JPH06506684A - Ibuprofen - decongestant formulation - Google Patents
Ibuprofen - decongestant formulationInfo
- Publication number
- JPH06506684A JPH06506684A JP4509691A JP50969192A JPH06506684A JP H06506684 A JPH06506684 A JP H06506684A JP 4509691 A JP4509691 A JP 4509691A JP 50969192 A JP50969192 A JP 50969192A JP H06506684 A JPH06506684 A JP H06506684A
- Authority
- JP
- Japan
- Prior art keywords
- ibuprofen
- salt
- substantially free
- phenylephrine
- stereoisomers
- 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
- 239000000203 mixture Substances 0.000 title claims description 27
- 239000000850 decongestant Substances 0.000 title claims description 19
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims description 16
- 229960001680 ibuprofen Drugs 0.000 title claims description 14
- 238000009472 formulation Methods 0.000 title claims description 11
- 150000003839 salts Chemical class 0.000 claims description 23
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 claims description 17
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 claims description 14
- -1 ephinephrine Chemical compound 0.000 claims description 13
- 208000002193 Pain Diseases 0.000 claims description 12
- 239000000150 Sympathomimetic Substances 0.000 claims description 12
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 claims description 12
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- HEFNNWSXXWATRW-SNVBAGLBSA-N levibuprofen Chemical compound CC(C)CC1=CC=C([C@@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-SNVBAGLBSA-N 0.000 claims description 10
- 229960003908 pseudoephedrine Drugs 0.000 claims description 10
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims description 10
- 229960001802 phenylephrine Drugs 0.000 claims description 9
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 claims description 9
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 8
- 229960000395 phenylpropanolamine Drugs 0.000 claims description 8
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 8
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Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
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Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 発明の名称 イブプロフェン−充血除去剤配合物 発明の背景 疼痛／炎症の治療に非ステロイド性抗炎症薬（ＮＳＡＩＤ）が用いられており、 この薬剤は風邪症状及び該症状に関連する疼痛の治療、管理及び緩和に有用であ ると開示されている。[Detailed description of the invention] name of invention Ibuprofen - decongestant formulation Background of the invention Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain/inflammation. This drug is useful in the treatment, management, and alleviation of cold symptoms and the pain associated with them. It is disclosed that.
イブプロフェン［２−（４−イソブチルフェニル）プロピオン酸］は良く知られ た、広く用いられるＮ５ＡＩＤである。最近、鏡像異性体＜Ｓ）−イブプロフェ ンを単独で用いるとラセミ体イブプロフェンを用いた場合に比較して疼痛軽減の 開始を早め、かつ鎮痛反応を強め得ることが判明したく例えば米国特許第４，８ ７７．８２０号参照）。Ibuprofen [2-(4-isobutylphenyl)propionic acid] is a well-known Another widely used N5AID. Recently, the enantiomer <S)-ibuprofe When used alone, Ibuprofen reduces pain compared to racemic ibuprofen. For example, US Pat. 77.820).
交感神経作用アミンであるフェニレフリン、フェニルプロパノラミン、プソイド エフェドリン、オキシメタゾリン、エフィネフリン、ナファゾリン、キシロメタ ゾリン、プロピルへキセドリン、レボ−デスオキシエフェドリンは、風邪、アレ ルギー、流行性感冒または洞状態（ｓｉｎｕｓ ｅｏｎｄｉ−ｔ １ｏｎｓ＞に 起因する鼻の充血の治療に有用な交感神経興奮薬（充血除去剤）である、これら の薬剤は鼻通路の細動脈のうちでもより細いものを収縮させることによって機能 し、充血除去効果を生じる。Sympathomimetic amines phenylephrine, phenylpropanolamine, pseudo Ephedrine, oxymetazoline, ephinephrine, naphazoline, xylometa Zolin, propylhexedrine, and levodesoxyephedrine are used to treat colds and allergies. lugie, epidemic cold or sinus condition (sinus eondi-t1ons) These are sympathomimetics (decongestants) useful in treating nasal congestion caused by The drug works by constricting the smaller arterioles in the nasal passages. and produces a decongestant effect.
イブプロフェンを充血除去剤と配合することは開示されたが、風邪を引いた／疼 痛を覚える者が急速でがっ著しい軽減を必要とするにもかがわらず、疼痛の治療 及びアレルギーや風邪の症状の軽減に充血除去剤と配合した（Ｓ）−イブプロフ ェンまたはその塩を用いることは考慮されてこなかった。Combining ibuprofen with decongestants was disclosed, but Treatment of pain even though the person experiencing the pain needs rapid and significant relief. and (S)-Ibuprof combined with decongestants to relieve allergy and cold symptoms. The use of ene or its salts has not been considered.
発明の詳細な説明 本発明は、哺乳動物における疼痛及び炎症の治療並びに鼻充血及び温圧（ｓｉｎ ｕｓ ｐｒｅｓｓｕｒｅ）症状の軽減に用いられる医薬組成物であって、 （ｉ）（Ｒ）−イブプロフェンを実質的に伴わない（Ｓ）−イブプロフェンまた はその塩を鎮痛及び消炎有効量で含有し、か（ｉｉ）交感神経作用アミン、即ち フェニレフリン、フェニルプロパノラミン、プソイドエフェドリン、オキシメタ ゾリン、エフィネフリン（ｅｐｈｉｎｅｐｈｒｉｎｅ）、ナファゾリン、キシロ メタゾリン、プロピルへキセドリン、レボ−デスオキシエフェドリンもしくはこ れらの物質の治療活性な立体異性体でその他の立体異性体を実質的に伴わないも のまたはその薬剤学的に許容可能な塩を少なくとも１種交感神経作用有効量で含 有する 組成物に係わる。Detailed description of the invention The present invention relates to the treatment of pain and inflammation in mammals, as well as nasal congestion and hyperthermia (sin). A pharmaceutical composition used for alleviating symptoms (us pressure), the composition comprising: (i) (S)-ibuprofen substantially free of (R)-ibuprofen or contains the salt in an analgesic and anti-inflammatory effective amount, or (ii) a sympathomimetic amine, i.e. Phenylephrine, phenylpropanolamine, pseudoephedrine, oxymeth Zoline, ephinephrine, naphazoline, xylo Metazoline, propylhexedrine, levodesoxyephedrine or therapeutically active stereoisomers of these substances that are substantially free of other stereoisomers; or a pharmaceutically acceptable salt thereof in a sympathetically effective amount. have Concerning the composition.
本発明はまた、疼痛及び炎症の治療を必要とする哺乳動物においてそのような治 療並びに鼻充血及び温圧の軽減を行なう方法であって、前記のような動物に（ｉ ）（Ｒ）−イブプロフェンを実質的に伴わない（Ｓ）−イブプロフェンまたはそ の塩を鎮痛及び消炎有効量で投与し、かつ （ｉｉ）交感神経作用アミン、即ちフェニレフリン、フェニルプロパノラミン、 プソイドエフェドリン、オキシメタゾリン、エフィネフリン、ナファゾリン、キ シロメタゾリン、プロピルへキセドリン、レボ−デスオキシエフェドリンもしく はこれらの物質の治療活性な立体異性体でその他の立体異性体を実質的に伴わな いものまたはその薬剤学的に許容可能な塩を少なくとも１種交感神経作用有効量 で投与する ことを含む方法の提供を目的とする。The present invention also provides for the treatment of pain and inflammation in mammals in need thereof. A method for the treatment and alleviation of nasal congestion and thermal pressure, the method comprising: ) (S)-ibuprofen or the like substantially free of (R)-ibuprofen. administering the salt in an analgesic and anti-inflammatory effective amount, and (ii) sympathomimetic amines, namely phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, Cilometazoline, propylhexedrine, levodesoxyephedrine or is the therapeutically active stereoisomer of these substances, substantially free of other stereoisomers. a sympathetically effective amount of at least one potato or a pharmaceutically acceptable salt thereof; administer with The purpose is to provide a method that includes
本発明はまた、疼痛及び炎症の治療を必要とする哺乳動物においてそのような治 療並びに鼻充血及び温圧の軽減を行なう方法であって、前記のような動物に（ｉ ）（Ｒ）−イブプロフェンを実質的に伴わない（Ｓ）−イブプロフェンまたはそ の塩を鎮痛及び消炎有効量で投与し、かつ （ｉｉ）交感神経作用アミン、即ちフェニレフリン、フェニルプロパノラミン、 プソイドエフェドリン、オキシメタゾリン、エフィネフリン、ナファゾリン、キ シロメタゾリン、プロピルへキセドリン、レボ−デスオキシエフェドリンもしく はこれらの物質の治療活性な立体異性体でその他の立体異性体を実質的に伴わな いものまたはその薬剤学的に許容可能な塩を少なくとも１種交感神経作用有効量 で投与する ことを含む方法の提供を目的とする。The present invention also provides for the treatment of pain and inflammation in mammals in need thereof. A method for the treatment and alleviation of nasal congestion and thermal pressure, the method comprising: ) (S)-ibuprofen or the like substantially free of (R)-ibuprofen. administering the salt in an analgesic and anti-inflammatory effective amount, and (ii) sympathomimetic amines, namely phenylephrine, phenylpropanolamine, pseudoephedrine, oxymetazoline, ephinephrine, naphazoline, Cilometazoline, propylhexedrine, levodesoxyephedrine or is the therapeutically active stereoisomer of these substances, substantially free of other stereoisomers. a sympathetically effective amount of at least one potato or a pharmaceutically acceptable salt thereof; administer with The purpose is to provide a method that includes
本発明の組成物及び方法は、疼痛及び炎症の治療、または疼痛及び炎症のいずれ か一方しか存在しなければ存在する方だけの治療を鼻充血及び温圧症状の治療と 同時に行なうのに用い得る。The compositions and methods of the invention are useful for treating pain and inflammation, or for treating pain and inflammation. If only one of them is present, treatment for only the one present should be considered as treatment for nasal congestion and temperature and pressure symptoms. Can be used to do both at the same time.
“（Ｒ）−イブプロフェンを実質的に伴わない”という語は、（Ｓ）−イブプロ フェン対（Ｒ）−イブプロフェンの比が少なくと６９０・１０であることを意味 すると理解されるべきである。交感神経作用アミンの立体異性体に関する“実質 的に伴わない”という語は、交感神経作用アミンの治療活性な立体異性体対その 他の全立体異性体の比が少なくとも９０ ： １０であることを意味すると理解 されるべきである。The term "substantially free of (R)-ibuprofen" means (S)-ibuprofen. means that the ratio of phen to (R)-ibuprofen is at least 690.10 It should be understood then. “Real facts regarding stereoisomers of sympathomimetic amines” The term "not associated with therapeutic activity" refers to the therapeutically active stereoisomer of a sympathomimetic amine versus its understood to mean that the ratio of all other stereoisomers is at least 90:10 It should be.
（Ｓ）−イブプロフェンの塩には、ナトリウムやカリウムなどのアルカリ金属と の塩、カルシウムなどのアルカリ土類金属との塩、あるいはまたマグネシウム、 アルミニウム、鉄、亜鉛、銅、ニッケルまたはコバルトといった他の金属との塩 が含まれる。(S)-Ibuprofen salt contains alkali metals such as sodium and potassium. salts, salts with alkaline earth metals such as calcium, or also magnesium, Salts with other metals such as aluminum, iron, zinc, copper, nickel or cobalt is included.
（Ｓ）−イブプロフェンの塩にはアミノ酸塩、特にリシン塩やアルギニン塩など の塩基性アミノ酸塩も含まれる。特に、上記組成物は（Ｓ）−イブプロフェン− （Ｓ）−リシン及び（Ｓ）−イブプロフェン−（Ｒ）−リシンを含有する。(S)-Ibuprofen salts include amino acid salts, especially lysine salts and arginine salts. Also included are basic amino acid salts. In particular, the composition is (S)-ibuprofen- Contains (S)-lysine and (S)-ibuprofen-(R)-lysine.
交感神経作用アミンの塩には、塩酸塩、硫酸塩、あるいはまた重酒石酸塩が非限 定的に含まれる。Salts of sympathomimetic amines include, but are not limited to, hydrochloride, sulfate, or bitartrate. Included qualitatively.
（Ｓ）−イブプロフェンは米国特許第４，８７７．６２０号に開示された操作に 従って製造し得る。イブプロフェンの金属塩は、水酸化物または炭酸塩をイブプ ロフェンと接触させれば得ることができる。イブプロフェンのアミノ酸塩はアミ ノ酸溶液をイブプロフェンと接触させることにより取得可能である。(S)-Ibuprofen was prepared by the procedure disclosed in U.S. Pat. No. 4,877.620. Therefore, it can be manufactured. The metal salts of ibuprofen are the hydroxide or carbonate salts of ibuprofen. It can be obtained by contacting Lofen. The amino acid salt of ibuprofen is It can be obtained by contacting a noic acid solution with ibuprofen.
鎮痛薬−充血除去剤配合物に（Ｓ）−イブプロフェンを用いることによって、ラ セミ体イブプロフェンを充血除去剤と配合した場合に優る重要な利点が得られる 。（Ｓ）−イブプロフェンはラセミ体イブプロフェンに比べて早期に疼痛軽減を 開始し、その際軽減度も向上させる。これらの長所は、充血除去剤が＜Ｓ）−イ ブプロフェンの作用を相乗的に増強し得るので、（Ｓ）−イブプロフェン−充血 除去剤配合物において増大する。このことはこれまで観察されておらず、なぜな ら当分野では（Ｓ）−イブプロフェン鏡像異性体を（Ｒ）−イブプロフェンの不 在下に充血除去剤と配合することが提案されなかったからである。更に、充血除 去剤は相乗作用によって鎮痛及び消炎反応の持続時間の延長も実現し得る。（Ｒ ）−イブプロフェンの存在はこのような相乗効果を損ないかねない。By using (S)-ibuprofen in an analgesic-decongestant formulation, Semi-ibuprofen offers important benefits when combined with decongestants . (S)-Ibuprofen provides faster pain relief than racemic ibuprofen. start, and at the same time improve the degree of mitigation. These advantages are that decongestants are <S)-i (S)-ibuprofen-hyperemia, as it can synergistically enhance the action of buprofen. Increased in remover formulations. This has not been observed before, and why In the art, the (S)-ibuprofen enantiomer is a This is because it was not proposed to combine it with a decongestant. In addition, decongestion A synergistic effect of the ejector may also result in a prolongation of the duration of the analgesic and anti-inflammatory response. (R ) - the presence of ibuprofen may impair such synergistic effects.
（Ｒ）−イブプロフェンの不在はまた、特に風邪、流行性感冒またはアレルギー の症状下に衰弱した患者にとって非常に有益である。風邪／アレルギー／流行性 感冒患者にとって特に有害となる恐れの有る、時にイブプロフェン投与に関連す るアレルギー禁忌が（Ｒ）−イブプロフェンを含有しない組成物には存在しない か、または存在しても僅がであり得る。The absence of (R)-ibuprofen can also be used especially for colds, mumps or allergies. It is very beneficial for patients who are debilitated under the symptoms of. Cold/allergy/epidemic A drug sometimes associated with ibuprofen administration that can be particularly harmful to cold patients. Allergic contraindications do not exist in compositions that do not contain (R)-ibuprofen. Or there may be little if any.
＜Ｓ）−イブプロフェン−充血除去剤配合物を用いる患者はもはや、（Ｒ）−鏡 像異性体の反転または除去に代謝エネルギーを振り向けなくともよい、上記反転 が行なわれないことにより、トリグリセリドを含むハイブリッド−イブプロフェ ンが生成して脂肪組織中に入り込むことが低減または阻止される０時にイブプロ フェン治療に関連する腎臓への負担または毒性は、実質的に（Ｒ）−イブプロフ ェンを含有しない組成物においては僅かであるか、または存在しない。Patients using <S)-ibuprofen-decongestant formulations no longer have The above-mentioned inversions do not require the allocation of metabolic energy to the inversion or removal of enantiomers. Hybrid-ibuprophenol containing triglycerides Ibuprotin is reduced or prevented from forming and penetrating into adipose tissue. The renal burden or toxicity associated with phen therapy is substantially In compositions that do not contain ene, it is minimal or absent.
不活性な鏡像異性体、特に（Ｒ）−イブプロフェンの不在は配合物の投与形態、 特に徐放投与形態の寸法及び重量に関する重要な利点をもたらす、イブプロフェ ンの徐放投与のために８００〜１０００ｍｇの重量が必要であったような場合で は、（Ｓ）−イブプロフェンの使用によって重量が６５０〜８００ｍｇに減少し 、かつイブプロフェン−充血除去剤配合物のためにより実用的な寸法の錠剤が実 現する。The absence of an inactive enantiomer, particularly (R)-ibuprofen, reduces the dosage form of the formulation, Ibuprofen offers important advantages, especially with respect to size and weight of extended-release dosage forms. in cases where a weight of 800 to 1000 mg was required for sustained release administration of The weight decreased to 650-800 mg with the use of (S)-ibuprofen. , and more practical tablet sizes for ibuprofen-decongestant formulations have been implemented. manifest.
充血除去剤のただ一つの立体異性体のみが活性である場合（治療活性な立体異性 体）、本発明の組成物中に不活性物質が存在しないことによって望ましくない毒 性相互作用が回避され得、また不活性体の除去に必要な代謝は明らかに回避され る。When only one stereoisomer of a decongestant is active (therapeutically active stereoisomer) body), undesirable toxins due to the absence of inert substances in the compositions of the invention. sexual interactions can be avoided, and the metabolism required for removal of inert forms is clearly avoided. Ru.
１回量の本発明組成物中に用いる（Ｓ）−イブプロフェンまたはその塩の有効量 は、（Ｓ）−イブプロフェン量が５０〜８００−ｇとなる量であり得る。好まし い（Ｓ）−イブプロフェン量は約１００〜４００ｍｇである。〈Ｓ）−イブプロ フェン−（Ｓ）−リジンなどの塩の量は、当該塩が有する（Ｓ）−イブプロフェ ンの量に基づいて決定する。Effective amount of (S)-ibuprofen or its salt used in a single dose of the composition of the invention may be an amount such that the amount of (S)-ibuprofen is 50 to 800-g. preferred The amount of i(S)-ibuprofen is about 100-400 mg. <S) - Ibupro The amount of salt such as phen-(S)-lysine is determined by the amount of (S)-ibuprophene that the salt has. Determine based on amount of water.
本発明の組成物に用いる交感神経作用アミン（充血除去剤）は、フェニレフリン 、フェニルプロパノラミン、プソイドエフェドリン、オキシメタゾリン、エフェ ドリン、ナファゾリン、キシロメタゾリン、プロピルへキセドリン、レボ−デス オキシエフェドリンまたはその薬剤学的に許容可能な塩の中から選択する。上記 各充血除去剤の任意のジアステレオマー及び／または鏡像異性体も本発明の範囲 内である。特定の治療活性立体異性体が市販されていない場合は、入手可能なラ セミ体混合物から標準化学的分割手法に従って製造し得る。The sympathomimetic amine (decongestant) used in the compositions of the invention is phenylephrine. , phenylpropanolamine, pseudoephedrine, oxymetazoline, efe Dorin, Naphazoline, Xylometazoline, Propylhexedrine, Revodes Selected from oxyephedrine or a pharmaceutically acceptable salt thereof. the above Any diastereomer and/or enantiomer of each decongestant is also within the scope of this invention. It is within. If a particular therapeutically active stereoisomer is not commercially available, use the available It can be prepared from semi-mixtures according to standard chemical resolution techniques.
本発明の実施に有用な充血除去剤の量は、特定の充血除去剤毎に約ＩＢから１０ ０ｅ＋ｇまで様々であり得る。プソイドエフェドリン塩酸などの塩の量は、当該 塩が有するプソイドエフェドリンなどの活性な充血除去剤の量に基づいて決定本 発明の組成物は、錠剤、カプセル剤、エリキシル剤、シロップ剤、ドロップ剤、 顆粒剤、液剤、鼻用噴霧吸入剤または懸濁剤の形態で投与し得る。経口投与のた めには活性成分を、ラクトース、澱粉、スクロース、セルロース、ステアリン酸 マグネシウム、リン酸二カルシウム、［＋２カルシウム、マンニトール、及び液 状組成物の場合はエチルアルコールなどの薬剤学的に許容可能な稀釈剤と混合し 得る。 ｐｖｐ、澱粉、ゼラチン、天然糖、コーン甘味料、アラビアゴムなどの 天然及び合成ゴム、アルギン酸ナトリウム、カルボキシメチルセルロース、ポリ エチレングリコール及び蝋などの許容可能な結合剤も活性成分と混合し得る。必 要であれば、ステアリン酸マグネシウム、タルクなどの滑沢側、澱粉、メチルセ ルロース、寒天、ベントナイト及びグアーゴムなどの崩壊剤、並びにドキュセー トナトリウムや、ナトリウム澱粉グリコレートや、架橋ＰＶＰといっな超崩壊剤 を添加することも可能である。The amount of decongestant useful in the practice of the present invention ranges from about IB to 10 B for each particular decongestant. It can vary up to 0e+g. The amount of salt such as pseudoephedrine hydrochloride is This is determined based on the amount of active decongestants such as pseudoephedrine that the salt has. The composition of the invention can be used as tablets, capsules, elixirs, syrups, drops, It may be administered in the form of granules, solutions, nasal sprays or suspensions. For oral administration Active ingredients include lactose, starch, sucrose, cellulose, and stearic acid. Magnesium, dicalcium phosphate, [+2 calcium, mannitol, and liquid In the case of a liquid composition, it may be mixed with a pharmaceutically acceptable diluent such as ethyl alcohol. obtain. PVP, starch, gelatin, natural sugar, corn sweetener, gum arabic, etc. Natural and synthetic rubber, sodium alginate, carboxymethyl cellulose, poly Acceptable binders such as ethylene glycol and waxes may also be mixed with the active ingredient. Must If necessary, use a lubricant such as magnesium stearate, talc, starch, or methyl sesame. disintegrants such as lulose, agar, bentonite and guar gum, and Super disintegrants such as sodium starch, sodium starch glycolate, and cross-linked PVP It is also possible to add.
活性成分を徐放製剤中に配合することもできる。徐放製剤は経口投与、皮膚投与 、直腸投与または膣投与に用い得る。そのような徐放形態には、明確な放出比を 示し、従って短期及び長期軽減の実現においてより有益であり得る層状製剤も含 まれる。The active ingredient can also be formulated in sustained release formulations. Sustained-release formulations can be administered orally or cutaneously. , may be used for rectal or vaginal administration. Such sustained release forms require well-defined release ratios. Also includes layered formulations, which may be more beneficial in achieving short-term and long-term relief. be caught.
以下の実施例は本発明の詳細な説明するものであり、このようなものが、本明細 書に添付した請求の範囲各項に提示した本発明を限定すると看做されるべきでな い。The following examples are detailed illustrations of the invention and as such are incorporated herein by reference. Nothing in this document should be construed as limiting the invention as set out in the claims appended hereto. stomach.
Ｋ１」土 Ｓ−イブプロフェン−５−１シン−、 ＰＶＰ １５ｍｇ ＾ｖｉｅｅｌ ＰＨ１０１４０ｅ＋ｇ ステアリン酸マグネシウム ４６ に１１１ Ｓ−ブプロフエンーＳ−１シン−、、 ＰＶＰ ３０ｍｇ ＾ｖｉｅｅｌ ＰＨＩＯＩ ８０ｍｇ ステアリン酸マグネシウム ８ｅ＋ｇ Ｍｅｔｈｏｃｅｌ ＥＩＯＭＣＲ６６ｍｇＭｅｔｈｏｃｅｌに１００ＭＬＶ ２ ００ｍｇ叉」１１１ Ｓ−ブブロフェンー 、、 Ｍｅｔｈｏｃｅｌ ＫＬＯＯＭＬＶ ＺＯＯｍｇ叉１ｊ１− ５− ブプロフェンー５−１シン−、 （Ｓ）−イブプロフェン−（Ｓ）〜リシン ３４Ｚ＋＊ｇプソイドエフェドリン ＨＣＩ １５Ｂ ｑ、ｓ、シロップ ５ｍ１ 国際調査報告 フロントページの続き ＫＲ，ＬＫ、ＭＧ、ＭＮ、ＭＷ、Ｎｏ、ＰＬ、ＲＯ，ＲＵ、ＳＤ、 ＵＳ （７２）発明者 シムズ、ロバート・ティーアメリカ合衆国、ペンシルバニア・ １８９２８、ホリコング、アンダーソン・ロード・５０８０（７２）発明者 ス リブカ、ウィリアムアメリカ合衆国、ペンシルバニア・１９１１８、ミ フィラ デルフィア、メドウブルック・レーン・９４２５K1” soil S-ibuprofen-5-1 syn-, PVP 15mg ^vieel PH10140e+g Magnesium stearate 46 111 S-Buprofen-S-1 Syn- PVP 30mg ^vieel PHIOI 80mg Magnesium stearate 8e+g Methocel EIOMCR66mgMethocel 100MLV 2 00mg or 111 S-bubrofen... Methocel KLOOMLV ZOOmg叉1j1- 5- Buprofen-5-1 Syn-, (S)-ibuprofen-(S)~ricin 34Z+*g pseudoephedrine HCI 15B q, s, syrup 5ml international search report Continuation of front page KR, LK, MG, MN, MW, No, PL, RO, RU, SD, US (72) Inventor: Sims, Robert Tee, Pennsylvania, USA 5080 (72) Anderson Road, Horikong, 18928 Inventor Rybka, William Mifila, Pennsylvania 19118, United States 9425 Meadowbrook Lane, Delphia
Claims (5)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67877391A | 1991-04-01 | 1991-04-01 | |
| US678,773 | 1991-04-01 | ||
| US81252391A | 1991-12-20 | 1991-12-20 | |
| US812,523 | 1991-12-20 | ||
| PCT/US1992/002388 WO1992017171A1 (en) | 1991-04-01 | 1992-03-24 | Ibuprofen-decongestant combinations |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06506684A true JPH06506684A (en) | 1994-07-28 |
Family
ID=27102083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4509691A Pending JPH06506684A (en) | 1991-04-01 | 1992-03-24 | Ibuprofen - decongestant formulation |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0577757A1 (en) |
| JP (1) | JPH06506684A (en) |
| AU (1) | AU1766292A (en) |
| CA (1) | CA2107331A1 (en) |
| WO (1) | WO1992017171A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001019638A (en) * | 1999-06-10 | 2001-01-23 | Mcneil Ppc Inc | Fast absorbing liquid composition |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0674527A1 (en) * | 1992-12-21 | 1995-10-04 | The Procter & Gamble Company | Use of s(+) antipodes of analgesic agents for the manufacture of a composition to treat respiratory disorders |
| WO1995007103A1 (en) * | 1993-09-07 | 1995-03-16 | The Procter & Gamble Company | Compositions containing an amino acid salt of propionic acid non-steroidal anti-inflammatory agent and at least one of a decongestant, an expectorant, an antihistamine and an antitussive |
| WO2000001379A1 (en) * | 1998-07-01 | 2000-01-13 | Warner-Lambert Company | (-)-pseudoephedrine as a sympathomimetic drug |
| US7973068B2 (en) | 1998-10-20 | 2011-07-05 | Omeros Corporation | Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation |
| US20030087962A1 (en) | 1998-10-20 | 2003-05-08 | Omeros Corporation | Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation |
| AU2011244930B2 (en) * | 1999-06-10 | 2012-08-30 | Mcneil-Ppc, Inc. | Rapidly absorbed liquid compositions |
| MXPA03001437A (en) * | 2000-09-08 | 2005-06-03 | Warner Lambert Co | Prevention of acute sinusitis and sinus attack. |
| CL2003002653A1 (en) | 2002-12-18 | 2005-04-22 | Wyeth Corp | PHARMACEUTICAL COMPOSITION THAT INCLUDES (A) AN NON-STEROID ANTI-INFLAMMATORY (NSAID), PREFERREDLY IBUPROFEN, (B) A DECONGESTIONANT, PREFERENTIALLY PSEUDOEFEDRINE AND (C) AN ANTIHISTAMINIC, PREFERENTLY CHLORINE; METHOD FOR YOUR PREPARATION |
| US20050192355A1 (en) * | 2004-02-17 | 2005-09-01 | Wyeth | Compositions of non-steroidal anti-inflammatory drugs and decongestants or anti-histamines |
| AU2022201576A1 (en) * | 2022-03-08 | 2023-09-28 | Aft Pharmaceuticals Limited | Medication |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4840962A (en) * | 1984-04-09 | 1989-06-20 | Analgesic Associates | Cough/cold mixtures comprising non-steroidal anti-inflammatory drugs |
| US4783465A (en) * | 1984-04-09 | 1988-11-08 | Analgesic Associates | Cough/cold mixtures comprising non-sedating antihistamine drugs |
| ES2055685T3 (en) * | 1986-11-14 | 1994-09-01 | Puetter Medice Chem Pharm | PROCEDURE FOR OBTAINING A MEDICINAL PRODUCT CONTAINING IBUPROFEN. |
| US4851444A (en) * | 1987-07-10 | 1989-07-25 | Analgesic Associates | Onset-hastened/enhanced analgesia |
| US4980375A (en) * | 1987-07-10 | 1990-12-25 | Sterling Drug Inc. | Onset-hastened/enhanced antipyretic response |
-
1992
- 1992-03-24 AU AU17662/92A patent/AU1766292A/en not_active Abandoned
- 1992-03-24 JP JP4509691A patent/JPH06506684A/en active Pending
- 1992-03-24 EP EP92910669A patent/EP0577757A1/en not_active Withdrawn
- 1992-03-24 WO PCT/US1992/002388 patent/WO1992017171A1/en not_active Ceased
- 1992-03-24 CA CA002107331A patent/CA2107331A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001019638A (en) * | 1999-06-10 | 2001-01-23 | Mcneil Ppc Inc | Fast absorbing liquid composition |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992017171A1 (en) | 1992-10-15 |
| AU1766292A (en) | 1992-11-02 |
| EP0577757A4 (en) | 1994-02-23 |
| EP0577757A1 (en) | 1994-01-12 |
| CA2107331A1 (en) | 1992-10-02 |
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