JP2023039899A - Composition for mitigating gout and/or inhibiting symptoms of gout from worsening - Google Patents
Composition for mitigating gout and/or inhibiting symptoms of gout from worsening Download PDFInfo
- Publication number
- JP2023039899A JP2023039899A JP2022070405A JP2022070405A JP2023039899A JP 2023039899 A JP2023039899 A JP 2023039899A JP 2022070405 A JP2022070405 A JP 2022070405A JP 2022070405 A JP2022070405 A JP 2022070405A JP 2023039899 A JP2023039899 A JP 2023039899A
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- symptoms
- gout
- composition
- affected area
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
本発明は、ヒト患者において痛風の症状、例えば、患部の痛み、患部の発赤、患部の発熱、痛風結節、結石と結石に伴う痛み、および／または、これらの症状に伴う活動レベルの低下を改善および／または症状の悪化を抑制するための組成物に関する。
本発明はまた、ヒト患者において痛風の上記症状を改善および／または症状の悪化を抑制する方法に関する。The present invention ameliorate the symptoms of gout in human patients, such as pain in the affected area, redness in the affected area, fever in the affected area, gouty nodules, stones and pain associated with stones, and/or decreased activity levels associated with these symptoms. and/or to a composition for suppressing aggravation of symptoms.
The present invention also relates to methods of ameliorating and/or inhibiting exacerbation of the above symptoms of gout in human patients.
痛風は、体内で尿酸が過剰になると、関節にたまって結晶化し、炎症を引き起こして腫れや痛みを生じる病気。風が患部に吹きつけるだけで激しい痛みが走ることから痛風と名づけられたといわれている。尿酸はプリン体が体内で分解されてできる物質で、血液中の尿酸の濃度が高くなり、７．０ｍｇ／ｄｌを超えると高尿酸血症の状態となる。この状態が長く続くと関節の中で尿酸が結晶化し、これを白血球が処理する際に炎症を引き起こす。医療の進歩により、薬も開発されており、正しい治療を行えば、これまで通りの健康な生活を送ることができる。しかしながら、放置してしまうと、関節の激痛を繰り返し引き起こしたり、体の至る所に結節ができたり、腎臓に影響を及ぼしたりしてしまう病気である。
近年、水素分子が細胞内および細胞のミトコンドリア内部で発生するヒドロキシルラジカルを消去することにより慢性炎症を抑制し、慢性炎症に起因する多くの疾病に対し効果を奏する可能性があることを提唱されている（非特許文献２）。しかしながら、ヒト痛風患者が水素ガス含有気体を吸入、吸引、飲用等した場合に、ヒト痛風の症状が改善および／または症状の悪化を抑制されるかについては報告されていない。Gout is a disease in which excess uric acid builds up in the body and crystallizes in the joints, causing inflammation, swelling, and pain. It is said that it was named gout because it causes severe pain when the wind blows on the affected area. Uric acid is a substance produced by the decomposition of purines in the body. When the concentration of uric acid in the blood increases and exceeds 7.0 mg/dl, hyperuricemia occurs. If this condition continues for a long time, uric acid crystallizes in the joints, causing inflammation when white blood cells process it. Thanks to advances in medical care, drugs have also been developed. However, if left untreated, it can cause recurring severe pain in the joints, form nodules all over the body, and affect the kidneys.
In recent years, it has been proposed that hydrogen molecules may suppress chronic inflammation by scavenging hydroxyl radicals generated in cells and mitochondria of cells, and may be effective against many diseases caused by chronic inflammation. (Non-Patent Document 2). However, it has not been reported whether the symptoms of human gout are improved and/or aggravation of the symptoms is suppressed when the human gout patient inhales, inhales, or drinks hydrogen gas-containing gas.
本発明の目的は、副作用の少ないかつ簡便に製造し得る新しい痛風の症状改善および／または症状の悪化を抑制するのための組成物を提供することである。 An object of the present invention is to provide a new composition for improving symptoms of gout and/or suppressing aggravation of gout symptoms, which can be easily produced with few side effects.
本発明者らは、鋭意研究の結果、意外にも、水素ガス含有気体が、ヒト患者において痛風の特定の症状を改善および／または症状の悪化を抑制することを見出した。
従って、本発明は、以下の特徴を包含する。
（１）水素を有効成分として含む、被験体において、痛風を原因とする症状を改善および／または症状の悪化を抑制するための組成物である。
（２）前記痛風を原因とする症状が、少なくとも患部の痛み、患部の発赤、患部の発熱、痛風結節、結石と結石に伴う痛み、および／または、これらの症状に伴う活動レベルの低下を含む（１）に記載の組成物である。
（３）前記患部が足の指、足の関節、足の甲、アキレス腱のつけ根、膝関節、股関節、手の指の関節、および／または、腕の関節であることを特徴とする（２）に記載の組成物である。
（４）前記水素の濃度が、０より大きく１８．５体積％以下である、（１）から（３）のいずれか１つに記載の組成物である。
（５）前記組成物が、吸入によって前記被験体に投与される、（１）から（４）のいずれか一つに記載の組成物である。
（６）前記被験体がヒトを含む哺乳類である、（１）から（５）のいずれか一つに記載の組成物である。
（７）前記（１）～（６）のいずれか１つに記載の組成物を作製する方法であって、前記組成物が水素ガス生成装置を用いて作製されることを特徴とする方法である。As a result of extensive research, the present inventors have unexpectedly found that hydrogen gas-containing gases improve certain symptoms of gout and/or suppress exacerbation of symptoms in human patients.
Accordingly, the present invention includes the following features.
(1) A composition for improving symptoms caused by gout and/or suppressing aggravation of symptoms in a subject, comprising hydrogen as an active ingredient.
(2) the symptoms caused by gout include at least pain in the affected area, redness in the affected area, fever in the affected area, gouty nodules, calculi and pain associated with calculi, and/or decreased activity levels associated with these symptoms. (1) is the composition described above.
(3) The affected part is a toe, a joint of the foot, the top of the foot, the root of the Achilles tendon, the knee joint, the hip joint, the joint of the fingers, and/or the joint of the arm. It is a composition according to.
(4) The composition according to any one of (1) to (3), wherein the hydrogen concentration is greater than 0 and 18.5% by volume or less.
(5) The composition according to any one of (1) to (4), wherein the composition is administered to the subject by inhalation.
(6) The composition according to any one of (1) to (5), wherein the subject is a mammal including humans.
(7) A method for producing the composition according to any one of (1) to (6) above, wherein the composition is produced using a hydrogen gas generator. be.
本発明により、水素ガスの吸入、吸引等によってヒト痛風において痛風を原因とする少なくとも患部の痛み、患部の発赤、患部の発熱、痛風結節、結石と結石に伴う痛み、および／または、これらの症状に伴う活動レベルの低下を含む症状を改善および／または症状の悪化を抑制することができる。 According to the present invention, at least pain in the affected area, redness in the affected area, fever in the affected area, gouty nodules, calculus and pain associated with calculus, and/or these symptoms caused by gout in human gout by inhalation, inhalation, etc. of hydrogen gas. can improve symptoms and/or inhibit worsening of symptoms, including decreased activity levels associated with
本発明をさらに詳細に説明する。
１．痛風
痛風とは、尿酸が体内で析出して結晶ができることにより、関節炎などを来たす疾患である。
本発明における痛風の原因は血液中の老廃物のひとつである尿酸である。尿酸が一定量以上に増えると、その結晶が関節部分に蓄積し、やがて炎症と激しい痛みを引き起こす。The present invention will now be described in more detail.
1. Gout Gout is a disease that causes arthritis and the like due to precipitation of uric acid in the body and formation of crystals.
The cause of gout in the present invention is uric acid, which is one of waste products in blood. When uric acid increases beyond a certain amount, its crystals accumulate in joints, eventually causing inflammation and severe pain.
２．水素ガス含有気体を含む痛風の症状を改善および／または症状の悪化を抑制するための組成物
本発明は、水素ガス含有気体を有効成分として含む、ヒト痛風患者において痛風を原因とする少なくとも、患部の痛み、患部の発赤、患部の発熱、痛風結節、結石と結石に伴う痛み、および／または、これらの症状に伴う活動レベルの低下を含む症状を改善および／または症状の悪化を抑制するための組成物を提供する。
本発明における「結石」には、腎臓結石、尿路結石が含まれる。
本発明における痛風の患部は、身体の関節であり、例えば、足の指、くるぶし等の足の関節、足の甲、アキレス腱のつけ根、膝関節、股関節、手の指の関節、腕の関節、耳などである。2. A composition for improving symptoms of gout and/or suppressing aggravation of symptoms containing a hydrogen gas-containing gas. to ameliorate and/or inhibit exacerbation of symptoms, including pain in the affected area, redness in the affected area, fever in the affected area, gouty nodules, calculi and pain associated with calculi, and/or decreased activity levels associated with these conditions A composition is provided.
The "calculus" in the present invention includes kidney stones and urinary calculi.
The affected part of gout in the present invention is a joint of the body, for example, a toe, a foot joint such as an ankle, the top of the foot, the base of the Achilles tendon, a knee joint, a hip joint, a finger joint, an arm joint, ears, etc.
本明細書中、本発明の組成物の有効成分である「水素」は分子状水素（すなわち、気体状水素）であり、特に断らない限り、単に「水素」又は「水素ガス」と称する。また、本明細書中で使用する用語「水素」は、分子式でＨ２、Ｄ２（重水素）、ＨＤ（重水素化水素）、又はそれらの混合ガスを指す。Ｄ２は、高価であるが、Ｈ２よりスーパーオキシド消去作用が強いことが知られている。本発明で使用可能な水素は、Ｈ２、Ｄ２（重水素）、ＨＤ（重水素化水素）、又はそれらの混合ガスであり、好ましくはＨ２であり、或いはＨ２に代えて、又はＨ２と混合して、Ｄ２及び／又はＨＤを使用してもよい。
水素ガス含有気体は、好ましくは、水素ガスを含む空気又は、水素ガスと酸素ガスを含む混合ガスである。水素ガス含有気体の水素ガスの濃度は、ゼロ（０）より大きく、かつ１８．５体積％以下、例えば０．５～１８．５体積％であり、好ましくは１～１０体積％、例えば２～８体積％、３～７体積％、３～６体積％、４～６体積％、４～５体積％、５～１０体積％、５～８体積％、６～８体積％、６～７体積％など、より好ましくは５～８体積％、例えば６～８体積％、６～７体積％などである。本発明では、爆発限界以下で水素ガス濃度が高いほど痛風の症状の改善効果および／または症状の悪化を抑制する効果が大きい傾向がある。As used herein, "hydrogen", which is the active ingredient of the composition of the present invention, is molecular hydrogen (ie, gaseous hydrogen), and is simply referred to as "hydrogen" or "hydrogen gas" unless otherwise specified. Also, the term "hydrogen" as used herein refers to H 2 , D 2 (deuterium), HD (hydrogen deuteride), or a mixture thereof by molecular formula. Although D2 is expensive, it is known to have a stronger superoxide scavenging effect than H2 . Hydrogen that can be used in the present invention is H2 , D2 (deuterium), HD (deuterium), or a mixture thereof, preferably H2 , or instead of H2 , or D2 and/or HD may be used mixed with H2 .
The gas containing hydrogen gas is preferably air containing hydrogen gas or a mixed gas containing hydrogen gas and oxygen gas. The hydrogen gas concentration of the hydrogen gas-containing gas is greater than zero (0) and not more than 18.5% by volume, such as 0.5 to 18.5% by volume, preferably 1 to 10% by volume, such as 2 to 8% by volume, 3-7% by volume, 3-6% by volume, 4-6% by volume, 4-5% by volume, 5-10% by volume, 5-8% by volume, 6-8% by volume, 6-7% by volume %, more preferably 5 to 8% by volume, such as 6 to 8% by volume, 6 to 7% by volume, and the like. In the present invention, there is a tendency that the higher the hydrogen gas concentration is below the explosive limit, the greater the effect of improving gout symptoms and/or suppressing the deterioration of gout symptoms.
水素は、可燃性かつ爆発性ガスであるため、痛風の症状の改善および／または症状の悪化の抑制においては、安全な条件で本発明の組成物に含有させて痛風患者に投与することが好ましい。
水素ガス以外の気体が空気であるときには、空気の濃度は、例えば８１．５～９９．５体積％の範囲である。水素ガス以外の気体が酸素ガスを含む気体であるときには、酸素ガスの濃度は、例えば２１～９９．５体積％の範囲である。Since hydrogen is a flammable and explosive gas, it is preferable to administer the composition of the present invention to gout patients under safe conditions in order to improve symptoms of gout and/or suppress aggravation of symptoms. .
When the gas other than hydrogen gas is air, the concentration of air is, for example, in the range of 81.5-99.5% by volume. When the gas other than hydrogen gas contains oxygen gas, the oxygen gas concentration is, for example, in the range of 21 to 99.5% by volume.
その他の主気体として窒素ガスを含有させることができる。空気中に含有する気体である二酸化炭素などのガスを、空気中の存在量程度の量で含有させてもよい。
本発明では、必要に応じて、水素ガス含有気体の投与と併用して水素溶存液体を痛風患者に投与する、もしくは摂取させることができる。
水素溶存液体と併用投与する場合には、本発明の組成物は、水素溶存液体の投与の前に、水素溶存液体の投与と同時に、又は水素溶存液体の投与の後に投与されうる。
水素溶存液体は、具体的には、水素ガスを溶存させた水性液体であり、ここで、水性液体は、非限定的に、例えば水（例えば滅菌水、精製水）、生理食塩水、緩衝液（例えばｐＨ４～７．４の緩衝液）、エタノール含有水（例えばエタノール含有量０．１～２体積％）、点滴液、輸液、注射溶液、飲料などである。水素溶存液体の水素濃度は、例えば１～１０ｐｐｍ、例えば２～８体積％、３～７体積％、３～６体積％、４～６体積％、４～５体積％、５～１０体積％、５～８体積％、６～８体積％、６～７体積％など、より好ましくは５～８体積％、例えば６～８体積％、６～７体積％などである。本発明では、爆発限界以下で水素ガス濃度が高いほど痛風の症状の改善および／または症状の悪化を抑制する効果が大きい傾向がある。Nitrogen gas can be contained as another main gas. A gas such as carbon dioxide, which is a gas contained in the air, may be contained in an amount about the amount present in the air.
In the present invention, if necessary, a hydrogen-dissolved liquid can be administered to a gout patient in combination with administration of a hydrogen gas-containing gas, or the gout patient can be made to take it.
When co-administered with a hydrogen-dissolved liquid, the composition of the present invention can be administered prior to the administration of the hydrogen-dissolved liquid, simultaneously with the administration of the hydrogen-dissolved liquid, or after the administration of the hydrogen-dissolved liquid.
Specifically, the hydrogen-dissolved liquid is an aqueous liquid in which hydrogen gas is dissolved. Here, the aqueous liquid includes, but is not limited to, water (e.g., sterilized water, purified water), physiological saline, and buffer solution. (eg, pH 4-7.4 buffer solution), ethanol-containing water (eg, ethanol content 0.1-2% by volume), infusion solution, infusion solution, injection solution, beverage, and the like. The hydrogen concentration of the hydrogen-dissolved liquid is, for example, 1 to 10 ppm, for example, 2 to 8% by volume, 3 to 7% by volume, 3 to 6% by volume, 4 to 6% by volume, 4 to 5% by volume, 5 to 10% by volume, 5 to 8% by volume, 6 to 8% by volume, 6 to 7% by volume, etc., more preferably 5 to 8% by volume, such as 6 to 8% by volume, 6 to 7% by volume. In the present invention, there is a tendency that the higher the hydrogen gas concentration is below the explosive limit, the greater the effect of improving gout symptoms and/or suppressing aggravation of gout symptoms.
水素溶存液体には、痛風を治療するための医薬品を添加してもよい。或いは、当該医薬品は、水素溶存液体又は水素ガス含有気体の投与と別に投与してもよい。
水素ガス含有気体又は水素溶存液体は、所定の水素ガス濃度になるように配合されたのち、例えば耐圧性の容器（例えば、ステンレスボンベ、アルミ缶、好ましくは内側をアルミフィルムでラミネーションした、耐圧性プラスチックボトル（例えば耐圧性ペットボトル）及びプラスチックバッグ、アルミバッグ、等）に充填される。アルミは水素分子を透過させ難いという性質を有している。或いは、水素ガス含有気体又は水素溶存液体は、投与時に、水素ガス生成装置、水素水生成装置、又は水素ガス添加装置、例えば、公知のもしくは市販の水素ガス供給装置（水素ガス含有気体の生成用装置）、水素添加器具（水素水生成用装置）、非破壊的水素含有器（例えば点滴液などの生体適用液バッグ内部へ非破壊的に水素ガスを添加するための装置）などの装置を用いてその場で作製されてもよい。A drug for treating gout may be added to the hydrogen-dissolved liquid. Alternatively, the medicament may be administered separately from the administration of the hydrogen-dissolved liquid or hydrogen gas-containing gas.
After the hydrogen gas-containing gas or hydrogen-dissolved liquid is blended so as to have a predetermined hydrogen gas concentration, for example, a pressure-resistant container (for example, a stainless steel cylinder, an aluminum can, preferably the inside is laminated with an aluminum film, a pressure-resistant It is filled in a plastic bottle (for example, a pressure-resistant PET bottle), a plastic bag, an aluminum bag, etc.). Aluminum has the property that it is difficult for hydrogen molecules to permeate through it. Alternatively, the hydrogen gas-containing gas or hydrogen-dissolved liquid is administered at the time of administration using a hydrogen gas generator, a hydrogen water generator, or a hydrogen gas addition device, such as a known or commercially available hydrogen gas supply device (for generating a hydrogen gas-containing gas). device), hydrogen adding device (hydrogen water generating device), non-destructive hydrogen adding device (e.g., device for non-destructively adding hydrogen gas to the inside of the bag of biologically applicable liquid such as infusion solution) may be made in situ.
水素ガス供給装置は、水素発生剤（例えば金属アルミニウム、水素化マグネシウム、等）と水の反応により発生する水素ガスを、希釈用ガス（例えば空気、酸素、等）と所定の比率で混合することを可能にする（日本国特許第５２２８１４２号公報、等）。あるいは、水の電気分解を利用して発生した水素ガスを、酸素、空気などの希釈用ガスと混合する（日本国特許第５５０２９７３号公報、日本国特許第５９００６８８号公報、等）。これによって０．５～１８．５体積％の範囲内の水素濃度の水素ガス含有気体を調製することができる。 The hydrogen gas supply device mixes the hydrogen gas generated by the reaction between the hydrogen generating agent (e.g., metal aluminum, magnesium hydride, etc.) and water and the diluent gas (e.g., air, oxygen, etc.) at a predetermined ratio. (Japanese Patent No. 5228142, etc.). Alternatively, hydrogen gas generated by electrolysis of water is mixed with a diluent gas such as oxygen or air (Japanese Patent No. 5502973, Japanese Patent No. 5900688, etc.). Thereby, a hydrogen gas-containing gas having a hydrogen concentration within the range of 0.5 to 18.5% by volume can be prepared.
水素添加器具は、水素発生剤とｐＨ調整剤を用いて水素を発生し、水などの生体適用液に溶存させる装置である（日本国特許第４７５６１０２号公報、日本国特許第４６５２４７９号公報、日本国特許第４９５０３５２号公報、日本国特許第６１５９４６２号公報、日本国特許第６１７０６０５号公報、特開２０１７－１０４８４２号公報、日本国特許第６１５９４６２号公報、等）。水素発生剤とｐＨ調整剤の組み合わせは、例えば、金属マグネシウムと強酸性イオン交換樹脂もしくは有機酸（例えばリンゴ酸、クエン酸、等）、金属アルミニウム末と水酸化カルシウム粉末、などである。これによって１～１０ｐｐｍ程度の溶存水素濃度の水素溶存液体を調製できる（例えば、商品名「セブンウォーター」（クオシア）、等）。 The hydrogenation device is a device that generates hydrogen using a hydrogen generating agent and a pH adjuster and dissolves it in a biologically applicable liquid such as water (Japanese Patent No. 4756102, Japanese Patent No. 4652479, Japan Japanese Patent No. 4950352, Japanese Patent No. 6159462, Japanese Patent No. 6170605, Japanese Patent Application Laid-Open No. 2017-104842, Japanese Patent No. 6159462, etc.). Combinations of the hydrogen generating agent and the pH adjuster include, for example, metallic magnesium and a strongly acidic ion exchange resin or organic acid (eg, malic acid, citric acid, etc.), metallic aluminum powder and calcium hydroxide powder, and the like. As a result, a hydrogen-dissolved liquid having a dissolved hydrogen concentration of about 1 to 10 ppm can be prepared (for example, trade name "Seven Water" (Quasia), etc.).
非破壊的水素含有器は、点滴液などの市販の生体適用液（例えば、ポリエチレン製バッグなどの水素透過性プラスチックバッグに封入されている。）に水素分子をパッケージの外側から添加する装置又は器具であり、例えばＭｉＺ（株）から市販されている（ｈｔｔｐ：／／ｗｗｗ．ｅ－ｍｉｚ．ｃｏ．ｊｐ／ｔｅｃｈｎｏｌｏｇｙ．ｈｔｍｌ）。この装置は、生体適用液を含むバッグを飽和水素水に浸漬することによってバッグ内に水素を透過し濃度平衡に達するまで無菌的に水素を生体適用液に溶解させることができる。当該装置は、例えば電解槽と水槽から構成され、水槽内の水が電解槽と水槽を循環し電解により水素を生成することができる。或いは、簡易型の使い捨て器具は同様の目的で使用することができる（特開２０１６－１１２５６２号公報、等）。この器具は、アルミバッグの中に生体適用液含有プラスチックバッグ（水素透過性バッグ、例えばポリエチレン製バッグ）と水素発生剤（例えば、金属カルシウム、金属マグネシウム／陽イオン交換樹脂、等）を内蔵しており、水素発生剤は例えば不織布（例えば水蒸気透過性不織布）に包まれている。不織布に包まれた水素発生剤を水蒸気などの少量の水で濡らすことによって発生した水素がプラスチックバッグを透過し生体適用液に非破壊的かつ無菌的に溶解される。 A non-destructive hydrogen adding device is a device or device that adds hydrogen molecules to commercially available liquids such as intravenous fluids (for example, enclosed in a hydrogen-permeable plastic bag such as a polyethylene bag) from the outside of the package. and is commercially available from, for example, MiZ (http://www.e-miz.co.jp/technology.html). In this device, by immersing a bag containing a fluid applicable to a living body in saturated hydrogen water, hydrogen permeates the bag and aseptically dissolves hydrogen in the fluid applicable to a living body until concentration equilibrium is reached. The device is composed of, for example, an electrolytic cell and a water tank, and water in the water tank circulates through the electrolytic cell and the water tank, and can generate hydrogen by electrolysis. Alternatively, simple disposable instruments can be used for the same purpose (Japanese Patent Application Laid-Open No. 2016-112562, etc.). This device contains a plastic bag (hydrogen permeable bag, such as a polyethylene bag) containing a biologically applicable fluid and a hydrogen generating agent (such as metallic calcium, metallic magnesium/cation exchange resin, etc.) inside an aluminum bag. The hydrogen generating agent is wrapped in, for example, a non-woven fabric (eg, a water vapor permeable non-woven fabric). Hydrogen generated by wetting the hydrogen generating agent wrapped in the non-woven fabric with a small amount of water such as steam permeates the plastic bag and is nondestructively and aseptically dissolved in the biologically applicable liquid.
上記の装置又は器具を用いて調製された、水素ガス含有気体や水素飽和生体適用液（例えば滅菌水、生理食塩水、点滴液、等）は、痛風患者に経口的に又は非経口的に投与されうる。
本発明の組成物の別の形態には、痛風患者に経口投与（もしくは摂取）するように調製された、消化管内で水素の発生を可能にする水素発生剤を含有する剤型（例えば、錠剤、カプセル剤、等）が含まれる。水素発生剤は、例えば食品もしくは食品添加物として承認されている成分によって構成されることが好ましい。A hydrogen gas-containing gas or a hydrogen-saturated biocompatible liquid (e.g., sterile water, physiological saline, infusion solution, etc.) prepared using the above device or instrument may be administered orally or parenterally to gout patients. can be
Another form of the composition of the present invention includes a dosage form containing a hydrogen generating agent capable of generating hydrogen in the gastrointestinal tract (for example, tablet , capsules, etc.). The hydrogen generating agent is preferably composed of ingredients approved as food or food additives, for example.
３．痛風の症状の改善および／または症状の悪化の抑制
本発明は、第２の態様により、痛風患者に、本発明の組成物を投与することを含む、該患者において痛風を原因とする少なくとも疲労感、倦怠感、労作に伴う息切れ、動悸、筋力低下、微熱、筋肉痛、関節痛、咽頭痛、頭痛、身体の痛み、脱力、認知機能障害、記憶障害、言語検索困難、胃腸障害、集中力低下、インフルエンザ様症状、起立時のめまい、虚弱、不規則な体温、冷たい手足、温熱および／または寒冷に対する不耐症、発汗、顔面潮紅、リンパ節圧痛、著しい体重の変動、耳鳴り、錯乱、睡眠障害、立ちくらみ、光や騒音や臭気に対する過敏性、食物や薬物や化学物質に対する新たな過敏性の獲得、および／または、これらの症状に伴う活動レベルの低下を含む症状を改善および／または症状の悪化を抑制する方法を提供する。3. Improvement of Gout Symptoms and/or Suppression of Exacerbation of Symptoms According to a second aspect, the present invention provides at least fatigue caused by gout in a gout patient, comprising administering the composition of the present invention to the patient. , malaise, shortness of breath with exertion, palpitations, muscle weakness, slight fever, muscle pain, arthralgia, sore throat, headache, body pain, weakness, cognitive impairment, memory impairment, language search difficulties, gastrointestinal disorders, concentration loss , flu-like symptoms, dizziness on standing, weakness, irregular body temperature, cold hands and feet, intolerance to heat and/or cold, sweating, hot flushes, lymph node tenderness, marked weight fluctuations, tinnitus, confusion, sleep disturbance , lightheadedness, sensitivity to light, noise, and odors; acquisition of new sensitivities to food, drugs, and chemicals; and/or reduced activity levels associated with these symptoms. To provide a method for suppressing deterioration.
本発明の組成物は、患者のＱＯＬ（生活の質）の改善を可能にする。
本発明の組成物を痛風の患者に投与する方法としては、水素ガスを有効成分とするとき、例えば吸入、吸引等による経肺投与が好ましい。ガスを吸入するときには、鼻カニューラや、口と鼻を覆うマスク型の器具を介して口又は鼻からガスを吸入して肺に送り、血液を介して全身に送達することができる。
また、水素溶存液体を患者に投与とするときには、経口投与又は静脈内投与もしくは動脈内投与（点滴を含む）が好ましい。経口投与する水素溶存液体については、好ましくは低温下に保存し、冷却した液体、又は常温で保存した液体をヒト痛風の患者に投与してもよい。水素は常温常圧下で約１．６ｐｐｍ（１．６ｍｇ／Ｌ）の濃度で水に溶解し、温度による溶解度差が比較的小さいことが知られている。或いは、水素溶存液体は、例えば上記の非破壊的水素含有器を用いて調製された水素ガスを含有させた点滴液又は注射液の形態であるときには、静脈内投与、動脈内投与などの非経口投与経路によって痛風患者に投与してもよい。The compositions of the present invention allow improvement of the patient's QOL (quality of life).
As a method for administering the composition of the present invention to gout patients, when hydrogen gas is used as an active ingredient, transpulmonary administration, for example, by inhalation or inhalation, is preferable. When a gas is inhaled, it can be inhaled through the mouth or nose through a nasal cannula or a mask-type device that covers the mouth and nose and is delivered to the lungs for systemic delivery via the blood.
When the hydrogen-dissolved liquid is administered to a patient, oral administration, intravenous administration, or intraarterial administration (including drip infusion) is preferred. Hydrogen-dissolved liquids for oral administration are preferably stored at a low temperature and may be administered to human patients with gout after being cooled or stored at room temperature. It is known that hydrogen dissolves in water at a concentration of about 1.6 ppm (1.6 mg/L) under normal temperature and normal pressure, and the solubility difference due to temperature is relatively small. Alternatively, when the hydrogen-dissolved liquid is, for example, in the form of a drip or injection containing hydrogen gas prepared using the above-described nondestructive hydrogen-containing device, parenteral administration such as intravenous administration and intraarterial administration It may be administered to gout patients by route of administration.
上記水素濃度の水素ガス含有気体又は上記溶存水素濃度の水素溶存液体を１日あたり１回又は複数回（例えば２～３回）、１週間～３か月又はそれ以上の期間、例えば１週間～６か月又はそれ以上にわたりヒト痛風の患者体に投与することができる。水素ガス含有気体が投与されるときには、１回あたり例えば１０分～２時間もしくはそれ以上、好ましくは２０分～４０分もしくはそれ以上、さらに好ましくは３０分～２時間かけて投与することができる。また、水素ガス含有気体を吸入、吸引等によって経肺投与するときには、大気圧環境下で、或いは、例えば標準大気圧（約１．０１３気圧をいう。）を超える且つ７．０気圧以下の範囲内の高気圧、例えば１．０２～７．０気圧、好ましくは１．０２～５．０気圧、より好ましくは１．０２～４．０気圧、さらに好ましくは１．０２～１．３５気圧の範囲内の高気圧環境下で痛風患者に当該気体を投与することができる。高気圧環境下での投与によって痛風患者での水素の体内吸収が促進されうる。 A hydrogen gas-containing gas having the above hydrogen concentration or a hydrogen-dissolved liquid having the above dissolved hydrogen concentration once or multiple times (eg, 2 to 3 times) per day for a period of 1 week to 3 months or more, such as 1 week to It can be administered to human gout patients for 6 months or longer. When the hydrogen gas-containing gas is administered, it can be administered for, for example, 10 minutes to 2 hours or more, preferably 20 minutes to 40 minutes or more, more preferably 30 minutes to 2 hours. In addition, when a hydrogen gas-containing gas is transpulmonally administered by inhalation, inhalation, etc., it is under an atmospheric pressure environment or, for example, in a range exceeding standard atmospheric pressure (about 1.013 atmospheres) and 7.0 atmospheres or less. High pressure within, for example, 1.02 to 7.0 atmospheres, preferably 1.02 to 5.0 atmospheres, more preferably 1.02 to 4.0 atmospheres, more preferably 1.02 to 1.35 atmospheres The gas can be administered to a gout patient in an internal hyperbaric environment. Administration in a hyperbaric environment can promote the absorption of hydrogen into the body in gout patients.
上記高気圧環境は、内部に、例えば上記水素ガス含有気体（例えば、水素含有酸素又は空気）を圧入して標準大気圧を超える且つ７．０気圧以下の高気圧を内部に形成することが可能である、十分な強度をもつように設計された高気圧筐体（例えば、カプセル状筐体）の使用によって作ることができる。高気圧筐体の形状は、耐圧性であるため、全体的に角がない丸みを帯びていることが好ましい。また高気圧筐体の材質は、軽量、高強度であることが好ましく、例えば強化プラスチック、炭素繊維複合材、チタン合金、アルミ合金などを挙げることができる。痛風患者は、上記高気圧筐体内で酸素ガスもしくは空気とともに水素ガスを含む、痛風の症状を改善および／または症状の悪化を抑制するのための組成物の投与を受けることができる。 The high-pressure environment is capable of injecting, for example, the hydrogen gas-containing gas (e.g., hydrogen-containing oxygen or air) into the interior to form a high pressure that exceeds the standard atmospheric pressure and is 7.0 atmospheres or less. , can be made through the use of a hyperbaric enclosure (eg, a capsule-like enclosure) designed to have sufficient strength. Since the shape of the high-pressure housing is pressure resistant, it is preferable that the entire shape is rounded without corners. Moreover, the material of the high-pressure housing is preferably lightweight and high-strength, and examples thereof include reinforced plastics, carbon fiber composite materials, titanium alloys, and aluminum alloys. A gout patient can be administered a composition containing hydrogen gas with oxygen gas or air in the hyperbaric enclosure to improve symptoms and/or prevent exacerbation of gout symptoms.
本発明の組成物による痛風の処置の際には、十分な治療効果と安全性が確認された水素ガス生成装置、水素水生成装置、又は水素ガス添加装置（例えば、上記の水素ガス供給装置（もしくは気体状水素吸入装置）、水素添加器具（もしくは水素水生成装置）、非破壊的水素含有器（水素透過性バッグに封入された点滴液などの生体適用液に非破壊的に水素ガスを溶解する装置）などの装置）を使用することが望ましい。 When treating gout with the composition of the present invention, a hydrogen gas generator, a hydrogen water generator, or a hydrogen gas addition device (for example, the above hydrogen gas supply device (for example, the above hydrogen gas supply device ( or gaseous hydrogen inhaler), hydrogen adding device (or hydrogen water generator), non-destructive hydrogen containing device (hydrogen gas is non-destructively dissolved in a biologically applicable fluid such as a drip sealed in a hydrogen permeable bag. It is desirable to use a device such as a device that
以下の実施例によって本発明をさらに具体的に説明するが、本発明の技術的範囲はこれらの実施例に限定されるものではない。 The present invention will be described in more detail with reference to the following examples, but the technical scope of the present invention is not limited to these examples.
水素ガス吸入による痛風症状の改善および／または症状の悪化の抑制
＜症例１＞
（１）水素ガスの吸入がなかった際の病状
患者は日本人男性、２０２１年時点で５６歳。６年前に痛風発作を発症。日常より抗尿酸治療のために用いられるアロプリノールの投薬を行っていた。鎮痛剤（ロキソプロフェン）を使用し、痛みは和らいだものの、発症翌日は歩行困難であった。発症２日後以降は、鎮痛剤（ロキソプロフェン）を使用して、杖をついて歩ける状態となった。発症４日後以降は、鎮痛剤を使用しなくても、杖をついて歩ける状態であった。発症７日目で違和感あるものの、杖なしで歩ける状態となった。完全に症状が消えたのは発症１０日後であった。Hydrogen gas inhalation improves gout symptoms and/or suppresses exacerbation of symptoms <Case 1>
(1) Medical condition without hydrogen gas inhalation The patient is a Japanese male, 56 years old as of 2021. I had a gout attack 6 years ago. Allopurinol, which is used for antiuric acid treatment, was routinely administered. An analgesic (loxoprofen) was administered, and although the pain was relieved, she had difficulty walking the day after the onset. Two days after the onset, he was able to walk with a cane after taking an analgesic (loxoprofen). Four days after the onset, the patient was able to walk with a cane without using analgesics. On the 7th day after the onset, she was able to walk without a cane, although she felt a sense of discomfort. It was 10 days after the onset that the symptoms disappeared completely.
（２）水素ガス吸入効果
患者は（１）の患者と同一人物である。日常より抗尿酸治療のために用いられるアロプリノールの投薬を行っていた。２０２１年８月３０日に痛風発作発症後、急激に足指の関節の痛みが増し、数時間後には歩行困難となった。発症した日に鎮痛剤（ロキソプロフェン）を服用した。同日にＭｉＺ株式会社（鎌倉市大船）の水素ガス吸入機（Ｊｏｂｓ－ｍｉｎｉ、水素濃度約２％～５％、１００％水素発生量は３０ｍｌ／ｍｉｎ）を用いて水素ガス吸入を開始した。水素ガスの吸入時間は一日当たり３時間から４時間であった。発症１日後には痛みは軽減し、杖をついて歩ける状態となった。発症２日後には鎮痛剤が不要となり、杖なしで歩ける状態となった。発症５日後にはほぼ症状が消えた。
（３）データまとめ(2) Hydrogen gas inhalation effect The patient is the same person as the patient in (1). Allopurinol, which is used for antiuric acid treatment, was routinely administered. After a gout attack on August 30, 2021, the pain in the joints of the toes suddenly increased, and after a few hours it became difficult to walk. An analgesic (loxoprofen) was taken on the day of onset. On the same day, hydrogen gas inhalation was started using a hydrogen gas inhaler (Jobs-mini, hydrogen concentration of about 2% to 5%, 100% hydrogen generation rate of 30 ml/min) manufactured by MiZ Co., Ltd. (Ofuna, Kamakura City). Hydrogen gas inhalation time was 3 to 4 hours per day. One day after the onset, the pain was relieved and she was able to walk with a cane. Two days after the onset of symptoms, painkillers became unnecessary, and she was able to walk without a cane. The symptoms almost disappeared 5 days after the onset.
(3) Data summary
本発明は、痛風患者に対し水素を投与するだけで痛風の、例えばヒト痛風において痛風を原因とする少なくとも患部の痛み、患部の発赤、患部の発熱、痛風結節、結石と結石に伴う痛み、および／または、これらの症状に伴う活動レベルの低下を含む症状を改善および／または症状の悪化を抑制することを可能にする。水素自体に、副作用が知られていないため、患者のＱＯＬを高めることができる。 By simply administering hydrogen to a gout patient, the present invention can be used to treat gout, for example, human gout. / Alternatively, it is possible to improve symptoms including a decrease in activity level associated with these symptoms and/or to suppress deterioration of symptoms. Since hydrogen itself has no known side effects, the QOL of patients can be improved.
Claims (7)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022070405A JP2023039899A (en) | 2021-09-09 | 2022-04-05 | Composition for mitigating gout and/or inhibiting symptoms of gout from worsening |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021167053A JP7414203B2 (en) | 2021-09-09 | 2021-09-09 | Composition for improving gout and/or suppressing worsening of symptoms |
| JP2022070405A JP2023039899A (en) | 2021-09-09 | 2022-04-05 | Composition for mitigating gout and/or inhibiting symptoms of gout from worsening |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021167053A Division JP7414203B2 (en) | 2021-09-09 | 2021-09-09 | Composition for improving gout and/or suppressing worsening of symptoms |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2023039899A true JP2023039899A (en) | 2023-03-22 |
Family
ID=85613723
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021167053A Active JP7414203B2 (en) | 2021-09-09 | 2021-09-09 | Composition for improving gout and/or suppressing worsening of symptoms |
| JP2022070405A Pending JP2023039899A (en) | 2021-09-09 | 2022-04-05 | Composition for mitigating gout and/or inhibiting symptoms of gout from worsening |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021167053A Active JP7414203B2 (en) | 2021-09-09 | 2021-09-09 | Composition for improving gout and/or suppressing worsening of symptoms |
Country Status (1)
| Country | Link |
|---|---|
| JP (2) | JP7414203B2 (en) |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008031164A (en) * | 2006-07-07 | 2008-02-14 | Daiichi Sankyo Healthcare Co Ltd | Pharmaceutical composition for preventing or treating hyperuricemia or disease caused thereby |
| US20090042887A1 (en) * | 2007-01-19 | 2009-02-12 | Tap Pharmaceutical Products, Inc. | Methods for Preventing or Reducing the Number of Gout Flares Using Xanthine Oxidoreductase Inhibitors and Anti-Inflammatory Agents |
| TWI569816B (en) * | 2014-04-18 | 2017-02-11 | 林信湧 | Inhalation-type pharmaceutical composition for gout and preparation method thereof |
| JP6800492B2 (en) * | 2018-06-29 | 2020-12-16 | ＭｉＺ株式会社 | Composition for suppressing or alleviating cancer pain containing hydrogen |
| CN111067911A (en) * | 2018-10-18 | 2020-04-28 | 刘琦 | Medical application of pulsatilla saponin B4 in resisting acute gouty arthritis |
| JP6971486B2 (en) * | 2019-06-10 | 2021-11-24 | ＭｉＺ株式会社 | Composition for improving symptoms of spinal cord injury |
| JP2021109860A (en) | 2020-01-15 | 2021-08-02 | ＭｉＺ株式会社 | Molecular hydrogen-containing composition for promotion of postoperative recovery |
-
2021
- 2021-09-09 JP JP2021167053A patent/JP7414203B2/en active Active
-
2022
- 2022-04-05 JP JP2022070405A patent/JP2023039899A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023039876A (en) | 2023-03-22 |
| JP7414203B2 (en) | 2024-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2022159439A (en) | Molecular hydrogen-containing composition for promotion of postoperative recovery | |
| JP6800492B2 (en) | Composition for suppressing or alleviating cancer pain containing hydrogen | |
| JP2021113239A (en) | Composition for improvement or prevention of symptoms of parkinson's disease | |
| JP6628449B1 (en) | Composition for controlling or reducing obstructive airway disease | |
| JP7414203B2 (en) | Composition for improving gout and/or suppressing worsening of symptoms | |
| JP6972449B2 (en) | Molecular hydrogen-containing composition for preventing and / or ameliorating inflammatory bowel disease | |
| US10076539B2 (en) | Pharmaceutical use of potassium hydroxide | |
| US20210275576A1 (en) | Molecular hydrogen-containing composition for prevention and/or improvement of genetic disorder | |
| US20210268017A1 (en) | Molecular hydrogen-containing composition for prevention and/or improvement of pneumonia | |
| JP2020015687A (en) | Composition for treating schizophrenia | |
| JP7220339B1 (en) | Composition for improving sudden deafness and/or suppressing worsening of symptoms | |
| JP7409586B2 (en) | Composition for improving myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and/or fibromyalgia (FM) and/or suppressing worsening of symptoms | |
| JP2024072231A (en) | Compositions and methods for preventing or ameliorating amyotrophic lateral sclerosis (ALS) and/or symptoms associated with ALS | |
| JP7366331B2 (en) | Compositions and methods for preventing and/or ameliorating organ-specific autoimmune diseases | |
| US20200368272A1 (en) | Composition for ameliorating post-cerebral stroke sequela | |
| JP2023107764A (en) | Composition for improving aftereffect of viral infection and/or inhibiting deterioration of symptom | |
| JP2022049676A (en) | Composition containing molecular hydrogen for preventing and/or improving chronic inflammation | |
| JP2022136069A (en) | Molecular hydrogen-containing composition for preventing or improving osteoporosis | |
| JP7414202B2 (en) | Molecular hydrogen-containing composition for maintaining lung function during human lung cancer and/or improving lung function decline caused by human lung cancer | |
| US20230256007A1 (en) | Composition for improving sequelae of viral infection and/or reducing worsening of symptoms | |
| JP2024004427A (en) | Composition and method for preventing or improving side reaction after vaccination | |
| JP2023031181A (en) | Molecular hydrogen-containing composition for preventing and/or ameliorating pneumonia | |
| US20230310496A1 (en) | Compositions and methods for preventing and/or ameliorating organ-specific autoimmune diseases | |
| JP2021151980A (en) | Molecular hydrogen-containing composition for prevention and/or improvement of encephalitis and/or meningitis and symptom associated with the encephalitis and/or meningitis |