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KR20030076287A - Remedy for hemicrania - Google Patents

Remedy for hemicrania Download PDF

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Publication number
KR20030076287A
KR20030076287A KR10-2003-0014985A KR20030014985A KR20030076287A KR 20030076287 A KR20030076287 A KR 20030076287A KR 20030014985 A KR20030014985 A KR 20030014985A KR 20030076287 A KR20030076287 A KR 20030076287A
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migraine
caffeine
ibuprofen
therapeutic agent
prophylactic
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키타야마히데오
마츠모토카즈오
히라노마사노리
오타키히로시
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에스에스 세야쿠 가부시키 가이샤
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52Purines, e.g. adenine
    • A61K31/522Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

본 발명은 이부프로펜 및 카페인류를 유효 성분으로서 함유하는 편두통의 예방 또는 치료제로 관한다.The present invention relates to a prophylactic or therapeutic agent for migraine, which contains ibuprofen and caffeine as active ingredients.

이 편두통의 예방 또는 치료제를 이용함으로써 편두통 및 그에 따른 오심, 구토, 빛이나 소리에 과민반응을 일으키는 것을 완화할 수 있다.By using this prophylactic or therapeutic agent for migraine headaches, it is possible to alleviate the sensitization of migraine headaches and the resulting nausea, vomiting, light or sound.

Description

편두통 치료제 {REMEDY FOR HEMICRANIA}Migraine treatments {REMEDY FOR HEMICRANIA}

본 발명은 편두통의 예방 또는 치료제로 관한 것이다.The present invention relates to a prophylactic or therapeutic agent for migraine headaches.

편두통은 앞쪽 옆머리가 지끈지끈 아픈 두통으로, 그의 4할은 한쪽만이 아니라 양쪽이 아프다. 그의 빈도는 한 달에 1∼2회, 많을 때에 1 주일에 1회, 반복하여 일어나며, 그것은 4∼72시간 계속된다. 그의 수반하는 증상으로서 오심, 구토이외에 빛이나 소리에 과민 반응을 일으키는 사람도 있다. 또한, 편두통이 일어나기 전에, 섬휘안점(scintillating scotoma) 등의 징조 현상이 있는 사람도 있다.Migraine is a painful headache in the front side, and his 40% hurt on both sides. His frequency occurs once or twice a month, once a week at many times, and repeats for four to 72 hours. His accompanying symptoms include hypersensitivity to light and sound in addition to nausea and vomiting. In addition, some people have symptoms such as scintillating scotoma before migraine occurs.

일본인의 약 8%는 편두통을 갖고 있다 하며, 그의 치료에는 수 %의 사람들은 의료기관에서 진찰을 받지만, 나머지의 반의 사람들은 대중약(OTC)을 복용하고, 그리고 어느 것도 하지 않는 나머지의 사람들은 참으면서 아픔이 지나가는 것을 기다리며 보낸다고 한다.About 8% of Japanese have migraine headaches, and in his treatment, a few percent of people see a medical institution, but the other half take OTC, and the rest do nothing. It is said to spend waiting for the pain to pass by.

편두통의 발생기서 및 원인에는, ①혈관설, ②신경설, ③3차(三叉)신경혈관설 등이 있으며, 현재 확정되어 있지 않지만, 어느 설에 있어서도 머리 내의 혈류가 변화하고 있는 것이 인정되고 있다. 따라서, 일본에서는, 머리 내의 혈관 수축작용을 가지는 졸미토립탄 제제, 숙신산 수마토립탄 제제, 또는 타르타르산 에르고타민 및 무수 카페인 배합 제제가 "편두통"의 효능·효과를 갖는 약제로서 존재한다.The causes and causes of migraine headaches include (1) vasculosis, (2) neural theory, and (3) tertiary neurovascular theory. Although it is not currently determined, it is recognized that blood flow in the head changes in any theory. Therefore, in Japan, zolmitriptan preparations having a vasoconstrictive action in the head, succinate sumatriptan preparations, or tartaric acid ergotamine and caffeine anhydrous formulations exist as drugs having the efficacy and effect of "migraine headache".

또한, 미국에서는, 아세토아미노펜, 아스피린 및 카페인을 유효 성분으로 하는 "Excedin Migraine" (Bristol-Myers 사)나, 이부프로펜을 유효 성분으로 하는 " Advil Migraine"(Whitehall-Robins 사) 및 "Mortrin Migraine Pain Caplets" (NcNeil Consumer 사)가 "편두통"의 효능·효과를 갖는 비처방전약으로서 판매되고 있으며, 일본에서도, 대중약으로서 판매되고 있는 이부프로펜이나 아세토아미노펜 등이 "편두통"의 효능·효과는 없는 것의 "두통"의 효능·효과를 가지고 있는 것으로부터, 편두통에 대해서 사용되고 있다.In the United States, "Excedin Migraine" (Bristol-Myers), which contains acetoaminophen, aspirin, and caffeine as active ingredients, "Advil Migraine" (Whitehall-Robins, Inc.), and "Mortrin Migraine Pain Caplets", which contain ibuprofen as an active ingredient. "NcNeil Consumer Co., Ltd." is sold as a non-prescription drug having the efficacy and effect of "migraine", and ibuprofen and acetoaminophen, which are sold as popular drugs in Japan, do not have the effect and effect of "migraine". It has been used for migraines because it has the efficacy and effect of.

그러나, 졸미토립탄 제제 등에 대해서는, 순환기계에의 부작용, 예를 들면 협심증이나 심근경색을 악화시킬 우려가 있다는 문제가 있으며, 또한 이부프로펜이나 아세토아미노펜을 단독으로 사용하는 경우, 고도의 편두통의 사람에 대해서는 충분한 치료 효과가 얻지 못하고 있는 것이 현상이다.However, the zolmitriptan preparations and the like have a problem that the side effects to the circulatory system, for example, angina and myocardial infarction, may be aggravated, and when ibuprofen or acetoaminophen is used alone, it may cause severe migraine headaches. It is a phenomenon that sufficient therapeutic effect is not obtained.

본 발명은 편두통의 예방 또는 치료가 뛰어난 효과를 발휘하며, 더욱이 안전성이 높은 약제를 제공하는 것을 목적으로 한다.An object of the present invention is to provide an excellent effect of preventing or treating migraine headaches, and to provide a safe drug.

본 발명자들은, 이러한 실정을 감안하여 예의 연구한 결과, 해열 진통제인 이부프로펜과 카페인류를 조합해 사용하는 경우, 이부프로펜을 단독으로 사용했을 경우에 비해 현저한 편두통 치료 효과가 있어, 편두통의 예방 또는 치료제로서 유용한 것을 발견했다.The present inventors have made a thorough study in consideration of such circumstances, and when using a combination of ibuprofen and caffeine, which are antipyretic analgesics, the inventors have a remarkable migraine treatment effect as compared to using ibuprofen alone, and as a preventive or therapeutic agent for migraine headaches. Found something useful

즉, 본 발명은 이부프로펜 및 카페인류를 유효성분으로 함유하는 편두통의 예방 또는 치료제를 제공하는 것이다.That is, the present invention provides a prophylactic or therapeutic agent for migraine containing ibuprofen and caffeine as an active ingredient.

[발명을 실시하기 위한 최선의 형태]Best Mode for Carrying Out the Invention

이부프로펜, 즉 2-(4-이소부틸페닐)프로피온산은, ①만성 관절 류머티즘, 관절통 및 관절염, 신경통 및 신경염, 요통, 경완 증후군, 자궁부속기염, 월경 곤란증, 홍반(결절성 홍반, 다형 참출성 홍반, 원심성 환상 홍반) 등의 소염·진통, ②수술 및 외상 후의 소염·진통, ③급성 상기도염(급성 기관지염을 수반하는 급성 상기도염을 포함한다)의 해열·진통을 효능·효과로서 시판되고 있는 약제이다.Ibuprofen, i.e. 2- (4-isobutylphenyl) propionic acid, is characterized by ① chronic arthritis rheumatoid arthritis, arthralgia and arthritis, neuralgia and neuritis, low back pain, cramping syndrome, uterine adnexitis, dysmenorrhea, erythema (nodular erythema, polymorphic erythema, Anti-inflammatory and analgesic such as centrifugal annular erythema), ② anti-inflammatory and analgesic after surgery and trauma, and ③ antipyretic and analgesic of acute upper respiratory tract infection (including acute upper respiratory tract with acute bronchitis). .

본 발명의 이부프로펜은 2-(4-이소부틸페닐)프로피온산의 염, 예를 들면 나트륨, 칼륨, 마그네슘, 칼슘, 암모늄, 메틸글리카민, 더욱이 리진 등의 아미노산과의 염이어도 좋다.Ibuprofen of the present invention may be a salt of 2- (4-isobutylphenyl) propionic acid, for example, a salt with amino acids such as sodium, potassium, magnesium, calcium, ammonium, methylglycine, and lysine.

본 발명의 카페인류로서는, 카페인, 무수 카페인이외, 벤조산나트륨 카페인, 카페인 염산염, 시트르산 카페인 등을 들 수 있으며, 이들 중 무수 카페인이 바람직하다.Examples of caffeine of the present invention include caffeine and anhydrous caffeine, sodium benzoate caffeine, caffeine hydrochloride and citrate caffeine, and among these, caffeine anhydride is preferred.

본 발명의 약제는 상기 이부프로펜과 카페인류를 조합하여 이용하는 것이며,후기 실시예에 나타낸 바와 같이, 이부프로펜을 단독으로 투여했을 경우와 비교하여 현저히 편두통을 억제하는 효과를 발휘한다. 따라서, 본 발명의 약제는 편두통의 예방 또는 치료에 유효하다.The medicament of the present invention uses a combination of ibuprofen and caffeine, and exhibits an effect of significantly suppressing migraine headache as compared with the case of administering ibuprofen alone as shown in later examples. Thus, the medicaments of the present invention are effective for the prevention or treatment of migraine headaches.

본 발명의 편두통의 예방 또는 치료제에서의 이부프로펜과 카페인류의 사용형태는 특히 한정되는 것은 아니다.The form of the use of ibuprofen and caffeine in the prophylactic or therapeutic agent for migraine headache of the present invention is not particularly limited.

즉, 이부프로펜과 카페인류를 제제학적으로 허용될 수 있는 희석제, 부형제 등과 함께 혼합하여 단일 제제로 하는 것, 또는 양 약제를 각각 제제화하여 세트 (킷트)로 하는 것도 좋다. 또, 양 약제를 각각의 제제로 하는 경우에는 각각 다른 제형으로 하여도 좋다.That is, ibuprofen and caffeine may be mixed together with a pharmaceutically acceptable diluent, excipient, and the like to form a single preparation, or both drugs may be formulated and set (kit). In the case where both drugs are used as separate formulations, different dosage forms may be used.

본 발명의 편두통의 예방 또는 치료제는 용법에 따라 각종 제형의 의약품 제제로 할 수가 있으며, 이러한 제형으로서는 예를 들면, 산제, 과립제, 세립제, 정제, 캅셀제, 액제, 시럽제 등을 들 수가 있다. 또한, 성분의 방출이 제어되는 서방성 제제의 형태를 할 수도 있다.The prophylactic or therapeutic agent for migraine headaches according to the present invention can be used as a pharmaceutical preparation in various dosage forms, and examples of such dosage forms include powders, granules, fine granules, tablets, capsules, solutions, and syrups. It may also take the form of a sustained release formulation in which release of the component is controlled.

이들의 제제는 그의 제형에 따라 제제학적으로 허용되는, 부형제, 붕괴제, 결합제, 활택제, 희석제, 완충제, 안정화제, 용해 보조제 등의 의약품 첨가물과 적당히 혼합, 희석 또는 용해하고, 통상의 방법에 따라 제조할 수가 있다.These preparations are suitably mixed, diluted or dissolved with pharmaceutical additives such as excipients, disintegrants, binders, glidants, diluents, buffers, stabilizers, dissolution aids, etc., which are pharmaceutically acceptable according to their formulation, Can be produced accordingly.

예를 들면, 산제는 유효 성분(이부프로펜 및 카페인류)을 필요에 따라서 적당한 부형제, 활택제 등을 첨가하여 잘 혼합하여 조제하면 좋고, 정제 및 과립제는 유당, 백당, 설탕, 포도당, 만니톨 등의 당류, 결정 셀룰로오스 등의 부형제; 젤라틴, 알긴산나트륨, 히드록시프로필메틸셀룰로오스, 폴리비닐피롤리돈, 카르복시메틸셀룰로오스 등의 결합제; 카르복시메틸셀룰로오스 칼슘, 저치환도 히드록시프로필셀룰로오스, 탄산칼슘 등의 붕괴제; 스테아린산마그네슘, 경화 피마자유 등의 수소 첨가 식물유, 탈크 등의 활택제 등을 필요에 따라서 첨가하고, 통상의 방법에 따라서 조제하면 좋다. 또한, 정제는 필요에 따라서 코팅을 하여 필름 코팅정, 당의정 등으로 할 수 있다.For example, the powder may be prepared by mixing the active ingredients (ibuprofen and caffeine) as necessary by adding appropriate excipients, lubricants, and the like, and the tablets and granules are sugars such as lactose, white sugar, sugar, glucose, and mannitol. Excipients such as crystalline cellulose; Binders such as gelatin, sodium alginate, hydroxypropylmethyl cellulose, polyvinylpyrrolidone, and carboxymethyl cellulose; Disintegrating agents such as carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose, calcium carbonate; Hydrogenated vegetable oils, such as magnesium stearate and hardened castor oil, and lubricating agents, such as talc, are added as needed, and what is necessary is to prepare according to a conventional method. In addition, tablets may be coated as necessary to form a film-coated tablet, dragee, or the like.

또한, 본 발명의 편두통의 예방 또는 치료제로는 편두통의 예방·치료 효과에 영향을 미치지 않는 한 다른 약효성분을 배합할 수가 있으나, 특히, 위점막 보호 및 즉효성 등의 점으로부터, 수산화마그네슘, 산화마그네슘, 메타규산알루민산마그네슘, 탄산마그네슘 등의 제산제를 배합하는 것이 바람직하다.In addition, as the prophylactic or therapeutic agent for migraine headaches of the present invention, other active ingredients can be blended as long as they do not affect the preventive and therapeutic effects of migraine headaches. It is preferable to mix | blend an antacid, such as magnesium aluminate silicate and magnesium carbonate.

본 발명의 편두통의 예방 또는 치료제로 둘 수 있는 이부프로펜 및 카페인류의 함량은 제제에 따라 적당 선택하면 좋지만, 이부프로펜에 대해서는 20∼50중량% , 카페인류에 대해서는 10∼30중량%인 것이 바람직하고, 이부프로펜 100중량부에 대해서, 카페인류 20∼70중량부를 배합하는 것이 바람직하다.The content of ibuprofen and caffeine, which can be used as a prophylactic or therapeutic agent for migraine headaches of the present invention, may be appropriately selected depending on the preparation, but it is preferably 20 to 50% by weight for ibuprofen and 10 to 30% by weight for caffeine, It is preferable to mix | blend 20-70 weight part of caffeine with respect to 100 weight part of ibuprofen.

본 발명의 편두통의 예방 또는 치료제의 투여량은 편두통의 종류 및 증상에 의해 적당하게 선택되지만, 이부프로펜에 대해서는 1일당 50∼600mg 바람직하기로는 100∼350mg, 카페인류에 대해서는, 1일당 20∼400mg, 바람직하기로는 40∼250mg을 1일 1회 내지 수회 나누어 투여하는 것이 바람직하다.The dosage of the prophylactic or therapeutic agent for migraine headaches of the present invention is appropriately selected depending on the type and symptoms of migraine headache, but 50 to 600 mg per day for ibuprofen, preferably 100 to 350 mg per day for caffeine, 20 to 400 mg per day for caffeine, Preferably, 40 to 250 mg is preferably administered once to several times a day.

실시예Example

실시예 1Example 1

하기 표 1에 나타낸 필름코팅정을 제조했다.The film coated tablets shown in Table 1 below were prepared.

본 발명품Invention 비교품Comparative product (A) 이부프로펜(A) Ibuprofen 150mg150 mg 150mg150 mg (B) 무수 카페인(B) anhydrous caffeine 80mg80 mg -- 담체(결정 셀룰로오스 외)Carrier (other than crystalline cellulose) (A)/(B) 중량비(A) / (B) weight ratio 100/53.3100 / 53.3

월 2회 정도, 경도의 편두통을 일으키는 자원 봉사 5명에, 표 1의 2 제제를 편두통 시에 1회씩 복용하여도 1시간 이내에 아픔이 사라졌을 때에 효과를 갖는 것으로 했다.Twice a month, five volunteers who cause mild migraine were considered to have an effect when the pain disappeared within one hour even if the two preparations in Table 1 were taken once during migraine.

그 결과, 본 발명품에서는 어느 자원 봉사도 1시간 이내에 아픔이 사라졌지만, 비교품에서는 4명만 1시간 이내에 아픔이 사라졌다는 회답이 얻어졌다. 또한, 본 발명품의 쪽이 아픔이 사라질 때까지의 시간이 약간 짧은 것 같다고 대답한 사람이 5명중 4명이었다.As a result, in the present invention, the pain disappeared within 1 hour in any volunteer, but only 4 people answered that the pain disappeared in 1 hour. In addition, four out of five people answered that the time until the pain disappears was slightly shorter in the invention.

본 발명의 편두통의 예방 또는 치료제에 의하면, 편두통 및 그에 수반하는 오심, 구토, 빛이나 소리에 과민반응을 일으키는 것을 완화할 수 있다.According to the prophylactic or therapeutic agent for migraine headaches of the present invention, it is possible to alleviate the hypersensitivity reaction to migraine headaches and accompanying nausea, vomiting, light or sound.

Claims (3)

이부프로펜 및 카페인류를 유효 성분으로서 함유하는 편두통의 예방 또는 치료제.A prophylactic or therapeutic agent for migraine, which contains ibuprofen and caffeine as active ingredients. 제 1항에 있어서, 이부프로펜 100중량부에 대해서 카페인류를 20∼70중량부 함유하는 편두통의 예방 또는 치료제.The preventive or therapeutic agent for migraine according to claim 1, which contains 20 to 70 parts by weight of caffeine based on 100 parts by weight of ibuprofen. 제 1항 또는 제 2항에 있어서, 다시 제산제를 추가로 함유하는 편두통의 예방 또는 치료제.The prophylactic or therapeutic agent for migraine according to claim 1 or 2, further comprising an antacid.
KR10-2003-0014985A 2002-03-20 2003-03-11 Remedy for hemicrania Ceased KR20030076287A (en)

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