JP2008031146A - Cough treatment composition - Google Patents
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- JP2008031146A JP2008031146A JP2007042526A JP2007042526A JP2008031146A JP 2008031146 A JP2008031146 A JP 2008031146A JP 2007042526 A JP2007042526 A JP 2007042526A JP 2007042526 A JP2007042526 A JP 2007042526A JP 2008031146 A JP2008031146 A JP 2008031146A
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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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
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
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Abstract
Description
本発明は、咳治療用組成物に関し、さらに詳細には、テオブロミンを有効成分として含有する咳治療用組成物に関する。 The present invention relates to a composition for treating cough, and more particularly, to a composition for treating cough containing theobromine as an active ingredient.
咳は、健康な人から共通的に現れる防御的な反射過程であるが、多様な疾患による持続的な咳は、患者の生活の質を軽減させ悪化させる。 Cough is a defensive reflex process that commonly appears in healthy people, but persistent cough due to various diseases reduces and exacerbates the patient's quality of life.
いままで広く利用されている鎮咳成分としては、コデイン（麻薬類）とデキストロメトルファンなどがある。このような鎮咳成分は、主に中枢神経に作用するものである。しかしながら、中枢神経に作用する鎮咳剤は、たびたび鎮静作用や胃腸障害のような好ましくないか、又は過度な副作用があるという問題がある。したがって、安全で、かつ末梢神経に作用して効果的に咳を緩和させることができる鎮咳剤の開発が試みられている。 Examples of antitussive components that have been widely used so far include codeine (drugs) and dextromethorphan. Such an antitussive component mainly acts on the central nervous system. However, antitussives that act on the central nervous system are often unfavorable or have excessive side effects such as sedation and gastrointestinal disorders. Accordingly, attempts have been made to develop antitussives that are safe and can effectively reduce cough by acting on peripheral nerves.
また、咳症状を誘発させる原因疾患としては、慢性閉鎖性肺疾患（慢性気管支炎、肺気腫）、気管支ぜんそく、肺ガン、瀰満性てんかん性肺疾患、気管支拡張症、後鼻漏、胃食道逆流など多様であるが、そのような原因疾患により、鎮咳剤の咳緩和効果が異って現れることがあるため、原因疾患に応じる鎮咳剤を開発する必要性がある。 The causative diseases that induce cough symptoms include chronic obstructive pulmonary disease (chronic bronchitis, emphysema), bronchial asthma, lung cancer, satiety epileptic lung disease, bronchiectasis, retronasal discharge, gastroesophageal reflux However, there is a need to develop an antitussive agent corresponding to the causative disease because the cough mitigating effect of the antitussive agent may appear differently depending on the causative disease.
本発明は、上述の問題点に鑑みてなされたもので、その目的は、安全で、かつ末梢神経に作用して、ぜんそく、後鼻漏及び胃食道逆流のような原因疾患により誘発される咳症状を効果的に緩和させることができる咳治療用組成物を提供することにある。 The present invention has been made in view of the above-mentioned problems, and its object is to provide a cough that is safe and acts on peripheral nerves and is induced by causative diseases such as asthma, retronasal discharge, and gastroesophageal reflux. The object is to provide a composition for treating cough that can effectively relieve symptoms.
本発明の技術的課題は、以上で言及した技術的課題に制限されず、言及していない他の技術的課題らは、以下の記載から当業者にとって明確に理解できるであろう。 The technical problems of the present invention are not limited to the technical problems mentioned above, and other technical problems that are not mentioned will be clearly understood by those skilled in the art from the following description.
上記の目的を達成すべく、本発明の一実施例に係る咳治療用組成物は、組成物の総重量を基準に、テオブロミン化合物又はその薬学的に許容可能な塩８０〜９９重量％と、滑沢剤１〜２０重量％と、を含む。 To achieve the above object, a composition for treating cough according to one embodiment of the present invention comprises, based on the total weight of the composition, 80 to 99% by weight of the theobromine compound or a pharmaceutically acceptable salt thereof, 1 to 20% by weight of a lubricant.
その他、実施例の具体的な事項は、詳細な説明及び図面に含まれている。 In addition, specific items of the embodiments are included in the detailed description and the drawings.
本発明の利点及び特徴、そしてそれらを達成する方法は、添付する図面と共に詳細に後述されている実施例を参照すると、明確になるはずである。しかしながら、本発明は、以下に開示される実施例に限定されるものではなく、互いに異なる多様な形態で具現されることができ。本実施例は、本発明の開示が完全になるように、本発明の属する技術分野における通常の知識を有した者に発明の範疇を完全に知らせるために提供されているものであり、本発明は、請求項の範疇範により定義されるのみである。 Advantages and features of the present invention, and methods for achieving them, will become apparent with reference to the embodiments described in detail below in conjunction with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below, and can be embodied in various different forms. This embodiment is provided in order to make the scope of the present invention completely known to those skilled in the art to which the present invention pertains so that the disclosure of the present invention is complete. Are only defined by the scope of the claims.
本発明に係る咳治療用組成物は、ぜんそく、後鼻漏、胃食道逆流のような原因疾患により誘発される咳の症状を緩和する効果が優れており、異常反応が少ないため、安全に服用することができる。 The composition for treating cough according to the present invention is excellent in the effect of alleviating cough symptoms induced by causative diseases such as asthma, postnasal drip, gastroesophageal reflux, and has few abnormal reactions. can do.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明の一実施例に係る咳治療用組成物は、有効成分としてテオブロミン（Ｔｈｅｏｂｒｏｍｉｎｅ）を含む。このようなテオブロミンは、テオブロミン遊離塩基の形態であるか、又はテオブロミンの薬学的に許容可能な塩形態であり得る。 The composition for treating cough according to one embodiment of the present invention includes theobromine as an active ingredient. Such theobromine can be in the form of theobromine free base or a pharmaceutically acceptable salt form of theobromine.
テオブロミンは、天然メチルキサンチンアルカロイドであって、茶葉（テアシネンシス（Ｔｈｅａ ｓｉｎｅｎｓｉｓ））、カカオ実（テオブロマカカオ（Ｔｈｅｏｂｒｏｍａ ｃａｃａｏ））及びコーヒー実（コーヒーアラビカ（Ｃｏｆｆｅａ ａｒａｂｉｃａ））から発見されるものと知られている。 Theobromine is a natural methylxanthine alkaloid known to be found in tea leaves (Thea sinensis), cacao fruit (Theobroma cacao) and coffee fruit (coffee arabica). ing.
化１で表されるとおり、テオブロミンは、異種原子環天然物であって、苦味の有る白色結晶粉末で、溶解度は極性である。２個の芳香族異種原子環に分布されている４個の窒素原子は、プリン塩基から由来した物質の特性を有する。テオブロミンは、４個の窒素のうち、２個の窒素原子がメチル化し、残りの２個の窒素原子は、ピリミジン塩基形態の配列を有する。それは、強い相互作用の能力（例えば塩基性を有して陽性子と結合し得る能力）を有する遊離した各々の電子対を含む。 As represented by Chemical Formula 1, theobromine is a heteroatom natural product, a white crystalline powder having a bitter taste, and its solubility is polar. The four nitrogen atoms distributed in the two aromatic heteroatomic rings have the properties of substances derived from purine bases. Theobromine has two nitrogen atoms methylated out of four nitrogens, and the remaining two nitrogen atoms have a pyrimidine base form sequence. It contains each free electron pair that has a strong interaction ability (eg, the ability to have basicity and bind positives).
このようなテオブロミン又はその薬学的に許容可能な塩は、末梢神経に作用して効果的に咳を鎮静することができる。本発明者らは、テオブロミン及びその薬学的に許容可能な塩と、これを含む咳治療用組成物に対する研究を重ねた結果、テオブロミン又はその薬学的に許容可能な塩は、特に、ぜんそく、後鼻漏及び胃食道逆流のような原因疾患により誘発された咳症状を緩和させるのに効果的であることを見出した。 Such theobromine or a pharmaceutically acceptable salt thereof can act on peripheral nerves to effectively sedate cough. The present inventors have conducted research on theobromine and a pharmaceutically acceptable salt thereof and a composition for treating cough containing the same, and as a result, theobromine or a pharmaceutically acceptable salt thereof is particularly asthma, It has been found effective in alleviating cough symptoms induced by causative diseases such as rhinorrhea and gastroesophageal reflux.
本発明の一実施例において、テオブロミン又はその薬学的に許容可能な塩は、組成物の総重量を基準に約８０〜９９重量％含まれる。これは、適切な剤形を維持し、かつ、薬効を最適化するための含量範囲である。また、有効成分としてテオブロミンは、１回服用量として約３００〜５００ｍｇになるように組成物内に含み得る。 In one embodiment of the invention, theobromine or a pharmaceutically acceptable salt thereof comprises about 80-99% by weight, based on the total weight of the composition. This is a content range for maintaining an appropriate dosage form and optimizing drug efficacy. Further, theobromine as an active ingredient can be included in the composition so as to be about 300 to 500 mg as a single dose.
テオブロミンに対する薬理効果などは、本出願の譲受人に共同譲渡された韓国公開特許第１０−２００１−００５６４２号に詳細に記載されており、前記特許の内容は、本明細書に完全に開示されているように、援用により組み含まれる。 The pharmacological effect on theobromine is described in detail in Korean Patent No. 10-2001-005642 co-assigned to the assignee of the present application, and the contents of the patent are fully disclosed in this specification. As such, it is included by incorporation.
また、本発明の一実施例に係る咳治療用組成物には、滑沢剤を含む。滑沢剤は、組成物内の固形成分の流れ、すなわち流動性を円滑にすることにより、剤形が安定的に形成され得るようにする。 The composition for treating cough according to one embodiment of the present invention includes a lubricant. Lubricants facilitate the formation of a stable dosage form by facilitating the flow, i.e., fluidity, of the solid components within the composition.
このような滑沢剤は、組成物の総重量を基準に約１〜２０重量％の含量で含む。このような含量は、有効成分のテオブロミンの薬効を阻害せず、かつ、有効成分のテオブロミン又はその薬学的に許容可能な塩やその他の固形成分の流動性などを考慮したものである。 Such lubricants are included at a content of about 1-20% by weight, based on the total weight of the composition. Such content does not inhibit the efficacy of the active ingredient theobromine, and takes into consideration the fluidity of the active ingredient theobromine or a pharmaceutically acceptable salt thereof and other solid ingredients.
この他にも、通常、咳治療用組成物に用いられることのできる添加物が、本発明の目的範囲内でさらに添加され得る。例えば、乳糖、とうもろこし澱粉、未結晶セルロースなどが用いられることができる。 In addition to these, additives that can usually be used in a composition for treating cough can be further added within the scope of the present invention. For example, lactose, corn starch, amorphous cellulose and the like can be used.
このような咳治療用組成物は、１日に１回〜４回程度服用できるが、症状と年齢により適切に調節され得ることはもちろんである。 Such a composition for treating cough can be taken about 1 to 4 times a day, but can be appropriately adjusted depending on symptoms and age.
本発明の一実施例に係る咳治療用組成物は、カプセル形態であっても良い。このとき、カプセルの表皮は、当業界において一般的に用いられるものを使用することができ、例えば、ゼラチンなどで作ることができる。 The composition for treating cough according to one embodiment of the present invention may be in capsule form. At this time, as the skin of the capsule, those generally used in the art can be used, and for example, it can be made of gelatin or the like.
以下では、テオブロミンの製造方法を例示的に説明する。テオブロミンは、天然材料から抽出して得ることもできるが、次のような製造工程により合成することもできる。 Below, the manufacturing method of theobromine is illustrated exemplarily. Theobromine can be obtained by extraction from natural materials, but can also be synthesized by the following production process.
第１工程：縮合（ｃｏｎｄｅｎｓａｔｉｏｎ）工程1st process: Condensation process
シアン酢酸を酢酸無水物の存在下にモノメチルウレアと反応させ、シアノ−アセチル−メチル−ウレア（Ｃｙａｎｏ−ａｃｅｔｙｌ−ｍｅｔｈｙｌ−ｕｒｅａ：ＣＡＭＵ）を形成する。 Cyanacetic acid is reacted with monomethylurea in the presence of acetic anhydride to form cyano-acetyl-methyl-urea (CAMU).
第２工程：環化工程Second step: cyclization step
第１工程から得られたＣＡＭＵを水酸化ナトリウムの存在下で環化して、４−アミノ−３−メチル−ウラシル（４−ａｍｉｎｏ−３−ｍｅｔｈｙｌ−ｕｒａｃｉｌ：ＡＭＵ）のナトリウム塩を形成し、続けて硫酸希釈液で処理する。 The CAMU obtained from the first step is cyclized in the presence of sodium hydroxide to form the sodium salt of 4-amino-3-methyl-uracil (AMU) and continued Treat with dilute sulfuric acid.
第３工程：ブロム化工程Third step: Bromination step
第２工程から得られたＡＭＵをブロムと反応させて、４−アミノ−５−ブロモ−３−メチル−ウラシル（４−ａｍｉｎｏ−５−ｂｒｏｍｏ−３−ｍｅｔｈｙｌ−ｕｒａｃｉｌ：ＡＢＭＵ）を形成する。 The AMU obtained from the second step is reacted with bromo to form 4-amino-5-bromo-3-methyl-uracil (ABMU).
第４工程：アミノメチル化工程Fourth step: aminomethylation step
第３工程から得られたＡＢＭＵをモノメチルアミンと反応させて、４−アミノ−５−メチルアミノ−３−メチルウラシル（４−ａｍｉｎｏ−５−ｍｅｔｈｙｌａｍｉｎｏ−３−ｍｅｔｈｙｌｕｒａｃｉｌ：ＮＭＵ）を形成する。 ABMU obtained from the third step is reacted with monomethylamine to form 4-amino-5-methylamino-3-methyluracil (NMU).
第５工程：ホルミル化工程5th process: Formylation process
第４工程から得られたＮＭＵをギ酸と反応させ、水酸化ナトリウムの存在下で環化してテオブロミンナトリウム塩を形成し、続けて塩酸で処理して、テオブロミンを得る。 The NMU obtained from the fourth step is reacted with formic acid and cyclized in the presence of sodium hydroxide to form theobromine sodium salt, followed by treatment with hydrochloric acid to give theobromine.
このような方法により製造され得るテオブロミンを有効成分とするカプセル剤を次のように製造した。 Capsules containing theobromine which can be produced by such a method as an active ingredient were produced as follows.
通常、カプセル剤を製造する工程によって、テオブロミン９９重量％、滑沢剤としてステアリン酸マグネシウム１重量％からなるカプセル剤を製造した。このとき、テオブロミンの含量がそれぞれ３００ｍｇ、５００ｍｇになるように、２種類のカプセル剤を製造した。 Usually, a capsule comprising 99% by weight of theobromine and 1% by weight of magnesium stearate as a lubricant was produced by a process for producing the capsule. At this time, two types of capsules were produced so that the theobromine contents were 300 mg and 500 mg, respectively.
以下では、製造されたカプセル剤の効能に対する臨床実験例を説明する。 Below, the clinical experiment example with respect to the effect of the manufactured capsule is demonstrated.
咳症状の緩和効果Alleviation of cough symptoms
前もって製造されたカプセル剤で被験者１２０人に対してＣＱＬＱ（Ｃｏｕｇｈ ｓｐｅｃｉｆｉｃ Ｑｕａｌｉｔｙ ｏｆ Ｌｉｆｅ Ｑｕｅｓｔｉｏｎｎａｉｒｅｓ，Ｃｈｅｓｔ，１２１，４，Ａｐｒｉｌ，２００２，Ｔｏｄｄ Ｍ．Ａｄａｍｓ）の変化量を利用して臨床実験を行った。それぞれのカプセル剤に対する被験者らは、７日間、一日２回服用した。ＣＱＬＱは、下記の表１に記載された２８ケの質問項目に対する書面照射方式で、それぞれ質問項目は４点尺度のリカートスケール（１．全く当てはまらない、２．当てはまらない、３．ほぼ当てはまる、４．完全に当てはまる）で測定した。 A clinical experiment was conducted on 120 subjects by using the amount of change of CQLQ (Choosing Specific Quality of Life Questionnaires, Chest, 121, 4, April, 2002, Todd M. Adams) with 120 capsules prepared in advance. Subjects for each capsule were taken twice a day for 7 days. CQLQ is a document irradiation method for 28 question items described in Table 1 below, and each question item is a four-point scale recurt scale (1. Not applicable at all 2. Not applicable 3. Almost true 4 Measured completely).
被験者は、ぜんそく、後鼻漏、胃食道逆流のような呼吸器疾患を有した咳患者であり、具体的な条件は次のとおりである。 The test subject was a cough patient having respiratory diseases such as asthma, postnasal drip, gastroesophageal reflux, and specific conditions were as follows.
＜被験者の選定基準＞<Subject selection criteria>
１．万１８才以上６０才以下の成人
２．気管支ぜんそく、後鼻漏、胃食道逆流のうち、何れか１つ以上の疾患により咳症状の発生した者
３．咳症状があって内科的治療を要する者として、時間当り平均３回以上の発作性咳（ｃｏｕｇｈｉｎｇ ｓｐｅｌｌ）症状がある者
４．生殖力のある男性及び妊娠かのうな女性の場合には、臨床試験期間の間、適切な承認された避姙法を使用する意志のある者
５．妊娠可能な女性の場合、臨床試験の登録前７日以内に血清妊娠検査結果が陰性である者
６．本臨床試験に自意で参加を決定し、書面にて同意した者
７．信頼でき、試験期間の間、精一杯協調し、制限事項を遵守する者
1. 1. Adults aged 18 to 60 years old 2. A person who has cough symptoms due to any one or more of bronchial asthma, retronasal discharge, and gastroesophageal reflux. 3. Those who have cough symptoms and require medical treatment, who have an average of 3 or more coughing spells per hour 4. In the case of fertile men and women who are pregnant, willing to use appropriate approved evacuation methods for the duration of the clinical trial. In the case of women who can get pregnant, those who have a negative serum pregnancy test result within 7 days before the registration of the clinical trial. 6. A person who decides to participate in this clinical study voluntarily and agrees in writing. A person who can be trusted and cooperates thoroughly during the test period and observes the restrictions.
本臨床試験は、ＧＣＰ（Ｇｏｏｄ Ｃｌｉｎｉｃａｌ Ｐｒａｃｔｉｃｅ）ガイドラインにしたがって行われた。本臨床試験に参加して投薬された全ての被験者１２０人を含むＩＴＴ（Ｉｎｔｅｎｄｅｄ Ｔｏ Ｔｒｅａｔｍｅｎｔ）分析と１０８人に対するＰＰ（Ｐｅｒ Ｐｒｏｔｏｃｏｌ）分析を実施した。 This clinical trial was conducted according to GCP (Good Clinical Practice) guidelines. An ITT (Intended To Treatment) analysis including 120 subjects who participated in this clinical study and a PP (Per Protocol) analysis for 108 subjects were performed.
その結果、図１に示すように、ＩＴＴ分析時、３００ｍｇ容量のカプセル剤を服用した試験１群のＣＱＬＱ変化量は、６．６８±９．９５点、５００ｍｇ容量のカプセル剤を服用した試験２群の場合には、７．４５±９．０６点、偽薬対照群は、２．６５±７．１５点であり、試験１群、試験２群の偽薬対照群対比検定結果は、それぞれｐ（ｓｉｇｎｉｆｉｃａｎｃｅ ｐｒｏｂａｂｉｌｉｔｙ）＝０．０４１４、ｐ＝０．０１０３と調査されて、偽薬対比して試験薬３００ｍｇ、５００ｍｇ両方とも優れたことを確認した。ＰＰ分析結果も、ＩＴＴ分析結果と似ており、試験１群、試験２群の偽薬対比検定結果は、それぞれｐ＝０．０４１０、ｐ＝０．０５０５と調査されて、ｐ＜０．１の範囲内で評価するとき、偽薬対比試験群の症状緩和効果が優れていることを確認した。 As a result, as shown in FIG. 1, the amount of change in CQLQ of Test 1 group taking a 300 mg capsule during ITT analysis was 6.68 ± 9.95 points, Test 2 taking a 500 mg capsule. In the case of the group, 7.45 ± 9.06 points, and the placebo control group is 2.65 ± 7.15 points. (significance probability) = 0.0414, p = 0.0103, confirming that both 300 mg and 500 mg of the test drug were superior to the placebo. The PP analysis results are also similar to the ITT analysis results, and the placebo comparison test results of Study Group 1 and Study 2 were investigated as p = 0.0410 and p = 0.0505, respectively, and p <0.1. When evaluated within the range, it was confirmed that the symptom alleviation effect of the placebo comparison test group was excellent.
異常反応発現症例率Abnormal response rate
本臨床試験期間の間、異常反応は、ＩＴＴ対象者１２０人中５３人で１１２件発生し（発現症例率４４．１７％）、試験１群では、１６人で３４件、試験２群では、１６人で２６件の異常反応が発生したと評価され（発現症例率それぞれ４０％）、偽薬対照群では、２１人で５２件の異常反応が発生したと評価された（発現症例率５２．５％）。発生した異常反応をカテゴリー別に分類した結果、最も多い異常反応は「神経（Ｎｅｕｒｏｌｏｇｙ）」系統（４０件）で最も多く、そのうち、３０件が「頭痛（ｈｅａｄａｃｈｅ）」であった。「胃腸（Ｇａｓｔｒｏｉｎｔｅｓｔｉｎａｌ）」系統の異常反応が３６件であり、「全身症状（Ｃｏｎｓｔｉｔｕｔｉｏｎａｌ ｓｙｍｐｔｏｍ）」が１６件であるなどの順で評価された。全体１２０件の異常反応のうち、重大な異常反応は一件もなく、９件の異常反応が重症（３等級）と評価された。重症として評価された異常反応には、頭痛が３件、腹部膨脹（ｄｉｓｔｅｎｓｉｏｎ）２件、下痢、不眠症、顔面浮腫、吐き気各１件ずつと評価され、全て試験薬と関連のある可能性があるか、又は関連のあるものと評価された。重症と評価された９件の異常反応のうち、４件は、偽薬対照群から発生した異常反応と確認された。 During this clinical trial period, 112 abnormal reactions occurred in 53 out of 120 ITT subjects (incidence case rate: 44.17%). In Study 1 group, 34 cases occurred in 16 people, in Study 2 group, It was evaluated that 26 abnormal reactions occurred in 16 people (incidence case rate 40% each), and in the placebo control group, 52 abnormal reactions were evaluated in 21 people (expression case rate 52.5). %). As a result of classifying the abnormal reactions that occurred, the most common abnormal reactions were the most in the “Neurology” strain (40 cases), of which 30 were “headaches”. The number of abnormal reactions in the “Gastrointestinal” strain was 36, and “Constitutional symptom” was evaluated in 16 cases. Of the 120 abnormal responses in total, none were serious, and 9 abnormal responses were rated as severe (grade 3). Abnormal reactions assessed as severe were assessed as 3 headaches, 2 abdominal distentions, 1 diarrhea, insomnia, facial edema, and nausea, all possibly related to study drug. Evaluated as being or relevant. Of the 9 abnormal responses rated as severe, 4 were identified as abnormal responses originating from the placebo control group.
また、活力の徴候、実験実績の検査などの各項目の投薬前後の比較（ｐａｉｒｅｄｔ−ｔｅｓｔ）では、特別な異常反応は観察されなかった。 In addition, no special abnormal reaction was observed in the comparison between before and after the administration of each item such as vital signs and examination of experimental results.
このように、本発明の一実施例に係る咳治療用組成物は、ぜんそく、後鼻漏、胃食道逆流による咳症状に対する緩和効果が優れており、安全であることが分かる。 Thus, it can be seen that the composition for treating cough according to one embodiment of the present invention is excellent in alleviating cough symptoms due to asthma, postnasal drip, and gastroesophageal reflux, and is safe.
上述した本発明の好ましい実施の形態は、例示の目的のために開示されたものであり、本発明の属する技術の分野における通常の知識を有する者であれば、本発明の技術的思想を逸脱しない範囲内で、様々な置換、変形、及び変更が可能であり、このような置換、変更などは、特許請求の範囲に属するものである。 The above-described preferred embodiments of the present invention are disclosed for the purpose of illustration, and those having ordinary knowledge in the technical field to which the present invention pertains depart from the technical idea of the present invention. Various substitutions, modifications, and alterations are possible within the scope of not being included, and such substitutions, alterations, and the like belong to the scope of the claims.
Claims (5)
下記の式で表されるテオブロミン化合物又はその薬学的に許容可能な塩８０〜９９重量％と、
滑沢剤１〜２０重量％と、を含む咳治療用組成物。
Theobromine compound represented by the following formula or a pharmaceutically acceptable salt thereof in an amount of 80 to 99% by weight;
A composition for treating cough, comprising 1 to 20% by weight of a lubricant.
The composition for cough treatment according to claim 1, wherein the composition is a capsule preparation.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020060069901A KR20080009994A (en) | 2006-07-25 | 2006-07-25 | Compositions for treating of cough |
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| JP2008031146A true JP2008031146A (en) | 2008-02-14 |
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| JP2007042526A Pending JP2008031146A (en) | 2006-07-25 | 2007-02-22 | Cough treatment composition |
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| Country | Link |
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| JP (1) | JP2008031146A (en) |
| KR (1) | KR20080009994A (en) |
| CN (1) | CN101112383B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013536257A (en) * | 2010-08-27 | 2013-09-19 | バイオコピア リミテッド | Theobromine in combination with expectorants or mucolytic agents for use in therapy |
| RU2564904C2 (en) * | 2009-12-14 | 2015-10-10 | ИнФерст Хэлткэр Лимитед | Theobromine-decongestant combination and application thereof for treating cough |
| JP2016041748A (en) * | 2009-11-13 | 2016-03-31 | バイオコピア リミテッドＢｉｏｃｏｐｅａ Ｌｉｍｉｔｅｄ | Drug combination with theobromine and use thereof in therapy |
| US9308211B2 (en) | 2009-06-16 | 2016-04-12 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US9314465B2 (en) | 2009-06-16 | 2016-04-19 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US10016437B2 (en) | 2009-06-16 | 2018-07-10 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103263533B (en) * | 2013-05-31 | 2014-11-05 | 杨宏伟 | Theobromine composition for treating cough and application and preparation thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001518928A (en) * | 1997-03-26 | 2001-10-16 | コーボニツツ，デツゾー | Antitussive composition |
-
2006
- 2006-07-25 KR KR1020060069901A patent/KR20080009994A/en not_active Application Discontinuation
-
2007
- 2007-02-16 CN CN2007100798952A patent/CN101112383B/en active Active
- 2007-02-22 JP JP2007042526A patent/JP2008031146A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001518928A (en) * | 1997-03-26 | 2001-10-16 | コーボニツツ，デツゾー | Antitussive composition |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9308211B2 (en) | 2009-06-16 | 2016-04-12 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US9314465B2 (en) | 2009-06-16 | 2016-04-19 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US9675618B2 (en) | 2009-06-16 | 2017-06-13 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US9700561B2 (en) | 2009-06-16 | 2017-07-11 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| US10016437B2 (en) | 2009-06-16 | 2018-07-10 | Infirst Healthcare Limited | Drug combinations and uses in treating a coughing condition |
| JP2016041748A (en) * | 2009-11-13 | 2016-03-31 | バイオコピア リミテッドＢｉｏｃｏｐｅａ Ｌｉｍｉｔｅｄ | Drug combination with theobromine and use thereof in therapy |
| RU2564904C2 (en) * | 2009-12-14 | 2015-10-10 | ИнФерст Хэлткэр Лимитед | Theobromine-decongestant combination and application thereof for treating cough |
| JP2013536257A (en) * | 2010-08-27 | 2013-09-19 | バイオコピア リミテッド | Theobromine in combination with expectorants or mucolytic agents for use in therapy |
| JP2016196504A (en) * | 2010-08-27 | 2016-11-24 | バイオコピア リミテッドＢｉｏｃｏｐｅａ Ｌｉｍｉｔｅｄ | Theobromine in combination with expectorant or mucolytic for use in therapy |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101112383B (en) | 2010-05-26 |
| CN101112383A (en) | 2008-01-30 |
| KR20080009994A (en) | 2008-01-30 |
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