SA113340787B1 - Methods and systems for treating cell proliferation - Google Patents

Abstract

NAMethods for the treatment of a cell proliferation disorder in a subject, involving: (1) administering to the subject at least one activatable pharmaceutical agent that is capable of effecting a predetermined cellular change when activated, either alone or in combination with at least one energy modulation agent; and (2) applying an initiation energy from an initiation energy source to the subject, wherein the applying activates the activatable agent in situ, thus causing the predetermined cellular change to occur, wherein the predetermined cellular change treats the cell proliferation disorder, preferably by causing an increase or decrease in rate of cell proliferation, and a kit for performing the method, a computer implemented system for performing the method, a pharmaceutical composition useful in the method and a method for causing an autovaccine effect in a subject using the method.

Description

_— \ _ Methods and systems for treating cell proliferation disorders Full description Background to the invention This application is a Sia application from Application No. 87907095, which was filed in the Kingdom of Saudi Arabia on 1 3 0 af AH and OK and 4 3 0 A 0 AM The present invention relates to methods and systems for the treatment of HIS disorders Treatment of a cell proliferation disorder © « From DA a better distinction is achieved between healthy normal cells WANs healthy cells patients with a cell proliferation disorder WMA (referred to hereinafter as “target cells” and preferably those performed using non-proliferation or minimal proliferation techniques). Cell proliferation disorders 0 There are many types of cell proliferation disorders Examples of cell proliferation disorders may include, but are not limited to, cancer ¢ bacterial infection; the immune response associated with organ transplant rejection “immune rejection response o f organ transplant solid tumors viral infection autoimmune disorders (eg arthritis lupus inflammatory bowel disease 0); Sjogrens syndrome multiple sclerosis (or a combination thereof) as well as conditions related to aplasia in which cell proliferation is low relative to healthy cells, such as anemia related to aplasia. Among these conditions, cancer may be

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It is more known. In general, the term "cancer" refers to a diverse category of cancer

Diseases commonly characterized by abnormal proliferation of diseased cells. A common feature is

All types of cancer known to result in the acquisition of abnormal traits in the genetic material of the cell

cancer and its offspring. Once the cell becomes cancerous; they reproduce regardless of natural boundaries ©; They invade and destroy nearby tissues; It may spread to distant anatomical sites by an operation

It's called penetration. These life-threatening malignant properties in carcinomas lead to

distinguish them from benign tumors; which are self-limiting in their growth and do not spread or penetrate.

In no way can the impact of cancer on society be overestimated. The disease may affect

on people of all ages; With a risk factor that increases dramatically with a person's age. 0 Cancer was one of the main causes of death in developed countries and it is expected; increasing ages

Our people believe that Jia is an even greater danger to our society and economy. This is why drugs were found

and effective treatments for cancer ¢ cara is one of the priorities of those involved in biomedical research.

treatment methods

Current treatments for Jie cell proliferation disorders include surgery; chemotherapy | 0 ¢ radiation therapy ¢ immunotherapy;

monoclonal antibody therapy; And many other lesser known methods. The choice depends

Treatment usually depends on the location and severity of the disorder. (goad) stage as well as the patient's response

While some treatments seek to control and alleviate the symptoms of the disorder; Yo The ultimate goal of any effective treatment is to completely remove or cure all of the disordered cells without causing any damage

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It is harmful to the rest of the body. And in the case of cancer; Although surgery may achieve this goal (bla), the tendency of cancer cells to invade axonal tissue or spread to distant sites through microinvasiveness limits the effectiveness of this option. Similarly, toxicity to other tissues in the body often results in Reducing the effectiveness of current chemotherapy © Radiation therapy has similar drawbacks to the aforementioned treatment methods It is known that most of these cancer treatment methods, including radiation therapy ¢ cause damage to the (DNA) which in Als leads to its failure to repair during a critical period of mitosis, that is, the division of the cell during its reproduction, to the organized death of cells, that is, the fading of cells. Also, radiation damages healthy cells, in addition to malignant tumor cells.

0 A number of patents describe the treatment of bodily fluids outside the body of an organism (al); For example blood. blood is obtained from a patient; treated with a photosensitizing agent; exposure to ultraviolet radiation; Solely injected into the patient (i.e. extracorporeal photopurification). alternatively; It is possible to treat the patient inside the body using a photosensitizing agent followed by taking a sample from the patient and treating it with UV emitters in the laboratory (outside the body of the organism).

_ neighborhood); And re-inject the patient with the treated sample. This method is known for obtaining an autovaccine. There is no description of how to treat a patient with a photosensitizing agent; And exposing the patient to an energy source and generating the effect of an auto-vaccine, all the steps of which are carried out in the body of the organism. See International Patent Application AAV [oF 0] US Patent Application No. 1,079,871 US Patent Application No. 1,705,0578; to request

0 US Patent No. 5,980,984; US Patent Application No. 1,745,575; calla US Patent No. 4,877,857; US Patent Application No. 6,651,764

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Co and US Patent Application No. 6,859,058. Furthermore it; Side effects of extracorporeal photorefining are well known and include nausea; vomiting; roseola; hypersensitivity to sunlight; and secondary malignancy in the blood. Researchers are trying to use photodialysis in experimental treatments of patients with autoimmune cardiac and respiratory allograft rejection; Autoimmune diseases pulmonary and renal allograft rejection © . ulcerative colitis and ulcerative colitis » diseases A research conducted on known treatment methods reveals that these methods involve a major difficulty when delivering treatment; Often, target cells have to do with distinguishing between normal cells and target cells. It is non-selective aie known as singlet oxygen. This is due to the production of single oxygen in addition to the need to carry out processes outside the body of the organism; Or from DAY in attacking it 0 such as surgical procedures to reach tissues at a depth of pS through highly invasive procedures. more than a few centimeters in the body of the treated individual photons US Patent Application No. 08,794454 describes the simultaneous excitation of two low-energy infrared Jie photons of optical agents using high-energy rays The excitation of a photon is compared . near infrared light (NRT) 10; where psoralen is treated with respect to derivatives of one photons and simultaneous excitation of two of the 255. UV or UV-NRT cells with a photoactive agent and is released by the patent application that treatment with low-energy radiation is beneficial because it is absorbed post it or NRI ultrasound however; longer use. UV emitters to a lesser degree than UV rays relate to tissue penetration to a depth of only a few centimeters. Led is known as UV emitters violet 0 and therefore any treatment in a place deeper than that in the body of the treated individual necessarily requires the use of wr

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Ex vivo methods or highly diffuse methods to allow the source of radiation

access to the tissue involved.

It describes each of:

1166 (2006); Kim et al, JACS, —Chen et al, J.

Nanoscience and Nanotech., 6:1159

© 1292669-(2007) £2675 US Patent Application No. 4/7007 7977701;

US Patent No. 49,979,975 Processing methods using various types of activating agents within

The body of an energy healer. However; The disadvantage of both of them is that the treatment depends on the production of oxygen

single oxygen sal) to produce the desired effect on the tissue being treated; And therefore

It largely involves indiscriminate effect on both healthy cells and diseased tissue Yo to be treated.

US Patent Application #1,408,891 discloses methods for irradiating tissue sterilization to reduce...

One or more levels of active biological contaminants or pathogens; Jie viruses

viruses ¢ bacteria s yeasts molds molds s fungi s spores s prions

or similar factors responsible; alone or in combination; Jal ve amenable spongiform encephalopathies and/or unicellular or multicellular parasites (DAD) so that the tissue can then be used for

Transplantation of organs to replace diseased and/or otherwise incapacitated tissue in an animal. It included

The method is to use a sensitivity agent, psoralen fie; a psoralen derivative or other agent

Photosensitization to increase radiation potency or reduce exposure necessary for tissue sterilization. However; no

The method is suitable for treating a patient and does not involve any mechanism for inducing photosensitizing agents; 0 indirectly.

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calla US Patent No. 177,508 discloses antiviral applications for

psorakens and other photoactive molecules. The request explains the method for canceling the event

Viral and bacterial contaminants from a biological solution. The method involves mixing blood with a sensitizing agent

photosensitizer, blocking agent and release mixture for photosensitizing agent induction; This leads to invalidation

© Significantly all contaminants in the blood; without destroying red blood cells. Block factor or block

It reduces adverse reactions to the photosensitizing agent that occur in Alla No Factor

ban. The modus operandi of the blocking agent is not mainly to suppress any of the types

reactive oxygen ¢ according to ref.

Further” US Patent Application 677255608 states that photosensitizing agents and halogenated 8-treated 0-blocking agents are suitable for substituting (8-11070) 8-methoxypsoralen in

photoselective and, in dallas, certain prevalent types of cancer; Especially solid tumors

dad) solid tumors that can be accessed through a fibre-optic device or other types of tumors

superficial skin cancer. However; This reference does not deal with Af specific particles for use in

Treatment of lymphoma or any other cancer. Instead of that; Reference describes a Vo photoselection process for antiviral treatments in untreated blood and plasma.

It is understood from US Patent Application No. 1,778,554 Disadvantages 1107-8 and

8-MOP and 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) and many other molecules

photoactivated; Which is indicated to have certain drawbacks. It is indicated as a preference for sensitizing agents

photocatalytic through fluorescence; However, the reference does not describe how to select a system for fluorescence photoactivation using fluorescent photosensitizers. Instead of that; He is

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The fluorescent photosensitizing agent H0008 is limited to the browning factor that binds to DNA. The reference states that the fluorescence indicates that this browning factor is less likely to catalyze oxygen bases. For this reason, the reference does not reveal a mechanism for photoactivation of an interfacial agent other than direct photoactivation by UV emitters » although a probe of UV emitters or X-rays has been proposed to penetrate in a gel form. in tissues. No ABS is provided for the use of 177 emitters UV probe or the use of x-rays. No example of x-ray stimulation is given for psoralen and related compounds: US Patent Application No. 173880800 further states that psoralen are natural compounds that have been used therapeutically for decades in Lal and Africa. The action of psoralen compounds and light has been used to treat vitiligo and psoriasis (ze) psoralen ays (Psoralen Ultra Viokt A ¢PUVA is able to bind to DNA double helices by mediating base pairs; (DNA) or dies (RNA). ) uracils sequential absorption of two UV-A photons psoralen in As excitably interacts with the 1_-thymine double bond or its dehydrogenase" and covalently binds JS from the two strands of a nucleic acid helix. The cross-linking interaction appears qualitative for a base of thymine (DNA) or its inhibitor (RNA) and binding occurs only if psoralen is intermediate in a site containing thymine or ¢ouracls but an initial photoadhesive complex must absorb a GB UVA photon to interact with A second thymine or uracil on the opposite strand of the helix to cross-link each of the two strands of the double helix, as shown below. This is 0 sequential absorption of two single photons as shown, as opposed to simultaneous absorption of two or more photons Eur

q — _ a 4 A quota 1 i “WE : between ws 18 button x h | 7 CY 5 NA £f A 4< P A N 93[ OCT 8 3 born TNA svasd TINA stead Iv VA (os plies) Fda, 8 43 of o Woo Ry PN X wi AL Monod 1 — 2 i Ry 1 H g [#3 D A ben, tile If VA poco i A EE hd es Lo T Is AAA A J B TO J 1 A THAR 1 a Tey” ~ NI 5 ES ® by evaneelink 8-MOP is not suitable for use as an antiviral because it destroys SIS cells and viruses. Lethal cell or viral damage occurs when soralen mediates ac laa nucleic acid at sites containing two thymines (or uracils) on opposite strands but only when it sequentially absorbs two UVA photons and is thymines (or "transporters") are present. US Patent Application No. 4,748,120 L.L

“ym illustrated an example of the use of A psoralen compounds that have been substituted through a photochemical decontamination process to treat blood or blood products. Additives are sometimes used; Jie Antioxidants 6l7l00: Htm with psoralen compounds; AMT 8-MOP (fis, 1 -1111; to scavenge singlet oxygen and other highly reactive oxygen species formed during the photoactivation of psoralens. It is well known that it results from activation with These O-RSs, which are capable of severely damaging otherwise healthy cells, may be much of the viral deactivation due to these O-RSs rather than any photoactivation effect of the psoralens. Note that there is no effect of autovaccine self-vaccine 0

Las » coumarins psoralen The best known photostable compounds are derived from two nucleic acid structural factors. The use of photosensitizing agents not considered beneficial to HEY Alla could lead to the emergence of alternative chemical pathways for elimination of coumarin s psoralen in relation to viral deactivation; or considered harmful to the process. For 16:6 AH: 0 PM and vehicles; This chemical pathway likely leads to the formation of a number of open coumarin Yo species: ring coumarin; Like shown below for pm to | A SA oP oN Be a or Br

PEE 0 or not

Research in this area involves an oversimplification of the mechanisms involved in the photoactivation mechanism and the formation of highly reactive oxygen species” such as singlet oxygen. Both may deactivate tumor cells, viruses, and healthy cells. However, none of them alone or with the other leads to the effect of an autovaccine. © This requires activating the body's immune system response to identify a malignant cell or virus as a dangerous potential and triggering an immune response that results in permanent cytotoxic effects directed at that dangerous potential. believes in a non-exclusive way in any way; Photoactivation and the resulting fading of malignant cells that occur in ex vivo selection leads to the activation of an immune response with toxic effects on untreated malignant cells. While researchers understand the complexity of the immune response and the effects of cytotoxins, a treatment that harnesses The system for successfully inducing the effect of an autovaccine against a target malignant cell remains elusive; the use of photoselective

Extracorporeal lymphoma treatment.

Jha: Midden (W.

R.

Midden, Psoralen DNA photobiology, 170111 (ed.

F.

P. Gaspalloco) CRC press, pp. 1. (1988) yo that the compounds of Je las psoralen photosynthesize with unsaturated fats and react photosynthetically with molecular oxygen to produce anoa 2 active oxygen such as superoxide and single oxygen which causes tals to form membranes. US Patent Application Sq 1 states that 8-AMT 3 MOP are unacceptable as sensitizing agents (Pp) because both of them indiscriminately damage both cells and viruses. Studies regarding the effects of the side chains are reviewed. Cationic Worla

_ \ \ —_

Psoralen DNA Photobiology, Vol I, as photosensitizing agents in coumarin g ysl) on eed. F Gaspano, CRC Press, Inc., Boca Raton, Fla., Chapter 2 The US patent application from that review states: Most amino compounds have a significantly lower ability to bind and cross-link with DNA compared to 8400-8 ; This suggests that the main 0-amino functional group is the preferred ionic species for both photo- and cross-linking. Heindel's US Patent No. 0117 discloses a large number of psoralen and coumarin compounds that have some activity as photoactive epidermal growth factor (EGF) inhibitors. Halogens and amine compounds belong to the large functional groups that can be included in the main series -psoralen/coumarin This reference is included in this order 1 0 as a reference. US Patent Application No. 0945778 discloses the use of extracorporeal photoreduction with 8-MOP to treat CMV-infected blood. The treated WAY is then used in addition to virus peptides, native subunits of the virus itself (released upon cell division and/or lysis into the blood) and/or dead and/attenuated non-infectious da pee viruses to generate Vo antibody (cu gyal) immune response, which was not present before treatment. Photodynamic therapy (PDT) Photodynamic therapy (PDT) is a treatment method that uses a photosensitizing agent and lasers to kill cells. PDT retains many photosensitizing factors in tumors longer than in normal tissues; It thus carries the potential to improve selectivity in treatment. A) See: EOAY

Comer C., “Determination of [3H]- and [14C] hematoporphyrin derivative distribution in malignant and normal tissue,” Cancer Res 1979, 39: 146-15 1; Young SW, et al, “Lutetium texaphyrin (PCI-0123) a near-infrared, water-soluble photosensitizer,"

Photochem Photobiol 1996, 63:892-897; and Berenbaum MC, et al., "Meso-

Tetrahydroxyphenyl)porphyrins, a new class of potent tumor photosensitisers with 2 favorable selectivity,” Br J Cancer 1986, 54:717-725 Through photodynamic therapy, light rays of a specific wavelength are used to activate the photosensitizing factor. Several light sources have been developed, including dye lasers and lasers. The light coupling provided by these types of lasers has been developed with Saddles PDT fiber optic diodes: photodiodes that allow light to be emitted to the desired location. See 0

Pass 1-11, "Photodynamic therapy in oncology: mechanisms and clinical use," J Natl

Cancer Inst 1993, 85443-456 Refer to photo-oxidation reactions; On PDT, the researchers believe that the cytotoxic effect of

Foote CS, “Mechanisms of photooxygenation,” Proa Clin, In the presence of Biol Res 1984, 1703-18 and singlet oxygen rules Jie call ) for the production of many species coxygen is a major effect; Effective. mainly due to the limited penetration of visible light used

Sie in the activation of the photosensitizing agent. This is why 007 is used to treat the surfaces of sensitive organs: the lungs or the organs inside the abdomen; Not to damage the tissues without it. However these same therapies require highly invasive approaches to treat the surface of affected organs. In clinical situations this procedure is used in addition to surgical excision to eliminate microscopic or minimally invasive macroscopic effects of the disease. It is possible for laser radiation to produce a small amount of microscopic effects and minimal macroscopic effects of the disease, a very small amount of damage. Preclinical data show that part of damaged tissue SAAD or tissue 0 autovaccine immune response is generated; However, clinical trials recorded that there was no effect of self-vaccination similar to that resulting from ex vivo photoselection in clinical conditions. Instead; The immune response appears strong only in limited circumstances and for a limited period of time only. Problems It is well known that one of the main problems associated with the methods of diagnosing and treating natural 15 LIAN proliferation disorders is the distinction between treatment of a cell proliferation khadia disorder and it is difficult to achieve this specific targeting through surgery because . target cells and the target cells Large enough of the affected area to contain all the cells eda The method here is to remove a patient who has spread to other distant sites. for chemotherapy; While some distinction can be made; However, healthy cells in general are adversely affected by chemical agents. As in surgery; The treatment method is to take into account that ae WAN is a huge group of JB as well as in chemotherapy there are much more normal cells than diseased cells until the organism recovers from the chemical attack. WAY By shining radiation therapy © or high-energy electrons or protons. These Jie photons lead to high-energy radiation, which in turn leads to cell death. High-energy radiation (DNA) ionizes the atoms that make up the chain of anesthesia and is characterized by radiation therapy. Unlike surgery, radiation therapy does not require the possibility of a cure Tumors located in the depths of the body through minimal spread in the body. However, the high doses of radiation required for these treatments damage healthy cells just as 0. Similar to surgery, differentiating healthy cells (dag) is as effective as destroying diseased cells. .Only based on location. Also, there is no radiation therapy, and the patient in radiation therapy has a self-medication that makes the beam distinguish between a healthy cell and a diseased cell. Advanced treatment images (son) include JED, and other methods may be more accurate. For example, for lymphoma, known as photodialysis outside the body, the patient's blood is drawn from his body into a tool 1 in which the white cells (tunica albuginea) are separated from the plasma and red blood cells. A small amount of the plasma separated in this process is then isolated and mixed with a photosensitizing agent (05); Any drug that can be activated by light. After that, the tunica albuginea is exposed to light to activate the drug. To the patient. In this example; It is possible to envisage a solution (processor blood sale) after which the problem related to the quality of targeting is accomplished by separating the blood from the rest of the body where 0 target components are detected.

However; This procedure has its drawbacks. As it requires drawing blood from the pana) which necessitates the presence of

Cumbersome machines to perform and may require a blood transfusion to maintain the volume of blood flowing into the machine. like that; limits

This is also from the size of the patient that can be treated; This is because the volume outside the body is

too much blood is drawn, which increases the risk of deficiency-related shock

© Blood Volume.

Method IX is restricted to the treatment of WAY-related disorders arising in Jie blood

lymphoma; It is not characterized by the ability to treat solid tumors, nor other types of tumors

Non-blood related WAN proliferative disorders.

One of the problems with PDT is the inability to treat target 0 areas that are more than a few centimeters below the surface of the skin without proper techniques.

highly diffusive; The work of PDT normally results in the generation of sufficient amounts of monooxygenase

single oxygen to cell lysis. However"; The monooxygenase in sufficient concentration does not lead to

Not only target cells are lysed, but healthy cells are also lysed indiscriminately.

Thus there remains data for better and more effective therapies that can precisely target diseased cells 1 without causing significant side effects or secondary damage to healthy tissues; And through it can

Treatment of solid tumors or other types of unrelated cell proliferation disorders

with blood.

General description of the invention

(Jal, One of the objectives of the present invention is to provide a method for dalled treatment of a cell proliferation disorder Y in a way that allows treating an individual in any area of

EOAY

body so that they are not at the same time diffusive and are characterized by high cell selectivity

The target cells are correct.

Jia AT objective of the present invention is to provide a method for dalled cell proliferation disorder

(Sa treatment of a cell proliferation disorder, through which any suitable source of energy © is used as the starting energy source to activate the activating pharmaceutical agent and thus bring about a specific cellular change

Previously used to treat cells affected by JIS disorder, cell proliferation disorder.

Jia AT objective of the present invention is to provide a method for dalled cell proliferation disorder

of a cell proliferation disorder called hearing"_using an energy flow to activate a viable pharmaceutical agent

To activate and then treat the disordered SK cells.

autovaccine One of the objectives of the present invention is to provide a method for generating the effect of an autovaccine AT is the objective of 0 and thus obviates the need to treat all as it can take place in the body of the organism cd) in one of the tissues or cells of an individual outside the body of the organism; Or it can take place outside the body of the living organism. Another objective of the present invention is to provide a computer-executed system to implement the Jia methods of the present invention.

1 The AT further of the present invention is to piggyback a pharmaceutical group and composition for use in the methods of the present invention. These and other objectives of the present invention are achieved; Which is further illustrated with the following detailed description of the preferred models; Either alone or in combination, discover a way to treat proliferation disorder WIA ISS for you in one Cua (JAY) that includes:

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Claims (1)

Noprotectors - 1 treatment group to implement the treatment of cell proliferation disorder WA; They include: at least one activating pharmaceutical agent capable of inducing predetermined cellular change; © at least one energy modulation agent capable of activating the pharmaceutical agent 6a20078186_at least one at salad) with energy; suitable containers for storing agents in fixed form; Where at least one of the psoralens, pyrene cholesteryloleate, acridine, porphyrin, fluorescein, rhodamine, 16-diazorcortisone, ethidium compounds » transition metal complexes of bleomycin is selected. ¢ transition metal complexes of deglycobleomycin organoplatinum complexes, alloxazines, vitamin Ks, vitamin L; vitamin metabolites; Substances producing vitamins naphthoquinones, naphthalenes, naphthols yo and their derivatives having planar Anya structures; porphorinporphyrins, dyes and phenothiazine derivatives, coumarins, . quinolones, quinones, and anthroquinones as well as instructions for administering Agent 1 Therapeutic Group 1 according to the Claim—at least one and at least one active pharmaceutical agent Ye to the treated individual and to activate the agent energy modulation agent 2017/818516._at least one by shedding an activable pharmaceutical agent starting power. Assel?”- therapeutic group according to claim 1 where the al activable pharmaceutical agent is chosen at least from the group consisting of coumarin psoralen ¢ or a derivative thereof. 0;- therapeutic group Gy of claimant (FY) where is the activated pharmaceutical agent at least one activeatable pharmaceutical agent is psoralen chosen from psoralen or .8-MOP 0— therapeutic group By of claim 1 where is the energy modulator modulation agent). SD-sized gold particle; water-soluble ALE quantum dot encapsulated by branched polyamidoamine molecules; luciferase enzyme; Photofluorescent Biocompatible Molecule; compact molecule that harvests electromagnetic energy; A lanthanide chelated complex capable of intense fluorescence. yo energy is Gua) of protection agent Gy therapeutic group — 1 energy At least one said modulation agent is one and is paired with at least one said modulation agent agent 0 for claim 1; Where the activated pharmaceutical agent Gy is the therapeutic group 1- A carrier capable of selling at least one of which is associated with an active pharmaceutical agent that binds to a receptor site. —A Yo Therapeutic group Gi, for protective factor FV where the carrier is selected from insulin, interleukin, thymopoietin or transferrin ¢ polypeptide. £OAY 4- Therapeutic group Ey of the protective element oF where at least one activatable pharmaceutical agent is associated with the carrier with a -01 0 bond The therapeutic group according to the protective element oF where the activatable pharmaceutical agent is at least one activetable pharmaceutical agent combined with the carrier with a non-11 bond Therapeutic group according to the oF element where the receptor site is selected from 0 nucleic acids of nucleated cells 0110168180 ; Antigen loci on WIA nucleated cells 0” or adhesion epitopes. Y ) = Gay therapeutic group of the oF protectant where at least one activated pharmaceutical agent has an affinity for a target cell. Vo -1" therapeutic group according to claim dua) at least one activateatable pharmaceutical agent can be preferentially absorbed by a target cell. -14 0 0 therapeutic group By for claimant 0 where at least one activated pharmaceutical agent induces a self-vaccinating effect in the treated individual interacting with a target cell. To activate an alg activatable pharmaceutical agent at least an intercalated DNA agent or a halogenated YO derivative thereof. A71 - Therapeutic group Ey of protective agent Cua) At least one activatable pharmaceutical agent Vaal is activated by one or more sequential single photons absorption events. —VY 0 Therapeutic group Ey of protective agent 0) wherein one active pharmaceutical agent 38011/8186A6 includes at least one active agent surrounded by the photoprotective Cala agent ¢ and upon exposure to said starting energy source the blocking agent dissociates spall for the active agent” so that the active agent becomes available. #18 - Pharmaceutical formula for the treatment of cell proliferation disorder Wa; They include: at least one activating pharmaceutical agent capable of inducing predetermined cellular change; at least one additive with a complementary therapeutic or diagnostic effect; wherein said additive, Yo, is at least one ingredient selected from the group of antioxidants; auxiliaries; chemical energy sources; and combinations thereof; a pharmaceutically acceptable carrier; Where at least one of the psoralens, pyrene cholesteryloleate, acridine, lye porphyrin, fluorescein, rhodamine, 16-diazorcortisone, ethidium complexes is chosen. Y. vasa transitionis from bleomycin; transition metal complexes of organoplatinum complexes of deglycobleomycin organoplatinum complexes, alloxazines, vitamin Ks, vitamin L; vitamin metabolites; Substances producing vitamins naphthoquinones, naphthalenes, naphthols and their derivatives having planar Anya structures; porphorinporphyrins, dyes and phenothiazine derivatives, coumarins, .quinolones, quinones, and anthroquinones Yo EOAY yi where VA is the pharmaceutical composition according to the claim - at least one is an activatable pharmaceutical agent . photoactivatable agent OA The pharmaceutical composition is selected according to the protective element -71 0 psoralens, at least one of the active pharmaceutical agent compounds pyrene cholesteryloleate, acridine, porphyrin, fluorescein, rhodamine , 16-; bleomycin transition metal complexes; transition metal complexes of 13201001115006, ethidium deglycobleomycin organoplatinum complexes, of organic platinum complexes of vitamin metabolites; Producing materials «alloxazines, vitamin Ks, vitamin L, vitamin 0 and their derivatives that have naphthoquinones, naphthalenes, naphthols structures for vitamins; compounds «phenothiazine dyes and derivatives» porphorinporphyrins i, sie molecular ,. anthroquinones and compounds ¢ quinones compounds » quinolones; coumarin pharmaceutical compounds of claim 17; where the activatable pharmaceutical agent is LEN -YY 1; and at least one psoralen is an activatable pharmaceutical agent or a derivative of both.” cOUmarin where the activateable pharmaceutical agent is Yo the pharmaceutical composition according to the claim YY AMT i.e. 8-MOP, at least one of which is an activatable pharmaceutical agent of 0, where the OA acceptable pharmaceutical agent of the pharmaceutical composition is selected according to the element of protection, YY, and at least one of the activatable pharmaceutical agent for activation 7,8—dimethyl-10-ribityl, isoalloxazine, 7,8,10-trimethylisoalloxazine, 7,8- dimethylalloxazine, isoalloxazine—adenine dinucleotide, alloxazine Yo EOAY 1 7 — mononucleotide, aluminum (lll) phthalocyanine tetrasulonate, hematophorphyrin, and phthadocyanine. V8 - Pharmaceutical composition according to OA claim where Jalal is pharmaceutical agent © 2007818516 At least one is associated with a carrier capable of binding to a receptor site. 5”- The pharmaceutical composition according to the claim (YE), where the carrier is chosen from insulin, interleukin, thymopoietin or transferrin. 7- The pharmaceutical composition according to the claim (VE) where at least one activatable pharmaceutical agent is associated with the carrier with a -YY bond 1 The pharmaceutical composition according to the claim VE where the activatable pharmaceutical agent is wlll activatable pharmaceutical agent at least combined with the carrier with a non-bond 74- Pharmaceutical composition according to the VE protection element where the receptor site is selected from Ye nucleic acids of nucleated cells 0110168180; antigenic sites on nucleated WIA nucleated cells 0” or ad epitopes 4- The pharmaceutical composition according to the protection element VA where at least one activated pharmaceutical agent has an affinity for a target cell. M 1 ©- The pharmaceutical composition according to the claim OA where at least one activateatable pharmaceutical agent can be absorbed preferably by a target cell. -©1 0 Pharmaceutical composition according to the claim OA, where at least one activated pharmaceutical agent produces a self-vaccinating effect in the treated individual interacting with a target cell. “?- A pharmaceutical composition according to the VA claim in which the alg activatable pharmaceutical agent is at least an intercalated DNA agent or ,. halogenated derivative treated with 0 in which the OA acceptable pharmaceutical agent “*?- pharmaceutical composition is activated according to at least one claim by a single event or an activatable pharmaceutical agent for single, sequential activation. photons More than the events of the absorption of photons, Vo, where the predetermined cellular change is OA, the pharmaceutical composition, according to the element of protection, TE. target cell from fading into a target cell that also includes an OA pharmaceutical modulation agent according to the protective element—at least one vo that will activate at least one energy modulation agent 0 when energized Activable pharmaceutical agent for energy activation. The modulation agent is Gua (70 pharmaceutical formulation according to the claim - and is paired candy for at least one of the said modulation agent with the pharmaceutical agent At least one of the above is activated. Yo L -"174- where the VA-activable pharmaceutical agent, the pharmaceutical composition according to the protective element YY, includes at least one active agent surrounded by a light-activating pharmaceutical agent; and upon exposure to the said starting energy source, the light-blocking agent separates from Cals the active agent” so that the active agent becomes available. lo} TA — pharmaceutical composition according to claim OA where at least one additive is a chemical energy source FA — pharmaceutical composition According to the FA protection element, where the chemical energy source is selected from From the group of phosphorescent compounds “chemiluminescent compounds” bioluminescent compounds and light emitting enzymes. £OAY “Am Ir ra 8 which Adie Pree EER IY rays pall 2 ahead ed Radin Sse SEY ¥ Fa Ba, Si Toa mak x 0 ES Yow Ya ' AE Xx A lb 81 63 2 pips § J i - il ga Waves dll Quqq rays 2 Radiant fa Rays 1 Ah FE A % RR 3 Violet 2 Grass | Radiant microriva Sgn either good: a es Pa oF ade Luminous mo _ for fluorescent light “B a CE RE IR 0 Hunger Sell now SES RE REIT l N L N L N L D A D A L N L N L N L D A D A D L N L N L N L A D A D L N L N L N L A L L N L A L A L L A L A L A L A L A L N A A A A L N L L D A L R A L A L FR A A A A A L Wen 3 am -A0- Al-Bisha: los cg b * b wi * a a I fo Kw Ry ' 3 Tsah Lea fo "2 You love God pre D A Ao sy gv For Fe & SEP Is | ILA - wa EE SI § oe LO 8 Vow wavelength {ins fod} form it RO LHR : La 2 3 0 s# Length [ sl] a pk form wt EOAY f-3 et 1 : ki : 8 8 : | i a BN i | - z 1 I R l d npr © r< a Sh « P CNY NP 4. a. 1 d 9 b sha £ OAY - Database | 1 L_| 8 2 LETEN a es | For LTT 1 data driver; data base; A or L factor 1 energy decreases to say edd | # 3 um TE N X ا ا ا ا ا ا ا ا ا ا ا * ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا ا* ا ا ا * ا ا ا* ا ا ا which a 3 l mmh I EIN > a 1 0 b SR 8 a ps by 3 3 Cs [ET i ? ew a a 1 4 b ERNIE Ss 1 vEey A H 8] 3 pt Kh RRA Kh Kt kX ᴀᴀʀᴀ ᴀ 8 ကပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပပ ¥ M § : fa B LER : TELE a SA EE 0 i 3 3 : 2 * : : L Gl Ca + Meg ¥ ERR 3 4 Ya Jah Dwyn Ilah Mada Mm Ddji DON Jada A HIN Aye Mahmoo Ala Maha AH HS Goog and Maa Lamrah Ce TERY Ig EOAY The validity period of this patent is twenty years from the date of filing the application, provided that the annual financial fee is paid for the patent and that it is not invalid or forfeited for violating any of the provisions of the patent system, layout designs of integrated circuits, plant varieties, and industrial designs, or its executive regulations issued by King Abdulaziz City for Science and Technology; Saudi Patent Office P.O. Box TAT Riyadh 57??11 ¢ Kingdom of Saudi Arabia Email: Patents @kacst.edu.sa