JP3233746U - Glucosamine-containing plaster preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a plaster preparation containing glucosamine for transdermal administration of glucosamine.
SOLUTION: A plaster agent 12 having a plaster layer 14 in which a medicinal ingredient is kneaded and a support 16 adhered on one surface of the plaster layer, and the other of the plaster layer of the plaster agent. It is a plaster preparation 10 provided with a peeling liner 18 to be adhered on the surface of the plaster, and the plaster layer is a hot melt adhesive in which the medicinal component is dispersed, and the medicinal component is water-soluble glucosamine. In the plaster layer, the fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the presence of the surfactant.
[Selection diagram] Fig. 1

Description

The present invention relates to a glucosamine-containing plaster preparation for the purpose of transdermally administering glucosamine.

Glucosamine (Chemical formula C ₆ H ₁₃ NO ₅ ) is a monosaccharide in which the hydroxyl group at the 2-position of glucose is replaced with a primary amino group, and is a kind of amino sugar. Since glucosamine is a component of articular cartilage in the human body, it is expected to have preventive and therapeutic effects on cartilage wear and disorders (osteoarthritis) due to aging. Glucosamine is diversified in nature as a chitin in the shell of crabs and shrimp, and in animals, it is a component of proteoglycan polysaccharides such as hyaluronic acid in the form of N-acetylglucosamine with acetylated amino groups. It has become.

It has been suggested that this glucosamine may suppress the function of neutrophils in vivo, exert an anti-inflammatory effect, and relieve inflammation, and its application to the prevention and treatment of various inflammatory diseases has been proposed. For the purpose of transdermal administration, a glucosamine-containing poultice having excellent storage stability of glucosamine, which is an active ingredient, has also been proposed (see, for example, Patent Document 1).

Japanese Unexamined Patent Publication No. 2003-128557

However, since the poultice contains a large amount of water in the base, it is considered to be effective in retaining water-soluble glucosamine, but the plaster agent is more advantageous in terms of transdermal absorption ability. That is, the plaster agent is more advantageous in consideration of the barrier function of the skin that prevents the invasion of foreign substances from the outside of the body and the evaporation of water in the body and the leakage of body fluids.

Specifically, there are two routes through which a drug or the like is percutaneously absorbed: a "transepidermal route" via pores and sweat pores and a "transepidermal route" via the stratum corneum. Absorption from the "transepidermal pathway" can be directly transferred to the dermis without going through the stratum corneum, which has a barrier function. It will be difficult to receive.

However, in reality, since the areas of pores and sweat pores are extremely small as compared with the area of the stratum corneum, it is considered that the transepidermal route mainly contributes to the percutaneous absorption of drugs and the like. Since the intercorneocyte lipids such as ceramide and cholesterol in the intercorneocyte interstitium have hydrophilic groups and hydrophobic groups in one molecule, a lipid layer and an aqueous layer are formed.

Therefore, in the intercorneocyte interstitium, lipid layers and aqueous layers are alternately overlapped and have a lamellar structure. Lipid-soluble drugs can pass through the stratum corneum mainly through the vicinity of the lipid layer (keratin intercellular lipid) in the intercellular pathway, and water-soluble drugs can pass through the stratum corneum mainly through the vicinity of the aqueous layer. As a result, the stratum corneum as a whole is highly lipophilic, so that the lipophilic drug is generally more easily absorbed transdermally than the water-soluble drug.

An object of the present invention is to obtain a glucosamine-containing plaster preparation to which glucosamine is transdermally administered.

The glucosamine-containing plaster preparation according to the invention according to claim 1 comprises a plaster layer in which a medicinal ingredient is kneaded and a plaster agent having a support adhered on one surface of the plaster layer. A plaster preparation comprising a release liner attached to the other surface of the plaster layer of the plaster agent.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredient is water-soluble glucosamine.
The oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the plaster layer in the presence of a surfactant.

The glucosamine-containing plaster preparation according to the invention according to claim 2 comprises a plaster layer in which a medicinal ingredient is kneaded and a plaster agent having a support adhered on one surface of the plaster layer. A plaster preparation comprising a release liner attached to the other surface of the plaster layer of the plaster agent.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredient is water-soluble glucosamine.
In the plaster layer, the oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the presence of a surfactant.
It is characterized in that L-menthol, which enhances the promotion of percutaneous permeation, is further blended in the plaster layer.

The glucosamine-containing plaster preparation according to the invention according to claim 3 comprises a plaster layer in which a medicinal ingredient is kneaded and a plaster agent having a support adhered on one surface of the plaster layer. A plaster preparation comprising a release liner attached to the other surface of the plaster layer of the plaster agent.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredients are water-soluble glucosamine and methylsulfonylmethane.
The oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the plaster layer in the presence of a surfactant.

The glucosamine-containing plaster preparation according to the invention according to claim 4 comprises a plaster layer in which a medicinal ingredient is kneaded and a plaster agent having a support adhered on one surface of the plaster layer. A plaster preparation comprising a release liner attached to the other surface of the plaster layer of the plaster agent.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredients are water-soluble glucosamine and methylsulfonylmethane.
In the plaster layer, the oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the presence of a surfactant.
It is characterized in that L-menthol, which enhances the promotion of percutaneous permeation, is further blended in the plaster layer.

The present invention has the effect of being able to obtain a glucosamine-containing plaster preparation to which glucosamine is transdermally administered.

It is explanatory drawing which shows the structure of one Example of the glucosamine-containing plaster preparation of this invention, FIG. a is a plan view, FIG. b is a side view, and FIG. It is a radar chart which compared the fatty acid composition component of the human cortex with the fatty acid composition component of emu oil. It is explanatory drawing which shows the manufacturing process of the plaster preparation containing glucosamine of this invention.

In the present invention, a plaster agent having a plaster layer in which a medicinal ingredient is kneaded and a support adhered on one surface of the plaster layer, and the other surface of the plaster layer of the plaster agent. A plaster formulation with a release liner attached on top. That is, the plaster preparation of the present invention has a so-called "matrix type preparation" structure.

Glucosamine is blended as the medicinal ingredient of the present invention, but since glucosamine is water-soluble, it is difficult to disperse in the plaster layer mainly composed of an oil-based synthetic rubber-based hot melt adhesive, and it is percutaneously absorbed. It becomes difficult to do. Therefore, it is considered that by mixing and dispersing water-soluble glucosamine and an oil and fat component containing emu oil in the presence of a surfactant, minute capsules of the water-soluble medicinal component are uniformly dispersed in the plaster layer. ..

That is, in order to retain water-soluble glucosamine in the oily plaster layer, a liposome-like capsule which is an artificial membrane imitating a lipid bilayer forming the basic structure of a cell membrane used in cosmetics and the like is used. The size of the microcapsules such as liposomes is considered to be about 0.1 to 0.2 μm. Since it is considered that the oil and fat component surrounds the minute capsule, it is considered that it is easily absorbed through the skin in contact with the plaster layer.

In the plaster agent of the present invention, an oil and fat component containing emu oil is blended and kneaded in the plaster layer in order to facilitate transdermal absorption of the medicinal ingredient into the skin in contact with the plaster layer. This will be described. Table 1 below shows the fatty acid composition ratios for each of human sebum, emu oil, olive oil, and rosehip oil, and FIG. 2 compares the fatty acid composition components of human cortex with the fatty acid composition components of emu oil. Figure a is a fatty acid in human cortex, and figure b is a fatty acid in emu oil.

As shown in Table 1 and FIG. 2, emu oil has a fatty acid composition ratio very similar to that of human sebum. For this reason, if emu oil is mixed in the plaster layer, it fits well on the skin and penetrates quickly. As a result, it is considered that even minute capsules of water-soluble medicinal ingredients dispersed in the same plaster layer can easily penetrate into human skin with emu oil.

The plaster layer of the plaster preparation of the present invention is a hot-melt adhesive in which a medicinal ingredient is dispersed. That is, examples of the hot melt adhesive include conventionally used diene-based polymer compounds, specifically, natural rubber, synthetic rubber, and rubber-based adhesive substances from a mixture thereof, but synthetic rubber is preferable. Examples of the synthetic rubber include styrene-isobutylene-styrene block copolymer rubber, styrene-butadiene rubber, polyisoprene rubber, butyl rubber, and silicone.

The thickness of the plaster layer of the present invention varies depending on the purpose of use, but when it becomes thin, the drug content per unit area of the plaster preparation becomes insufficient and the adhesive strength becomes insufficient, and when it becomes thick, it becomes the plaster layer near the support. The medicinal ingredient contained is not sufficiently diffused, and the sustained release of the drug is lowered. Therefore, 20 to 500 μm is preferable.

As the support of the present invention, a flexible material is selected in which the components of the plaster layer do not strike through and can be fitted to the affected area. Specific examples thereof include elastic woven fabrics and non-woven fabrics. Examples of the material of the release liner of the present invention include polyester type, polypropylene type, polyethylene type, alkylbenzenesulphonic acid type, polyvinyl chloride type, metal film type and the like.

The medicinal ingredient used in the plaster agent of the present invention is glucosamine. The glucosamine may be glucosamine, which is a component extracted by acid decomposition, such as glucosamine hydrochloride or glucosamine sulfate, but N-acetylglucosamine, which is the same natural glucosamine as the component existing in the skin and joints, is preferable. be. Since it is a natural glucosamine, it is expected to be smoothly absorbed through the skin.

Further, as another medicinal ingredient that can be blended with glucosamine, if it is water-soluble, minute capsules are formed in the plaster layer together with glucosamine and are absorbed transdermally. Other suitable medicinal ingredients include methylsulfonylmethane. Like glucosamine, this methylsulfonylmethane is water-soluble and is an organic sulfur component contained in grains, milk, green and yellow vegetables, etc., and is involved in the production of proteins, collagen, keratin, etc. in the human body. Since it is a component, it is expected to be absorbed transdermally together with glucosamine to assist the medicinal effect of glucosamine.

The plaster agent of the present invention may contain a component that enhances the promotion of permeation through the skin. For example, human skin is produced by blending vanillyl butyl, which gives a feeling of warmth and heat when in contact with the skin, L-menthol, which has a local vasodilatory effect, a skin stimulating effect, capsaicin, and the like. It is expected that emu oil, which has a fatty acid component similar to that of capsaicin, will improve the permeability.

It is also preferable to add tocopherol acetate. It is absorbed directly from the skin, promotes blood circulation in the skin, raises the skin temperature, and suppresses the hyperpermeability of microvessels. In addition, it exerts various actions and effects such as prevention of skin keratin, suppression of damage to lipid peroxide, moisturizing effect, suppression of melanin deposition, anti-inflammatory effect, hair growth promoting effect, ultraviolet protection effect, and improvement of cosmetic stability.

FIG. 1 is an explanatory view showing the configuration of an embodiment of the glucosamine-containing plaster preparation of the present invention, where a is a plan view, b is a side view, and c is a cross-sectional view including an enlarged view. FIG. 2 is a radar chart comparing the fatty acid composition of human cortex with the fatty acid composition of emu oil. FIG. 2 is a fatty acid of human cortex, and FIG. 2 is a fatty acid of emu oil. FIG. 3 is an explanatory diagram showing a manufacturing process of the glucosamine-containing plaster preparation of the present invention.

As shown in FIG. 1, in the glucosamine-containing plaster preparation 10 of this example, a substantially rectangular plaster agent 12 is attached to a release liner 18. As shown in the enlarged view of FIG. 1C, the plaster agent 12 includes a plaster layer 14 spread and formed between the release liner 18 and the support 16.

The plaster layer 14 contains a medicinal ingredient. As shown in the enlarged view of the plaster layer 14 in FIG. 1C, glucosamine as a medicinal ingredient is composed of a hot melt adhesive, liquid paraffin, etc. by a surfactant together with other water-soluble medicinal ingredients. By being emulsified by stirring and mixing in the layer, it is dispersed and blended in the paraffin layer 14 as minute capsules 20 of medicinal ingredients.

Specifically, since glucosamine and methylsulfonylmethane as medicinal ingredients are water-soluble, there is a problem in simply dispersing them in the plaster component forming the plaster layer. Therefore, it is emulsified by being stirred and mixed with a surfactant (polysorbate 80, sorbitan monooleate) in oily liquid paraffin in advance.

Polysorbate 80, methylsulfonylmethane, and N-acetylglucosamine are put into a stirrer, and further, sorbitan monooleate and liquid paraffin are put into the same stirrer and mixed by stirring. As a result, a premixture I in which the medicinal ingredient is emulsified is obtained. It is considered that this is a minute capsule containing the medicinal ingredient in which water-soluble glucosamine and methylsulfonylmethane are uniformly dispersed in liquid paraffin.

Further, as a preliminary mixture II, an oil and fat component is prepared. This oil and fat component is blended and kneaded in the plaster layer in order to facilitate transdermal absorption of the medicinal component into the skin in contact with the plaster layer 14. Since the plaster layer 14 is oily, it is considered that the oily component is uniformly dispersed in the plaster layer 14. In particular, as shown in FIG. 2, the composition component of the fatty acid of emu oil in this fat and oil component has a component composition very similar to the composition component of the fatty acid of human skin, and therefore, it is contained in the plaster layer. When it contains emu oil, it blends well with the skin and penetrates quickly.

As a result, it is considered that even minute capsules of medicinal ingredients dispersed in the same plaster layer can easily penetrate into human skin with emu oil. Specifically, liquid paraffin, vanillyl butyl, jojoba oil, tocopherol acetate, and emu oil are put into a stirrer and mixed by stirring to obtain a premix II.

After the premixture I and the premixture II are obtained, the plaster layer 14 is prepared. As the hot melt adhesive that forms the basis of the plaster layer 14, styrene-isobutylene-styrene (SIS) block copolymer is used as the plaster base, and the tackifier resin and the like are stirred and kneaded with a stirrer to prepare the premixture I and Prepare a plaster by blending the premixture II and the like.

Specifically, polyisobutylene, terpene resin, styrene-isobutylene-styrene block copolymer, dibutylhydroxytoluene, and liquid paraffin are put into a stirrer having a tank temperature of 120 ° C. or higher, and the mixture is stirred to prepare a plaster base. .. The premixture I and the premixture II prepared in advance are put into the plaster base in the stirrer tank together with L-menthol and stirred to obtain a plaster base.

A plaster preparation is prepared using the obtained plaster base. As shown in FIG. 3, the release liner tape 28, which becomes the release liner 18 when cut, is carried out while being released from the release liner roll 38. The width of the release liner tape 28 is at least longer than the longitudinal side of the substantially rectangular plaster agent.

The plaster base 34 is transferred onto the release liner tape 28 to spread the plaster base layer 24. The plaster base 34 is conveyed from below the base tank 33 through the first transfer roll 35 to the second transfer roll 37 as the plaster base layer 24 while being spread and applied to the entire surface of the release liner tape 28. Further downstream in the transport direction, the support tape 26, which becomes the support 16 when cut, is carried out while being unwound from the support roll 32, and is attached onto the surface of the plaster base layer 24 and transported. It is adhered by the pressure welding roller 39 and conveyed in the downstream direction as the plaster agent tape 22.

As shown in FIG. 3, among the laminates of the release liner tape 28 and the plaster agent tape 22 (plaster base layer 24 and support tape 26), the plaster agent is formed by the cutting drum 50 for half-cutting and the opposing drum 52. The plaster agent 12 having a substantially rectangular tape 22 is punched so as to line up on the release liner tape 28. The perimeter plaster tape region 54, which is punched out into a substantially rectangular shape, is removed upward from the laminated body to be conveyed.

In the laminate from which the plaster agent tape region 54 around the rectangular shape has been removed, the plaster agent 12 is punched and cut together with the release liner tape 28 by the cutting drum 60 for all cutting and the opposing drum 62 arranged on the downstream side. , The plaster formulation 10 and the surrounding region 64 are divided.

10 ... Glucosamine-containing plaster preparation,
12 ... Plaster agent,
14 ... Plaster layer,
16 ... Support,
18 ... Peeling liner,
20 ... Microcapsules of medicinal ingredients,
22 ... Plaster tape,
24 ... Plaster base layer,
26 ... Support tape,
28 ... Release liner tape,
32 ... Support roll,
33 ... Base tank,
34 ... Plaster base,
35 ... 1st transfer roll,
37 ... Second transfer roll,
38 ... Peeling liner roll,
39 ... Pressure welding roller,
50 ... Cutting drum (for half cut),
52 ... Oncoming drum,
54 ... Surrounding plaster tape area,
60 ... Cutting drum (for all cuts),
62 ... Oncoming drum,
64 ... Surrounding laminate area,

Claims (4)

A plaster agent having a plaster layer in which a medicinal ingredient is kneaded and a support adhered on one surface of the plaster layer, and the plaster agent adhered on the other surface of the plaster layer. A plaster formulation with a release liner to be made.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredient is water-soluble glucosamine.
A glucosamine-containing plaster preparation characterized in that an oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the plaster layer in the presence of a surfactant. A plaster agent having a plaster layer in which a medicinal ingredient is kneaded and a support adhered on one surface of the plaster layer, and the plaster agent adhered on the other surface of the plaster layer. A plaster formulation with a release liner to be made.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredient is water-soluble glucosamine.
In the plaster layer, the oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the presence of a surfactant.
A glucosamine-containing plaster preparation characterized in that L-menthol, which enhances the promotion of percutaneous permeation, is further blended in the plaster layer. A plaster agent having a plaster layer in which a medicinal ingredient is kneaded and a support adhered on one surface of the plaster layer, and the plaster agent adhered on the other surface of the plaster layer. A plaster formulation with a release liner to be made.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredients are water-soluble glucosamine and methylsulfonylmethane.
A glucosamine-containing plaster preparation characterized in that an oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the plaster layer in the presence of a surfactant. A plaster agent having a plaster layer in which a medicinal ingredient is kneaded and a support adhered on one surface of the plaster layer, and the plaster agent adhered on the other surface of the plaster layer. A plaster formulation with a release liner to be made.
The plaster layer is a hot-melt adhesive in which a medicinal ingredient is dispersed.
The medicinal ingredients are water-soluble glucosamine and methylsulfonylmethane.
In the plaster layer, the oil and fat component containing emu oil and the water-soluble medicinal component are uniformly mixed and dispersed in the presence of a surfactant.
A glucosamine-containing plaster preparation characterized in that L-menthol, which enhances the promotion of percutaneous permeation, is further blended in the plaster layer.

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