NO792260L - PROCEDURE FOR THE EXTRACTION OF A NATURALLY EXISTING POLAR FRACTION WITH ANTIPSORIATIC EFFECT - Google Patents
PROCEDURE FOR THE EXTRACTION OF A NATURALLY EXISTING POLAR FRACTION WITH ANTIPSORIATIC EFFECTInfo
- Publication number
- NO792260L NO792260L NO792260A NO792260A NO792260L NO 792260 L NO792260 L NO 792260L NO 792260 A NO792260 A NO 792260A NO 792260 A NO792260 A NO 792260A NO 792260 L NO792260 L NO 792260L
- Authority
- NO
- Norway
- Prior art keywords
- polypodium
- extraction
- solution
- rhizomes
- evaporated
- Prior art date
Links
- 238000000605 extraction Methods 0.000 title claims description 8
- 230000002682 anti-psoriatic effect Effects 0.000 title claims description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 239000000243 solution Substances 0.000 claims description 11
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 241000723185 Cyathea Species 0.000 claims description 2
- 241000487005 Phlebodium decumanum Species 0.000 claims description 2
- 241000244324 Polypodium aureum Species 0.000 claims description 2
- 241000592274 Polypodium vulgare Species 0.000 claims description 2
- 241001362840 Serpocaulon triseriale Species 0.000 claims description 2
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- 229940075984 polypodium leucotomos Drugs 0.000 claims description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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- 241000282472 Canis lupus familiaris Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000001840 Dandruff Diseases 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
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- 241000393483 Dryopteris crassirhizoma Species 0.000 description 1
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- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
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- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000985694 Polypodiopsida Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
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- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 239000000902 placebo Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/11—Pteridophyta or Filicophyta (ferns)
- A61K36/12—Filicopsida or Pteridopsida
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Alternative & Traditional Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Dermatology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
Denne oppfinnelse angår fremstillingen av en naturlig,This invention relates to the production of a natural,
polar fraksjon med antipsoriatisk virkning, ved ekstraksjon fra blader og rotstokker av diverse bregner. polar fraction with antipsoriatic effect, by extraction from leaves and rhizomes of various ferns.
Den vitenskapelig-terapeutiske utvikling til tross, finnes der intet legemiddel som er i stand til å forbedre tilstanden hos, enn si helbrede, pasienter som lider av psoriasis Despite the scientific-therapeutic development, there is no drug capable of improving the condition of, let alone curing, patients suffering from psoriasis
og de dermatologiske problemer som er forbundet med parapsoriasis. and the dermatological problems associated with parapsoriasis.
Kjennskapen til psoriasis er meget gammel, og mange for-Knowledge of psoriasis is very old, and many
søk har vært gjort på å helbrede sykdommen. Bestrebelsene har imidlertid kun ført til meget beskjedne resultater, og i de fleste tilfeller anvendes droger og medikamenter som i løpet av kort tid kan medføre fatale konsekvenser for pasienten. Searches have been made to cure the disease. However, the efforts have only led to very modest results, and in most cases drugs and medications are used which can have fatal consequences for the patient within a short time.
Interessant nok har man nu på ny begynt å ta i bruk de tidligere behandlingsformer, fordi de er uskadelige, og fordi Interestingly enough, people have now started to use the previous forms of treatment again, because they are harmless, and because
de gir pasienten en viss symptomatologisk lindring. Dog er dethey provide the patient with some symptomatic relief. However, they are
aldri i stand til å helbrede sykdommen eller å medføre noen be-merkelsesverdig forbedring i tilstanden. never able to cure the disease or bring about any remarkable improvement in the condition.
Problemet blir så meget alvorligere som antallet av psoriatiske pasienter øker fra dag til dag. Det antas åt det dreier seg om genetisk overføring av sykdommen, og at sykdommen enten kommer til syne hos slektens individer klart og tydelig eller i en innledende form, eller foreligger som en latent mulighet, i hvilket sistnevnte tilfelle sykdommen vil manifestere seg kun dersom utløsende patologiske faktorer får gjøre seg gjeldende. The problem becomes much more serious as the number of psoriatic patients increases from day to day. It is assumed that this is a matter of genetic transmission of the disease, and that the disease either appears in the individuals of the family clearly and distinctly or in an initial form, or exists as a latent possibility, in which latter case the disease will manifest itself only if triggering pathological factors may come into play.
Hele kroppsoverf laten påvirkes-, og ett av. hovedområdendeThe entire body surface is affected, and one of main area
er hodeskallen, hvor tilstanden gir seg uttrykk ved "flass", som pasienten som oftest ikke tar notis av før mange år er gått og is the scalp, where the condition manifests itself in "dandruff", which the patient usually does not notice until many years have passed and
han blir klar over at problemet er blitt verre til tross for lokal behandling. Tilstedeværelsen av "flass", når psoriasis angriper andre hudpartier, observeres i 90 % av tilfellene. Sykdommen angriper således en hvilken som helst del av kroppsover-flaten, uansett personens alder. Derfor kan nyfødte babier like- he becomes aware that the problem has worsened despite local treatment. The presence of "dandruff", when psoriasis attacks other parts of the skin, is observed in 90% of cases. The disease thus attacks any part of the body surface, regardless of the person's age. Therefore, newborn babies can like-
så vel som gamle mennesker i 60- eller 70-årene bli angrepet. as well as old people in their 60s or 70s being attacked.
Sykdommen er utbredt over hele kloden og skiller ikke mel-lom rasene. Muligens er hyppigheten noe mindre for den sorte rase. The disease is widespread all over the globe and does not discriminate between races. Possibly the frequency is somewhat less for the black race.
Den vanligste komplikasjon som knytter seg til sykdommen,The most common complication associated with the disease,
er arthropatia, men sykdommen vil også etterhvert innvirke på de edlere vev, såsom lever- og nyrevev. is arthropathy, but the disease will also eventually affect the nobler tissues, such as liver and kidney tissue.
Kort sagt er psoriasis og parapsoriasis patologiske le-sjoner som er lette å diagnostisere, selv når anatomisk-patolo-gisk diagnose er påkrevet. Forsiktig anslått lider 1 % av verdens befolkning av sykdommen. Hittil er det ikke funnet noe effektivt legemiddel, og psoriatiske pasienter har måttet nøye seg med lindrende midler. In short, psoriasis and parapsoriasis are pathological lesions that are easy to diagnose, even when anatomical-pathological diagnosis is required. It is conservatively estimated that 1% of the world's population suffers from the disease. So far, no effective drug has been found, and psoriatic patients have had to make do with palliatives.
Det har nu vist seg at en naturlig fraksjon som isoleresIt has now been shown that a natural fraction that is isolated
fra rotstokker og blader avDryopteris crassirhizoma, Polypodium vulgare, Linn, Polypodium leucotomos, Phlebodium decumanum og Cyathea taiwaniana og fra rotstokker av Polypodium aureum Linn og Polypodium triseriale, har helbredende egenskaper ved behandling from rhizomes and leaves of Dryopteris crassirhizoma, Polypodium vulgare, Linn, Polypodium leucotomos, Phlebodium decumanum and Cyathea taiwaniana and from rhizomes of Polypodium aureum Linn and Polypodium triseriale, have healing properties when treated
av psoriatiske og parapsoriatiske pasienter av begge kjønn og alle aldere. Det samme gjelder forøvrig derivater av fraksjonens stoffer, såsom estere, amider, osv. Mer enn 300 pasienter som led av psoriasis, ble behandlet oralt med en liten mengde, f.eks. 5 mg daglig pr. kg kroppsvekt. Resultatet var at 80 % av pasientene . som ble behandlet i ca. 3 måneder, ble fullstendig helbredet. En dobbel blindprøve ble utført på en gruppe bestående av 50 pasienter. Legemidlet viste seg å være effektivt sammenlignet med et placebo-preparat som hadde samme organoleptiske størrelse, of psoriatic and parapsoriatic patients of both sexes and all ages. The same also applies to derivatives of the fraction's substances, such as esters, amides, etc. More than 300 patients suffering from psoriasis were treated orally with a small amount, e.g. 5 mg daily per kg body weight. The result was that 80% of the patients. which was treated for approx. 3 months, was completely cured. A double blind test was performed on a group consisting of 50 patients. The drug proved to be effective compared to a placebo preparation that had the same organoleptic size,
form og karakteristika. Disse fraksjoner og derivatene av de aktive stoffer er blitt anvendt for alle former av psoriasis og på alle stadier.av denne patologiske lesjon. form and characteristics. These fractions and derivatives of the active substances have been used for all forms of psoriasis and at all stages of this pathological lesion.
I toksikologisk henseende ble ingen effekt påvist. I løpet av 12 års forskning er det ved haematologiske prøver, benmargs-prøver, prøver med hensyn til leverens og nyrenes funksjonering og urinanalyse aldri blitt påvist endringer. I henhold til de retningslinjer som er gitt av F.D.A. i USA, og i henhold til "Guidelines for reproduction studies for safety evaluation of drugs for human use" endrer ikke forbindelsene fruktbarheten hos rotter og mus og andre pattedyr (hunder). Heller ikke er det blitt påvist noen theratofenisk virkning i løpet av fire generasjoner av rotter og mus og to generasjoner av hunder. In toxicological terms, no effect was detected. During 12 years of research, haematological tests, bone marrow tests, tests with regard to the functioning of the liver and kidneys and urinalysis have never shown any changes. According to the guidelines given by the F.D.A. in the USA, and according to the "Guidelines for reproduction studies for safety evaluation of drugs for human use", the compounds do not alter fertility in rats and mice and other mammals (dogs). Nor has any theratofenic effect been demonstrated during four generations of rats and mice and two generations of dogs.
Ingen carcinogenetisk virkning er blitt påvist. Disse undersøkelser ble foretatt på mus, som daglig, i 24 uker, ble gitt en oral dose på 1 mg pr. kg kroppsvekt. Fra og med den syvende uke ble dyrene avlivet med og uten innføring av glass-partikler i urinblæren. Metodene som ble benyttet ved disse under-søkelser, er- beskrevet av Jull, J.W. Brit J. Cancer 5 328 (1951), og den statistiske bedømmelse som benyttet, er beskrevet i Arcos et al., Chemical Induction of Cancer, Pag. Academic Press inc., New York (1963) . No carcinogenic effect has been demonstrated. These investigations were carried out on mice, which were given an oral dose of 1 mg per day for 24 weeks. kg body weight. Starting from the seventh week, the animals were euthanized with and without the introduction of glass particles into the urinary bladder. The methods used in these investigations are described by Jull, J.W. Brit J. Cancer 5 328 (1951), and the statistical evaluation used is described in Arcos et al., Chemical Induction of Cancer, Pag. Academic Press inc., New York (1963).
Den polare fraksjons virkningsmekanisme er som følger:The polar fraction's mechanism of action is as follows:
(a) en økning av gjennomtrengningen, gjennom cellemembranet,(a) an increase in permeability, through the cell membrane,
av sukkerarter såsom glucose, saccharose og fructose, og for aminosyrer, såsom valin, lysin og andre som forekommer i mindre mengder, of sugars such as glucose, sucrose and fructose, and for amino acids such as valine, lysine and others that occur in smaller amounts,
(b) en økning av cellemembranbærernes bevegelseskapasitet,(b) an increase in the movement capacity of cell membrane carriers,
(c) en økning av vannutvekslingen på cellémembrannivå,(c) an increase in water exchange at the cell membrane level,
(d) en økning av aktiviteten av hepatocytes (denne observerte økning har muligens sammenheng med de ovennevnte økninger), (e) en økning i collagenets vekst- og modningsaktivitet. (d) an increase in the activity of hepatocytes (this observed increase is possibly related to the above-mentioned increases), (e) an increase in the growth and maturation activity of the collagen.
Fraksjonen har ikke steroidal aktivitet. Hva dens virkning på andre organer og systemer angår, har den en bradycardiakalsk virkning tilsvarende virkningen av digitalis, muligens som følge av dens virkning på de myocardiale cellemembraner. The fraction has no steroidal activity. As regards its action on other organs and systems, it has a bradycardic effect similar to that of digitalis, possibly as a result of its action on the myocardial cell membranes.
Fremgangsmåten ifølge oppfinnelsen muliggjør ekstraksjon av denne polare fraksjon i industrielt aksepterbare utbytter og i aksepterbare mengder fra de ovennevnte deler av plantene, for anvendelse ved fremstilling av farmasøytiske preparater. For å oppnå et optimalt utbytte bør bladene innsamles etterat plantene The method according to the invention enables the extraction of this polar fraction in industrially acceptable yields and in acceptable quantities from the above-mentioned parts of the plants, for use in the manufacture of pharmaceutical preparations. To achieve an optimal yield, the leaves should be collected after the plants
har utviklet sporer.have developed spores.
Fremgangsmåten ifølge oppfinnelsen omfatter de følgende trinn: The method according to the invention includes the following steps:
TørkingDrying
Rotstokkene bør foreligge f-, eks. i strimler av lengde 2 -The rootstocks should be present f-, e.g. in strips of length 2 -
3 cm, mens bladene tørkes i den tilstand de innsamles. Tørkingen finner sted ved at materialet kontinuerlig tilføres en konven-sjonell tørker som f.eks. kan bestå av en roterende metallwireduk av bredde ca. 5 cm og lengde 25 m, som beveges i et varmt rom ved en temperatur av høyst 70°C. Ved å avpasse hastigheten av den roterende metallwireduk kan ca. et halvt tonn fuktig materiale tørkes pr. time. 3 cm, while the leaves are dried in the state in which they are collected. The drying takes place by continuously feeding the material to a conventional dryer such as can consist of a rotating metal wire cloth of width approx. 5 cm and length 25 m, which is moved in a warm room at a temperature of no more than 70°C. By adjusting the speed of the rotating metal wire cloth, approx. half a tonne of moist material is dried per hour.
GranuleringGranulation
Det tørre materiale (med restfuktighet mindre enn 8 %) granuleres i en skivemølle som er innstilt til å gi partikler på The dry material (with residual moisture less than 8%) is granulated in a disc mill which is set to give particles of
2 mm.2 mm.
Ekstråks j on- inndampningEvaporation of exhaust gases
Ekstråksjonen kan utføres med et hvilket som helst opp-løsningsmiddel (med dielektrisk konstant i området fra 1,890 The extraction can be carried out with any solvent (with a dielectric constant in the range from 1.890
til 9,08), som fortrinnsvis er methanol anvendt i volumforholdet 1:4. to 9.08), which is preferably methanol used in the volume ratio 1:4.
Inndampningen foretas slik at det fåes et residuum svarende til 1/5 av det opprinnelige volum. The evaporation is carried out so that a residue corresponding to 1/5 of the original volume is obtained.
RensningCleaning
1. Det halvfaste residuum.fra ekstraksjons- og inndampnings-operasjonen tas opp i et system av ikke-blandbare oppløsnings-midler, nemlig n-hexan og vann (10:4). Blandingen tillates å stå natten over i separatorer, hvoretter lipider og harpikser fraskilles i hexanfasen. 2. Den fraskilte og filtrerte vandige oppløsning føres gjennom en utvekslingskolonne. 1. The semi-solid residue from the extraction and evaporation operation is taken up in a system of immiscible solvents, namely n-hexane and water (10:4). The mixture is allowed to stand overnight in separators, after which lipids and resins are separated in the hexane phase. 2. The separated and filtered aqueous solution is passed through an exchange column.
3. Ca(0H)2tilsettes for nøytralisering.3. Ca(OH)2 is added for neutralization.
4. Til den ovennevnte oppløsning tilsettes porsjoner av aktivt carbon inntil op<p>løsningen er klarnet. 5. Oppløsningen inndampes til 1/10 av det opprinnelige volum, og det foretas utfelning i en med vann blandbar, vannfri organisk væske, såsom f.eks. absolutt alkohol. 6. Utfeiningen frafiltreres ved sugning, hvorved det fåes en første, pulverformig masse, og moderluten inndampes på ny, hvorved det fåes en annen, pulverformig masse. 4. Portions of active carbon are added to the above solution until the solution is clear. 5. The solution is evaporated to 1/10 of the original volume, and precipitation is carried out in a water-miscible, anhydrous organic liquid, such as e.g. absolute alcohol. 6. The skimming is filtered off by suction, whereby a first, powdery mass is obtained, and the mother liquor is evaporated again, whereby a second, powdery mass is obtained.
Dette pulver tørres i vakuum inntil det er blitt meget hvitt. This powder is dried in a vacuum until it has become very white.
Den annen, hvite, krystallinske masse, som er det produkt som fåes ved fremgangsmåten ifølge oppfinnelsen, er ikke noe vel-definert kjemisk stoff, men et sammensatt materiale som vil variere med arten av den anvendte droge og med ekstraksjons- og rensningsmetodene som benyttes . The other, white, crystalline mass, which is the product obtained by the method according to the invention, is not a well-defined chemical substance, but a composite material that will vary with the nature of the drug used and with the extraction and purification methods used.
At D-glucose og D-fructose er tilstede i en samlet mengde av 70 % er blitt påvist ved vanlige kvalitative tester foruten ved isolering og fullstendig identifisering av de tilsvarende acetylerte derivater. Tilstedeværelsen av de sure forbindelser som ikke lett lar seg separere fra sukrene, blir på den annen side bestemt ved kromatografering og ved vanlige spektroskopiske metoder. That D-glucose and D-fructose are present in a total amount of 70% has been demonstrated by usual qualitative tests in addition to the isolation and complete identification of the corresponding acetylated derivatives. The presence of the acidic compounds which cannot be easily separated from the sugars, on the other hand, is determined by chromatography and by conventional spectroscopic methods.
Farmasøytiske preparater i de konvensjonelle doserings-former fremstilles ved at der i den polare fraksjon som fåes ved fremgangsmåten ifølge oppfinnelsen, innlemmes farmasøytiske bærere i henhold til vanlig farmasøytisk praksis. Den aktive bestanddel, dvs. den polare fraksjon, vil være tilstede i preparatene i tilstrekkelig mengde til å gi en antipsoria tisk virkning. Pharmaceutical preparations in the conventional dosage forms are prepared by incorporating pharmaceutical carriers in the polar fraction obtained by the method according to the invention in accordance with normal pharmaceutical practice. The active ingredient, i.e. the polar fraction, will be present in the preparations in sufficient quantity to produce an antipsoriatic effect.
Preparatene inneholder fortrinnsvis, fra 10 til 100 mg av den aktive bestanddel pr. enhetsdose. Den farmasøytiske bærer kan f.eks. være et fast stoff eller en væske. Lactose, magnesium-stearat, alba terra, saccharose, talkum, stearinsyre, gelatin, agar, pectin, gummi arabicum, aerosil og lignende er eksempler på faste bærere. The preparations preferably contain from 10 to 100 mg of the active ingredient per unit dose. The pharmaceutical carrier can e.g. be a solid or a liquid. Lactose, magnesium stearate, alba terra, sucrose, talc, stearic acid, gelatin, agar, pectin, gum arabic, aerosil and the like are examples of solid carriers.
Eksempler på væskeformige bærere, er alkoholer (såsom ethanol eller propylenglycol), vann inneholdende et oppløseliggjørende middel såsom polyethylenglycol, peanøttolje, olivenolje og lignende. Bæreren eller fortynningsmaterialet kan inneholde et re- tarderende. middel, såsom glycerylmonostearat eller glyceryldi-stearat, alene eller sammen med en voks. Examples of liquid carriers are alcohols (such as ethanol or propylene glycol), water containing a solubilizing agent such as polyethylene glycol, peanut oil, olive oil and the like. The carrier or dilution material may contain a retardant. agent, such as glyceryl monostearate or glyceryl di-stearate, alone or together with a wax.
Et stort antall farmasøytiske former kan anvendes. Dersom en fast bærer anvendes, kan preparatet overføres til tabletter, innføres i en hård gelatinkapsel i form av et pulver eller i form av granuler, eller det kan gies form av sugetabletter. Mengden av fast bærer kan variere innenfor vide grenser men er fortrinnsvis fra 25 til 300 mg. Dersom en væskeformig bærer benyttes, kan preparatet gies form av en sirup, en emulsjon, myke gelatinkapsler, en suspensjon eller en flytende oppløsning, eller det kan gies en steril, injiserbar form for parenteral anvendelse, f.eks. i en ampulle. A large number of pharmaceutical forms can be used. If a solid carrier is used, the preparation can be transferred to tablets, introduced into a hard gelatin capsule in the form of a powder or in the form of granules, or it can be given in the form of lozenges. The amount of solid carrier can vary within wide limits but is preferably from 25 to 300 mg. If a liquid carrier is used, the preparation can be given in the form of a syrup, an emulsion, soft gelatin capsules, a suspension or a liquid solution, or it can be given in a sterile, injectable form for parenteral use, e.g. in an ampoule.
De farmasøytiske preparater i væskeformige suspensjoner eller oppløsninger innbefatter ikke de enkle væskeformige suspensjoner eller oppløsninger av den aktive bestanddel i de vanlige oppløsningsmidler som er uegnede for' innvendig admini-strering for frembringelse av denønskede farmakologiske aktivitet. The pharmaceutical preparations in liquid suspensions or solutions do not include the simple liquid suspensions or solutions of the active ingredient in the usual solvents which are unsuitable for internal administration to produce the desired pharmacological activity.
Administreringen kan skje oralt eller parenteralt, fortrinnsvis oralt. Den aktive bestanddel vil fortrinnsvis bli ad-ministrert i en daglig dose fra 50 mg til 900 mg, helst fra 100 til 300 mg. Det er fordelaktig å administrere preparatene fra 1 til 4 ganger pr. dag. Når adminstreringen skjer som ovenfor beskrevet, oppnåes en antipsoriatisk aktivitet. The administration can take place orally or parenterally, preferably orally. The active ingredient will preferably be administered in a daily dose of from 50 mg to 900 mg, preferably from 100 to 300 mg. It is advantageous to administer the preparations from 1 to 4 times per day. When the administration takes place as described above, an antipsoriatic activity is achieved.
Da psoriasis er en kronisk, snikende prosess med en genetisk etiopathogeni, er det fordelaktig å anvende kapsel- eller As psoriasis is a chronic, insidious process with a genetic etiopathogenesis, it is advantageous to use capsule or
tablettformen, som opprettholder stabile blodkonsentrasjoner og som tillater en kontinuerlig virkning av medikamentet. Ved behandling av alvorlige utbrudd av psoriasis, som kari være forårsaket av bruken av andre medikamenter, såsom steroider, eller kan være forårsaket av sykdommen selv, kan uten tvil intravenøs injeksjon eller kontinuerlig, dråpevis tilførsel av serum benyttes for å avverge krisen. the tablet form, which maintains stable blood concentrations and which allows a continuous effect of the drug. In the treatment of severe outbreaks of psoriasis, which may be caused by the use of other drugs, such as steroids, or may be caused by the disease itself, no doubt intravenous injection or continuous, dropwise administration of serum may be used to avert the crisis.
Det bør også påpekes at dråper eller emulsjoner har vært anvendt for barn av åpenlyse grunner, og i tilfelle av voksne med problemer i den øvre fordøyelseskanal kan stikkpiller anvendes. It should also be pointed out that drops or emulsions have been used for children for obvious reasons, and in the case of adults with problems in the upper digestive tract, suppositories can be used.
De farmasøytiske preparater fremstilles ved konvensjon-nelle metoder som blanding, granulering og pressing, når dette er nødvendig, eller ved blanding og oppløsning av de passende be-standdeler. The pharmaceutical preparations are prepared by conventional methods such as mixing, granulation and pressing, when this is necessary, or by mixing and dissolving the appropriate ingredients.
De følgende eksempler illustrerer oppfinnelsen.The following examples illustrate the invention.
Eksempel 1Example 1
12 kg tørre blader, granulert i en nr. 10 sikt (2,5 mm) ble ekstrahert med 48 liter 95%-ig ethanol i en og en halv time ved 70°C. 12 kg of dry leaves, granulated in a No. 10 sieve (2.5 mm) were extracted with 48 liters of 95% ethanol for one and a half hours at 70°C.
Residuet ble tatt opp i en blanding av n-hexan/vannThe residue was taken up in a mixture of n-hexane/water
(15:10 liter), og det hele ble tillatt å stå natten over i en separator. Hexanfasen ble fraskilt, og den vandige fase ble filtrert. (15:10 liters), and the whole was allowed to stand overnight in a separator. The hexane phase was separated and the aqueous phase was filtered.
Filtratet ble ført gjennom en utvekslingskolonne, som deretter ble nøytralisert med alkali. The filtrate was passed through an exchange column, which was then neutralized with alkali.
Den således nøytraliserte oppløsning ble klaret og inndampet nesten til tørrhet under et moderat vakuum i 4 8 timer (utbytte : ca. 150 g). The thus neutralized solution was clarified and evaporated almost to dryness under a moderate vacuum for 48 hours (yield: approx. 150 g).
Det tørre, faste stoff ble på ny oppløst i methanol og ble tillatt å krystallisere natten over ved 40°C. The dry solid was redissolved in methanol and allowed to crystallize overnight at 40°C.
Eksempel 2Example 2
36 kg, tørr, hel plante, som var granulert, i en skivemølle utstyrt med en nr. 10 sikt (2,5 mm), ble ekstrahert i 16 timer med n-hexan ved romtemperatur. Hexanoppløsningen ble konsentrert og tillatt å stå i vann natten over i en separator. Hexanfasen ble fraskilt, og den vandige fase ble inndampet. 36 kg, dry, whole plant, which was granulated, in a disc mill equipped with a No. 10 sieve (2.5 mm), was extracted for 16 hours with n-hexane at room temperature. The hexane solution was concentrated and allowed to stand in water overnight in a separator. The hexane phase was separated and the aqueous phase was evaporated.
Planteresiduet som var ekstrahert med hexan, ble tatt opp i en tilstrekkelig mengde varm ethanol og tillatt å stå natten over for dannelse av en mettet ekstrakt. Oppløsningen ble filtrert, tilsatt til den vandige fase og ført gjennom en utvekslingskolonne. The plant residue extracted with hexane was taken up in a sufficient amount of hot ethanol and allowed to stand overnight to form a saturated extract. The solution was filtered, added to the aqueous phase and passed through an exchange column.
Oppløsningen ble deretter nøytralisert og klaret og deretter inndampet nesten til tørrhet. The solution was then neutralized and clarified and then evaporated almost to dryness.
Det fåste stoff ble deretter på ny oppløst i 70%-ig ethanol og tillatt å krystallisere natten over ved romtemperatur. Krystallene ble fraskilt, den overskytende væske ble inndampet, The substance obtained was then re-dissolved in 70% ethanol and allowed to crystallize overnight at room temperature. The crystals were separated, the excess liquid was evaporated,
og utbyttet (180 g) ble tørret under vakuum.and the yield (180 g) was dried under vacuum.
Eksempel 3Example 3
12 kg tørre rotstokker, som var granulert i en skivemølle forsynt med en nr. 10 sikt (2,5 mm) ble kontinuerlig ekstrahert med kloroform ved romtemperatur. 12 kg of dry rhizomes, which had been granulated in a disc mill fitted with a No. 10 sieve (2.5 mm) were continuously extracted with chloroform at room temperature.
Ekstrakten ble konsentrert og på ny oppløst i en blanding av n-hexan og vann. The extract was concentrated and redissolved in a mixture of n-hexane and water.
Hexanfasen ble fraskilt og den vandige fase inndampet. The hexane phase was separated and the aqueous phase evaporated.
Residuet av de ekstraherte rotstokker ble tatt odp iThe residue of the extracted rhizomes was taken odp i
varm methanol og tillatt å stå i 16 timer. Blandingen ble filtrert og ledet gjennom en utvekslingskolonne. hot methanol and allowed to stand for 16 hours. The mixture was filtered and passed through an exchange column.
Ekstrakten ble nøytralisert og klaret, hvoretter den ble inndampet og anbragt natten over i 9 5%-ig ethanol i en krystalli-sator. Krystallene ble fraskilt, hvoretter den overskytende væske ble inndampet og den erholdte rest tørret under vakuum (utbytte: 84 g) . The extract was neutralized and clarified, after which it was evaporated and placed overnight in 95% ethanol in a crystallizer. The crystals were separated, after which the excess liquid was evaporated and the residue obtained dried under vacuum (yield: 84 g).
Eksempel 4Example 4
Ved oppvarmning med tilbakeløpskjøling i en og en halv time ble 12 kg granulert, tørret plante (nr. 10 sikt, 2,5 mm) esktra-hert med 90 % methanol ved 70°C. By heating with reflux for one and a half hours, 12 kg of granulated, dried plant (No. 10 sieve, 2.5 mm) was extracted with 90% methanol at 70°C.
Ekstrakten ble filtrert, inndampet og tatt opp i en blanding av hexan og vann (3:2) . Blandingen ble tillatt å stå, hvoretter hexanfasen ble fraskilt og den vandige fase ble filtrert og inndampet. The extract was filtered, evaporated and taken up in a mixture of hexane and water (3:2). The mixture was allowed to stand, after which the hexane phase was separated and the aqueous phase was filtered and evaporated.
Residuet ble oppløst i 90%-ig varm ethanol og ført gjen-om en utvekslingskolonne. The residue was dissolved in 90% hot ethanol and passed through an exchange column.
Ekstrakten ble nøytralisert og inndampet til en tiendedel av dens opprinnelige volum, hvoretter den ble tillatt å krystallisere kaldt. The extract was neutralized and evaporated to one-tenth of its original volume, after which it was allowed to crystallize cold.
Etter filtrering av blandingen ble krystallene fraskilt og moderluten tørret under vakuum (utbytte: 240-250 g). After filtering the mixture, the crystals were separated and the mother liquor dried under vacuum (yield: 240-250 g).
De følgende eksempler på farmasøytiske preparater vil ytterligere illustrere oppfinnelsen. The following examples of pharmaceutical preparations will further illustrate the invention.
Eksempel 1 Example 1
Bestanddelene ble blandet, siktet og innført i hårde gelatinkapsler. En kapsel fremstilt som ovenfor beskrevet admini-streres tre ganger pr. dag. The ingredients were mixed, sieved and introduced into hard gelatin capsules. A capsule prepared as described above is administered three times per day.
Eksempel 2Example 2
Fraksjonen og stivelsen ble blandet og granulert med en oppløsning av 10%-ig gelatin inneholdende polyvinylpyrrolidonet. Granulene ble siktet, tørret og deretter blandet med kaolin og talkum. De ble så siktet og overført til tabletter. The fraction and the starch were mixed and granulated with a solution of 10% gelatin containing the polyvinylpyrrolidone. The granules were sieved, dried and then mixed with kaolin and talc. They were then sieved and transferred to tablets.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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ES471572A ES471572A1 (en) | 1978-07-07 | 1978-07-07 | Anti-psoriatic fern extracts |
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NO792260L true NO792260L (en) | 1980-01-08 |
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NO792260A NO792260L (en) | 1978-07-07 | 1979-07-06 | PROCEDURE FOR THE EXTRACTION OF A NATURALLY EXISTING POLAR FRACTION WITH ANTIPSORIATIC EFFECT |
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ES470204A1 (en) * | 1978-05-24 | 1979-01-01 | Conrad Ltd | Natural terpenes having an antipsoriatic activity |
ES8104315A1 (en) * | 1980-04-02 | 1981-04-16 | Conrad Ltd | Arthritis treatment with fern extracts |
NO150880C (en) * | 1981-06-01 | 1985-01-16 | Borregaard Ind | NEW AZA CROWN ETERS AND USE THEREOF |
JPH0653672B2 (en) * | 1987-12-23 | 1994-07-20 | プソリツル・リミテッド | Therapeutical compositions against psoriasis |
EP0503208A1 (en) * | 1991-03-08 | 1992-09-16 | Maracuyama International, S.A. | Procedure for obtaining a natural water-soluble extract from the leaves and/or rhizomes of various immunologically active ferns |
JPH0633820U (en) * | 1992-10-13 | 1994-05-06 | マルヤス機械株式会社 | Roller conveyor |
ES2068163B1 (en) * | 1994-05-06 | 1995-09-01 | Esp Farmaceuticas Centrum Sa | PROCEDURE FOR OBTAINING A PLANT EXTRACT WITH ACTIVITY IN THE TREATMENT OF COGNITIVE DYSFUNCTIONS AND / OR NEUROINMUNES. |
ATE222112T1 (en) * | 1994-05-06 | 2002-08-15 | Esp Farmaceuticas Centrum Sa | PHARMACEUTICAL COMPOSITION CONTAINING FERN EXTRACT(S) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES. |
ES2137900B1 (en) * | 1998-06-02 | 2000-08-16 | Helsint S A L | USE OF FORMULATIONS BASED ON A WATER-SOLUBLE FRACTION OF PHLEBODIUM DECUMANUM AS A NUTRITIONAL SUPPLEMENT IN THE TREATMENT OF KAQUECTIC SYNDROME IN ONCOLOGICAL PATIENTS. |
ES2124675B1 (en) * | 1997-07-30 | 1999-10-01 | Helsint S A L | "FORMULATIONS BASED ON A WATER-SOLUBLE FRACTION OF PHLEBODIUM DECUMANUM, AND ITS USE IN THE TREATMENT OF THE KAQUECTIAL SYNDROME IN SICK PEOPLE WITH AIDS". |
EP1040834A1 (en) * | 1997-07-30 | 2000-10-04 | Helsint S.A.L. | HYDROSOLUBLE FRACTIONS OF $i(PHLEBODIUM DECUMANUM) AND USE THEREOF AS NUTRITIONAL COMPLEMENTS IN AIDS AND CANCER PATIENTS |
FR2863163B1 (en) * | 2003-12-04 | 2006-02-24 | Oreal | COMPOSITION, ESPECIALLY COSMETIC, COMPRISING EXTRACTS OF FOUGERE AND NACRE |
FR2876032B1 (en) * | 2004-10-05 | 2008-10-31 | Greentech Sa Sa | USE OF EXTRACTS OF FOUGERES IN COSMETIC OR DERMATOLOGICAL PREPARATIONS |
US20060246115A1 (en) * | 2005-03-04 | 2006-11-02 | Ricardo Rueda | Nutritional products for ameliorating symptoms of rheumatoid arthritis |
AT515350A1 (en) * | 2014-02-10 | 2015-08-15 | Christoph Dipl Ing Brandstätter | Process for the preparation of a concentrate of a wood preservative, concentrate produced therewith and process for the treatment of wood |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB256768A (en) * | 1925-07-17 | 1926-08-19 | Francesco Fumarola | Process for extraction of the active biological principles from the ether extract of male fern |
US3395223A (en) * | 1965-05-13 | 1968-07-30 | Carter Wallace | Fern extract for treating gastric ulcers |
FR2395266A1 (en) * | 1977-06-23 | 1979-01-19 | Suffren Ste Parti Brevets | -LACTONE MONOMERS AND THEIR POLYMERS, SALTS AND DERIVATIVES, USED IN PARTICULAR AS COLORS, TANNING ADDICTS AND MEDICINAL PRODUCTS |
JPS5464870A (en) * | 1977-10-21 | 1979-05-25 | Gte Laboratories Inc | Solid state microwave power supply for electrodeless light source |
-
1978
- 1978-07-07 ES ES471572A patent/ES471572A1/en not_active Expired
- 1978-12-27 AR AR274971A patent/AR230188A1/en active
- 1978-12-28 GR GR57991A patent/GR65334B/en unknown
-
1979
- 1979-01-11 DE DE19792900887 patent/DE2900887A1/en not_active Withdrawn
- 1979-01-12 PT PT69067A patent/PT69067A/en unknown
- 1979-01-29 FR FR7902226A patent/FR2434819A1/en active Granted
- 1979-02-01 IT IT7919807A patent/IT7919807A0/en unknown
- 1979-02-27 BE BE193723A patent/BE874483A/en not_active IP Right Cessation
- 1979-03-28 CA CA324,314A patent/CA1106285A/en not_active Expired
- 1979-04-27 SE SE7903762A patent/SE7903762L/en unknown
- 1979-05-02 DK DK180379A patent/DK180379A/en not_active Application Discontinuation
- 1979-05-22 CH CH477779A patent/CH642085A5/en not_active IP Right Cessation
- 1979-05-24 JP JP54064871A patent/JPS6026376B2/en not_active Expired
- 1979-05-24 GB GB7918174A patent/GB2024622B/en not_active Expired
- 1979-05-29 MX MX798029U patent/MX5596E/en unknown
- 1979-07-04 IL IL57721A patent/IL57721A/en unknown
- 1979-07-05 LU LU81464A patent/LU81464A1/en unknown
- 1979-07-05 NL NL7905251A patent/NL7905251A/en not_active Application Discontinuation
- 1979-07-05 FI FI792128A patent/FI792128A/en not_active Application Discontinuation
- 1979-07-05 IS IS2495A patent/IS2495A7/en unknown
- 1979-07-06 MA MA18709A patent/MA18512A1/en unknown
- 1979-07-06 OA OA56841A patent/OA06288A/en unknown
- 1979-07-06 HU HU79CO371A patent/HU179689B/en unknown
- 1979-07-06 PL PL1979216905A patent/PL124244B1/en unknown
- 1979-07-06 NO NO792260A patent/NO792260L/en unknown
- 1979-07-06 CS CS794777A patent/CS215008B2/en unknown
- 1979-07-06 AT AT0471479A patent/AT371715B/en not_active IP Right Cessation
- 1979-07-06 NZ NZ190933A patent/NZ190933A/en unknown
- 1979-07-06 ZA ZA793398A patent/ZA793398B/en unknown
- 1979-07-07 EG EG415/79A patent/EG14496A/en active
- 1979-07-07 RO RO7998089A patent/RO76833A/en unknown
- 1979-07-09 AU AU48764/79A patent/AU4876479A/en not_active Abandoned
- 1979-07-09 PH PH22755A patent/PH14338A/en unknown
- 1979-07-09 DD DD79214207A patent/DD144719A5/en unknown
- 1979-08-08 IE IE1274/79A patent/IE48526B1/en unknown
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