Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from hypericum
Reexamination Certificate
2000-08-11
2001-11-27
Tate, Christopher R. (Department: 1651)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
Containing or obtained from hypericum
C514S729000, C514S730000, C514S731000, C514S732000
Reexamination Certificate
active
06322824
ABSTRACT:
The invention relates to the use of hyperforin and hyperforin-containing extracts of
Hypericum perforatum L.
(St. John's wort) in the treatment and prophylaxis of dementia diseases such as for example Alzheimer's disease.
The phloroglucin derivative hyperforin of the following structural formula
is one of the main constituents of St. John's wort. Since the substance is chemically unstable, its content decreases upon drying of the fresh plant. With rapid drying and under gentle conditions, the St. John's wort drug still contains hyperforin in a high concentration which is comparable with the content of fresh plants.
Hypericum extracts have been used for many years or the treatment of depression and psychovegetative disorders (cf. Linde et al., BMJ, Vol. 313, pp. 253-258, (1996)). A method of preparing hypericum extracts is described in the German Patent 196 19 512, which [contain] a stable [hyperforin content of at least 2%]
1
.
1
N. B. The text corresponding to the words in square brackets has been omitted from the PCT application as filed.
Dry extracts of hypericum and methods of preparing them, which are poor in.
Dry extracts of hypericum and methods of preparing them, which are poor in hypericin but have a higher content of hyperforin than the vegetable starting material, are known from EP-A-0 599 307. These extracts have a strongly serotonin-antagonistic effect, and they are used for the preparation of medicines with a psychovegetative and anti-depressive effect. These extracts are used for the treatment of anxiety disorders, nervous agitation, migraines, gastrointestinal disorders and vomiting. In addition, for various preparations, which contain a hypericum extract alone or in combination with other substances, many applications are described in the fields of medicine and cosmetics. In particular, anti-viral and anti-bacterial effects are also known. In this way, the use of hypericum extracts for the treatment of viral diseases, in particular HIV, is known from WO 97/22354, while anti-bacterial effects and the use of ointments containing hypericum extract for the prevention of diseases transmissible through sexual inter-course are described in the Russian Patent RU-C1-2 031 645.
In investigations involving experiments on animals a significant influence upon cognitive functions by hyperforin and hyperforin-containing extracts of
Hypericum perforatum L.
has now surprisingly been found. Such an effect has not been described previously either for hyperforin or for hyperforin-containing extracts and, on the basis of the previously known pharmacological and clinical effects, was also not expected. Within the scope of the present invention an effect upon the memory capacity by a hyperforin-rich hypericum extract and by hyperforin itself has been found for the first time. Hyperforin and hyperforin-containing extracts can thus be used for the therapy of neurological disorders which accompany dementia.
Dementia is defined as a significant reduction in the intellectual capacity which appears as a reduction in the memory and the power to reason and is linked to a deterioration in the personal activities of daily life. Large-scale autopsy statistics and clinical-epidemiological investigations show that, at approximately 60%, neurodegenerative diseases are the most common cause of dementia. After that, approximately 20% of cases are the so-called vascular forms of dementia and a further 20% are other causes (cf. Rösler et al.,
Fortschr. Med.
114, pp. 351-356 (1996)). No generally recognized method of therapy for dementia diseases has existed until now, so that treatment has had to be restricted to the amelioration of the clinical symptoms.
Alzheimer's dementia or Alzheimer's disease is an illness which starts insidiously and which is characterized by initial forgetfulness, increasing lapses of memory and the loss of further cognitive abilities. It ends with the total intellectual decay and personality loss of the patient. A satisfactory causally orientated therapy of this illness has not previously been available (cf. K. Mendla, “
Die Alzheimer
-
Krankheit: Neue Ansätze in der Pharmakotherapie
” [Alzheimer's Disease: New starting points in pharmacotherapy],
Pharm. Zeitung
141, pp. 351-356 (1996)). Alzheimer's dementia is treated with acetylcholinesterase inhibitors in order to increase the quantity of acetylcholine available in the brain. This treatment leads to a number of undesired side-effects which do not permit permanent therapy (cf. Shvaloff et al., Psychopharmacology Bulletin, Vol. 32, pp. 343-352 (1996)).
The object of the invention is therefore to make available substances having an anti-dementia effect and compositions containing such substances, which have fewer side-effects than the medicaments used hitherto for this indication.
The subject of the invention is therefore the use of hyperforin and hyperforin-containing extracts of
Hypericum perforatum L.
(St. John's wort) in the treatment and prophylaxis of dementia diseases, including Alzheimer's disease, vascular dementia and mixed forms of dementia, and thus the use of hyperforin and hyperforin-containing extracts as a medicament for the treatment of diseases which accompany a disorder of the memory or learning ability, as well as the use of hyperforin and hyperforin-containing extracts of St. John's wort in the preparation of a medicament for the treatment and prophylaxis of dementia diseases, in particular Alzheimer's disease, vascular dementia and mixed forms of dementia.
Without wishing to be bound by a specific theory, the use of hyperforin and hyperforin-containing extracts appears to have a causally therapeutic starting point, since it has surprisingly been found that hyperforin and the extracts named are powerful stimulators of the protein kinase C&ggr;. This protein kinase C&ggr; activates the &agr;-secretase, which in turn prevents the occurrence of the pathogenic amyloid A&bgr;. A special advantage of hyperforin and hyperforin-containing extracts is thus that not only do they prevent the formation of amyloid A&bgr; in a desired manner, but in addition it is possible to combat effectively the psychiatric attendant symptoms, such as anxiety, depression and other psychovegetative disorders, which frequently occur in dementia diseases, in particular Alzheimer's.
REFERENCES:
patent: 4713376 (1987-12-01), Kuzuya
patent: 5733926 (1998-03-01), Gorbach
patent: 6117855 (2000-09-01), Carlson et al.
patent: 6159986 (2000-12-01), Altman
patent: 19619512 (1997-07-01), None
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patent: WO 00/57707 (2000-10-01), None
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Buxbaum, Joseph D., et al., Processing of Alzheimer &bgr;/A4 amyloid precursor protein: Modulation by agents that regulate protein phosphorylation; Proc. Natl. Acad. Sci, USA, vol. 87, pp. 6003-6006 (Aug., 1990).
Chatterjee, Shyam Sunder, et al., Hyperforin and Hypericun Extract: Interactions with some neurotransmitter systems (abstract); 2ndInternational Congress on Phytomedicine, (1996).
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Games, Dora, et al., Alzheimer-type neuropathology in transgenic mice overexpressing V717F &bgr;-amyloid precursor protein; Nature, vol. 373, pp. 523-527 (Feb., 1995).
Giacobini, Ezio, Cholinomimetic Therapy of Alzheimer Disease: Does It Slow Down Deterioration?; Int Acad Biomed Drug Res. Basel, Karger, vol. 7, pp. 51-57 (1994).
Herberhold, C., Pflanzliche Arzneien bessern den Score im Hirnleistungstest, Fortschritte der Medizin, Bd 111, Nr. 6, p. 50 (1993).
Hsiao, Karen, et al., Correlative memor
Chatterjee Shyam Sunder
Erdelmeier Clemens
Noldner Michael
Frost Brown Todd LLC
Tate Christopher R.
Willmar Schwabe GmbH & Co.
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