WO2009144514A2

WO2009144514A2 - Cooperative induction of apoptosis of prostate tissue - prostate cancer prevention - new practice of peripheral androgenic exclusion construction of complex tablet

Info

Publication number: WO2009144514A2
Application number: PCT/GR2009/000031
Authority: WO
Inventors: Nikolaos Dimofilos
Original assignee: Nikolaos Dimofilos
Priority date: 2008-05-29
Filing date: 2009-05-22
Publication date: 2009-12-03
Also published as: GR1006492B; WO2009144514A3

Abstract

After induction of apoptosis, with hydrochloric Terazosine, acting on the elimination of the prostate tissue due to the preceded atrophy - marasmus due to Dutasteride or Finasteride, the most rapid in immediate/medium-term and long-term practice for reduction of prostate tissue may be promoted in comparison to the separate action of - N- or -Φ-. At the same time, our conclusion is revealed, crucially secure and self- evidenced that, resulting by this fact, the prostate cancer is promoted and achieved in actions and not words, thanks to the crucial elimination of time - and not only - margin for the development of malignancy either further evolution - as happens often - of an already existing hidden, which has not reached yet and will not reach the limit of 1/10 cells [or approximate time limit of 8-10 years old). Furthermore, elimination on time of dysplastic-metaplastic cells due to stimulation of production and, inevitably, destruction from P53, the protein of apoptosis that destructs selectively all cells that are not functioning well from morphological point of view. With Fenretinide, an explosive collaborative prevention, harmless to the prevention of cancer to special population groups mentioned in the description and the indications of our practice. The additions of Verapamile/Diltiazeme, within the frame of particularities of action and application field, distinguish in the annulment of MDR, the imprisonment of PgP170 and in fact save the population of patients we address to. TECHNIQUE LEVEL We know nothing respective to our entire methodological conclusion.

Description

DESCRIPTION

COOPERATIVE INDUCTION OF APOPTOSIS OF PROSTATE TISSUE

- PROSTATE CANCER PREVENTION -

NEW PRACTICE OF PERIPHERAL ANDROGENIC EXCLUSION CONSTRUCTION OF COMPLEX TABLET

The substances Dutasteride [in brief - N-] and Finasteride [-Φ-] belong to the substances that engage-eliminate the 5-a anagogase [in brief 5-a-], enzyme of crucial importance for the nutrition of the prostate tissue because it is the converter- transformer of Testosterone [-T] into Dihydrotestosterone [DHT]. The second and not the first, related to the cellular, molecular and nuclear receptors of the prostate tissue practices the main nutritive action and the rest biological functional tissue necessities either of normal or neoplasmatic tissue.

So, the reception of one or the other, qualitative and quantitative, leads, according to the known action places, to reduction of the prostate tissue volume [and improvement of urodynamic parameters] for which they were granted with the circulation permit with this exact indication. Let us explain that Φ eliminates only one equivalent form of 5-a and N eliminates both its two equivalent forms of 5-a anagogase. Thus, the cells are atrophied due to hunger and eliminated through known functional procedures of the phenomenon of apoptosis. However, our concept

[but also common sense] is realized at percentage extent - from the use of the one or the other - with the passing of time, reduction of risk for the growth of prostate cancer since it is more difficult, the feeding conditions and the general developmental status to be reduced, the healthy of cells to be deteriorated and the risk of cancer growth to be increased. Despite all these, our belief and scientific methodological practice proceeds to an innovative way of addition of another contractual substance which aims at the attribution of catalytic qualities to the tablet we intend to form.

For years now, it is known that the substance Terazosine [hydrochloride], used also for the treatment of hypertension and the normalization of the symptoms of the lower urinary system [L. U. T. S], improves the known symptoms of starting-intermediary prostate hyperplasia [B. P. H]. The reason for the decisive inferential participation is that, according to the study of Mrs Kyprianou, researcher in Mayo Klinik-USA, Terazosine increases greatly a special protein of the organism, P53, known internationally as protein of apoptosis, the scheduled cell death, that is the forcing the selected cell to suicide, where selected cell is all irregular morphologically, atrophic, old, injured etc cell due to radiation, burn etc. They are forced to be differentiated, with nucleus segmentation and other forced apoptotic procedures, to ...die-suicide. The whole resulted cognitive concept is that, apart from everyday victims [see prostate cells], due to the action of -Φ- or -N-, most of them are neighbors of already dead cells - are not found in better condition, deprived by the feeding but how they did not reach today the final point of decline, which will happen inevitably tomorrow, the other day, soon/the soonest possible. In natural, relaxing way, we are obliged to expect that Terazosine, our second cooperator, with the induction of P53, will recognize them - P53- as non normal and self-inductive by the chain interactions, continuously promoted by Terazosine, will lead them to apoptosis course, by eliminating cooperatively, much more cells in given time unit, e.g one day in comparison to the result of effect of -Φ- or -N-. We think that common sense, purely and directly scientific reasons, comply with our conviction regarding the irrefutable and innovative panel of our collaborative methodology. Our goal is not the reveal some mentioned qualities in the circulation permit of substances and the bright demonstration of, maybe unknown to more people, collaborative features, with bright - as we think- obvious preventive profits, as we are doing in our everyday clinic practice for 9 years now. It is commonly known that, at least typically, a cancer needs 8-10 years to reach the crucial limit of 1/10 cells, that is the size-1cm.

With our intervention, the everyday consumption of our complex preparation will avoid further developmental hyperplasia by exercising bigger destructive cooperation, by depriving in the hyperplastic, possibly dysplastic-metaplastic prostate tissue like in the latent non recognized yet cancer: t h e t i m e, in order to be developed and fed properly, by default, impossible!! We keep our constructive discretion for the participation of -N- or -Φ- [always one out of two] in our complex tablet.

However, the crowning of our whole report regards the possibility of a second substance to participate, concerning the part of prevention of the most severe male cancer. The substance is called Fenretinide, it is newer derivative of 13-trans retinoic acid, without side effects [according to W. H. O], leads mainly to apoptosis, with comparative result, its plasmatic accumulations in long-term modification of a steroid receptor in order to keep maintaining the inhibitory activity of retinoic acid in the multiplication signs, increases the production of endogenous lnterferones but the most important part of participation regards its inhibitory quality in the lnsuline Growth Factor-1 , former called Somatomedine-C or otherwise Insulin Growth Factor due to the similarity of actions with the lnsuline particle. It has autocrine and paracrine action, related to the engaged proteins. [BPs] and its mother hormone is Growth Hormone, it constitutes the resident and messenger of its actions. This factor constitutes the main, pre-required motivator for prostate cancer (depends on the epithelium), the breast, the lungs, the ovary intestine, cervix, also depended on the epithelium. Fenretinide (4-HPR-N-G Hydroxyphenyl retinamide), apart from the pre- mentioned qualities, due to the inhibitory effect on this risky factor, will be used for further assurance of our preventive practice in prostate [since long time, it has been used in the long-term prevention, without side effects, together with Tamoxifen for breast cancer], in men who are positive in the factor [not all] as purely preventive participation and those patients [from now on] who, for reasons of big health problems [heart etc] cannot be operated - either due to old age over 75kg and with local or local advanced CaPr or P.I.N 1/P.I.N 2 (Prostate Intraepithelial Neoplasy) within the frame of application of Androgenic Peripheral Exclusion [with Floutamide or Bikaloutamide which is especially mentioned below]. Results from the same studies show that approximately 98 men out of 1000 are positive to IGF-1 , 11 are hyperpositive [hyperexpression]. In simple words, this means that they have 4 times more the certainty of risk for prostate cancer growth in comparison to the general risk of the population = 4 X100=400%!!!

This entire pleasant perspective was known in 1998, on January, in publication of Science magazine, by the professor M.Pollak.McGill Univ.Toronto Canada + Harvard School of Public Health. In addition, the triple participation (N or Φ, + Terazosine + Fenretinide) in container of separate color will be administered to patients with Diabetes Mellitus, thanks to the action of this factor, known that the diabetes population [type 1 and 2] has increased risk of growth over the general average, by 1.52 [X100]. [American Veteran Study.... on 1.000.000 population]. - See accompanying study = Recognition of subject goals...-

Unfortunately, when the mother is involved, that is the growth hormone, we notice positiveness in IGF-1, p.c Parkinson, Acromegaloid, men with dwarfism who have consumed growth hormone preparations in order to get tall. Fenretinide intervenes without side effects in the dynamic of insulin growth factor by reducing it dramatically, by imposing thus the misfire of the whole system of post-combustion in the whole evolution of the initial and further procedure of cancer dynamism. To sum up, there will be care for the special population groups with increased risk for prostate cancer, that is patients as above described, with PIN 1/PIN 2 or patients with local or local advanced [endoprostate] cancer who usually and due to age [over 70-75 years old] are set in Watchfull Waiting treatment technique, that means in simple Greek language that the cancer will explode clinically and then we'll give treatment [we strongly oppose to that]. In different colour with tri-complex union = Φ or N [with the usual dosage] + Terazocine 5mg + Fenretinide 50mg, there will be chance for those patients to deal dynamically with their situation.

A separate and particular situation is formed by a special part of individual patients who suffer from cancer of low grade/stage, they cannot/don't want to experience the risk of radical prostatectomy either they have already proceeded to one prostatectomy and, being already old, they are subject to biochemical breed either the whole status became androgen-depended situations etc that belong to the sphere of shilly-shallying....

At that moment, the Peripheral Androgen Exclusion is granted aiming at the deprivation of androgens from the prostate cancer, by adding in the treatment Bicalutamide/Flutamide and, usually, Finasteride. So, especially for similar situations, there will be from our behalf a special category of complex tablet, of four collaborative substances, that is 4 in 1 , with the addition of antagonist Calcium, Veraepamile or Diltiazeme [usual minimum dosage] which, apart from the quality to act against hypertonia [circulation license] in our practice they will be used for two different qualities, we believe that those are not wider known. With our current/future constructive discretion of the one out of two that will be decided to participate in our tablet, we remind that they delay the degradation of Dutasteride, so the time of half life is postponed as well as the time of best penetration in prostate cells, given the fact that Dutasteride may act only in prostate cells, either in maternal focus or in hidden metastatic foci, by forming additional treatment profits, in our ignorance. Multiple international works -see attached report about Glucoprotein and the phenomenon of multidrug resistance - the Calcium antagonists, especially the above mentioned substances, induced decisive destructive attacks in malignant cells, eliminate MDR Phenomenon [Multi Drug Resistance] and keep silent Glucoprotein PgP170, the responsible for the phenomenon of multidrug resistance but at the same time due to the boycottage of calcium channels in new cells, the calcium level within an endoplasmatic net of cancer cell falls under a strictly precise level, within 24 hours it is obliged to suicide, being entered in the procedure of apoptosis. In detail, they are mentioned with the bibliography in the attached document of our claim suggestion.

So, as resulted, our collaborative hypostasis undoubtedly corresponds to scientific base/es and innovative coordinate collaborative rational result.

To conclude, we focus again in the compromising innovative collaborative policy and our methodological leading in our suggestions.

1) The Induction of Apoptosis, 2) the clearly revealed suggestion by the collaborative coordinate knowledge about the (non surgical) method-course of prostate cancer prevention in general/special population groups, 3) the innovative collaborative destruction and no further evolution of neo-cells in the special subcategories of the disease, in separate vessels, of different color and our discretion, of separate dosage of the collaborative substances.

Claims

1^η. We claim the patent of the substances = dutasteride, finasteride, fenretinide, terazosine, verapamil, diltiazem. The reasons were described clearly. The whole collage-panel of our methodology is included, under the notion of another intervention point of view and practice, in the clinical practice, towards the prevention and further subservient approach/treatment of patients.

2^η. We claim the patent of all versions and conjunctive - absorbing - covering substances that are already included in the preparations to be patented but also the forms of versions of controlled release, currently in general use and also the future versions that will regard the general intention and notion of our methodology and the substances, one or more, for the aims already stated.

3^η. Indisputably, we reserve at our discretion any quantitative use of the substances of our tablet/s, as well as the selective participation of one or another substance in the tablet.

4^η. We claim for protection from similar bootleg attempts of the intention and use of our cooperative potential, with the addition or additions of "innovative" further drugs or and vehicles of those drugs, if even a fraction of the substance we claim for protection participates.

In addition, we bind the substance Nifedipine, Amiodarone [similarly calcium inhibitors] for their eventual future participation.