JPH11504044A - Treatment method and pharmaceutical preparation - Google Patents

Treatment method and pharmaceutical preparation

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Publication number
JPH11504044A
JPH11504044A JP9528627A JP52862797A JPH11504044A JP H11504044 A JPH11504044 A JP H11504044A JP 9528627 A JP9528627 A JP 9528627A JP 52862797 A JP52862797 A JP 52862797A JP H11504044 A JPH11504044 A JP H11504044A
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Prior art keywords
phenyl
loratadine
sodium
thio
formulation
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JP9528627A
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Japanese (ja)
Inventor
ダーレン，スベン―エリツク
スコルニツク，エドワード・エム
Original Assignee
メルク エンド カンパニー インコーポレーテッド
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Priority claimed from GBGB9608927.1A external-priority patent/GB9608927D0/en
Application filed by メルク エンド カンパニー インコーポレーテッド filed Critical メルク エンド カンパニー インコーポレーテッド
Publication of JPH11504044A publication Critical patent/JPH11504044A/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—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
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Abstract

(57)【要約】 喘息、アレルギー及び炎症の治療方法であり、ロイコトリエン阻害剤とロラタジンを個別に含む投与剤形を同時に、又は単一医薬製剤中に混合させて投与することによる治療を包含する。   (57) [Summary] A method for treating asthma, allergy and inflammation, which includes treatment by administering a dosage form containing a leukotriene inhibitor and loratadine individually or simultaneously in a single pharmaceutical preparation.

Description

【発明の詳細な説明】 治療方法及び医薬製剤 発明の背景 ロラタジン(Loratadine)は、アレルギーの治療に有用なＨレセプターアンタゴ ニストという性質を有する抗ヒスタミン剤であり、米国特許第４，２８２，２３ ３号に記載されている。 ロイコトリエンアンタゴニストは、喘息、アレルギー反応及び炎症の治療に有 用であることが知られている。 本発明により、一方の薬剤だけよりも効力のある上記２種の薬剤の組合せによ る喘息、アレルギー及び炎症の治療方法が提供される。発明の概要 本発明は、有効量のロラタジンと有効量のロイコトリエンアンタゴニスト［ロ イコトリエンアンタゴニストは、 Ａ． １−（（（Ｒ）−（３−（２−（７−クロロ−２−キノリニル）エテニル ）フェニル）−３−（２−（２−ヒドロキシ−２−プロピル）フェニル）チオ） メチル）シクロプロパン酢酸ナトリウム（欧州特許第４８０，７１７号） Ｂ． １−（（（Ｒ）−（３−（２−（６，７−ジフルオロ−２−キノリニル） エテニル）フェニル）−３−（２−（２−ヒドロキシ−２−プロピル）フェニル ）チオ）メチル）シクロプロパン酢酸ナトリウム（米国特許第５，２７０，３２ ４号） Ｃ． １−（（（１（Ｒ）−（３−（２−（２，３−ジクロロチエノ［３，２− ｂ］ピリジン−５−イル）−（Ｅ）−エテニル）フェニル）−３−（２−（１− ヒドロキシ−１−メチルエチル）フェニル）プロピル）チオ）メチル）シクロプ ロパン酢 酸又はそのナトリウム塩（米国特許第５，４７２，９６４号） Ｄ． Ｎ−［４−オキソ−２−（１Ｈ−テトラゾル−５−イル）−４Ｈ−１−ベ ンゾピラン−８−イル］−ｐ−（４−フェニルブトキシ）ベンズアミド（欧州特 許第１７３，５１６号） Ｅ． シクロペンチル−３−［２−メトキシ−４−［（ｏ−トリルスルホニル） カルバモイル］ベンジル］−１−メチルインドール−５−カルバメート（欧州特 許第１９９，５４３号） から選択される］を、本質的に同時投与で、又は単一医薬製剤中に混合して投与 することによる喘息、アレルギー及び炎症の治療方法に関する。発明の詳細な説明 本発明の新規医薬製剤は、活性成分として上記の、ロラタジンと、Ａ、Ｂ、Ｃ 、Ｄ及びＥから選択されるロイコトリエンアンタゴニストの組合せ、並びに場合 によっては腸内投与又は非経口投与に適した医薬として許容できる担体を含む。 該製剤は、固体剤形、例えば錠剤やカプセル、又は液体剤形、例えばシロップ、 エリキシル剤、懸濁剤及び注射剤でありうる。医薬投与剤形の製剤では、一般的 に水、ゼラチン、乳糖、澱粉、ステア リン酸マグネシウム、タルク、植物油、ベンジルアルコール、ゴム、ポリアルキ レングリコール及びペトロラタムのような賦形剤を用いる。好適な製剤は以下の 実施例で十分に記載する。 本発明の新規治療方法では、ロラタジンとロイコトリエンアンタゴニストは、 分離した投与剤形として実質的に同時に投与できるし、又は本発明の新規医薬製 剤中に混合して投与することができる。 必要な投与量は、患者の年齢、性別、体重及び治療する疾患の程度のような因 子によって決定されるが、好適なヒト経口投与量の範囲は、ロラタジンが約５〜 ２０ｍｇ、１日１〜３回、好ましくは約１０ｍｇ、１日１回である。ロイコトリ エンアンタゴニストの場合には、ヒト投与範囲はまた、約５〜２０ｍｇ、１日１ 〜３回、好ましくは約１０ｍｇ、１日１回である。 実施例 モンテルカストナトリウム１０ｍｇ及びロラタジン１０ｍｇフィルム被覆錠剤 DETAILED DESCRIPTION OF THE INVENTION Therapeutic Methods and Pharmaceutical Formulations Background of the Invention Loratadine is an antihistamine with the property of an H receptor antagonist useful in the treatment of allergies and is described in US Pat. No. 4,282,233. Have been. Leukotriene antagonists are known to be useful in treating asthma, allergic reactions and inflammation. The present invention provides a method for treating asthma, allergy and inflammation by a combination of the above two drugs which is more effective than only one drug. SUMMARY OF THE INVENTION The present invention provides an effective amount of loratadine and an effective amount of a leukotriene antagonist. 1-(((R)-(3- (2- (7-chloro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) thio) methyl) cyclopropane Sodium acetate (EP 480,717) B. 1-(((R)-(3- (2- (6,7-difluoro-2-quinolinyl) ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl) thio) methyl) Sodium cyclopropaneacetate (US Patent No. 5,270,324) C. 1-(((1 (R)-(3- (2- (2,3-dichlorothieno [3,2-b] pyridin-5-yl)-(E) -ethenyl) phenyl) -3- (2 -(1-hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclopropaneacetic acid or its sodium salt (US Pat. No. 5,472,964) D. N- [4-oxo-2- (1H-tetrazol-5-yl) -4H-1-benzopyran-8-yl] -p- (4-phenylbutoxy) benzamide (EP 173,516) E. FIG. Cyclopentyl-3- [2-methoxy-4-[(o-tolylsulfonyl) carbamoyl] benzyl] -1-methylindole-5-carbamate (EP 199,543) Selected from the group consisting of a pharmaceutically acceptable salt thereof, or a mixture thereof in a single pharmaceutical preparation. DETAILED DESCRIPTION OF THE INVENTION The novel pharmaceutical formulation of the present invention comprises a combination of loratadine as described above as active ingredient and a leukotriene antagonist selected from A, B, C, D and E, and optionally enteral or parenteral administration It includes a pharmaceutically acceptable carrier suitable for administration. The formulations can be solid dosage forms, such as tablets or capsules, or liquid dosage forms, such as syrups, elixirs, suspensions and injections. Pharmaceutical dosage form formulations generally employ excipients such as water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene glycols and petrolatum. Suitable formulations are described fully in the examples below. In the novel method of treatment of the present invention, loratadine and the leukotriene antagonist can be administered substantially simultaneously as separate dosage forms or can be administered in admixture with the novel pharmaceutical formulation of the present invention. The required dosage is determined by factors such as the patient's age, sex, weight, and the extent of the disease being treated, but a suitable human oral dosage range is about 5-20 mg loratadine, 1-day per day. Three times, preferably about 10 mg once a day. In the case of leukotriene antagonists, the human dosage range will also be about 5-20 mg, 1-3 times daily, preferably about 10 mg once daily. Example 10 mg Montelukast Sodium and Loratadine 10 mg Film-Coated Tablets

───────────────────────────────────────────────────── フロントページの続き (81)指定国 ＥＰ(ＡＴ，ＢＥ，ＣＨ，ＤＥ， ＤＫ，ＥＳ，ＦＩ，ＦＲ，ＧＢ，ＧＲ，ＩＥ，ＩＴ，Ｌ Ｕ，ＭＣ，ＮＬ，ＰＴ，ＳＥ)，ＯＡ(ＢＦ，ＢＪ，ＣＦ ，ＣＧ，ＣＩ，ＣＭ，ＧＡ，ＧＮ，ＭＬ，ＭＲ，ＮＥ， ＳＮ，ＴＤ，ＴＧ)，ＡＰ(ＫＥ，ＬＳ，ＭＷ，ＳＤ，Ｓ Ｚ，ＵＧ)，ＵＡ(ＡＭ，ＡＺ，ＢＹ，ＫＧ，ＫＺ，ＭＤ ，ＲＵ，ＴＪ，ＴＭ)，ＡＬ，ＡＭ，ＡＵ，ＡＺ，ＢＡ ，ＢＢ，ＢＧ，ＢＲ，ＢＹ，ＣＡ，ＣＮ，ＣＵ，ＣＺ， ＥＥ，ＧＥ，ＨＵ，ＩＬ，ＩＳ，ＪＰ，ＫＧ，ＫＲ，Ｋ Ｚ，ＬＣ，ＬＫ，ＬＲ，ＬＴ，ＬＶ，ＭＤ，ＭＧ，ＭＫ ，ＭＮ，ＭＸ，ＮＯ，ＮＺ，ＰＬ，ＲＯ，ＲＵ，ＳＧ， ＳＩ，ＳＫ，ＴＪ，ＴＭ，ＴＲ，ＴＴ，ＵＡ，ＵＳ，Ｕ Ｚ，ＶＮ，ＹＵ (72)発明者 スコルニツク，エドワード・エム アメリカ合衆国、ニユー・ジヤージー・ 07065、ローウエイ、イースト・リンカー ン・アベニユー・126────────────────────────────────────────────────── ─── Continuation of front page    (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, L U, MC, NL, PT, SE), OA (BF, BJ, CF) , CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG), AP (KE, LS, MW, SD, S Z, UG), UA (AM, AZ, BY, KG, KZ, MD , RU, TJ, TM), AL, AM, AU, AZ, BA , BB, BG, BR, BY, CA, CN, CU, CZ, EE, GE, HU, IL, IS, JP, KG, KR, K Z, LC, LK, LR, LT, LV, MD, MG, MK , MN, MX, NO, NZ, PL, RO, RU, SG, SI, SK, TJ, TM, TR, TT, UA, US, U Z, VN, YU (72) Inventors Skornitsk, Edward M             New Jersey, United States             07065, Lowway, East Linker             N Avenue 126

Claims (1)

【特許請求の範囲】 １． 活性成分として、ロラタジンと、 （Ａ）モンテルカストナトリウム； （Ｂ）１−（（（Ｒ）−（３−（２−（６，７−ジフルオロ−２−キノリニル） エテニル）フェニル）−３−（２−（２−ヒドロキシ−２−プロピル）フェニル ）チオ）メチルシクロプロパン酢酸ナトリウム； （Ｃ）１−（（（１（Ｒ）−（３−（２−（２，３−ジクロロチェノ［３，２− ｂ］ピリジン−５−イル）−（Ｅ）−エテニル）フェニル）−３−（２−（１− ヒドロキシ−１−メチルエチル）フェニル）プロピル）チオ）メチル）シクロプ ロパン酢酸又はそのナトリウム塩； （Ｄ）プランルカスト；及び （Ｅ）ザフィルルカスト； から選択されるロイコトリエンアンタゴニスト、並びに医薬として許容できる担 体を含むことを特徴とする医薬製剤。 ２． 経口投与用に設計されることを特徴とする請求項１に記載の製剤。 ３． ロラタジン１０ｍｇと、（Ａ）、（Ｂ）、（Ｃ）、（Ｄ）及び（Ｅ）から 選択されるロイコトリエンアンタゴニスト１０ｍｇを含むことを特徴とする請求 項２に記載の製剤。 ４． ロイコトリエンアンタゴニストはモンテルカストナトリウムであることを 特徴とする請求項１に記載の製剤。 ５． 経口投与用に設計されることを特徴とする請求項４に記載の製剤。 ６． 各活性薬剤１０ｍｇを含むことを特徴とする請求項５に記載の製剤。 ７． 喘息、アレルギー及び炎症の治療の必要のある患者における治療方法であ って、有効量のロラタジンと、有効量の、 （Ａ）モンテルカストナトリウム； （Ｂ）１−（（（Ｒ）−（３−（２−（６，７−ジフルオロ−２−キノリニル） エテニル）フェニル）−３−（２−（２−ヒドロキシ−２−プロピル）フェニル ）チオ）メチル）シクロプロパン酢酸ナトリウム； （Ｃ）１−（（（１（Ｒ）−（３−（２−（２，３−ジクロロチエノ［３，２− ｂ］ピリジン−５−イル）−（Ｅ）−エテニ ル）フェニル）−３−（２−（１−ヒドロキシ−１−メチルエチル）フェニル） プロピル）チオ）メチル）シクロプロパン酢酸又はそのナトリウム塩； （Ｄ）プランルカスト；及び （Ｅ）ザフィルルカスト； から選択されるロイコトリエンアンタゴニストを、個別に含んだ投与剤形を実質 的に同時に、又は請求項１に記載の単一の医薬製剤中に混合して投与することを 特徴とする該方法。 ８． 医薬製剤は経口投与用に設計されることを特徴とする請求項７に記載の方 法。 ９． 個別の投与剤形及び単一医薬製剤が、ロラタジン１０ｍｇと、（Ａ）、（ Ｂ）、（Ｃ）、（Ｄ）及び（Ｅ）から選択されるロイコトリエンアンタゴニスト １０ｍｇを含むことを特徴とする請求項７に記載の方法。 １０． ロイコトリエンアンタゴニストが（Ａ）モンテルカストナトリウムであ ることを特徴とする請求項７に記載の方法。 １１． 個別の投与剤形及び単一医薬製剤が、経口投与用に設計されることを特 徴とする請求項１０に記載の方法。 １２． 個別の投与剤形及び単一医薬製剤が、ロラタジン１０ ｍｇと（Ａ）モンテルカストナトリウム１０ｍｇを含むことを特徴とする請求項 １１に記載の方法。[Claims] 1. As active ingredients, loratadine, (A) Montelukast sodium; (B) 1-(((R)-(3- (2- (6,7-difluoro-2-quinolinyl)) Ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl ) Thio) sodium methylcyclopropaneacetate; (C) 1-(((1 (R)-(3- (2- (2,3-dichlorocheno [3,2- b] pyridin-5-yl)-(E) -ethenyl) phenyl) -3- (2- (1- Hydroxy-1-methylethyl) phenyl) propyl) thio) methyl) cyclop Lopanacetic acid or its sodium salt; (D) pranlukast; and (E) zafirlukast; Leukotriene antagonists selected from the group consisting of A pharmaceutical preparation comprising a body. 2. The formulation according to claim 1, wherein the formulation is designed for oral administration. 3. Loratadine 10mg, from (A), (B), (C), (D) and (E) Claims comprising 10 mg of a selected leukotriene antagonist Item 6. The preparation according to Item 2. 4. Leukotriene antagonist is montelukast sodium The preparation according to claim 1, characterized in that: 5. The formulation according to claim 4, characterized in that it is designed for oral administration. 6. The formulation according to claim 5, comprising 10 mg of each active agent. 7. A method of treatment for patients in need of treatment for asthma, allergy and inflammation. Thus, an effective amount of loratadine and an effective amount of (A) Montelukast sodium; (B) 1-(((R)-(3- (2- (6,7-difluoro-2-quinolinyl)) Ethenyl) phenyl) -3- (2- (2-hydroxy-2-propyl) phenyl ) Thio) methyl) cyclopropaneacetate sodium; (C) 1-(((1 (R)-(3- (2- (2,3-dichlorothieno [3,2- b] pyridin-5-yl)-(E) -etheni Phenyl) -3- (2- (1-hydroxy-1-methylethyl) phenyl) Propyl) thio) methyl) cyclopropaneacetic acid or its sodium salt; (D) pranlukast; and (E) zafirlukast; A leukotriene antagonist selected from the group consisting of Administration at the same time or in a single pharmaceutical preparation according to claim 1. The method characterized by the above. 8. 8. The method according to claim 7, wherein the pharmaceutical preparation is designed for oral administration. Law. 9. Separate dosage forms and a single pharmaceutical formulation comprise 10 mg of loratadine, (A), ( B) Leukotriene antagonists selected from (C), (D) and (E) The method of claim 7, comprising 10 mg. 10. The leukotriene antagonist is (A) montelukast sodium The method of claim 7, wherein: 11. It is noted that separate dosage forms and single pharmaceutical formulations are designed for oral administration. 11. The method according to claim 10, wherein the method comprises: 12. Separate dosage forms and a single pharmaceutical formulation are available for loratadine 10 and (A) 10 mg of montelukast sodium. 12. The method according to 11.
JP9528627A 1996-02-08 1997-02-04 Treatment method and pharmaceutical preparation Pending JPH11504044A (en)

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AU2257997A (en) 1997-08-28
WO1997028797A1 (en) 1997-08-14
CN1210465A (en) 1999-03-10
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CA2245162A1 (en) 1997-08-14
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