal absorption preparation according to the present invention is characterized in that the lipophilic component contains mineral oil.
The transdermal preparation according to the present invention is characterized in that the transdermal preparation further contains a polyolefin having a branched structure.
The transdermal patch of the present invention is characterized in that, in the present invention, the polyolefin having a branched structure is a hydrogenated C6-14 olefin polymer.
Effects of the invention
The present invention relates to a phosphatidylcholine transdermal absorption preparation, which is configured such that a binder layer formed on at least one surface of a support contains phosphatidylcholine, a binder component, and a lipophilic component. This makes it possible to fix the preparation to the affected part, and has the advantages of better handling properties than liquid preparations and the like, and the preparation is a patch, and in addition, phosphatidylcholine is stably present in the adhesive layer, and therefore, by being applied to the skin of the human body or the like, the transdermal absorption of phosphatidylcholine is utilized to dissolve local obesity such as subcutaneous fat, and the like, thereby exerting the effect of reducing fat, and the like, and a patch-type transdermal absorption preparation functioning as a fat-reducing agent containing phosphatidylcholine can be produced.
Drawings
Fig. 1 is a front view showing one embodiment of a transdermal absorption preparation according to the present invention.
Fig. 2 is a sectional view taken along line a-a of fig. 1.
Detailed Description
(I) Constitution of
Hereinafter, one embodiment of the phosphatidylcholine
The phosphatidylcholine transdermal absorption preparation (transdermal absorption preparation) 1 according to the present invention is a
(II)
In the present invention, the
The thickness of the
As shown in fig. 1 and 2, the
The thickness of the
In order to facilitate the peeling from the pressure-sensitive
(III)
The
Examples of the phosphatidylcholine include conventionally known egg yolk phosphatidylcholine, soybean phosphatidylcholine, egg yolk lysophosphatidylcholine, soybean lysophosphatidylcholine, hydrogenated egg yolk phosphatidylcholine, hydrogenated soybean phosphatidylcholine, hydrogenated egg yolk lysophosphatidylcholine, hydrogenated soybean lysophosphatidylcholine, and the like, and 1 kind of these can be used alone, or 2 or more kinds can be used in combination.
The content of phosphatidylcholine in the pressure-sensitive
Carnitine may be added to phosphatidylcholine. The presence of carnitine improves the stability of phosphatidylcholine in the
The amount of carnitine added is preferably 8.5 to 12.0 parts by mass, and more preferably 9.0 to 10.5 parts by mass, based on 100 parts by mass of phosphatidylcholine.
Next, as an adhesive component forming the
Specific examples of the styrenic block copolymer (including hydrogenated copolymers, the same applies hereinafter) of the thermoplastic elastomer include a styrene-butadiene block copolymer, a hydrogenated styrene-butadiene block copolymer, a styrene-butadiene-styrene block copolymer, a hydrogenated styrene-butadiene-styrene block copolymer, a styrene-isoprene block copolymer, a hydrogenated styrene-isoprene block copolymer, a styrene-isoprene-styrene block copolymer, and a hydrogenated styrene-isoprene-styrene block copolymer. Further, there may be mentioned a styrene-ethylene/butylene block copolymer, a styrene-ethylene/butylene-styrene block copolymer, a styrene-ethylene/propylene-styrene block copolymer, a styrene-isobutylene-styrene block copolymer and the like, and hydrogenated block copolymers thereof and the like. These styrene block copolymers may be used alone in 1 kind, or may be used in combination in 2 or more kinds.
In the above, the expression "ethylene/butene" refers to a copolymer block of ethylene and butene, and the expression "ethylene/propylene" refers to a copolymer block of ethylene and propylene.
Among the above-mentioned styrenic block copolymers, at least one selected from the group consisting of a styrene-butadiene block copolymer, a hydrogenated styrene-butadiene block copolymer, a styrene-isoprene block copolymer, a hydrogenated styrene-isoprene block copolymer, a styrene-isoprene-styrene block copolymer, and a hydrogenated styrene-isoprene-styrene block copolymer is preferably used from the viewpoint of having good skin adhesiveness and low skin irritation, and being easily available and easy to handle.
The styrene-butadiene block copolymer (including a hydrogenated copolymer) preferably contains a styrene component in an amount of 5 to 55% by mass, particularly preferably 10 to 50% by mass. Further, the weight average molecular weight (hereinafter, the same as) measured by gel filtration chromatography or the like is preferably 10000 to 5500000, and particularly preferably 15000 to 500000.
The styrene-isoprene block copolymer (including a hydrogenated copolymer) preferably contains a styrene component in an amount of 5 to 55 mass%, particularly preferably 10 to 50 mass%. The weight average molecular weight is preferably 10000 to 5500000, and more preferably 15000 to 500000.
Further, as the styrene-isoprene-styrene block copolymer (including hydrogenated copolymer), the content of the styrene component in the copolymer is preferably 5 to 65% by mass, and particularly preferably 10 to 60% by mass. The weight average molecular weight is preferably 18000 to 5500000, and particularly preferably 20000 to 500000.
The content of the adhesive component such as a thermoplastic elastomer in the
It is preferable to blend a polyolefin having a branched structure for the purpose of improving the hardness and transparency of the pressure-
The content of the polyolefin having a branched structure in the
The lipophilic component is an effective component for forming the phosphatidylcholine and the binder component into the
Further, examples of the lipophilic component include fatty acids such as palmitic acid, oleic acid, and stearic acid; vegetable oils such as avocado oil, linseed oil, almond oil, perilla oil, torreya oil, rapeseed oil, olive oil, corn oil, castor oil, safflower oil, sunflower seed oil, cottonseed oil, jojoba oil, macadamia nut oil, wheat germ oil, soybean oil, peanut oil, coconut oil, palm kernel oil, camellia oil, evening primrose oil and the like; animal oils such as mink oil, fish oil, lard, and beef tallow; hydrocarbons such as liquid paraffin, squalene, squalane, polybutene, and hydrogenated polyisobutene; diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, N-alkylethyleneglycol monoisostearate, isocetyl isostearate, trimethylolpropane triisostearate, cetyl 2-ethylhexanoate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol di-2-ethylhexanoate, glycerol tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, pentaerythritol tetra-2-ethylhexanoate, cetyl octanoate, octyl dodecyl gum, oleyl oleate, octyl dodecyl oleate, decyl oleate, neopentyl glycol didecanoate, triethyl citrate, 2-ethylhexyl succinate, pentyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, Esters such as butyl stearate, diisopropyl sebacate, di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptylundecyl palmitate, cholesterol 12-hydroxystearate, dipentaerythritol fatty acid esters, isopropyl myristate, 2-octyldodecyl myristate, 2-hexyldecyl myristate, myristyl myristate, hexyldecyl dimethyloctanoate, ethyl laurate, hexyl laurate, 2-octyldodecyl N-lauroyl-L-glutamate, and diisostearyl malate; silicones such as dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, tetramethyltetrahydrocyclotetrasiloxane and fluorine-modified polysiloxane; fluorine-containing oils such as perfluorodecane, perfluorooctane and perfluoropolyether. The lipophilic components mentioned above may be used alone in 1 kind, or in combination of 2 or more kinds.
The content of the lipophilic component in the pressure-
In the pressure-
The antioxidant is not particularly limited, and examples thereof include ascorbic acid derivatives such as ascorbyl palmitate and ascorbyl tetraisopalmitate, chelating agents such as sodium edetate, sodium sulfite, tocopherols and tocopherol derivatives such as butyl hydroxyanisole, butyl hydroxytoluene and tocopherol, and quinoline derivatives such as hydroxyquinoline sulfate.
The plasticizer is not particularly limited, and examples thereof include glycols such as ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, polyethylene glycol, and polypropylene glycol; oils and fats such as olive oil, castor oil, squalene, lanolin, etc.; hydrocarbons such as liquid paraffin; fatty acid esters such as diisopropyl adipate, diisobutyl adipate, benzyl benzoate, cetyl 2-ethylhexanoate, oleyl oleate, decyl oleate, benzyl acetate, diisopropyl sebacate, diethyl sebacate, sorbitol trioleate, sorbitol tristearate, cetyl palmitate, octyldodecyl myristate, cetyl myristate, myristyl myristate, isopropyl myristate, and the like, and 1 kind of these may be used alone or 2 or more kinds may be used in combination.
The filler is not particularly limited, and examples thereof include kaolin, bentonite, and titanium dioxide. The drug dissolution aid is not particularly limited, and examples thereof include cyclodextrins such as α -cyclodextrin, β -cyclodextrin, and γ -cyclodextrin (which can also be used as an excipient described later). The antibacterial agent is not particularly limited, and examples thereof include benzalkonium chloride, benzoic acid, and methylparaben. The skin irritation reducing agent is not particularly limited, and examples thereof include silicic anhydride. The excipient is not particularly limited, and examples thereof include cyclodextrin, lactose, cellulose-based powders, and the like (excipients such as cyclodextrin are usually used after mixing with carnitine and the like in advance).
In order to obtain the
In the case of using the
The coating liquid for forming the pressure-
As described above, the phosphatidylcholine
The transdermal
Namely, the reason is presumed as follows: by attaching the
Further, in the mechanism of percutaneous absorption, low-molecular components permeate the stratum corneum, but unlike high-molecular components, cells on the inner walls of pores already present on the skin surface, such as sweat glands and hair follicles, are the main permeation pathway. The low-molecular component diffuses in the inside of the lipophilic base (adhesive layer 3) and the stratum corneum, spreads in the epidermis, diffuses in the dermis, is absorbed into the cells and capillaries, and the high-molecular component diffuses in the lipophilic base and the pores, spreads to the cells on the inner wall of the pores, and reaches the dermis without passing through the stratum corneum. In the present invention, it is considered that the stratum corneum swells by the sealing effect of the lipophilic component or the like, thereby promoting diffusion in the pores and improving the permeation efficiency of the active ingredient.
The
The embodiment described above is one embodiment of the present invention, and the present invention is not limited to the above embodiment, and it goes without saying that modifications and improvements within a range in which the object and the effect can be achieved with the configuration of the present invention are included in the content of the present invention. It is to be understood that the specific configuration, shape, and the like in carrying out the present invention may be other configurations, shapes, and the like within a range in which the object and the effect of the present invention can be achieved. The present invention is not limited to the above embodiments, and modifications and improvements within a range that can achieve the object of the present invention are included in the present invention.
For example, in the above-described embodiment, as the configuration of the
In the above-described embodiment, a configuration in which the pressure-
In the above-described embodiment, the shape of the transdermally-
The specific configuration, shape, and the like in carrying out the present invention may be other configurations and the like within a range in which the object of the present invention can be achieved.