AU657283B2 - Extract of tropical plants, process for producing the same and its use as a medicament - Google Patents

Description

OPI DATa 25/06/q2 AOJP DATE 06/08192

IN'

APPLN. D I'll, 1 PCT NUMBER PCT/ClH91/n0241 P jENS (PCIT) (51) Internationale Patentklassifikation 5 (11) Internationale Veriirrentlichungsnummer: WO 92/09295 A61K 35/78, C07G 17/00 Al (43) Internationales Veriiffentlichungsdatum: 11. Juni 1992 (11.06,92) (21) Internationales Aktenzeichen: PCT/CH-91/00241 Verbffentlicht A'!it internationalem Reclgerclhenberic/u.

(22) Internationales Anmeldedatum: 27. November 1991 (27.11.9 1) Prioritiitsdaten: 3744/90-4 27. November 1990 (27.11.90) CH Spitalrain 22, CH-5200 Brugg (CH).

(74) Anwalt: R.A, EGLI CO.; Horneggstr. 4, D-8008 Zurich

(CH).

(81) Bestimmungsstaaten: AT (europilisches Patent), AU, BE (europiiisches Patent), BF (OAPI Patent), BJ (QAPI Patent), BR, CA, CF (QAPI Patent), CG (QAPI Patent), CH (europiiisches Patent), CI (QAPI Patent), CM (QAPL Patent), DE (europfiisches Patent), DK (europflisches Patent), ES (europflisches Patent), FR (europflisches Patent), GA (QAPI Patent), GB (europllisches Patent), GN (OAPI Patent), GR (europiiisches Patent), IT (europllisches Patent), LK, LU (europiiisches Patent), MG, ML (QAPI Patent), MR (QAPI Patent), MW, NL (europitisches Patent), SD, SE (europ~iisches Patent), SN (OAPI Patent), TD (QAPI Patent), TG (QAPI Patent), US.

(54) Title- EXTRACT OF TROPICAL PLANTS, PROCESS FOR PRODUCING THE SAME AND ITS USE AS A MEDI-

CAMENT

(54) Bezeichnung: EXTRAKT AUS TROPISCHEN PFLANZEN, EIN VERFAH' kEN ZU DESSEN HERSTELLUNG SO- WIE DESSEN VERWENDUNG ALS HEILMITTEL (57) Abstract An extract is produced from tropical plants, of which the individual parts, such as roots, stems, seeds, flowers and leaves, are administered to the person under treatment according to his or her age, origin and stage of disease, The used parts of the plant are sliced, mixed with ethanol or alcohol and macerated for a week at ambiant temperature. The ratio between the amount of plant matter and the amount of admixed fluid lies in the range of 1:4 to 1:9 and depends on the part or parts of the plant that are used. The extract is used to heal congenital syphilis, although it is supposed that other tropical diseases may also be treated with the same substances.

(57) Zusamnmenfassung Der Extrakt wird aus tropischen Pflanzen hergestellt, von welchen die einzelnen Teile, wie Wurzel, Stamm, Samen, Blten und Bllitter ie nach der Krankheitsstufe, dem Alter und der Herkunft der zu behandelnden Person eingesetzt: werden. Die verwendeten Teile dler Pflanze werden zerschnitten, mit Xthanol oder Alkohol vermischt und bei Zimmertemperatur w~1hrend einer Woche einer Mazeration unterworfen. Das Verhijltnis der Menge der Pflanze zur Menge der beigemischten Flllssigkeit liegt im Bereich von 1:4 bis 1:9 und ist davon abhilngig, wvelcher Teil oder welche Teile der Pflanze verwendet wird/werden. Der Extrakt ist zur Heilung von angeborener Syphilis vorgesehen, obschon noch vermutet wird, dass sich andere Tropenkrankheiten mit dem gleichen Mittel behandeln lassen.

This invention relates to the use of Calotropis procera for preparing a tincture for treating congenital syphilis.

Congential syphilis as well as a form of this illness, called "bejel" is widespread, particularly in tropical territories. It is transferred through lesions, but particularly across the placenta of an infected woman to the child. Of course, this illness may be transferred further. It leads to a hard ulcer at the site of infection, to swellings of lymph nodes, to fever, to a rash and after some time, sometimes after years, to tumour-like masses, but in any case to pains of the infected woman.

For curing this illness generally penicillin is used, but the illness is, nevertheless, increasing in spite of some initial success, and, moreover, allergic reactions have been observed with some persons when penicillin is administered. Thus, there is a need of a remedy avoiding allergic reactions and formation of resistant strains, but, in any case, may be used as an alternative, and this is the object of this invention.

**o This object is solved according to the invention by the

S

characteristics of claim 1.

S..:The plants The most important of all the plants is the apple of Sodom, also known as the Mudar plant, Calotropis procera. This plant belongs to the Asciepiadaceae,the silk weed and is widespread from West-Africa to South-East-Asia where it often occurs on a huge scale on dry steppes and on desert-like habitats. The basically woody plant reaches more than 4 m in height and can grow to a small tree. The-plant Calotropis procera is known per se. The components, above all the Calotropine, are related to the heart glycosides. Biol. Abstracts, Vol. 84 (1987), Ref.No.\ reports, however, also about the effects of a 50 extract that has been administered in the case of cancer-like ulcers for 1 to 9 days and resulted in 60% of all cases in a degeneration of them.

Insofar, the discovery forming the base of the present invention is surprising that such an extract of the plant proves itself as a remedy in the case of the above dicussed syndrome, although therapy takes more time. Without wishing to be bound to any theory, it may play a part that just this syndrome too involves the formation of ulcers and of tumour-like masses. As is usual, the green stems with the green apples, the old leaves, but also the young plant with the roots are taken for the tincture, each part being suitably prepared individually.

However, as will become apparent from the literature, a pure therapy with Calotropis procera can lead to problems due to its heart glycoside effect which, for the present purposes, constitutes an undesirable side-effect. This may be combatted by a decrease of the dose, but it has been found that the extract of the socalled ginger lily or garland flower, also Hedychia, a ginger plant, is a valuable supplement.

The genus Hedychium includes 50 species, of which most are widespread in tne East Indies. 2 in the Phillipines and 2 in Madagascar. Among them, the most important is H. coronarum which is known as a medicinal plant [see Biol. Abstracts, Vol.

82 (1986), Ref.-No. 37351, where an extract of 50:50 in aqueous ethanol is administered after evaporating of ethanol in a dosage of 40 ml/kg; likewise, Biol. Abstracts, Vol. 87 Ref.- No. 32970; but its use against the syndrome discussed above is described in Biol. Abstracts, 91 Ref.-No. 123003]. Also in this case, the diuretic effect described constitutes a sideeffect which is not always desirable. By combining, however, the tinctures of both plants, a concentrated effect will be achieved with respect to the syphilis troubles, while the sideeffects are diminished.

This is particularly the case, if in accordance with claim 2 the peace lily is used too, of which there are about 36 species, most of them in the tropics of America. Only 2 species are found in the Indo-Malaysian island archipelago, among these Spathiphyllumcommutatum from the Phillipines. For the tincture, the stem with the leaves is taken. Spathiphyllumcommutatum is the third most important plant within the framework of the object therapy. Its use for the present purpose has neither been described nor suggested up to now.

The following plants may be used as well, all in view of a concentration to the object purpose diminishing the sideeffects as much as possible. They all are employed with their 0* stems, flowers and leaves for preparing the tinctures.

*o It is substantially the question of plants of the banana family or Musaceae the number of species used being not of importance: Heliconia psittacorum, parrot heliconia Heliconia rostrata, beaked heliconia Heliconia wagneriana, Wagnerian heliconia Strelitzia reginae, Paradise Bird flower Strelitzia nicolai, white-flowered strelitzia Red, White or Yellow Ginger.

The latter plant is more related to the Hedychia. The calabash tree and Crescentia cujete are usable as well. Die genus Crescentia is widespread in the tropics of the USA as far as Florida. The best known is C. cujete. As already mentioned, the stem and the leaves of these latter series of plants are used, and in the latter case also the gourd-like fruits are taken. As in the case of the extract of Calotropis, a separate preparation of the individual parts of the plants is suitable.

-Ak\V Fu?-puvoco. TY'CU^ o,-so\e= ~e It is to be understood that, since it is the question of minimizing the side-effects, it is.not of importance whether the individual extracts are administered separately or in 4 amixture. A particularly effective composition is defined in claim 3.

Description of the Treatment First, a tincture of plants of the banana family, as indicated above, were applied for slowly commencing the treatment. At the same time, a mixt tincture of Spathiphyllum hybridum and Hedychium coronarium was administered so that the patient obtained already a specific remedy generally acknowledged in medicine.

In the concrete case, the gastro-intestinal tract was apparently especially affected so that a bowel movement began with a yellow stinking mass.

Immediately afterwards, the treatment tincture was changed, and the extract of Calotropis procera was administered. This ex- S•tract is, as already mentioned earlier, quite known per se in medicine. Depending on the dosage, also in this case there was S. a yellowish excretion through the intestine.

If this result is obtained, it will always be indicated to S change the treatment tincture for another time. In the concrete case, a tincture from the gourd of Crescentia was taken. With this, an easing of the gastro-intestinal tract was achieved, and the intestinal excretions became normal.

Finally, the whole composition of the tinctures of plants of the banana family was taken once more for a short time which had a roborizing effect to the body.

If here the case of a patient to be treated rather cautiously is reported, it should be mentioned that the reaction of more robust persons of black skin colour or of patients at an initial stage of the disease give less reason for reservations so that, in case, one can begin with the extract of Calotropis procera. In doing so it can also lead to liquid excretions, but xi^ also to swellings of the feet. As already mentioned, the sideeffects may be limited by changing the tinctures. A foot bath, e.g. in salt water, may alleviate' swellings of the feet where a white rim may form so that some attention has to be paid to the condition of the skin, especially because one has to to reckon with some purulent rash already due to the disease.

With patients who suffer from the disease for a longer time, in a concrete case it was a patient who had the disease for about 7 years, a more intense treatment is advisable, i.e. it recommends itself to begin with Calotropis procera and to continue with a tincture of older leaves in a relatively intense manner. Then, a change is made to Hedychium coronarium and Spathiphyllumas mentioned above. At the end, again a tincture of Crescentia is administered and finally one of the other plants.

o In general, the patients received light, vitamin-rich food, since symptoms of fatigue were obvious.

Duration of the treatment By using the tincture of Calotropis procera, healing is promoted, while the general condition has to be controlled. Depending on the stage and the age of the patient, a treatment up to 30 months may be necessary suitably altering the tinctures, as described above. The treatment, however, will extent at least over a 3 month period.

Dosage The dosage depends on age of the patient, duration of the disease, general condition of the patient, but, interestingly enough, also on the skin colour. It has been found that persons of black skin colour can be administered a higher dosage than to white people. ~ci.dentally;. F ndG to .4 'a n rir e In total, about 40 to 48 liters of tincture are necessary up to curing, i.e. 5 to 6 liters of each plant.

In the case of weaker patients, particularly white people, the whole composition, e.g. as defined in claim 3, is administered whereby the particularly effective amount of Calotropis procera is present in a minimal proportion in order not to put too much strain on the heart.

Preparation of the tinctures Although the preparation of the tinctures is widely known from the prior literature, it should be discussed in detail herein, particularly with respect to some specialities in the present case. Each plant (fresh) of this composition is chopped 50 mm small. In detail, it is referred to Pharmacopoea H. VII.

Calotropis procera: 2 parts oZ chopped drug 8 parts (stem, seeds and flowers of 70% ethanol. Maceration at as well as old leaves) room temperature for 1 week, then filtration squeezing off.

Hedychium spec. as above, squeezing off may be omitted.

0 Spathiphyllum+ Hedychium 1 part of chopped plant 9 parts (stem and leaves) of 70% alcohol, for the rest as a above.

Plants of the banana family: Procedure as with Spatiphyllum (Heliconia Strelitzia) Hedychium Crescentia cujete: Preparation as with Calotropis procera.

The above treatment with the tinctures has been described for curing congenital syphilis, but it is supposed that the tinctures, and especially the tincture of Calotropis procera, may also be suitable against diseases caused by amoebae.

V-i"

AN-

-7 The following three examples are of treatments of patients in accordance with the present invention.

Example 1 A 26 year old white woman suffering from congenital syphilis that had been treated without success with penicillin and other medicines was given a 4 ccm extract from Calotropis procera each morning after breakfast and after lunch. After dinner she was given a dose of 2 ccm of a mixture of Calotropis, Hedychium and Spathiphyllum extract. The extracts were made according to the description in Biological Extracts Volume 84, 1997, which also shows how these extracts are standardised. From the first to the third month, the patient said she felt better, and after three months there were visible signs of success.

In total, about 5 litres of Calotropis extract and 3 litres of each of Hedychium and Spathiphyllum extract were necessary.

Example 2 .o o In a similar way as described above in Example 1, a 0.

20 35 year old black man who has had congenital syphilis for about 15 years was treated. The treatment began with about 4 ccm of Calotropis extract after breakfast and after S"lunch. After dinner he received 4 ccm of a mixture of Calotropis, Hedychium and Spathiphyllum extract. After a week he did not feel well and the doses of Calotropis extract were reduced to 2 ccia taken after breakfast. When he felt better and the rhythm of his heart was normal again, the initial higher doses were resumed. The doses were changd several times in his treatment to allow for his 30 heart rhythm. After about 3 months he felt better and after about 5 months he had been treated of his condition as could be observed from visual inspection. The total amount of extract of Calotropis that was used was about 7 to 8 litres and 4 litres of Hedychium and Spathiphyllum extract were used.

a/keep/RETYPES/89028.91.07.07.94 Example 3 A black man of about 45 years old who has had congenital syphilis for a very long time (he was very uncertain and vague about the time) was in a relatively unhealthy state. He was given a mixture of 12 ccm of Calotropis, Hedychium and Spathiphyllum extract after breakfast, after lunch and after dinner.

After a few days he had a yellowish secretion. From that day on he was also given an extract of Strelitzia reginae, Heliconia rostrata, Heliconia wagneriana and Heliconia psittacorum, 2 hours after taking the first mixture of extract. The secretion turned blackish, and the treatment was replaced by 6 ccm of extract for Crescentia cujate which was given before the meals. For the first days the secretion remained as it had been. Then it improved, and the doses were reduced to 4 ccm.

In this case, the man relapsed, and the treatment had to be resumed so that the cure took more time than in the previous cases referred to in Examples 1 and 2. Another 20 effect was a swelling of the feet probably as a result of the relatively higher doses of Calotropis extract. After a while, the skin turned whitish and hardened on the feet.

Thus, it is clear that when using this treatment special care has to be taken to maintain the condition of the skin.

S 25 Moreover, care has to be taken to replace the liquid which the patient loses in the treatment. These steps had also been taken in the treatment of the patients in Examples 1 and 2 above. Although in this latter case in Example 3 the disease was particularly difficult to treat the patient was 30 well within less than a year.

c/koep/RETYPES/89028.91.07.07.94

Claims (7)

1. A method of treatment of congenital syphilis, comprising the step of administering to a patient in need of such treatment an effective dose of an extract of Calotropis procera, optionally in conjunction with an effective dose of an extract of at least one plant selected from the group consisting of Hedychium coronarium, Spathiphyllum hybridum, Heliconia rostrata, Heliconia psittacorum, Heliconia wagneriana, Strelitzia reginae, Strelitzia nicolai, Alpina purpurata, Hedychium gardneranum and Crescentia cujate.

2. A method according to Claim 1, wherein the extract is a mixed extract of Calotropis procera, Hedychium coronarium and Spathiphyllum hybridum.

3. A method according to Claim 1, comprising the steps of sequential treatment with: a) an extract of Calotropis procera; b) an extract of Hedychium coronarium, together with an extract of Spathiphyllum hybridum; and c) an extract of Heliconia rostrata, Heliconia psittacorum or Heliconia wagneriana, together with an extract of Strelitzia reginae or Strelitzia nicolai.

4. A method according to any one of Claims 1 to 3, wherein each of the plant extracts is a predominantly ethanolic tincture.

5. A method according to any one of Claims 1 to 4, "wherein each extract is administered orally.

6. A composition for treatment of congenital syphilis, comprising an extract of Calotropis procera together with an extract of at least one plant selected from the group consisting of Hedychium coronarium and Spathiphyllum hybridum, and a pharmaceutically acceptable carrier suitable for oral administration. DATED this 20th day of December 1994 MAGDALENA MRAK By Her Patent Attorneys GRIFFITH HACK CO Fellows Institute of Patent Attorneys of Australia ./k..,IRETYPES/89028.91.07.07.94 INTERNATIONAL SEARCH REPORT International Application No PC.T/rH Q1 /nnAal I. CLASSIFICATION OF SUBJECT MATTER (II several classification symbols apply, Indicate all) i According to International Patent Classification (IPC) or to both National Classification and IPC A 61 K 35/78 C 07 G 17/00 II. FIELDS SEARCHED Minimum Documentation Searched 7 Classification System Classification Symbols A 61 K C 07 G Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included In the Fields Searched I ill. DOCUMENTS CONSIDERED TO BE RELEVANT s Category I Citation of Document, 11 with indication, where appropriate, of the relevant passages 12 Relevant to Claim No. 13 X Biological Abstracts volume 84, N 0 1, 1987 (Philadelphia,PA, US) S.K. Bhatnagar et al.: "Effects of 50 percent ethanol extract of Calotropis procera AIT.f.on ulcers caused by assorted types of carcinoma", see page AB-739, abstract 6510, J.Econ.Taxon.Bot. C

489-490 1986 X Biological Abstracts, volume 82,No 4,1986 (Philadelphia, PA, US) R.Ribeiro et al.: "Acute-antihypertensive effect in conscious rats produced by some medicinal plants used in the state of Sao Paulo (Brazil)", see page AB-37, abstract 37351,& J.Ethnopharmacol., 15(3),261-70,1986 Special categories of cited documents: 10 later document published after the International filing date document defining the general state ol the art which is not or priority date and not In conflict with the application but "Aconsidered to be ofpart lar rele h a rt w h c h ot cited to understand the principle or theory underlying the condered to be of particular relevance Invention earlier document but published on or after the International document of particular relevance; the claimed invention filing date cannot be considered novel or cannot be considered to document which may throw doubts on priority claim(s) or involve an inventive step which is cited to establish the publication date of another document of particular relevance;' the claimed nvention citation or other special reason (as specified) cannot be considered to Involve an Inventive step when the document referring to an oral disclosure, use, exhibition or document is combined with one or more other such docu- other means ments, such combination being obvious to a person skilled document published prior to the International filing date but in the art. later than the priority date claimed document member of the same patent family IV. CERTIFICATION Date of the Actual Completion of the International Search Date of Mailing of this International Search Report 18 February 1992 (18.02.92) 12 March 1992 (12.03.92) International Searching Authority Signature of Authorized Officer EUROPEAN PATENT OFFICE Form PCT/ISA/210 (second sheet) (January 1985) International Application No. PCT/CH 91/00241 fit. DOCUMENTS CONSIDERED TO BE RELEVANT (CONTINUED F~ROM THE SECOND SHEET) Category Citation of Document. with indication, where appropriate. of the relevant passages Relevant to Claim No X Biological Abstracts,volume 87,N 0 3,1989 (Philadelphia, PA, US) R.Ribeiro et al.:"Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of Sao Paulo (Brazil)",see page AB-1060, abstract 32970, J. Ethnopharmacol., 24(1), 19-30,1988 X Biological Abstracts, volume 91, NO 11, 1 June 1-6 1991(Philadelphia, PA, US) I.Basualdo et al.: "Medicinal plants of Paraguay: Underground organs", s-e page AB-951, abstract 123003, Econ.Bot., 45(1), 86-96, 1991 Form PCTIISA/210 (extra &heet) (January 1955) International Application No. FURTHER INFORMATION CONTINUED FROM THE SECOND SHEET C SERVATIONS WHERE CERTAIN CLAIMS WERE FOUND UNSEARCHABLE I This international search report has not been established In respect of certain claims under Article 17(2) for the following reasons: Claim because they relate to subject matter not required to be searched by this Authority, namely: "Note: Although Claim 6 refers to a method for treatment of the human or animal body the search was carried out and based on the indicated effects of the compound/composition." 2.r7 Claim because they relate to parts of the International application that do not comply with the prescribed roqulre- ments to such an extent that no meaningful International search can be carried out, specifically: 3 Claim because they are dependent claims and are not drafted In accordance with the second and third sentencou of PCT Rule 6.4(a). VI.F OBSERVATIONS WHERE UNITY OF INVENTION IS LACKING 2 This International Searching Authority found multiple Inventions In this International application as follows: As all required additional search fees were timely paid by the applicant, this International search report covers all searchable claims of the International application. As only some of the required additional search fees were timely paid by the applicant, this International search report covers only those claims of the international application for which fees were paid, specifically claims: 3. No required additional search fees were timely paid by the applicant. Consequently, this International search report Is restricted to the Invention first mentioned In the claims; it Is covered by claim numbers: As all searchable claims could be searched without effort justifying an additional fee, the International Searching Authority did not Invite payment of any additional fee. Remark on Protest The additional search fees were accompanied by applicant's protest. M No protest accompanied the payment of additional search fees. Form PCTIISAf210 (supplemental sheet (January 1985) INTERNATIONALER RECHERCH ENBERICHT Internationaies Akt.wzeichen PCT/C- 91/00241 1. I(LASSIIKATION DES A.NMELDUNGSGEGENSTANDS (bet mehrerve Klassifikationssymbolen tind alle anzugeben) 6 Nach der Internatioaiez patentiasslfkatian (TPC) otter nach der nationalen Iflassifikat ion und der ITC A 61 K 35/78 C 07 G 17/00 nI. RECHERCHIERTE SACHGEBIETE Recherchierter Mindestprilfstoff Kiassifikationssytem Kiassifikationssymboie A 61 K C07 G Recherchierte aichi zun rMindnptprll'sioff gebbreade Vcrtiffentiichungen, soweit die unter die recherchierten Sachgebiete fallen III. EINSCHLAGIGE VEROFFENTLUCINGEN 9 Art. 0 Kennzeichnueg der Vertiffcntlichung 1 soweit erforderlich unter Angabe der allgeblicbee Teile~ 32Mr. Anspruch Nr1 X Biological Abstracts, Band 84, Nr. 1, 1987 (Philadelphia, PA, US) S.K. Bhatnagar et al.: "Effects of 50 percent ethanol extract of Calotropis procera AIT.f. on ulcers caused by assorted types of carcinoma", siehe Seite AB-739, Zusammenfassung 6510, &t J. Econ. Taxon. Bot. 489-490, 1986 X Biological Abstracts, Band 82, Nr. 4, 1986 (Philadelphia, PA, US) R. Ribeiro et al.: "Acute-antihypertensive effect in conscious rats produced by some medicinal plants used in the state of Sao Paulo (Brazil)", siehe Seite AB-37, Zusammenfassung 37351, J. Ethnopharmacol., 15(3), 261-70, 1986 0 Betondere Kaiegorien von angegebeeen Verbffentlicbungen 'A Veriflentiichuing, die den aligetneinen Stand der Techeik T17 Sp~tere Veridffentiichung, die each den internationalen An- definiert, aber nidtt 21s besonders bedeutsam anzaseben hsi tneldedatuat oder dent Priorititsdaium verolffentlichi warden kteres Dakument, das ledoch erst am oder acd hiIntrn- 1st und t der Anmeldung nicht koilidiert, soedern our zum ticoalen Anmeidedatuze verfealt wrdn Ist Verstindeis des der Erfindung zugrundeliegenden Priozips Lf Veroffentlichung, die geeignet ist, einen Priorit~tsanspruch oder der ibi zugrundeliegenden Th~orie angegebee let zweifelhaft erscbeinen zu lassen, oder dutch die das Verif- IX Verdiffentlichung von besonderer Bedeutung; die beanspruch- fentiichungsdatum eer 20dertn im Reclterchenbericht ge- te Erfindung kano nicht als eu oder auf erfinderistber Tutig- eannien Verliffentliiiung belegt werdee soil oder die aus eem keit beruhend betrachtet weeden anderen besoaderen Grund angegeben i (wie ausgefuhrt) Y' Vetttffentiichung von besnderer Bedeutung; die Smeispruch- Vertiffentiicbung, die sich auf eine mlandliche Offenbarueg, te Erfindung kann nicht ais auf edfinderischer TitigLeit be- ruhend betraditet weiden, wen die Vtrtlffentlicbung teit ee Benutzung. eine Aussteliung otter andere Maileabinen einer oder menrecen anderen Vertiffeetiichnngen dieser Kate- beziebt gonie In Verbindueg gebracht wird und diese Verbiedung fur 11' Veiltffentiichung. die var dens inlenationaien Anteeldeda- etnen Fachmnen nabeiiegend i turn, abet nach dens beansprucbten Priarititsdatum vertiffeat- W& Vertifentiicbung, die Mitgiied derselbee Patentfailiie Ist iicht warden i IV. BESCHEINIGUNG Datum des Abschiusses der ieternationaien Recherche Absendedatum des internatioaalen Rechercheebericbts 18-02-1992 J'2. 03. 92 Internatianale Recisercbenbebbrde t~bi!,~ea~~sitnBdesee j EUIIOPAISCHES PATENTAMT an der Has Famblilt PCr/ISAIZIO (Blatt 2) t.Jnw 1995) Intcrlationales At*zelchen Seite 2 PCT/CH 91/00241 1H1. EJINSCHLAGIGE VEROFFENTUCHUNGEN (Fonsetzung von Blatt 2) At? Kennzelchnung der Verdfferntichung, soweit erforderlicb urner Ang~be der zoallgelichen Telle Beir. AJnsprucb Nr. X Biological Abstracts, Band 87, Nr. 3, 1989 (Philadelphia, PA, US) R. Ribeiro et al.: "Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of Sao Paulo (Brazil)", siehe Seite AB-1060, Zusammenfassung 32970, J. Ethnopharmacol., 24(1), 19-30, 1988 P,X Biological Abstracts, Band 91, Nr. 11, 1. Juni 1-6 1991 (Philadelphia, PA, US) I. Basualdo et al.: "Medicinal plants of Paraguay: Underground organs", siehe Seite AB-951, Zusammenfassung 123003, Econ. Bat., 45(1), 86-96, 1991 FombatU PCTIISAIZIO (Znvzbore*I (Jawar 19s) Internallotnaler 'ionzelchen PCT/ CH9 1/00241 WE1TER EAN GASEN ZU BLA iT 2 7 V.111 BEMERKUNGEN ZU DEN ANSPROCHEN, DIE SICH ALS NICHT RECHERCHIER13AR ERMESEN HAB3EN I Arikal 17 Absatz 2 Suchstaba a sind bestimnita Ansprilcha aiis folgande Griindmn nicht Gaganstand der Intamnationaian Recherche gewasan: 1. M Ansprilche Nr well ii sich auf Gamnstinda bai~ahen. dim zu racharchieaw die Bahdrds nicht "Bemerkung: Obwohl Anspruch 6 sich auf ein verfahren zur Behandlung des menschlichen/tierischen KOrpers bezieht, wurde die Recherche durchgefiihrt und gri~ndete sich auf die angefUhrten Wirkungen der Verbi ndung/Zusanimensetzung." 1. El Azispriicha Nr wall si. sich auf Tail. dir intamnationsion Anmaidung baishan. die don vrgeschriabonan Aintorderungen so wanig entsprachan, daft mine sininvolia Internationals Recherche nieht durchgefiihrt warden kann. nAmnlich: 3. El Anspniche Nr Ragal 6.4(a) PCT abgsa at sind. wail ii abhiingige Mnsprticha und nicht anesprachand Satz 2 und 3 der V.I BEMERKUNGEN BE[ MANGELNDER EINHEITLICHKEIT DER ERFINDUNG2 Die International* Racherchanbehdrde hat festgestalit, dadt dies@ Internationals Annialdung mahrar* Erflndungan anthill: 2. ElaO der Aniider nur minge der arforderlchan zusaitzichan Racharchangebhnmn rachtzeitig rnntrchtat hat, arstruckt sich der International@ 3. ear Anmalder hat die arfordarllchan zusittichan Racharrhangsbilhronnicht rechitzaitig anirtchtst. Der Internationals Recharchenberichi bachrinkt sich dahar auf die In don Anaprtlchan zuerst arwihnla Erfindung; sii it Infolgandan Ansprilchan arfaalt 4. ElDa far all@ rocharchieibaran Aflspriiche ama Recherche ohn: ainan Arbeitsautwand durchgtfiihrt warden konnta, dar vini ;rusitziche Racharchangsbiihr gurachtffedigt hitta. hat die InentoasRacharchenbehdrda @i@vih abli ih arlangt. Bemerkung hlnsichtlch sines WIderspruchs ElDie zusitflchan Gibtihrmn wurden vomn Artnaidar untar Wtderapruch gazahit. El Di Zahlung zusalzIlcher Gabtihren arfolgte ohns Widarspruch. Formbliu T/ISA/2IO0 (Er ganzungsbogen P91 12B