NO318672B1 - Ernaeringsmateriale til behandling av liggesar samt anvendelser derav. - Google Patents
Ernaeringsmateriale til behandling av liggesar samt anvendelser derav. Download PDFInfo
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- NO318672B1 NO318672B1 NO20000128A NO20000128A NO318672B1 NO 318672 B1 NO318672 B1 NO 318672B1 NO 20000128 A NO20000128 A NO 20000128A NO 20000128 A NO20000128 A NO 20000128A NO 318672 B1 NO318672 B1 NO 318672B1
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- arginine
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Description
Den foreliggende oppfinnelse vedrører ernærings-tilskuddsmaterialer egnet for behandling av liggesår, samt anvendelse av en kombinasjon av arginin, askobinsyreekvivalenter og alfatokoferolekvivalenter for fremstilling ave et materiale for behandling av liggesår.
Bakgrunn.
Liggesår (decubitus) opptrer relativt ofte, særlig hos kirurgiske pasienter og ubevegelige personer, såsom noen av de eldre som må ligge i sengen i lengre tidsrom. Noen deler av kroppen, f.eks. albuer, hæler, hofter, hoftebein, kors-bein, skulderblad, påvirkes av trykkrefter som utøves av vekten av kroppen. Alvoret av liggesår klassifiseres i for-skjellige stadier. I det første stadium forårsaker trykk og forskyvning klemming av det subkutane vev, okklusjon av kapillarårer og lymfene og dårlig vaskularisering i dype vevslag. Langvarig trykk starter vevskade i hudoverflaten. Dette resulterer i nedsatt celleproduksjon i huden og at huden blir tynnere. Blodårer i huden svekkes og forårsaker rødhet. I det andre stadium løsner basalmembranen fra overhuden. Det opptrer ødemer og blærer. I det tredje stadium blir overhuden mer og mer svekket og hudoverflaten blir også påvirket. I videre stadier blir nekrose av dype vevslag synlige på hudoverflaten. Den ernæringsmessige tilstand hos liggesårpasienter er ofte dårlig som resultat av util-strekkelig ernæring etter kirurgiske operasjoner, feil-ernæring, tap av bestanddeler fra sår, ubevegelighet, fysiske handikap eller andre besvær.
Hindring eller helbredelse av liggesår krever først og fremst bedring av ytre faktorer rundt sårområdet, såsom reduksjon av trykk, friksjons- og skjærkrefter, fuktighet og temperatur.
En metode til å stimulere sårhelbredelse ved administrering av sink, vitaminene A og C, selen, A-karoten og tiamin er kjent fra EP-A-564804. Et flytende preparat som inneholder 62,5 g/l (25 energi%) proteiner, 34 g/l (30 energi%) fett og 113 g/l {45 energi%) karbohydrater kan anvendes. Andre vitaminer og sporelementer kan også være tilstede. Liggesår nevnes blant de tilstander som ville nødvendiggjøre slik økt sårhelbredelse.
I EP-A-367724 beskrives immunitetsstimulerende preparater inneholdende per enhetsdose (i 1,5 liter) 3-40 g (18,75 g) arginin, 0,1-4 g (1,9 g) RNA, 0,1-20 g (3 g) co-3-polyumettede fettsyrer inneholdende 1-2 g EPA og 0,25-1 g DHA, og 0,1-20 g (3,6 g) (o-6-polyumettede fettsyrer (linolsyre). Preparatene inneholder 22 energi% proteiner, 28 energi% fett og 53 energi% karbohydrater. Liggesår nevnes ikke som tilstander som de immunitetsstimulerende preparater ville kunne være anvendelige til.
Fra US-patentskrift 5.053.387 er det kjent et preparat til behandling av traumatisk skade, inneholdende arginin (1-3 energi%), intakt protein (20-30 energi%), fett (7-15 energi%, inneholdende EPA og linolsyre med et forhold på ca. 1,5 mellom <d-6 og co-3) samt karbohydrater (65-70 energi%), og dessuten sink, vitamin A og vitamin C.
Et flytende næringspreparat inneholdende arginin for traume- og kirurgipasienter, men ikke omfattende liggesårpasienter, er kjent fra WO 93/16595. Preparatet inneholder 20 energi% protein, 24 energi% fett og 56 energi% karbohydrater. Arginin utgjør 1-3 energi% av energien. Forholdet mellom linolsyre og a-linolensyre er mellom 3,5 og 5,5. Kaloriinnholdet er 1,2-1,5 kcal/ml, og forholdet mellom kalori og nitrogen er mellom 112 og 145. Preparatet inneholder dessuten vitaminer og sporelementer i 1 til 2 ganger de anbefalte daglige mengder.
I WO 96/08966 beskrives det en fremgangsmåte for økning av sårhelbredelse med nitrogenmonoksid (NO), som omfatter administrering av NO-økende forbindelser, såsom nitrosylerte aminer, antioksidanter, såsom vitaminene C og E, samt andre bestanddeler, såsom analgetika. Hverken liggesår- eller ernæringsmidler er omtalt i denne publika-sjon.
Beskrivelse av oppfinnelsen.
Ernæringstilskuddsmaterialet i følge oppfinnelsen er kjennetegnet ved at det inneholder proteiner, karbohydrater og fett, samt at det inneholder per liter: 6 til 20 g arginin; 400 til 1800 mg askobinsyreekvivalenter; 100 til 600 mg alfatokoferolekvivalenter; og minst en komponent valgt fra: 16 til 80 mg flavonoider; 20 til 60 mg sink; 2,5 til 12 mg kopper; 1,6 til 24 mg karotenoider. Ytterlige utførelser av oppfinnelsen er angitt i underkravene 2-4.
Ernæringstilskuddsmaterialet i følge oppfinnelsen inneholder per 1000 kcal: 6 til 18 g arginin; 400 til 1500 mg askobinsyreekvivalenter; 100 til 500 mg alfatokoferolekvivalenter ; og minst en komponent valgt blant: 16 til 60 mg flavonoider; 20 til 50 mg sink; 2,5 til 10 mg kopper; 1,6 til 20 mg karotenoider. Ytterlige utførelser i følge oppfinnelsen er angitt i underkrav 6.
Videre omfatter oppfinnelsen anvendelse av en kombinasjon av arginin, askobinsyreekvivalenter og alfatokoferolaekvivalenter for fremstilling av et ernæringstilsetningsmateriale for anvendelse i behandling av liggesår. Ytterligere utførelser av dette aspekt er gitt i kravene 8-14.
Det er følgelig funnet at et materiale som er effektivt mot liggesår bør inneholde en kombinasjon av næringsstoffer som ikke bare bedrer sårhelbredelse, men også har en effekt i de foregående stadier med bedring av blodsirkulasjon og kontroll av betennelse. Et slikt effektivt materiale bør i væskeform inneholde arginin (3-15 g/l, fortrinnsvis 5-10 g/l), vitamin C (3-14 ganger det anbefalte daglige nivå, RDA), vitamin E (5-40 ganger RDA) samt fortrinnsvis også sink i en mengde på minst 8 mg per liter eller per dag med et passende forhold sink/kobber. Et ytterligere forbedret materiale inneholder også økte mengder av karotenoider, mineraler (Na, K, Cl) og/eller flavonoider (8-40 mg/l).
Argininet kan være i form av den frie aminosyre eller i form av argininrike peptider eller proteiner, såsom erte-proteiner, eller som metaboliske ekvivalenter av arginin, såsom ornitin eller sitrullin. Mengden arginin som skal anvendes er 3-15 g/dag, fortrinnsvis 5-10 g/dag.
Nivået av vitamin C uttrykkes her som askorbinsyreekvivalenter, som omfatter vitamin C (askorbinsyre) og forbindelser som kan omdannes til askorbinsyre i kroppen, såsom dehydroaskorbinsyre, askorbylpalmitat og andre askor-bylestere. Mengden askorbinsyreekvivalenter er fra 180 mg eller 200 opptil 840 mg eller mer per dag. Det foretrukne område er 300-780, særlig 350-700 mg/dag.
Nivået av vitamin E uttrykkes her som tokoferolekvivalenter, som omfatter a-tokoferol og ekvivalenter. Således tilsvarer en cx-tokoferolekvivalent (TE) (= 1,5 IU av vitamin E) 1 mg D-a-tokoferol, 2,0 mg D-ii-tokof erol, 10 mg D-y-tokoferol, 30 mg D-5-tokoferol, 2 mg D-ot-tokotrienol eller 18,6 mg D-Ji-tokotrienol. Mengden tokof erolekvivalent som skal anvendes er 50-400 mg/dag. Fortrinnsvis er det laveste nivå 100, mer foretrukket 120, særlig 180 mg/dag, og den foretrukne øvre grense er 320, mer foretrukket 250 mg/dag.
Effektiviteten til kombinasjonen som er beskrevet ovenfor økes ytterligere i nærvær av flavonoider, f.eks. i et nivå på 8-40, særlig 10-30 mg/dag. Ifølge oppfinnelsen forstås flavonoider å omfatte hydroksysubstituerte forbindelser som har flavonskjelettet (2-fenyl-kromon = 2-fenyl-benzopyron) og isomerer derav, såsom isoflavonene (3-fenyl-kromoner), chalkoner (2-cinnamoyl-fenoler) og auroner (2-benzyliden-benzofuranoner). Også antocyanidinene (som avviker fra flavonene ved nærværet av en pyrylium-gruppe istedenfor pyrongruppen) betraktes som flavonoider. Hydroksyfunksjonene i flavonoidforbindelse kan være, og er fortrinnsvis, delvis alkylert eller glykosylert, slik som i naturlige forbindelser, såsom antocyaner (= glykosylerte antocyanidiner) og glykosylerte flavonoler. Blant flavonene foretrekkes flavonolene, særlig flavonotetraolene og høyere hydroksylerte analoger, såsom kaempferol, kversitin og myresitin, og de metylerte analoger, såsom sinensetin, tangeretin og nobilstin, samt glykosidene, såsom rutin og myrisitrin. Blant isoflavonene er daidzein og genistein eksempler på foretrukne forbindelser, og blant antocyanidinene er peonidin, cyanidin, pelargonidin, delfini-din, petunidin og valvidin foretrukne. Flavanoner {= 2,3-dihydroflavoner), såsom hesperetin og naringin, er andre foretrukne flavonoider. Anvendelse av en blanding av flavonoider, såsom i naturlige planteekstrakter eller blandinger av planteekstrakter (f.eks. sitron, te, drue) er fordelaktig. Fortrinnsvis inneholder flavonoidene ifølge oppfinnelsen minst 40% flavonoler og minst 10% antocyaner, mer foretrukket henholdsvis minst 60% og minst 15%. Analoger, såsom katechiner, proantocyanidiner og andre tanniner, er fortrinnsvis ikke tilstede, dvs. utgjør mindre enn 3% av flavonoidene.
Materialet ifølge oppfinnelsen er beregnet på å bedre blodsirkulasjon, akselerere helbredelse og bedring av immunstatusen og på å kompensere for tap av næringskompo-nenter som opptrer under sykdom. Det stabiliserer også cellemembraner mot stråleangrep. I tillegg til tokoferolene og askorbatet økes denne funksjon av glutation og NADPH, som gjøres tilgjengelige ved tilførsel av metionin, ko-faktorer og energi (karbohydrater).
Andre foretrukne bestanddeler er vitaminene B6 (pyridoxal), B12 (cyanokobalamin) og folinsyre, som hver foreligger i ca. 3 ganger det anbefalte daglige tilførsels-nivå (som nevnte RDA). Vitaminene Bl (tiamin) og B2 (ribo-flavin), kobber, sink og mangan foreligger hver i to ganger RDA. Forholdet mellom sink og kobber bør fortrinnsvis være i området 7-14, særlig 8-11. Jern, kobolt, jodid, krom, selen, fluorid, molybden og pantotensyre, vitamin A (i retinolekvivalenter, RE), vitamin D, vitamin K, niacin (i niacinekvivalenter, NE), biotin og inositol, foreligger fortrinnsvis i 0,5-4, særlig 1-2 ganger RDA-verdiene for hver. Mineraler bør fortrinnsvis foreligge som følger (mengder per dag): natrium 200-1200 mg, klorid 240-1400 mg, kalium 500-1800 mg, kalsium 500-1000 mg, fosfor 400-900 mg og magnesium 150-400 mg.
Karotenoider (som for formålet med oppfinnelsen omfatter xantiner og xantofyller) foreligger fortrinnsvis i et nivå på 0,8-16 mg, fortrinnsvis 1-6 mg, per dag. Karotenoidene er med fordel i sin naturlige form slik de kan finnes i ekstrakter fra planter som tomat, pepper, ringblom og frukt fra oljepalme. Fortrinnsvis blandes slike ekstrakter, og blandingen kan f.eks. inneholde lutein (20-60%), lykopen (1-30%), a-karoten (5-25%), B-karoten (5-40%), kryptoxantin (1-15%) og zeaxantin (1-15%).
Cholin eller en metabolisk ekvivalent av denne, såsom betain eller fosfatidylcholin, foreligger fortrinnsvis i et nivå på 20-3000 mg/dag, som kan omfatte f.eks. 1 g eller mer av fosfatidylcholin. Karnitin, kreatin og taurin kan foreligge i nivåer på henholdsvis 10-100 mg, 100-1000 mg og 10-100 mg per dag.
Langkjedete, flerumettede fettsyrer i co-3-serien, særlig EPA og DHA, kan også med fordel være tilstede. Totalen av EPA og DHA er med fordel mellom 0,1 og 1,0 g/dag. Forholdet co-6/a>-3 i de langkjedete, flerumettede fettsyrer er mellom 1 og 6, fortrinnsvis mellom 2 og 5. Linolsyre (co-6) kan også være tilstede, fortrinnsvis i et nivå på minst 0,1 g/dag.
En annen fordelaktig gruppe av bestanddeler i materialet er kostfibre, som kan omfatte løselige ikke-stivelsespolysakkarider, såsom gummi arabicum eller pektin, uløselige ikke-stivelsespolysakkarider, såsom cellulose, hemicellulose og lignin, oligosakkarider, såsom inulin, eller galakto-oligosakkarider og/eller resistent stivelse. Det foretrukne nivå av kostfiber er 3-20 g/dag eller 3-20 g/liter.
Karbohydrater, smaksstoffer og gjærekstrakter kan bedre materialets ernæringsmessige og organoleptiske kvalitet ytterligere. Produktet pakkes fortrinnsvis i en form som beskytter det mot oksygen og lys, særlig UV, f.eks. i 100-1000 ml enheter. De mindre mengder er anvendelige som matsupplementer, mens de større mengder er egnet som komplette matvarer, for enteral anvendelse.
Mengdene av de viktige bestanddeler arginin, vitamin C og vitamin E kan også defineres i forhold til et enhets-energiinnhold (1000 kcal) eller til et enhetsvolum (1 liter), slik som i de etterfølgende krav. En tilsvarende definisjon kan gis for de foretrukne bestanddeler, såsom flavonoider (16-60 mg/1000 kcal, 16-80 mg/l), Karotenoider (1,6-20 mg/1000 kcal, 1,6-24 mg/l), sink (18-60 mg/1000 kcal, 18-75 mg/l) og kobber (2,5-10 mg/1000 kcal, 2,5-12 mg/l).
Som oppsummering viser tabell 1 anbefalte og foretrukne områder for sammensetninger og eksempler på formu-leringer som kan benyttes som et flytende materiale som gir den totale, daglige minste næringstilførsel og som kan suppleres med energi etter behov.
Eksempel I
Bestanddelene som er angitt i tabell 1 i 1000 ganger de mengder som er angitt i siste spalte i tabell 1 ble blandet i en beholder, homogenisert ved kjente metoder og brakt på et totalt volum på 1000 liter. Blandingen ble pakket i 500 ml flaske for anvendelse som sondeforing.
Eksempel II
Bestanddelene som er angitt i tabell 1 i 1000 ganger mengdene som angitt i 6. spalte i tabell 1 ble blandet i en beholder, homogenisert under anvendelse av kjente metoder og brakt på et totalt volum på 400 liter. Blandingen ble pakket i 200 ml kartonger.
Eksempel III
Følgende bestanddeler: natrium 600 g, klorid 900 g, tokoferoler 150 g, cholin 800 g, ingen flavonoider og ingen karotenoider, og de ytterligere bestanddeler i 1000 ganger mengden i 6. spalte i tabellen ble blandet og pakket som i eksempel II. Produktet er en hvitaktig drikk og er særlig egnet for behandling av liggesår etter betydelig mineral-tap, som i tilfeller med kronisk åpne sår.
Claims (14)
1. Ernæringstilskuddsmateriale egnet for behandling av liggesår, karakterisert ved at materialet inneholder proteiner, karbohydrater og fett, samt at det inneholder per liter: 6 til 20 g arginin; 400 til 1800 mg askobinsyreekvivalenter; 100 til 600 mg alfatokoferolekvivalenter; og minst en komponent valgt fra: 16 til 80 mg flavonoider; 20 til 60 mg sink; 2,5 til 12 mg kopper; 1,6 til 24 mg karotenoider.
2. Materiale i samsvar med krav 1, karakterisert ved at det inneholder 50 til 100 g/l proteiner, 60 til 180 g/l karbohydrater og 20 til 40 g/l fett, hvor fettet omfatter 0,05 til 0,5 g/l DHA og som har et omega 6/omega 3-forhold på mellom 2 og 5.
3. Materiale i samsvar med krav 1 eller 2, karakterisert ved at det ytterligere omfatter per 1000 ml minst en av 0,2 til 1,5 mg retinolekvivalenter, 8 til 20 mg vitamin D, 2 til 5 mg tiamin, 1,7 til 5 mg riboflabin, 80 til 200 mg kolinekvivalenter, 6 til 24 mg pantotenisk syre, 50 til 500 ug Biotin, 4 til 20 mg mangan, 5 til 20 mg jern og 70 til 140 ug selen.
4. Materiale i samsvar med et av kravene 1-3, karakterisert ved at det inneholder 0,9 til 1,3 kg kal/ml.
5. Ernaeringstilskuddsmateriale egnet for behandling av liggesår, karakterisert ved at det omfatter proteiner, karbohydrater og fett, og at det inneholder per 1000 kcal: 6 til 18 g arginin; 400 til 1500 mg askobinsyreekvivalenter; 100 til 500 mg alfatokoferolekvivalenter ; og minst en komponent valgt blant: 16 til 60 mg flavonoider; 20 til 50 mg sink; 2,5 til 10 mg kopper; 1,6 til 20 mg karotenoider.
6. Materiale i samsvar med krav 5, karakterisert ved at det inneholder 22 til 38 energiprosenterproteiner, 36 til 60 energiprosenter karbohydrater og 20 til 30 energiprosenter fett, hvor fettet omfatter 0,05 til 0,5 g/l DHA, og har et omega 6/omega 3-forhold på mellom 2 og 5.
7. Anvendelse av en kombinasjon av arginin, askobinsyreekvivalenter og alfatokoferolaekvivalenter for fremstilling av et ernæringstilsetningsmateriale for anvendelse i behandling av liggesår.
8. Anvendelse i samsvar med krav 7, hvor anvendelsen omfatter administrering av nevnte materiale for å avgi en daglig dosering av 3 til 15 g arginin eller ekvivalenter derav, 180 til 840 mg askobinsyreekvivalenter og 50 til 400 mg alfatokoferolekvivalenter.
9. Anvendelse i samsvar med et av kravene 7 eller 8, omfattende administrering av en daglig dosering av minst en av: 5 til 10 g arginin eller ekvivalenter derav, 300 til 700 mg askobinsyreekvivalenter, 80 til 250 mg tokoferolekvivalenter og 8 til 80 mg sink.
10. Anvendelse i samsvar med et av kravene 7-9, hvor anvendelsen ytterligere omfatter administrering av en daglig dosering av 8 til 40 mg, fortrinnsvis 10 til 30 mg flavonoider, hvor flavonoidene fortrinnsvis omfatter flavonoler og antosianer.
11. Anvendelse i samsvar med et av kravene 7-10, hvor anvendelsen ytterligere omfatter administrering av en daglig dosering av 14 til 45 mg (fortrinnsvis 18 til 36 mg) sink, og/eller 2 til 10 mg (fortrinnsvis 2,5 til 6 mg) kopper, med et molart sink til kopper forhold av mellom 7 og 14.
12. Anvendelse i samsvar med et av kravene 7-11, hvor anvendelsen ytterligere omfatter administrering av en daglig dosering av 0,8 til 16 mg karotenoider, hvor karotenoidene fortrinnsvis omfatter lutein (20 til 60 %), lykopen (1 til 30 %), alfakaroten (5 til 25 %), betakaroten (5 til 40 %), kryptoeksantin (1 til 15 %) og seaeksentin (1 til 15 %).
13. Anvendelse i samsvar med et av kravene 7-12, hvor anvendelsen ytterligere omfatter administrering av en daglig dosering av minst en av 0,8 til 15 g (fortrinnsvis 1 til 3 g) metionin, 0,4 til 1,2 mg fonisk syre, 4 til 10 mg vitamin B6 og 2 til 20 ug cyanokobalamin.
14. Anvendelse i samsvar med et av kravene 7-13, hvor anvendelsen omfatter administrering av en daglig dosering av minst 800 mg natrium og/eller minst 1200 mg klorid.
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EP98201576A EP0960572A1 (en) | 1998-05-12 | 1998-05-12 | Nutritional composition for the treatment of pressure ulcers |
PCT/NL1999/000295 WO1999058000A1 (en) | 1998-05-12 | 1999-05-12 | Nutritional composition for the treatment of pressure ulcers |
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AU2019345982A1 (en) | 2018-09-25 | 2021-05-06 | Roquette Freres | Food composition containing a mixture of leguminous proteins and casein |
DE102018124227A1 (de) | 2018-10-01 | 2020-04-02 | sanaFactur GmbH | Zubereitung zur Verbesserung körpereigener Wundheilung |
US10918654B1 (en) * | 2019-09-23 | 2021-02-16 | Alps Pharmaceutical Ind. Co., Ltd. | Rutin compositions |
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US5053387A (en) * | 1987-02-20 | 1991-10-01 | Shriners Hospitals For Crippled Children | Omega-3 fatty acids in traumatic injury treatment |
EP0367724B1 (en) * | 1988-10-31 | 1993-02-10 | Sandoz Nutrition Ltd. | Improvements in or relating to organic compounds |
CA2123678A1 (en) * | 1991-11-26 | 1993-06-10 | Alain Martin | Wound healing compositions containing a pyruvate, an antioxidant and a mixture of fatty acids |
US5221668A (en) * | 1992-02-26 | 1993-06-22 | Abbott Laboratories | Nutritional product for trauma and surgery patients |
AU3374593A (en) | 1992-04-10 | 1994-04-14 | Clintec Nutrition Company | Improved high protein liquid nutrition for patients with elevated wound healing requirements |
GB2274235B (en) * | 1993-01-13 | 1996-06-26 | Neo Life Company Of America | Carotenoid food supplement |
GB9318611D0 (en) * | 1993-09-08 | 1993-10-27 | Sandoz Nutrition Ltd | Improvements in or relating to organic compounds |
GB9403935D0 (en) * | 1994-03-01 | 1994-04-20 | Sandoz Nutrition Ltd | Improvements in or relating to organic compounds |
US5656588A (en) * | 1994-07-19 | 1997-08-12 | Wake Forest University | Wound healing formula |
US6190704B1 (en) | 1994-09-23 | 2001-02-20 | New York Society For The Ruptured And Crippled Maintaining The Hospital For Special Surgery | Regulation of wound healing by nitric oxide |
US5733884A (en) * | 1995-11-07 | 1998-03-31 | Nestec Ltd. | Enteral formulation designed for optimized wound healing |
US6139872A (en) * | 1996-08-14 | 2000-10-31 | Henkel Corporation | Method of producing a vitamin product |
DE69826253D1 (de) * | 1997-03-20 | 2004-10-21 | Coventry Group Ltd | Nährungsergänzungsmittel für kardiovasküläre gesundheit |
US5968896A (en) * | 1998-01-16 | 1999-10-19 | Beth Israel Deaconess Medical Center | Nutritional supplement for preoperative feeding |
EP0960572A1 (en) * | 1998-05-12 | 1999-12-01 | N.V. Nutricia | Nutritional composition for the treatment of pressure ulcers |
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1998
- 1998-05-12 EP EP98201576A patent/EP0960572A1/en not_active Withdrawn
- 1998-05-12 ID IDW20000053A patent/ID24710A/id unknown
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1999
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- 1999-05-12 WO PCT/NL1999/000295 patent/WO1999058000A1/en active IP Right Grant
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- 1999-05-12 BR BR9906438-3A patent/BR9906438A/pt not_active Application Discontinuation
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- 1999-05-12 EP EP10184241.7A patent/EP2277394B1/en not_active Revoked
- 1999-05-12 AT AT99922654T patent/ATE516715T1/de active
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- 1999-05-12 JP JP2000547864A patent/JP2002514574A/ja active Pending
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2004
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