JP2013505981A - Dissolvable film strip with natural ingredients - Google Patents
Dissolvable film strip with natural ingredients Download PDFInfo
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
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- 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
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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
- A61K31/716—Glucans
- A61K31/719—Pullulans
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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)
- A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Abstract
本発明は、天然産物製剤を含み、口腔粘膜から吸収され得るフィルムストリップに関する。このフィルムストリップは天然成分を含み、公知の剤型よりも低用量で口腔粘膜から適用されたとき、急速に吸収されることによって、短時間で強力な抗酸化効果を示す。 The present invention relates to a film strip that contains a natural product formulation and can be absorbed from the oral mucosa. This film strip contains natural ingredients and exhibits a strong antioxidant effect in a short time by being rapidly absorbed when applied from the oral mucosa at lower doses than known dosage forms.
Description
本発明は、天然産物製剤を含み、口腔粘膜から吸収され得るフィルムストリップに関する。 The present invention relates to a film strip that contains a natural product formulation and can be absorbed from the oral mucosa.
薬物は病気の治療に用いられ、その構成に提供されるいくつかの成分は体内などに取り込まれる。病気の治療は、これらの活性物質により可能である。例えば、メラトニンは、最も強力な天然の細胞保護性および抗ガン効果を有することが知られている化合物である。メラトニン化合物は、フリーラジカルを除去できるようにするという点で、その効果を示す。メラトニンは、人の体内で夜に分泌されるホルモンである。メラトニンレベルは夜に死亡した人において高いことが死後調査により分かった。大人の平均血漿中メラトニンレベルは約60から70pg/mlである。さらに、乳ガンはメラトニン欠乏で発症する病気であると1978年に提唱された後、多くの臨床学的研究が、ガン患者におけるメラトニン分泌を定量するために、行われてきた。いくつかのヒト細胞型において、松果体およびメラトニンの抗腫瘍効果が報告された。 Drugs are used in the treatment of illnesses, and some of the components provided in the composition are taken into the body and the like. Disease treatment is possible with these active substances. For example, melatonin is a compound known to have the most potent natural cytoprotective and anti-cancer effects. Melatonin compounds show their effect in that they can remove free radicals. Melatonin is a hormone secreted at night in the human body. A postmortem study found that melatonin levels were higher in those who died at night. The average plasma melatonin level in adults is about 60 to 70 pg / ml. Furthermore, after being proposed in 1978 as breast cancer is a disease that develops due to melatonin deficiency, many clinical studies have been conducted to quantify melatonin secretion in cancer patients. In several human cell types, the antitumor effects of pineal gland and melatonin have been reported.
強力な抗酸化効果を有するもうひとつの成分はリスベラトロールである。天然産物である赤ワインの構成中にリスベラトロールがある。しかしながら、どの赤ワインの組成にもリスベラトロールがあるわけではない。赤ワインを作るときに用いる土壌産物は、土壌状態、生育や気候条件、年月さえによっても変化するであろう。赤ワインに赤みと渋みを与えるプロアントシアニジンがある。これらの物質も強力な抗酸化特性を有する。これらとは別に、緑茶は強力な抗酸化特性を有する天然産物である。緑茶中のカテキンのようなアルカロイド、それにカテキンおよびEGCG (epigallocatechin gallate; 没食子酸エピガロカテキン)、ならびにフラボノイド類がある。特に減量の目的での緑茶エキスの使用は、近年科学的に決定されたその脂肪分解特性のため、このところ広がっている。 Another component that has a strong antioxidant effect is resveratrol. There is resveratrol in the composition of the natural red wine. However, not all red wine compositions have resveratrol. Soil products used to make red wine will vary with soil conditions, growth and climatic conditions, and even years. Proanthocyanidins give red wine redness and astringency. These substances also have strong antioxidant properties. Apart from these, green tea is a natural product with strong antioxidant properties. There are alkaloids like catechins in green tea, catechin and EGCG (epigallocatechin gallate), and flavonoids. The use of green tea extract, especially for weight loss purposes, has been widespread recently due to its lipolytic properties that have been scientifically determined in recent years.
薬理学分野で病気の治療で用いられる薬物は、錠剤、シロップ剤、粉剤などのさまざまな剤型に調製できる。これらの薬物の適用にはいくつかの問題がある。薬物と食物との相互作用に依存して、胃でのそれらの吸収が減少し、かくして体内での薬物のバイオアベイラビリティーは十分に発生しない。薬物のバイオアベイラビリティーが有効であるためには、栄養素または薬物は最適な量で体に与えられるべきである。例えば、使用者に推奨されるリスベラトロールの日用量を天然で摂取するためには、人は毎日500から1000mlの赤ワインを消費する必要がある。この場合、肝臓アルコール摂取に依存して、肝臓損傷などの深刻な健康問題が発生する。一方、どの赤ワインにもリスベラトロールがあるわけではない。それゆえ、消費されたワインがリスベラトロールを含むか含まないかはわからない。同様に、天然で緑茶を消費することによって体内にEGCGを取り込むことは可能である。しかしながら、大量の緑茶を消費する必要はない。大量に緑茶を消費することは、肝臓および腎臓の機能に重大な問題を引き起こすかもしれない。大量に緑茶を消費することは、便秘の問題も引き起こすかもしれない。薬物の使用の際に発生するもうひとつの問題は、経口で体内に摂取される丸薬が水で飲みこめないとき、潰瘍効果を示す。薬物の製剤に依存して、損傷効果も増大するであろう。しかしながら、薬物特性におけるこれらとは別に、薬理学的効果を有さず、マルトトリオース分子からなるポリマーである多糖類構造にプルラン構造がある。それらは、口腔粘膜から吸収され得るフィルムストリップとして市場にある。例えば、リステリン(登録商標)は、プルラン構造の製品であり、口腔衛生に用いられ、口腔粘膜から吸収され得る。その製品は毎日使用して、口にいい香りを与える。 Drugs used in disease treatment in the pharmacology field can be prepared in various dosage forms such as tablets, syrups and powders. There are several problems with the application of these drugs. Depending on the interaction between the drug and food, their absorption in the stomach is reduced and thus the bioavailability of the drug in the body does not fully occur. For drug bioavailability to be effective, nutrients or drugs should be given to the body in optimal amounts. For example, to naturally take the daily dose of resveratrol recommended for users, one needs to consume 500 to 1000 ml of red wine daily. In this case, depending on liver alcohol intake, serious health problems such as liver damage occur. On the other hand, not all red wines have resveratrol. Therefore, it is not known whether the wine consumed contains or does not contain resveratrol. Similarly, EGCG can be taken into the body by consuming green tea naturally. However, it is not necessary to consume a large amount of green tea. Consuming large amounts of green tea may cause serious problems with liver and kidney function. Consuming large amounts of green tea may also cause constipation problems. Another problem that arises when using drugs is that when pills taken orally by the body cannot be swallowed with water, they show an ulcer effect. Depending on the drug formulation, the damaging effect will also increase. However, apart from these in drug properties, there is a pullulan structure in the polysaccharide structure which is a polymer composed of maltotriose molecules without pharmacological effects. They are on the market as film strips that can be absorbed from the oral mucosa. For example, Listerin® is a pullulan structured product that can be used in oral hygiene and absorbed from the oral mucosa. The product is used daily to give a good scent to the mouth.
米国特許出願公開US2009-004254 A1号、技術水準の出願は、口腔内で溶解可能かつ食用のフィルムの形態の活性薬物を開示する。そのフィルムは水溶性ポリマーで成型される。その薬物は、患者の口の中で溶解可能な結着剤およびこの剤中に分散する活性薬物を含み、かくして、薬理学上有効用量の薬物が、患者の口の中で溶けることによって体内に摂取される。 US Patent Application Publication No. US2009-004254 A1, a state of the art application discloses an active drug in the form of an orally soluble and edible film. The film is molded with a water soluble polymer. The drug includes a binder that is soluble in the patient's mouth and the active drug dispersed in the agent, thus allowing a pharmacologically effective dose of drug to enter the body by dissolving in the patient's mouth. Ingested.
日本国特許出願公開第JP63-093717 A号、技術水準の出願は、ポリマルトトリオースを含み、口腔粘膜に高い接着特性を示す剤を開示する。この剤を用いて、口腔における粘膜に薬物を固定することができる。この接着性剤は治療用の薬物に添加することによって適用できる。 Japanese Patent Application Publication No. JP63-093717 A, a state-of-the-art application discloses an agent comprising polymaltotriose and exhibiting high adhesive properties to the oral mucosa. Using this agent, the drug can be fixed to the mucous membrane in the oral cavity. This adhesive can be applied by adding it to a therapeutic drug.
本発明の目的は、公知の剤型よりも低用量で口腔粘膜から適用されたとき、急速に吸収されることによって、短時間で強力な抗酸化効果を示し、かつ、天然成分を含むフィルムストリップを実現することにある。 An object of the present invention is a film strip that exhibits a strong antioxidant effect in a short time by being rapidly absorbed when applied from the oral mucosa at a lower dose than known dosage forms, and contains natural ingredients Is to realize.
もうひとつの本発明の目的は、胃腸での消化プロセスを経ることなく急速効果を示し、天然成分を含むフィルムストリップを実現することにある。なおもうひとつの本発明の目的は、容易に持ち運べ、天然成分を含むフィルムストリップを実現することにある。 Another object of the present invention is to realize a film strip that exhibits a rapid effect without going through a digestive process in the gastrointestinal tract and includes a natural component. Yet another object of the present invention is to provide a film strip that is easy to carry and includes natural ingredients.
さらなる本発明の目的は、水を必要とせずに経口で摂取され得、天然成分を含むフィル A further object of the present invention is to provide a fill containing natural ingredients that can be taken orally without the need for water.
なおさらなる本発明の目的は、強力な抗酸化効果を有し、天然成分を含むフィルムストリップを実現することにある。そのうえさらなる本発明の目的は、充填剤も添加剤も用いない天然フィルムストリップを実現することにある。 A still further object of the present invention is to realize a film strip having a strong antioxidant effect and containing natural ingredients. A further object of the present invention is to realize a natural film strip that uses no fillers or additives.
付随する本発明の目的は、容易に製造できるフィルムストリップを実現することにある。 The accompanying object of the invention is to realize a film strip that can be easily manufactured.
本発明の口腔内で吸収可能なフィルムストリップの調製において、凍結乾燥法でフリーズドライされた天然成分とメラトニンとして知られるマルトトリオースポリマーの粉末の混合物を、0.001〜0.5g/mlの間の量の蒸留水と混合する。得られた混合物を薄いフィルムの形態の滑らかで平坦な非接着層上に注ぐ。注がれたフィルムを、乾燥庫中、50%の相対湿度および室温にて一晩フリーズドライする。得られたフィルムを薄く切り分ける。最終的に、天然成分−マルトトリオース複合体を、薄いフィルムの形態で得る。得られたフィルムストリップは、弾力性、接着性かつ容易に口腔内で溶解可能である。 In the preparation of an orally absorbable film strip of the present invention, 0.001 to 0.5 g / ml of a mixture of a natural ingredient freeze-dried by freeze-drying and a powder of maltotriose polymer known as melatonin is used. Mix with between the amount of distilled water. The resulting mixture is poured onto a smooth, flat, non-adhesive layer in the form of a thin film. The poured film is freeze-dried overnight in a drying cabinet at 50% relative humidity and room temperature. Cut the resulting film into thin pieces. Finally, the natural component-maltotriose complex is obtained in the form of a thin film. The resulting film strip is elastic, adhesive and can be easily dissolved in the oral cavity.
本発明の口腔内で吸収可能なフィルムストリップの具体例において、天然成分は赤ワインである。赤ワインを凍結乾燥法でフリーズドライし、赤ワイン粉末をマルトトリオース ポリマーと混合し、人が摂取すべき量のリスベラトロールを供するようにする。その結果、赤ワイン-マルトトリオース複合体を得る。すべてのワインにリスベラトロールはないが、トルコ産のボアズケレ (Bogazkere)およびオキュズギョズ (Okuzgozu)ブドウで造られたワインに高い割合のリスベラトロール物質があることが分かった。全てのワインにはリスベラトロールがないので、凍結乾燥されるワインは、原産のブドウ種類のボアズケレおよびオキュズギョズから選択される。リスベラトロールの消化管系からの吸収は、小腸でのたったの20%の割合である。粉末形態のリスベラトールの経口バイオアベイラビリティーは低いが、その口からの吸収は、製剤になされる変更(例えば、リポソームリスベラトロール)によって増大することが知られている。赤ワインの中のリスベラトロールがフィルムストリップの形態で経口適用されると、消化器系からの吸収と比較して、より高いレベルの吸収が得られる。赤ワインの組成に入れられるプロシアニジン類はリスベラトロールの吸収を増大し、その抗酸化特性などのために効果に寄与する。さらに、フィルムストリップ中の成分は口から吸収されて直接血液と混ざるので、消化器系代謝(初回通過代謝)を受けない。かくして、肝臓は疲労せず、体内における代謝物により生じるかもしれない潜在的な毒性リスクを排除し得る。 In the embodiment of the film strip absorbable in the oral cavity of the present invention, the natural ingredient is red wine. Freeze-dry the red wine and mix the red wine powder with maltotriose polymer to provide the amount of resveratrol that humans should consume. As a result, a red wine-maltotriose complex is obtained. Although all wines are free of resveratrol, wines made with Turkish Bogazkere and Okuzgozu grapes were found to have a high proportion of resveratrol substances. Since all wines are free of resveratrol, the freeze-dried wines are selected from the native grape varieties Boaz Kele and Oczu gyoz. The absorption of resveratrol from the gastrointestinal system is only 20% in the small intestine. Although oral oral bioavailability of resveratrol in powder form is low, its absorption through the mouth is known to increase with changes made to the formulation (eg, liposomal resveratrol). When resveratrol in red wine is applied orally in the form of a film strip, a higher level of absorption is obtained compared to absorption from the digestive system. Procyanidins included in the composition of red wine increase the absorption of resveratrol and contribute to the effect due to its antioxidant properties and the like. Furthermore, since the components in the film strip are absorbed from the mouth and mixed directly with the blood, they do not undergo digestive metabolism (first pass metabolism). Thus, the liver does not fatigue and can eliminate potential toxicity risks that may be caused by metabolites in the body.
赤ワイン-マルトトリオース複合体の構成におけるフィルムストリップは、以下の効果を有する:循環器系疾患において、血液(抗血小板)を希釈し、抗酸化効果に依存する心臓発作のリスクを低減し、善玉コレステロール(HDL)を増大し、かつ、悪玉コレステロール(LDL)の参加を防止する。さらに、科学的研究によって、その抗酸化効果に依存して、特別の喫煙関連ガンおよび前立腺ならびに抗加齢効果に予防的および治療的効果を有することが提唱されている。 Film strips in the configuration of red wine-maltotriose complex have the following effects: In cardiovascular disease, dilute blood (antiplatelet), reduce the risk of heart attacks that depend on the antioxidant effect, good Increases cholesterol (HDL) and prevents the participation of bad cholesterol (LDL). Furthermore, scientific research has suggested that depending on its antioxidant effects, it has prophylactic and therapeutic effects on special smoking-related cancers and prostate and anti-aging effects.
本発明のもう一つの具体例において、EGCG (没食子酸エピガロカテキン)剤を含む緑茶を用いる。したがって、緑茶エキスは凍結乾燥法でフリーズドライされ、緑茶粉末はマルトトリオースポリマーと混合し、人が摂取すべき量のEGCG (没食子酸エピガロカテキン)を供するようにする。薄いフィルムとして得られた生成物は緑茶-マルトトリオース複合体の構成にある。 In another embodiment of the invention, green tea containing EGCG (epigallocatechin gallate) agent is used. Therefore, the green tea extract is freeze-dried by freeze-drying, and the green tea powder is mixed with maltotriose polymer to provide an amount of EGCG (epigallocatechin gallate) that should be taken by humans. The product obtained as a thin film is in the form of a green tea-maltotriose complex.
EGCGは、単経口用量として1600mgまで適用しても安全であることが報告される。 EGCG is reported to be safe to apply up to 1600 mg as a single oral dose.
緑茶を含む薄いフィルムストリップは、その脂肪分解特性のため、減量の目的で用いられる。しかしながら、カフェインの使用は、心臓病患者(血圧を上昇させるから)または腸疾患を患う患者(胃酸を増加させるから)において、普通、問題を生じる。そのため、本発明の具体例において、薄いフィルムストリップは、カフェインを含まない純粋なEGCGを直接用いるEGCG-マルトトリオース複合体の構成で得る。 Thin film strips containing green tea are used for weight loss purposes due to their lipolytic properties. However, the use of caffeine usually causes problems in patients with heart disease (because they increase blood pressure) or patients with bowel disease (because they increase gastric acid). Thus, in an embodiment of the invention, a thin film strip is obtained in the form of an EGCG-maltotriose complex using directly EGCG without caffeine.
本発明の口腔内で吸収可能なフィルムストリップのもう一つの具体例において、メラトニンは天然成分として選択される。経口でのメラトニンのバイオアベイラビリティーは15%である。その吸収は速い。なぜならば、フィルムおよび血液との混合物の形態で直接口から摂取され、効率が高いからである。メラトニンは、人の体内で分泌される天然の細胞保護ホルモンである。科学的研究は、それは強力な抗酸化特性および抗ガン効果を有すると提唱する。メラトニンを含む薄いフィルムストリップはメラトニンにとって適当な剤型であり、その使用は近年除々に増加し、それは、特に国際旅行の時差ボケの不満を軽減するために迅速、有効かつ簡便な使用を提供する製品形状である。 In another embodiment of the orally absorbable film strip of the present invention, melatonin is selected as a natural ingredient. Oral melatonin bioavailability is 15%. Its absorption is fast. This is because it is taken directly from the mouth in the form of a mixture with film and blood and is highly efficient. Melatonin is a natural cytoprotective hormone that is secreted in the human body. Scientific research suggests that it has strong antioxidant properties and anti-cancer effects. Thin film strips containing melatonin are a suitable dosage form for melatonin, and its use has gradually increased in recent years, which provides a quick, effective and convenient use, especially to reduce the dissatisfaction of jet lag during international travel Product shape.
Claims (13)
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TR2009/07338A TR200907338A1 (en) | 2009-09-28 | 2009-09-28 | A film strip containing natural ingredients. |
TR2009/07338 | 2009-09-28 | ||
PCT/IB2010/054121 WO2011036599A1 (en) | 2009-09-28 | 2010-09-14 | A dissolvable film strip comprising natural components |
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WO2011036599A1 (en) | 2011-03-31 |
TR200907338A1 (en) | 2011-04-21 |
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