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WORLD INTELLECTUAL PROPERTY ORGANIZATION 
International Bureau 




INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) 



(51) International Patent Classification 4 : 

A61K 35/20, 37/02, C07K 3/24 
C07K 15/00 //A61K 7/48 



Al 



(11) International Publication Number: WO 86/ 00525 

(43) International Publication Date: 30 January 1986 (30.01.86) 



(21) International Application Number: PCT/HU85/00042 

(22) International Filing Date: 12 July 1985 (12.07.85) 



(31) Priority Application Number: 

(32) Priority Date: 

(33) Priority Country: 



2751/84 
13 July 1984(13.07.84) 
HU 



(71) Applicant (for all designated States except US): ECON- 

OMIX kOzgazdasz egyetemi kisszOvet- 

KEZET [HU/HU]; Dimitrov ter 8, H-1093 Budapest 
(HU). 

(72) Inventor; and 

(75) Inventor/Applicant (for US only) : SZAB6, Szigfrid 
[HU/HU]; Szivarvany u. 1. 1/8, H-2040 Budaors (HU). 

(74) Agent: PATENTBUREAU DANUBIA; P.O. Box 198, 
H-1368 Budapest (HU). 



(81) Designated States: AT (European patent), AU, BE (Eu- 
ropean patent), BG, BR, CH (European patent), DE 
(European patent), DJC, FI, FR (European patent), 
GB (European patent), IT (European patent), JP, LU 
(European patent), NL (European patent), NO, RO, 
SE (European patent), SU, US. 



Published 

With international search report. 



(54) Title: PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL COMPOSITION INFLUENCING 
THE TISSUE METABOLISM AND HAVING A REGENERATING ACTION 

(57) Abstract 

Preparation of a pharmaceutical composition influencing the tissue metabolism and having a -regenerating action, 
which comprises adding crystal water-free potassium aluminium sulphate to a milk kept at a temperature above 90°C, then 
separating the solid material from the solution after the segregation of the obtained dispersion and optionally adding an 
aromatizing, perserving or colouring agent to the solution. The composition of the invention has an excellent regenerating 
action on the skin, muscle and bones. The metabolism disturbances of the tissues are also abolished, whereby the improve- 
ment of e.g. vascular stenoses can be achieved. 



FOR THE PURPOSES OF INFORMATION ONLY 
Codes used to identify States party to the PCT on the front pages of pamphlets publishing international appli- 



cations under the PCT. 










AT Austria 


GA 


Gabon 


MR 


Mauritania 


AU Australia 


GB 


United Kingdom 


MW 


Malawi 


BB Barbados 


HU 


Hungary 


NL 


Netherlands 


BE Belgium 


IT 


Italy 


NO 


Norway 


BG Bulgaria 


JP 


Japan 


RO 


Romania 


BR Brazil 


KP 


Democratic People's Republic 


SD 


Sudan 


CF Centra] African Republic 




of Korea 


SE 


Sweden 


CG Congo 


KR 


Republic of Korea 


SN 


Senegal 


CH Switzerland 


LI 


Liechtenstein 


su 


Soviet Union 


CM Cameroon 


LK 


Sri Lanka 


TD 


Chad 


DE Germany, Federal Republic of 


W 


Luxembourg 


TG 


Togo 


DK Denmark 


MC 


Monaco 


US 


United States of America 


Fl Finland 


MG 


Madagascar 






FB France 


ML 


Mali 







WO 86/00525 



PCT/HU8S/00042 



PROCESS FOR THE PREPARATION OF A PHARMACEUTICAL COMPOSITION 
INFLUENCING THE TISSUE METABOLISM AND HAVING A REGENERATING 

ACTION 

5 • 

Technical field 

The invention relates to a process for the prepara- 
tion of a pharmaceutical composition influencing the 
tissue metabolism and having a regenerating action, the 

10 effect of which mainly appears in promoting the tissue 

regeneration and assuring the tissue metabolism; however, 
this composition is also useful, inter alia for abolish- 
ing spastic muscle states and for relieving pain. 

It has unexpectedly been recognized that a composi- 

15 tion having the effects mentioned above can be obtained 

by adding crystal water-free potassium aluminium sulphate 
to a milk kept at a temperature above 90 °C , then separating 
the solution from the solid material after the segregation 
of the obtained dispersion and optionally adding aromatiz- 

20 ing, preserving and colouring agents to the solution. 

Disclosure of the invention 

Based on these facts, the invention relates to the 
preparation of a pharmaceutical composition influencing 

25 the tissue metabolism and having a regenerating action. 
The process of invention comprises adding crystal water- 
-free potassium aluminium sulphate to a milk kept a 
temperature above 90 °C , separating the solution from the 
solid material after the segregation of the dispersion thus 

30 obtained and optionally adding aromatizing, preserving 
and colouring agents to the solution. 

It can be supposed that the active agent of the 
composition prepared -by using the process of invention is 
the. whey obtained in the way described above. Although no 

35 mode of action is postulated, it is supposed that for the 



WO 86/00525 



PCT/HU85/00042 



- 2 - 



tissue metabolism the products, the appropriate 
concentration of which is indispensable for the tissue 
regeneration in a given period, are provided by the amino 
acid content of the whey. 
5 It has been proved by investigating the acid-base 

balance and the gas tension parameters as well as the 
changes in the whole resting respiratory function of the 
human body that the composition is rapidly and significant- 
ly absorbed through the skin. The acid-base balance is 

10 shifted to a moderately metabolic acidosis which is then 
later shifted back to a mild alkalosis as a consequence 
of the amino acid metabolism. 

In addition to the general action mentioned above, 
the function of the respiratory system also becomes more 

15 economical and the capacity thereof is enhanced by the 
composition of the invention. 

All these observations indicate that by using the 
composition of the invention metabolizing acidic substances 
which are indispensable for a tissue regeneration, can be 

20 advantageously introduced into the organism through the 

skin, that is, in a fully new way. These acidic substances 
exert an advantageous influence on the interior homeostasis 
of the cells and of the intercellular substance through the 
acid-base balance. The substances required for the tissue 

25 regeneration are directly provided to the cells by the 

amino acid content of the composition of invention through 
a direct diffusion, i.e. without the intervention of the 
systemic blood circulation. As. the application through the 
skin of such substances is- unknown to our best knowledge, 

30 a comparison to known oral or parenteral compositions is 
void of any sense. 

As starting "materials of the process of invention, 
fatty cow milk can preferably be used, however a less 
fatty cow milk or e.g. goat's ©ilk can also t>e us^ed. 

35 For treating the milk, crystal water-free potassium 



WO 86/00525 



PCT/HU85/00042 



aluminium sulphate, suitably alum heated at a temperature 
between 300 °C and 400 °C is used. 

According to a practical embodiment of the process 
of invention, 1.6 to 2.1 g, depending from the* fat content 
5 of the milk, of crystal water-free potassium aluminium 
sulphate are suitably added portionwise to 1 litre of 
milk, preferably at. the boiling point of the milk, whereby 
the casein and fatty material's are precipitated. After 
some time, the supernatant becomes substantially pure 

10 and can be separated. For this purpose filtration and/or 
centrifugation are suitably used. 

On carrying out the process of invention with a 
crystal water-free potassium aluminium sulphate obtained 
by heating natural or amorphous alum at 250 °C to melting ' 

15 and then up to the re-solidification /a spongy structure 
being formed/, after the segregation of the dispersion" 
a completely pure solution is obtained, whereby a filtra- 
tion becomes unnecessary. 

The thus-obtained solution is actually suitable 

20 for a therapeutical use, but an aromatizing agent should 
be added for. masking the inconvenient odour of the 
materials arising from the milk and a preserving agent 
has to be mixed in for preventing the decomposition of 
the materials arising from the milk. A colouring agent may 

25 also be added optionally to the composition for promoting 
the acceptability of the use thereof. 

According to a preferred embodiment of the process 
of invention, an extract arising from a medicinal plant 
/herb/ is used as an aromatizing agent, whereby the in- 

30 convenient odours are fully masked and simultaneously, the 
medicinal plant extract may have an own advantageous 
action. The aqueous extract of woundwort /Solidago gigantea 
Ait. or Solidago serotina/, of Glechoma hederaoea L., and 
of herb-ovy /Teucrium chamaedrys L./, or of silver-weed 

35 /Potentilla anserina L./ together with the above-mentioned 



WO 86/00S2S 



PCT/HU85/0G042 



three medicinal plants may suitably be used as aromatiz- 
ing agent. The aqueous extract can be prepared in a 
manner known in the art, suitably by boiling a mixture 
containing an 1:1 ratio. by weight of. the medicinal plants 
5 with water for 5 minutes and queezing the juice obtained 
through a press. 

Instead of the medicinal plant extracts mentioned 
above, any other aromatizing agent commonly used in- the 
pharmaceutical industry, such as pine, hay or orange 

10 aroma, may be -used as aromatizing agent. 

Similarly, preservatives commonly used for prepar- 
ing pharmaceutical compositions may be used as preserving 
agents in the process of the invention. It is suitable to 
use ethanol, preferably pure ethanol "of 96 Within a 

15 large-scale production, e.g. 70 % by volume of whey, 23 % 
by volume of pure 96 % ethanol and 7 % by volume of a 
medicinal plant extract /optionally containing 96 % 
ethanol, suitably 1 litre of pure 96 % ethanol for each 
4 litres of the aqueous .extract/, calculated for 1 litre 

20 of the pharmaceutical composition, may be used. Instead 
of ethanol, other preservatives may also be employed, by 
the use of which the whey liable to fermentation is preserved 
the amino acid contents are not damaged, the treated skin 
is not irritated and the preservating effect is exerted 

25 even if the composition of the invention comes into 
contact with the skin. 

Industrial applicability 

The compositions prepared by using the process of 
30 the invention are utilized for pharmaceutical purposes 
as follows . 

Suitable ready-f or-use formulations of the composi- 
tions of the invention are the liniment, lotion and spray 
which may be prepared in a manner well-known in the 
35 pharmaceutical industry, optionally by employing the 



WO 86/0052S 



- 5 - 



PCT/HU8S/00042 



additives commonly used for these types of pharmaceutical 
formulations. 

Obviously, the amount and manner of the active 
substances used for a therapeutic purpose are dependent 
5 on a number of factors such as the status of the patient, 
the effectivity and concentration of the active substance 
as well as the formulation. 

The composition of the invention is suitably applied 
by infriction to the body part to be treated daily 2 to 5 
10 times. 

An optimum effect on diseases caused by vascular 
stenoses is provided by three treatments per day. 

The treatment is carried out as follows. 

The composition of the invention is applied to the 
15 surface to be treated by 'hand or in a spray form. After 
absorption, the treatment is repeated and, after the 
second absorption, a third infriction is made. It is 
essential to keep the surface to be treated wet for about 
10 minutes. As mentioned above, this treatment can be 
20 accomplished daily 3 times. 

In the course of a rehabilitation after knee opera- 
tions, the use of lotions is convenient . " In this case, it 
is suitable to pour the agent daily 5 to 10 times onto 
the body part covered with a compress. 
25 The main therapeutic effects of the compositions 

prepared according to the process of the invention are as 
follows. 

1. On the basis of the mode of action described 
above, it can be stated that the cellular activity is 

30 stimulated and normalized by the amino acids introduced 
by the composition into the tissues, as the* substances 
required thereto are provided in the appropriate quantity, 
time and manner. 

2. A therapeutic chain reaction in several directions 
35 is started in the organism as a consequence of the 



WO 86/00525 



PCT/HU85/00042 



regenerated advantageous cellular activity, whereby a 
rapid improvement or recovery is achieved in the following 
cases: 

a/ A regenerating action on the skin, muscle and 
5 bones : the restoration of ulcers, gangrenes and other 
wounds, as well as a rapid rehabilitation after muscle 
lesions, cartilage- and syndesmoplasty operations and the 
like; 

b/ Abolishment of metabolic disturbances : a restoring 
10 effect in vascular stenoses is achieved by the improvement 
of the metabolic economy in the musculature of the 
extremities, i.e. the metabolic disturbances thereof are 
abolished, while the blood circulation remains unchanged 
and the deficient states get a balance /in the case s. of 
15 arteriosclerosis obliterans, endarteriitis obliterans and 
the consequences thereof/;. 

c/ The composition of the invention shows an out- 
standing analgesic effect : the pain is abolished or ' 
alleviated to a minimum at 10 to 15. minutes after the 
20 infriction. 

Modes of carrying out the invention 
The invention is illustrated by the following non- 
-limiting Examples. 

25 

Example 1 

Commercially available crystalline alum /""potassium 
aluminium sulphate; KAL/SO^/ 2 . 12H 2 0_7 is heated at a 
temperature between 300 °C and 400 °C , whereby the alum 
30 becomes free from the crystal water, then it melts and re- 
-solidifies. A spongy-structured material is obtained. 

Fatty milk is heated to the boiling point and 1.8 g 
of the above-described spongy alum, calculated for 1 litre 
. of milk, are added under continuous boiling. The mixture 
35 is then boiled for 10 minutes and after the complete 



WO 86/00525 



PCT/HU85/00042 



precipitation of casein, the supernatant solid materials 
are removed from the milk surface by using a filter bag 
to give an opalescent, transparent liquid. After cooling 
down of the filtrate to a temperature between 35 °C and 
5 AO °C, 1 litre of 96 % ethanol, calculated for each 4 litres 
of the filtrate, is added, 

A decoction is prepared from 250 g of woundwort, 
250 g of Glechoma hederacea L. and 250 g of herb-ovy with- 
6 litres of water during 5 minutes, whereupon the juice of 
10 the medicinal plants are queezed through a press to give a 
decoction of about 4 litres. Each 4 litres of this decoction 
is mixed with 1 litre of 96% ethanol'. 

75 ml of the decoction containing ethanol are added 
to 925 ml of the filtrate prepared as described above. 

15 

Example 2 

The process described in Example 1 is followed, 
except that 200 g of woundwort, 200 g of Glechoma hederacea L., 
200 g of herb-ovy and 200 g of. silver-weed are used as 
20 medicinal plants. 



The results of the pharmacological s'tudy on the 
compositions prepared according to the process of invention 
are described in the following Test Examples. 

25 

Test Example 1 

The action of the composition prepared as described 
in Example 1 was investigated on 60 patients suffering from 
vascular stenosis /arteriosclerosis obliterans or endarteritis 

30 obliterans/. Simultaneously, a control group consisting of 
25 patients was treated by a traditional method commonly 
used in the medicinal practice and a control group consist- 
ing of 25 patients was treated with a liquid having the 
same colour and odour as that of the agent but containing 

35 no whey /negative control/. The agent was applied daily 



WO 86/00525 



PCT/HU85/00042 



3 times to the affected body. parts by infriction as 
described above. No improvement was stated on the negative" 
control group; a little improvement was observed on the 
patients treated by the traditional method; and an ameliora- 
5 tion of the clinical symptoms in the temperature of the 
extremity and in the restoration of trophic ulcerations 
were observed in all cases on the patients treated with 
the composition of Example 1. Thus, the distance of 
claudication was increased from 100 meters or 200 meters 

10 to an infinite value, i.e. the patient became free from 
complaints, the frequent nocturnal sura spasms were 
abolished and the demarcation and drying of pyelous ulcers, 
crust formation, detachment of the crusts and the epithelium 
formation were observed even on aged patients. 

15 In the course of the acute action of the composition 

of Example 1, the skin temperature was decreased by 3 to 4 C, 
then it warmed back gradually and reached the original 
value as measurable on healthy individuals within 50 to 60 
minutes. It was observed on using the composition of 

20 Example 1 for the treatment of vascular stenoses that the 
temperature of the sick side was lower than that of the 
healthy one. The above temperature decrease was observed 
also here, but it is considered to be very significant that 
the temperature of the sick extremity did not increase only 

25 to the starting value, but to a temperature identical with 
that of the healthy side, i.e. to a temperature higher 
than the starting value. When the agent was chronically 
applied, the resting skin temperature of the sick extremity 
was increased by 2 °C on using infrictions daily 5 times 

3.0 for 2 weeks. An oscillometric examination was made on the 
patients to decide if the agent had any effect on the 
vascular stenosis or the tissue metabolism were improved 
with the retention of an unchanged vascular lumen. The 
oscillometric value was increased on the most part of the 

35 patients /over the ankle, below and over the knee/; however 



WO 86/00S2S 



PCT/HU8S/00042 



the conclusion was made that the status of the blood vessel 
was actually not influenced by the agent and the excellent 
action was achieved by an improvement in the economy of 
metabolism, while the blood circulation remained unchanged, 

5 

Test Example 2 

The composition prepared according to Example 1 was 
used on 17 patients within the course of rehabilitation 
following a plaster-bandage used 6 weeks after knee 

10 operations /cartilage and syndesmoplasty/. Here, a compress 
was used as described above. It was- stated that the severe 
pain appearing at the initial movements was significantly 
or nearly completely alleviated and the enhanced muscular 
tonus was also abolished. Thus, the restoration of the 

15 passive motion limits of the articulation was enhanced 
within a very short period and the tiredness, known as 
muscular strain, did not appear in the extremity during 
the active curative gymnastics. As a consequence, the rehabi- 
litation period was shortened by 20 to 50 % and the 

20 troubles connected with the movements of the patients were 
significantly reduced. 

These effects were not observed on 10 control 
patients. 

25 Test Example 3 

The action of the composition prepared as described 
in Example 1 was studied on 14 patients /as compared "to 
8 control patients/ on such types of neuritic diseases, 
where the irritation of a nerve was caused -by a change of 

30 . the condition of the musculature /functional neuritis/. 
In these cases, a trophic trouble was observed on the 
supplied area and a local blood circulation trouble was 
also found . The extent of the condition change was judged 
from the temperature of the sick area: the cooler was this 

35 area, the more pronounced was considered the change. The 



WO 86/00525 



PCT/HU85/00042 



- 10 - 

agent was applied to the affected area daily 5 times by 
infriction for 2 weeks. After ending the treatment, the 
collateral difference of 3 to 4 °C disappeared. 

5 Test Example 4 

In addition to the general action of the composition 
prepared as described in Example 1, it was observed that 
the respiratory mid-position was shifted to a lower level 
on all treated patients, i.e. the inspiratory reserve 

10 volumen was increased, while the expiratory reserve volumen 
was decreased. Thus, it has been proved that the composition 
exerted a very advantageous effect on the economy of the 
respiratory system. The maximum ventillation volumen was 
increased, a fact showing that the capacity of the respiratory 

15 system was also enhanced in addition to the economizing 
effect. 

In the course of our investigations the following 
devices have been used: 

1. Skin thermometer /Servintern Rolitron licence 
20 "Thermini 130"/ f 

•2. Thermovision equipment /AGA thermovision 780 type/. 



WO 86/00525 



11 - 



PCT/HU85/00042 



What we claim is: 

1. A process for the preparation of a pharmaceutical 
composition influencing the tissue metabolism and having 

5 a regenerating action, which comprises adding 
crystal water-free potassium aluminium sulphate to a milk 
kept at a temperature above 90 °C, then separating the 
. .. solid material from the solution after the segregation of the 
obtained dispersion and optionally adding an aromatizing, 
10 preserving or- colouring agent to the solution, 

2. A process as claimed in claim l f which 
comprises using 1.6 to 2.1 g of crystal water- 
-free potassium aluminium sulphate, calculated for one 
litre of milk. 

15 3. A process as claimed in claim 1 or claim 2, 

which comprises using alum heated at 300 to 
400 °C as crystal water-free potassium aluminium sulphate. 

4. A process as claimed in claim 1 or claim 2, 
which comprises using fatty cow milk as milk. 

20 5. A process as claimed in any one of the claims 

1 to 4, which comprises using a medicinal 
plant extract as aromatizing agent. 

6. A process as claimed in claim 5, which 
comprises using an aoueous extract of woundwort 

25 /Solidago gigantea Ait. or Solidago serctina/, Glechoma 
hederacea L. and herb-ovy /Teucrium chamaedrys L./ as a 
medicinal plant extract. 

7. A process as claimed in claim 5, which 
comprises using an aqueous extract of woundwort, 

30 Glechoma hederacea L., herb-ovy and silver-weed /Fotentilla 
anserina L./ as a medicinal plant extract. 

8. A process as claimed in any one of the claims 
1 to 7, which comprises using ethanol as a 
preservative. 

35 9. Pharmaceutical compositions whenever prepared 

by the process a c coning to any of claims 1-8. 



INTERNATIONAL SEARCH REPORT 

«iw*mnanl ApQitemoii wo PCT/HU 85/00042 



1. CLAMmCAmo* 09 SuaJtCT HATTM (if foverai ciaaein cation aymbols apply, indicate all) • 


According to International Patent Claaeiftcatlon (IPC) or to both nttlefieJ CUssMcstiOft and IK 

1 //A 61 *K 7/^°' A 61 K 3?/02, C ° 7 K 3/24 ' C 07 K 15/00 


II. P1ILO* SIAftCHIO 




Minimum Oocumtntitlon SMfciM* » 


CUeerflcatfon Syatam 


CtaMMeattoo Symbol! 


Int. CI. 4 : 


A 61X 35/20, 35/12, 37/02, 33/06, 33/14; C 07 K 15/00, 
C 07 K 15/24, 3/02, 3/24; A. 61 K 7/48. 


Documentation Scorched other than Minimum Documentation 
to ma Citant that such Document* are Included In (ho Fields Searched • 


AT 


III. OOCUMIMTS CONSIOffttO TO ■! MtLfVANT* 


Category • 


| Citation of Oecument, " with indication, where appropriate, of tho relevant paaaagao '* 


Relevant to Claim Ho. " 


A 


AT, B, 41 810 (CASEIN AND MILK INDUSTRIES 
LIMITED), 11 April 1910 (11.04.10), see 
claim; page 1 , lines 11-34. 


(i) 

• 


A 


G-B, A, 6 247/ A. D. 1908 (CARL ALBRECHT 
BAECHLER), 24 September 1908 (24.09.08), see 
claim 1; page 1, lines 21-43; page 2, lines 
1-6, 14-29. 


(i) 


A 


US, A, 2 721 861 (LAURENE 0. PATERSON), 
25 October 1955 (25.10.55), see claims 1-5; 
column 3, lines" 8-14; column 5, lines 7-14, 
23-27. 


(i) 


A 

j 

i 
■ 


DE, Al, 3 001 300 (SOCIETE DES PRODUITS 
NESTLE S.A.), 24 July 1980 (24.07.80), see 
claims 1-4; page 3, lines 4-11; page 6, 
lines 8-16. 


(i) 

! 


A ; 

1 

i 
1 

| 
! 


DE, C, 959 219 (MERZ & CO.), 28 February 
1957 (28.02.57), see claims 1-4; page 1, 
lines 1-6; page 2, lines 30-44. 


(1) 


* Spacial catcgonee of cited doc urn em a: 
"A" document dafimng me general aiete of tho art which la not 
considered to bo of particular relevance 

Mriier document out pubhened en or aflat the internstional 
filing data 

"I* document whicii may throw double on priority ciaim(i) or 
which ta cited to aetaoi<an the publication data of another 
citation ot other special raaaon us • pea fled) 

"0" document referring to an oral ditdoaure. ueo, eahibMen or 
other meana 

document ouoltehed onor to the international Atlng dot* out 
later than the priority data claimed 


"T* later document publiehod after the international filing attt 
or ononty data and not In conflict with the application out 
cited to unoeratand tno principle or theory underlying \n% 
invention 

*X* document of particular relevonco; tho claimed invention 
cannot bo considered novo* or cannot be cofteioereo to 
involve an inventive it eg 

M Y*° document of parti cuter relevonco;' tho claimed invention 
cannot be conetderedJ to involve an inventive tree tr<e 
document <a combined) with one or . more other twcn 'docu- 
ments, aucn combination being obvious to a per ion »ft».«o 
in tho art 

"a," document member of the eamo patent family 


IV. C1ATIFICATION " 


Oate of the Actual Completion of the International Search 

14 October 1985 (14.10.85) 


Otta of Moiling of this Intarnetionei Search ftegori 

17 October 1985 (17.10.85) 


International Searching Authority 

AUSTRIAN PATENT OFFICE 


Signature of Authorised Officer 



*orm PCT/1SA/310 'aecond aheet) (January tsttr 



IntamatlonaJ Aflslieation No. PCT/HU 85/00042 



III. DOCUMIHTS CONS10IRIO TO M AIL1VAMT (CONT1NUIO H*OH THI SICOMO SHUT) 



Category * 



Citation of Document. wrtf> indication, whom tooropnito. of tr* r«*v«m pasiaoca 



Rafavant to Claim No 



DE , Al , 3 029 263 (DORIS COSMETIK WERK 
MARTIN EBERLE & CO), 19 March 1981 (19.03.81 
see claims 1-4; page 2, lines 18-22. 

GB, A, 2 052 979 (PIERRE-JEAN ASSIER DE 
POMPIGNAN, SERGE LIOTET), 4 February 1981 
(04.02.81), see abstract; claims 1,2; page 
1, lines 1-55. 

EP, Al, 0 009 464 (VERB AND AARGAVISCHER 
KASEREI- UND MILCHGENOSSENSCHAFTEN) , 
2 April 1980 (02.04.80), see abstract; 
claims 1-3. 



(i) 
(i) 

(i) 



Form PCT ISA, 210 («tra anaat) (January i MS) 



Anhang zum interna tio- 
nalen Recherchenbericht 
liber die international 
Patentanmeldung 
Nr. 



Annex to the International 
Search Report on Interna- 
tional Patent Application 
No. PCT/HU 85/00042 



Annexe au rapport de 
recherche internationale 
relatif a la demande de 
brevet international 



In diesem Anhang sind 
die Mitglieder der 
Patentfamilien der im 
4 obengenannten interna- 
' tionalen Recherchenbe- 
richt angefuhrten 
' Patentdokumente ange- 
geben. Diese Angaben 
dienen nr zur Uhtarrich- 
tung und erfolgen ohne 
Gewahr . 



This Annex lists the patent 
family members relating to 
the patent documents cited 
in the above-mentioned Inter- 
national search report. The 
Austrian Patent Office is in 
no way. liable for these par- 
ticulars which are merely 
given for the purpose of in- 
formation. 



La presente annexe indique 
les membres de la famille de 
brevets relatifs aux docu- 
ments de brevets cites dans 
le rapport de recherche inter- 
national vise ci-dessus, Les 
renseignements fournis sont 
donnes a titre indicatif et 
n'engagent pas la responsa- 
bilite de 1* Off ice autrichien 
des brevets. 



Im Recherchenbericht 
angefuhrtes Patent- 

dokument 
Patent document cited 

in search report 
Document de brevet cite 
dans le rapport 
de recherche 



Datum der 
Veroffentlichung 
Publication 
date 
Date de 
publication 



Mitglied(er) der 
Fatentfamille 
Patent family 
member (s) 
Membre(s) de la 
famille de 
brevets 



Datum der 
Verb f f en 1 1 ichung 
Publication 
date 
Date de 
publication 



AT-B - 41 810 11/04/1910 

GB-A - 6 247/A.D. 24/09/1908 
1908 

US-A -2 721 861 25/10/1955 

DE-Al -3 001 300 24/07/1980 



DE-C - 959 219 28/02/1957 
DE-Al -3 029 263 19/03/1981 

GB-A -2 052 979 04/02/1981 



None 
None 



None 










AR-A1 




219 


654 


29/08/ 1980 


BE-Al 




881 


154 


15/07/1980 


CA-A1 


-1 


131 


■561 


14/09/1982 


CH-A 




641 


345 


29/02/1984 


FR-A1 


-2 


446 


634 


14/08/1980 


FR-B1 


-2 


446 


634 


18/06/ 1982 


GB-Al 


-2 


046 


691 


19/11/1960 


GB-B-2 


-2 


046 


591 


30/03/1983 


JP-A2 


-55-098110 


25/07/1980 


NL-A 


-8 


000 


249 


18/07/ 1980 


US-A 


-4 


463 


017 


31/07/1964 


None 










AT-A 


_ i 


5 695/79 


15/12/1960 


AT-B 




363 


193 


10/07/1981 


BE-Al 




883 


935 


16/10/ 1980 


CH-A 




644 


269 


31/07/1984 


DE-Al 


-3 


024 


623 


22/01/1981 


FR-A1 


-2 


460 


135 


23/01/1981 


FR-B1 


-2 


460 


135 


19/11/1982 


JP-A2 


-56-053612 


13/05/1981 



Fortsetzung Seite 2 



FCT/HU 85/00042 



GB-A -2 052 979 04/02/1981 NL-A -8 003 802 06/01/1981 

US-A -4 342 747 03/08/1982 

EP-A1-0 009 464 02/04/1980 CH-A - 635 512 15/04/1983 



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