WO2016153015A1 - 高分子薬効成分を含有した口腔内施用物および口腔内への高分子薬効成分の投与方法 - Google Patents
高分子薬効成分を含有した口腔内施用物および口腔内への高分子薬効成分の投与方法 Download PDFInfo
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- WO2016153015A1 WO2016153015A1 PCT/JP2016/059525 JP2016059525W WO2016153015A1 WO 2016153015 A1 WO2016153015 A1 WO 2016153015A1 JP 2016059525 W JP2016059525 W JP 2016059525W WO 2016153015 A1 WO2016153015 A1 WO 2016153015A1
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/82—Theaceae (Tea family), e.g. camellia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
Definitions
- the present invention relates to a technique that enables efficient absorption of a high molecular weight medicinal ingredient having a large molecular weight and difficult to be transdermally absorbed.
- Drugs containing various high-molecular medicinal ingredients such as pharmaceuticals, quasi drugs, and supplements have been developed.
- Developed drugs are effective when administered to the body.
- the drug includes a direct injection preparation by injection, an oral administration preparation, a percutaneous absorption preparation, and the like if attention is paid to the administration method of the high molecular weight pharmaceutical ingredient into the body.
- liquid pharmaceuticals are directly injected into the affected area through a syringe.
- the injection is a medical practice performed by a doctor and is not performed by the patient himself with some exceptions such as insulin injection.
- Inhalation infusion formulations are also performed using dedicated medical equipment.
- Oral and percutaneous absorption preparations may be applied by the user himself.
- Oral preparations come in various styles such as pills, powders, capsules, and drinks.
- Orally administered preparations undergo denaturation by gastric acid, digestion by digestive enzymes, and metabolism by the liver, and finally systemically. To be disseminated.
- the effectiveness of a medicine that has a medicinal effect in the process of denaturation, digestion, and metabolism may be reduced.
- transdermally absorbable preparation promotes absorption into the body percutaneously by application to the skin and mucous membranes (sublingual, nasal cavity, eye cavity, rectal cavity, etc.).
- Transdermal absorption preparations have styles such as suppository solid preparations, sublingual lozenges, lotions, ointments, creams, patches, and the like, and ingredients that exhibit various medicinal effects by percutaneous absorption are blended.
- Transdermal absorption preparations are distributed throughout the body without being digested by digestive enzymes, and without undergoing gastric acid denaturation, digestive enzyme digestion, or liver metabolism.
- a medicinal component is a substance that can be easily digested, it is often advantageous to use a transdermal absorption preparation rather than an oral administration preparation.
- the percutaneous absorption preparation is roughly divided into the skin and mucous membranes, but in the case of skin, it is often absorbed mainly by cells applied to the skin, and is not for systemic drug administration but for local administration. It is often used for. Systemic administration is possible even in the case of skin, and an effective amount for systemic administration is ensured by administration several times.
- the administration destination is mucosa, abundant blood flow is secured in the sublingual mucosa and rectal mucosa, which is advantageous for relatively systemic drug administration.
- the present invention relates to a transdermally absorbable preparation.
- transdermal absorption is more suitable for so-called injection administration or It can be said that it is superior to that by oral administration.
- transdermal absorption preparations there are problems with transdermal absorption preparations.
- the first is that some transdermally absorbable preparations may not be easy to administer.
- suppository injection into the rectal mucosa which is widely used for the administration of systemic drugs, is applicable. Injecting a suppository into the rectal mucosa requires taking off the pants and pants and pushing the suppository through the anus. For example, administration is often difficult when going outside.
- sodium hyaluronate is a linear high-molecular polysaccharide formed by alternately binding N-acetyl-glucosamine and D-glucuronic acid, and is known as a substance that forms the outer cell wall together with collagen. It is used as a therapeutic agent for cell retention, tissue lubrication prevention, bacterial infection prevention, arthritis and keratoconjunctival epithelial disorder. In recent years, it is also used as a moisturizing ingredient for cosmetics because of its excellent moisturizing properties.
- Patent Document 1 As a method of taking sodium hyaluronate, a method of injecting directly into an affected part such as a joint by injection is often employed as a medical practice.
- the user himself when the user himself applies, particularly in cosmetic applications, it is contained in an external preparation for skin and percutaneously absorbed into the skin, or is orally administered by mixing with food or drink (for example, Patent Document 1).
- the sodium hyaluronate-containing solution has a high rate of digestion in the digestive tract and is not suitable for oral administration in the first place.
- sodium hyaluronate has a very high viscosity, it is difficult to drink by simply dissolving it.If the viscosity is lowered until it is suitable for drinking, the content of sodium hyaluronate will eventually decrease, so that further medicinal effects cannot be expected. It was.
- the high viscosity hyaluronic acid has low water solubility, the manufacturing process is inevitably complicated and long, and it has been difficult to provide consumers with a hyaluronic acid-containing beverage at a low price.
- collagen, EGF, astaxanthin, placenta extract, eggshell membranes and the like have the same problems as the above sodium hyaluronate.
- the present invention provides a new administration method that can easily introduce a high molecular weight medicinal ingredient having a high molecular weight, which is unsuitable for oral administration and unsuitable for percutaneous absorption, into the body.
- the purpose is to provide.
- the intraoral application of the present invention comprises a base material that can be applied to the oral cavity by sticking or coating, and a high molecular weight medicinal component having a molecular weight that is difficult to percutaneously contained in the base material. It is an intraoral application containing a high molecular weight medicinal component that enables efficient absorption of the high molecular weight medicinal component by applying it inside. There can be a plurality of types depending on the difference in the base material and the polymeric medicinal component.
- the base material is formed into a sheet shape, and is applied by being stuck in the oral cavity.
- a sheet-like base material there is one containing at least one selected from collagen, sodium hyaluronate, gelatin, sodium alginate, carrageenan, agar, pullulan, xanthan gum, and cariboxymethylcellulose.
- the base material is a gel lump, which is applied to the oral cavity.
- a base material for the gel mass there is a material containing at least one selected from collagen, sodium hyaluronate, hydroxyethyl cellulose, and cellulose gum.
- the polymer medicinal component can be a polymer compound that contributes to beauty.
- various components can be targeted as the polymeric medicinal component. Examples thereof include one selected from collagen, sodium hyaluronate, aloe vera extract, tea extract, epidermal growth factor, astaxanthin, placenta extract, eggshell membrane, or a combination thereof.
- the appliance which improves the intraoral environment which applied the intraoral application thing of this invention can be provided.
- a massager that massages the inner wall surface of the oral cavity to which an intraoral application is applied.
- the oral massaging device of the present invention includes an oral contact body, a shaft support portion that supports the oral contact body, and a handle portion connected to the shaft support portion. Efficient absorption of the intraoral application and massage of the intraoral application site are performed by bringing the oral contact body into contact with and rubbing the intraoral application site where the intraoral application of the present invention is applied. Is.
- the oral contact body is made of a silicon or metal material and can be slightly vibrated at a frequency of 2000 to 5000 times per minute. The massage effect is improved by vibration, and the oral mucosa is not damaged because of the slight vibration.
- the oral mucosa is a portion that is relatively easy to absorb even a high molecular weight medicinal component that is relatively difficult to be absorbed into the human body, such as a polymer substance.
- the present invention since it is in the form of a film sheet, the state of being stuck to the oral mucosa can be kept relatively long, and the high molecular medicinal component can be brought into contact with the oral mucosa for a relatively long time. As a whole, the amount of absorption increases.
- Next is the simplicity of application. If it is in the oral cavity, there is an advantage that it can be easily applied even on the go. Other mucous membranes such as the rectum are practically difficult to apply on the go, and are much easier to apply than those.
- the intraoral application of the present invention comprises a base material that can be applied to the oral cavity by sticking or coating, and a high molecular weight medicinal component having a molecular weight that is difficult to percutaneously contained in the base material. It is an intraoral application that enables efficient absorption of the high-molecular-weight medicinal component by applying it inside.
- FIG. 1 illustrates the type of intraoral application according to the present invention and the manner of application according to type.
- the intraoral application 100 of this invention is equipped with the base material and the polymeric medicinal ingredient contained in it.
- FIG. 1A shows an intraoral application 100a whose base material is a gel type
- FIG. 1B shows an intraoral application 100b whose base material 110 is a film type.
- the base material of the gel mass may be any component that can be finished into a gel and is not toxic even if absorbed by the human body.
- Examples include collagen, sodium hyaluronate, hydroxyethyl cellulose, and cellulose gum. There may be a mixture of at least one selected. These are also widely used in foods and have proven results as edible substances.
- the type of the film sheet-like substrate may be any component that can be finished into a film sheet and is not toxic even if absorbed by the human body.
- a high molecular weight medicinal component can be applied as long as it is a substance having a large molecular weight that is difficult to absorb through the skin.
- a substance having a large molecular weight that is difficult to absorb through the skin For example, there are polymer substances that contribute to beauty.
- Various ingredients can be formulated depending on the purpose of the cosmetic, but examples of the high molecular medicinal ingredients include collagen, sodium hyaluronate, aloe vera extract, tea extract, epidermal growth factor, astaxanthin, placenta extract, eggshell membrane, etc. A combination of these is also possible.
- Both gel type and film type are applied by applying or sticking to the inner mucosa of the user's oral cavity, so-called cheek inner wall.
- the oral mucosa is a portion that is relatively easy to absorb even a high molecular weight medicinal component that is relatively difficult to be absorbed into the human body, such as a polymer substance.
- a high molecular weight medicinal component that is relatively difficult to be absorbed into the human body, such as a polymer substance.
- the film sheet-like material can be kept on the oral mucosa for a relatively long time, and the polymeric medicinal ingredients can be brought into contact with the oral mucosa for a relatively long time. .
- FIG. 2 is a simple model of the structure of the test sample.
- each of the mucosa model (HOE) and the epidermis model (RHE) has a structure including a tissue model 210 and a reservoir 220 below the tissue model 210.
- Polymeric medicinal ingredients are applied and immersed on these models, and the amount of penetration is examined.
- the amount of what has passed through the tissue model 210 and reaches the reservoir 220 permeated through the epithelium and absorbed into the human body is evaluated as “epithelial permeation amount”, and the amount remaining in the tissue model 210 is within the epidermis and mucous membranes.
- the amount absorbed was evaluated as the “epithelial residue”.
- the combination of these “epithelial residual amount” and “epithelial permeation amount” is the “skin absorption amount”.
- FIG. 3 is a diagram showing the results of a comparative experiment of sodium hyaluronate absorption using a tissue model.
- FIG. 3 (a) shows the total amount of sodium hyaluronate absorbed through the tissue model (skin absorption amount), the amount that remained in the tissue model 210 (epithelial residual amount), and reached the reservoir 220, respectively. Amount (epithelial permeation amount).
- FIG. 3B is a graph showing the amount of absorbed skin, which is the total amount of sodium hyaluronate absorbed through the tissue model.
- the mucous membrane model (HOE) has a significantly higher skin absorption than the epidermis model (RHE). Furthermore, the epithelial permeation amount does not increase after 3 hours in the epidermis model (RHE), but increases over time in the mucosa model (HOE) after 3 hours.
- sodium hyaluronate having a molecular weight of about 1 million can increase the amount absorbed from the mucous membrane over time, but it is considered difficult to increase the amount absorbed from the skin.
- FIG. 4 is a diagram showing the results of a comparative experiment of collagen absorption using a tissue model.
- FIG. 4 (a) shows the total amount of collagen absorbed through the tissue model (skin absorption amount), the amount remaining in the tissue model 210 (epithelial residual amount), and the amount reached the reservoir 220, respectively. It shows (epithelial permeation amount).
- FIG. 4B is a graph showing the amount of absorbed skin, which is the total amount of collagen absorbed through the tissue model.
- the mucous membrane model (HOE) has a significantly higher skin absorption than the epidermis model (RHE), and the difference exceeds 170 times after 24 hours.
- collagen is more effective as an administration method through the mucosa than through the skin. 4 is about 30 times larger than that in FIG. It can be seen that collagen having a molecular weight of about 150,000 absorbs more than sodium hyaluronate having a molecular weight of about 1 million.
- tissue model was embedded in a frozen section preparation compand placed in a plastic mold and frozen.
- the compound removed from the plastic mold was fixed to a sample stage in a cryosection preparation chamber (cryostat).
- a skin section of each application sample was prepared with a thickness of 4 ⁇ m and attached to a glass slide.
- the tissue section on the slide glass was fixed with 4% paraformaldehyde and then blocked with 1.0% BSA.
- FIG. 5 shows immunostained images of sections of the epidermis model (RHE) and mucosal model (HOE) of the experiment using sodium hyaluronate. Similar to the results shown in FIG. 3, it was confirmed that sodium hyaluronate was incorporated in a large amount in the mucosal tissue.
- FIG. 6 shows immunostained images of sections of the epidermis model (RHE) and mucosal model (HOE) of the experiment using collagen. Similar to the results shown in FIG. 4, it was confirmed that a large amount of collagen was incorporated in the mucosal tissue.
- FIG. 5 shows immunostained images of sections of the epidermis model (RHE) and mucosal model (HOE) of the experiment using sodium hyaluronate. Similar to the results shown in FIG. 3, it was confirmed that sodium hyaluronate was incorporated in a large amount in the mucosal tissue.
- FIG. 6 shows immunostained images of sections of the epidermis model (R
- FIG. 7 shows hematoxylin and eosin stained images of sections of the epidermis model (RHE) and mucosal model (HOE) of the experiment using collagen. Similar to the results shown in FIG. 4, it was confirmed that a large amount of collagen was incorporated in the mucosal tissue.
- the intraoral application of the present invention as a means for supplying a high molecular weight medicinal ingredient to the oral mucosa, it is included in a film base that can be applied to the oral mucosa or a gel base that can be applied to the oral mucosa. Therefore, the high molecular weight medicinal component having a high molecular weight can be absorbed through the intraoral mucosa as revealed by the verification experiment.
- FIG. 8 is a diagram simply showing the basic structure of the intraoral massage device 300.
- FIG. 8A shows a simple oral contact body of a spherical type
- FIG. 8B shows a simple oral contact body of a brush type.
- the intraoral massage device 300 includes an oral contact body 310, a shaft support portion 320, a handle portion 330, and optionally a thermal control unit 340, a vibration control unit 350, and a power source 360.
- the oral contact body 310 is a part that gives a massage effect by contacting the oral mucosa.
- the oral contact body 310 is brought into contact with and rubbed against the application site in the oral cavity to which the intraoral application 100 shown in Example 1 is applied to provide a massage effect and promote the absorption of the oral application 100. It is something to be made.
- a covering body 311 that covers the surface is provided, and the inside of the covering body 311 includes a warming part 312 that generates heat and a vibrating body 313 that generates vibration.
- the covering 311 has a spherical shape.
- the material is preferably made of silicon or metal. It is because it is easy to wash and it is easy to maintain it in a sanitary good state.
- the shape is preferably a part that directly touches the oral mucosa and does not have sharp protrusions so as not to damage the oral mucosa.
- the size is preferably a size that can be contained in the cheek.
- the covering 311 is provided with a large number of brushes.
- the material is preferably plastic. A brush similar to a so-called electric brush may be used.
- the heat generating part 312 is a heat generating part that gives a heat effect to the mucous membrane in the oral cavity, and preferably generates a heat of 40 to 45 ° C., for example.
- a heat of 40 to 45 ° C. for example.
- the vibrating body 313 is a member that vibrates when a small motor or the like is charged. Improve the massage effect by rubbing the oral mucosa. For example, a slight vibration may be generated at a frequency of 2000 to 5000 times per minute. Note that electric power is supplied from the power supply 360.
- the shaft support portion 320 supports the oral contact body 310, and is a rod-like member like a shaft of a so-called electric toothbrush here.
- the thickness is preferably such that it can be lightly contained in the mouth.
- the handle part 330 is a part that the user holds.
- the thermal control unit 340 is a part that controls the heat generation of the thermal generation unit 312 that is prepared inside the oral contact body 310.
- the temperature of the heat generating unit 312 is controlled to be set to 40 to 45 ° C.
- the vibration control unit 350 is a part that controls the vibration of the vibration body 313 prepared in the oral cavity contact body 310, and it is preferable that the vibration frequency and the strength of vibration can be set. For example, when “vibration is strong” is set, the frequency is controlled 4000 times per minute, and when “vibration is weak” is set, the frequency is controlled to 2000 rpm.
- FIG. 9 is a diagram simply showing an example of use of the oral massager 200.
- Examples of use of the oral massager 200 include use before application of the intraoral application 100 to the oral mucosa (Use Example 1) and after application (Use Example 2).
- the user prior to applying the oral application 100 to the oral mucosa The massager 200 is added to the mouth, and the oral mucosa, which is the planned application site, is gently brushed from above.
- Brushing using the oral massager 200 has an effect of satisfactorily adjusting the oral mucosal environment, such as smoothing the oral mucosa, which is the planned application site of the intraoral application 100, increasing the absorption efficiency, Health promotion through brushing can be expected.
- the user first converts the oral application 100 into the oral mucosa.
- the mouth massager 200 is added to the mouth and brushed gently from above the intraoral application 100. At this time, it is preferable to brush gently so that the intraoral application 100 is not broken or stirred.
- the absorption efficiency of the intraoral application 100 can be increased, and health promotion through brushing in the oral cavity can be expected.
- the intraoral application of the present invention can be widely applied as an application that can efficiently absorb into the body a high molecular weight medicinal ingredient that is not suitable for oral administration and is not suitable for transdermal absorption.
- the medicinal part for example, it can be provided as an application of a high-molecular substance that contributes to beauty such as collagen, sodium hyaluronate, EGF, astaxanthin, placenta extract, eggshell membrane and the like.
Abstract
Description
薬剤には、高分子薬効成分の体内への投与方法に着目すれば、注射による直接注入製剤や、経口投与製剤や、経皮吸収製剤等などがある。
経口投与製剤は、丸薬、粉末薬、カプセル薬、ドリンク薬など様々なスタイルがあるが、経口投与した製剤は、胃酸による変性、消化酵素による消化、肝臓による代謝を経た後、最終的に全身に流布される。
しかし、経口投与製剤は、上記変性、消化、代謝の過程で薬効作用をもたらす医薬品の有効性が減少してしまう場合もあり得る。
経皮吸収製剤は、座薬固形剤、舌下トローチ剤、ローション剤、軟膏剤、クリーム剤、パッチ剤等のスタイルがあり、経皮吸収により種々の薬効を発揮する成分が配合されている。
一方、投与先が粘膜の場合、舌下粘膜や直腸粘膜には豊富な血流量が確保されているため比較的全身性の薬剤投与に有利とされている。
第1には、一部の経皮吸収製剤では、その投与が手軽ではない場合があるということである。特に、全身性薬剤の投与として普及している直腸粘膜への座薬の投入が該当する。直腸粘膜への座薬の投入はズボンやパンツなどを脱いで肛門から座薬を押し入れる必要があり、例えば外出先などでは投与が困難な場合が多い。
皮膚は、本来は体外からの異物の侵入を防ぐための機能を有するので、充分な経皮吸収量が得られず、充分な薬効が得られない場合が多い。特に、分子量の大きな高分子物質の場合、その経皮吸収はきわめて困難であった。
そのため、分子量の大きな高分子薬効成分の体内投入は、経口投与も不向きであるばかりではなく、経皮吸収も不向きであり、基本的には注射投与が効果的であるとされてきた。
例えば、ヒアルロン酸ナトリウムは、N-アセチル-グルコサミンとD-グルクロン酸とが交互に結合して形成された直鎖状の高分子多糖であり、コラーゲン等とともに細胞外壁を構築する物質として知られており、細胞の保持、組織の潤滑性の保持、細菌感染の防止、関節炎や角結膜上皮障害の治療薬として利用されている。また、近年では、保湿性に優れていることから化粧品等の保湿成分としても利用されている。
基材や高分子薬効成分の違いにより、複数のタイプがあり得る。
例えば、シート状の基材としては、コラーゲン、ヒアルロン酸ナトリウム、ゼラチン、アルギン酸ナトリウム、カラギーナン、寒天、プルラン、キサンタンガム、カリボキシメチルセルロースから選ばれる少なくとも一種を配合したものがある。
例えば、ゲル塊の基材としては、コラーゲン、ヒアルロン酸ナトリウム、ヒドロキシエチルセルロース、セルロースガムから選ばれる少なくとも一種を配合したものがある。
シートタイプ、ゲルタイプ、いずれのタイプにおいても高分子薬効成分としては多様な成分を対象とすることができる。例えば、コラーゲン、ヒアルロン酸ナトリウム、アロエベラエキス、茶エキス、上皮成長因子、アスタキサンチン、プラセンタエキス、卵殻膜より選ばれた一つまたはこれらの組み合わせなどがある。
本発明の口腔マッサージ器は、口腔当接体と、前記口腔当接体を支える軸支部と、前記軸支部につながるハンドル部を備えたものである。本発明の口腔内施用物が施用されている口腔内の施用箇所に対して口腔当接体を当接させて擦ることにより口腔内施用物の効率的吸収と口腔内の施用箇所のマッサージを行うものである。
さらに、マッサージ器のマッサージ効果を高めるため、口腔当接体がシリコンまたは金属製の素材であり、毎分2000回から5000回の振動数で微振動するものとすることもできる。振動によりマッサージ効果が向上し、また、微振動であるので口腔内粘膜を傷付けることもない。
次に、施用の簡易性である。
口腔内であれば外出先でも気軽に施用できるという利点がある。直腸など他の粘膜の箇所は外出先での施用は事実上難しく、それらに比べると格段に施用の簡便性がある。
以下、本発明の口腔内施用物の生成について述べる。
本発明の口腔内施用物は、口腔内に貼着または塗布による施用可能な基材と、前記基材に含有させた経皮吸収が困難な程度に分子量の大きな高分子薬効成分を備え、口腔内に施用することにより前記高分子薬効成分の効率的吸収を可能とした口腔内施用物である。
図1に見るように、本発明の口腔内施用物100は、基材と、その中に含有させた高分子薬効成分を備えたものとなっている。図1(a)は基材がゲルタイプである口腔内施用物100aとなっており、図1(b)は基材110がフィルムタイプである口腔内施用物100bとなっている。
まず、口腔内粘膜は、一般の表皮とは異なり、比較的、高分子物質など人体内に吸収されにくい分子量の大きな高分子薬効成分であっても吸収しやすい箇所である。この口腔内粘膜を施用箇所とすることにより分子量の大きな高分子薬効成分について吸収率を高めることができる。フィルムシート状のものを口腔粘膜に貼着した状態を比較的長く保つことができ、高分子薬効成分を比較的長い時間にわたり口腔粘膜内に接触させることができるため、全体として吸収量が大きくなる。
実験を通じて口腔内に施用することで高分子薬効成分の吸収率が向上することを確認した。実際の人体の口腔内粘膜を用いた効果確認に代え、表皮モデルと粘膜モデルを用いて検証した。
口腔粘膜モデルとして株式会社ニコダームリサーチ製のSkinEthic(TM) HOE(以下、HOEと略記する)と、皮膚表皮モデルとして株式会社ニコダームリサーチ製のSkinEthic(TM) RHE(以下、RHEと略記する)を、PBS(-)2mLを滴下した12穴プレートの各ウェルに各々設置した。
これらモデルの上に高分子の薬効成分を塗布浸漬してその浸透量を調べる。組織モデル210を通過してリザーバー220に到達したものが上皮を透過して人体内に吸収された量を「上皮透過量」として評価し、組織モデル210に留まっている量は表皮や粘膜内に吸収された量を「上皮残留量」として評価した。
そしてこれら「上皮残留量」と「上皮透過量」を併せたものが「皮膚吸収量」である。
なお、図4は図3に比べてスケールが30倍程度大きい。やはり分子量15万程度のコラーゲンは分子量100万程度のヒアルロン酸ナトリウムよりも吸収量が多いことが分かる。
スライドグラス上の組織切片を、4 %パラホルムアルデヒドで固定した後、1.0 % BSAでブロッキングした。次いで、100倍希釈したAnti-human type I collagen rabbit antibodyで4 °Cにて一昼夜反応させ (一次抗体反応)、500倍希釈したAnti rabbit IgG goat Alexa Fluor488で37 °Cにて1時間反応させた (二次抗体反応)。免疫染色した組織切片は、蛍光顕微鏡にて外界側から適用したI型コラーゲン由来の蛍光を観察した (100倍率、BP:485 FT:510)。また、同様に、4 μmの厚さにて作製した切片を用いたヘマトキシリン・エオシン染色 (HE染色) にて顕微鏡観察を行った (100倍率)。
図6にコラーゲンを用いた実験の表皮モデル(RHE)および粘膜モデル(HOE)の切片の免疫染色撮影画像を示した。図4に示した結果と同様、コラーゲンが粘膜組織内に多量にとりこまれていることが確認された。
図7にコラーゲンを用いた実験の表皮モデル(RHE)および粘膜モデル(HOE)の切片のヘマトキシリン・エオシン染色撮影画像を示した。図4に示した結果と同様、コラーゲンが粘膜組織内に多量にとりこまれていることが確認された。
今回使用された皮膚表皮モデル(RHE)には角質層はないが、角質層のある人皮膚表皮では、吸収効率の差はこれ以上大きくなることが予想される。
口腔内マッサージ器300は、口腔内施用物100の吸収促進と、口腔内のマッサージを通じた美容効果の向上を狙ったものである。
図8は、口腔内マッサージ器300の基本的構造を簡単に示した図である。
図8(a)は口腔当接体が球タイプのもの、図8(b)は口腔当接体がブラシタイプのものを簡単に図示したものである。
この構成例では表面を覆う被覆体311を持ち、さらに、被覆体311の内部には、温熱を発する温熱部312と振動を発する振動体313を内蔵した構造となっている。
図8(b)のブラシタイプであれば、被覆体311は多数の刷毛が設けられたものとなったものである。このブラシタイプの被覆体311の場合、素材としてはプラスチック製のものが良い。いわゆる電動ブラシと同様のブラシで良い。
温熱制御部340は、口腔当接体310内部に仕込んだ温熱発生部312の発熱を制御する部分である。利用者が温熱発生部312を利用する場合、温熱発生部312の温度を40~45℃に設定するよう制御する。
口腔マッサージ器200の使用例には、口腔内施用物100の口腔内粘膜への施用前の使用(使用例1)と、施用後(使用例2)がある。
図9(a)に示した口腔内施用物100の口腔内粘膜への施用前の使用(使用例1)の場合、利用者は口腔内施用物100の口腔内粘膜への施用に先立ち、口腔マッサージ器200を口にくわえて、その施用予定箇所となる口腔内粘膜を上からやさしくブラッシングする。この口腔マッサージ器200を用いたブラッシングにより口腔内施用物100の施用予定箇所となる口腔内粘膜を滑らかにする等、口内粘膜環境を良好に整える効果があり、吸収効率を高めるとともに、口腔内のブラッシングを通じた健康増進が期待できる。
次に、図9(b)に示した口腔内施用物100の口腔内粘膜への施用後の使用(使用例2)の場合、利用者は先に、口腔内施用物100を口腔内粘膜に施用しておき、その後、口腔マッサージ器200を口にくわえて、その口腔内施用物100の上からやさしくブラッシングする。この際、口腔内施用物100が破壊したり撹拌したりすることがないよう、やさしくブラッシングすることが好ましい。この口腔マッサージ器200を用いたブラッシングにより口腔内施用物100の吸収効率を高めるとともに、口腔内のブラッシングを通じた健康増進が期待できる。
200a 表皮モデル
200b 粘膜モデル
210 組織モデル
220 リザーバー
300 口腔内マッサージ器
310 口腔当接体
311 被覆体
312 温熱部
313 振動体
320 軸支部
330 ハンドル部
340 温熱制御部
350 振動制御部
360 電源
Claims (13)
- 口腔内に貼着または塗布による施用可能な基材と、前記基材に含有させた経皮吸収が困難な程度に分子量の大きな高分子薬効成分を備え、口腔内に施用することにより前記高分子薬効成分の効率的吸収を可能とした、高分子薬効成分を含有した口腔内施用物。
- 前記基材がフィルムシート状に成型されたものであり、口腔内に貼着して施用するものである請求項1に記載の高分子薬効成分を含有した口腔内施用物。
- 前記基材がゲル塊であり、口腔内に塗布して施用するものである請求項1に記載の高分子薬効成分を含有した口腔内施用物。
- 前記フィルムシート状の基材が、コラーゲン、ヒアルロン酸ナトエリウム、ゼラチン、アルギン酸ナトリウム、カラギーナン、寒天、プルラン、キサンタンガム、カリボキシメチルセルロースから選ばれる少なくとも一種を配合したものである請求項2に記載の高分子薬効成分を含有した口腔内施用物。
- 前記ゲル塊の基材が、コラーゲン、ヒアルロン酸ナトリウム、ヒドロキシエチルセルロース、セルロースガムから選ばれる少なくとも一種を配合したものである請求項3に記載の高分子薬効成分を含有した口腔内施用物。
- 前記高分子薬効成分が美容に資する高分子化合物であり、口腔内施用化粧品である請求項1から5のいずれか1項に記載の高分子薬効成分を含有した口腔内施用物。
- 前記高分子薬効成分が、コラーゲン、ヒアルロン酸ナトリウム、アロエベラエキス、セチルピリジニウムクロリド、ビタミンE、グリチルリチン酸二カリウム、茶エキス、上皮成長因子、アスタキサンチン、プラセンタエキス、卵殻膜より選ばれた一つまたはこれらの組み合わせを含むものである請求項6の高分子薬効成分を含有した口腔内施用物。
- 口腔当接体と、前記口腔当接体を支える軸支部と、前記軸支部につながるハンドル部を備え、請求項1から8のいずれか1項に記載の高分子薬効成分を含有した口腔内施用物の施用済箇所または施用予定箇所に対して前記口腔当接体を当接させて擦ることにより前記口腔内施用物の効率的吸収と前記口腔内の施用箇所のマッサージを行う口腔マッサージ器。
- 40~45℃の温熱を発生させる温熱制御部を備えたものであることを特徴とする請求項8に記載の口腔マッサージ器。
- 前記口腔当接体がシリコンまたは金属製の素材であり、毎分2000回から5000回の振動数で微振動するものであることを特徴とする請求項8または9に記載の口腔マッサージ器。
- 口腔内に貼着または塗布による施用可能な基材と、前記基材に含有させた経皮吸収が困難な程度に分子量の大きな高分子薬効成分を備えた口腔内施用物を用い、口腔内に施用することにより前記高分子薬効成分の効率的吸収を可能とする、口腔内への高分子薬効成分の投与方法。
- 前記基材がシート状に成型されたものであり、口腔内に貼着して施用するものである請求項11に記載の口腔内への高分子薬効成分の投与方法。
- 前記基材がゲル塊であり、口腔内に塗布して施用するものである請求項11に記載の口腔内への高分子薬効成分の投与方法。
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CN107468539A (zh) * | 2017-08-14 | 2017-12-15 | 北京明弘科贸有限责任公司 | 一种含有维生素c的亚凝胶及其制备方法与应用 |
WO2020045504A1 (ja) * | 2018-08-29 | 2020-03-05 | ライオン株式会社 | 口腔内マッサージ用組成物、口腔内マッサージ用組成物入り容器、及び口腔内マッサージセット |
CN115487128A (zh) * | 2022-08-26 | 2022-12-20 | 广州舒客实业有限公司 | 一种用于口腔黏膜修复的组合物、凝胶及在口腔护理产品中的应用 |
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KR102221453B1 (ko) * | 2019-07-19 | 2021-03-02 | 한국프라임제약주식회사 | 저분자 콜라겐 펩타이드 및 천연추출복합물을 포함하는 구강점막부착형 필름 조성물 및 이를 이용하여 제조된 구강점막부착형 필름 |
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CN107468539A (zh) * | 2017-08-14 | 2017-12-15 | 北京明弘科贸有限责任公司 | 一种含有维生素c的亚凝胶及其制备方法与应用 |
WO2020045504A1 (ja) * | 2018-08-29 | 2020-03-05 | ライオン株式会社 | 口腔内マッサージ用組成物、口腔内マッサージ用組成物入り容器、及び口腔内マッサージセット |
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WO2023054436A1 (ja) * | 2021-09-29 | 2023-04-06 | 株式会社西尾 | 美容方法 |
CN115487128A (zh) * | 2022-08-26 | 2022-12-20 | 广州舒客实业有限公司 | 一种用于口腔黏膜修复的组合物、凝胶及在口腔护理产品中的应用 |
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