EP1796695A2 - Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire - Google Patents

Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire

Info

Publication number
EP1796695A2
EP1796695A2 EP05800702A EP05800702A EP1796695A2 EP 1796695 A2 EP1796695 A2 EP 1796695A2 EP 05800702 A EP05800702 A EP 05800702A EP 05800702 A EP05800702 A EP 05800702A EP 1796695 A2 EP1796695 A2 EP 1796695A2
Authority
EP
European Patent Office
Prior art keywords
protein
receptor
composition
kinase
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05800702A
Other languages
German (de)
English (en)
Inventor
Zoser B. Salama
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Esteve Pharmaceuticals GmbH
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from EP04090376A external-priority patent/EP1640012A1/fr
Priority claimed from US10/948,753 external-priority patent/US20060067942A1/en
Application filed by Individual filed Critical Individual
Priority to EP05800702A priority Critical patent/EP1796695A2/fr
Publication of EP1796695A2 publication Critical patent/EP1796695A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • composition comprising amino acids, peptides,
  • the invention relates to a composition of peptide and / or protein components of the cellular components of the blood, wherein the components have a molecular weight of less than 10,000 Da, a pharmaceutical composition comprising the composition, the preparation of the composition and the use of these for the treatment of defects of the cellular Immunity, in particular cancer, sepsis, allergic reactions and the prophylactic use of the pharmaceutical agents in the treatment of a patient in cancer, for example with cytostatics or high-energy radiation.
  • the environment of humans or animals contains a large number of infectious microbes such as viruses, bacteria, fungi and parasites. Furthermore, disorders or modifications of the metabolism, especially cell division, can lead individuals to adjoin themselves
  • Immune responses of the individual to environmental influences or to pathogenic changes within the individual can be divided into two major groups: humoral and cellular immune responses, whereby it is often not possible to associate a disease process or a recovery process exclusively with one of these two immune responses, since they interact with each other and are interdependent.
  • the expression of cell-mediated immunity was originally coined for those local responses to organisms, usually intracellular pathogens, which are primarily caused by lymphocytes and phagocytes rather than antibodies that are part of humoral immunity. In the meantime, however, the expression of the cell-mediating immunity is needed for any immune response in which the antibodies do not play the central role.
  • Cell-mediated and antibody-mediated reactions can not be considered separately from one another since, for example, cells are also involved in the formation of antibodies, and the antibodies are involved in numerous cell-mediating reactions mediating limb occur.
  • the cellular immune response is particularly associated with macrophages, B cells, T cells, lymphocytes, NK cells, monocytes and many others.
  • the cells mentioned are responsible for liberating cytokines, such as TNF, M-CSF or GM-CSF. From the interaction of the cells of the cytokines as well as environmental influences and reactions of the individual himself, such as the humoral immunity, resulting ⁇ a microbicidal and tumoricidal activity, inflammatory responses and fever, a lymphocyte activation and tissue reorganization and tissue damage.
  • cytokines such as TNF, M-CSF or GM-CSF.
  • autoimmune diseases such as psoriasis, atopic eczema, rheumatoid arthritis or juvenile diabetes
  • good treatment options provided that the cellular immune response is improved in a patient.
  • cancer vaccines an attempt is made to target the body's own cellular defense system against tumor cells.
  • the aim of the previous cellular immunotherapies for cancer is to block the blockade of the immune system by the tumor and to activate cytotoxic T cells against the tumor.
  • Known methods consist of first isolating immune cells from the blood or the bone marrow and multiplying them outside the body in a test tube in order to then return them to the patient.
  • cells of the own body can be used (autologous cells) or cells of a foreign donor (alogene cells). The more different the donor and recipient cells are, the higher the likelihood that the transferred cells will be able to recognize the tumor cells.
  • Dendritic cells play a key role in the activation of the immune response. You present show conspicuous features that distinguish tumor cells from other cells to the immune system in such a way that a pronounced reaction can take place, which also goes beyond individual cells in terms of number.
  • the dendritic cells are taken by the patient himself and brought together specifically with tumor cells or parts thereof and then returned to the patient. In the body, the dendritic cells loaded in this way should then present fragments of tumor cells and thus trigger an immune reaction against the tumor.
  • stem cell transplantation was introduced to renew the damaged bone marrow of leukemia patients by high-dose treatment with chemotherapy or radiation.
  • the cells transferred from a foreign donor also have a direct effect against cancer cells, precisely because they almost never coincide with those of the recipient in all tissue characteristics.
  • Activation of the cellular immune response is a highly regulated process that requires a high level of energy from a biochemical point of view and is also associated with the risk of an autoimmune response. Therefore, such clinical procedures have the risk of disadvantages and side effects for the patient.
  • WO 89/06538 A discloses compositions of whole blood which are subjected to papain hydrolysis and alcohol denaturation. With the compositions according to WO 89/06538 only conditional activations of wound healing are possible, since the compounds have numerous side effects.
  • US 4,384,991 in the prior art presentation, discloses about 25 different cell extracts, substantially all of which are derived from white blood cells. That One skilled in the art will appreciate that there are a variety of compositions derived from such cells. These compositions according to US Pat. No. 4,384,991 differ in particular by the degree of purity which is determined by the respective preparation process or by their starting material. Particularly advantageous horse or calf leukocytes are used as starting material. Cell extracts from horse and calf parent compounds are suitable for obtaining therapeutic products.
  • the core of the teaching according to US Pat. No. 4,384,991 is the isolation of a pure individual peptide. This peptide is characterized as so-called fingerprint features as a highly pure molecule. The high-purity isolation succeeds by cleaning steps, such as ion exchange chromatography or
  • the crude fraction according to US Pat. No. 4,384,991 is washed with acetone and then freeze-dried.
  • the acetone treatment (as well as the hydrolysis and alcohol treatment in WO 89/06538) leads to structural changes of the protein components of the crude fraction.
  • the isolation of the desired peptide is achieved in particular by the accumulation of granulocytes, i. There is a separation of lymphocytes and monocytes.
  • the granulocyte extract from horse or calf blood can not be used effectively in practice because it appears to have a certain effect only in high concentrations and also has toxic effects.
  • EP 0 140 134 discloses an extract of mammalian or cell culture organs. Furthermore, extracts of cell cultures derived from fresh calf blood or calf blood serum are disclosed. The disclosed compositions are essentially calf blood serum, fresh calf blood, or defibrinated calf blood, without the constituents greater than 10,000 Da. Such extracts lead to unwanted defense reactions in a target organism.
  • the object of the present invention is furthermore to provide a technical teaching, in particular a pharmaceutical agent, which can be brought into contact prophylactically with a patient in the event of serious accidents, but also in the case of chemotherapeutic and / or radiation treatment, in order to determine its general status - preferably via the improvement of the cellular immune response - to optimize.
  • the object of the invention is furthermore to provide a means for prophylactic use and / or for the treatment of the fatigue syndrome as a result of shock and / or physical, emotional, nervous, pathological or radioactive effects.
  • the technical object of the invention is achieved by a method according to claim 1, in particular for the preparation of a composition comprising complete and / or
  • the teaching according to the application therefore provides a development-tightening performance which eliminates misconceptions of the experts on the solution of the abovementioned problem.
  • the technical progress that is achieved by the teaching of the invention is particularly evident in the improvement and performance of the process and the products thus obtained, the cost, the savings in time, material, work stages, costs and difficult to obtain
  • Composition including complete and / or fractions of interleukin 18 receptor 1 precursor, interleukin 1 receptor-like protein and mucin 4, transient receptor of potential cation channel, ectonucleotide pyrophosphatase / phosphodiesterase, SWI / SNF-related matrix-associated actin-dependent Chromatin regulator, SWI / SNF chromatin modulating complex subunit OSAl B120, OSAl core protein, MYC binding protein 2, cullin 7, dissolved carrier family 5 (sodium iodide symporter) member 5, glutamate rich WD repeat containing 1, MAP Kinase interacting serine / threonine kinase 1, ATP binding cassette, DMBT1, extracellular linker domain
  • Rho GTPase activating protein 8 isoform 2, desintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, AS12 protein, mitochondrial ribosomal protein S9, 28S ribosomal protein S9, Protein kinase substrate MK2S4, NP220, putative G protein-coupled receptor, dynein, axonemal-heavy
  • Polypeptide 5 N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D, leukotrine B4 receptor, G protein-coupled receptor 16, proprotein convertase subtilisin / kexin type 1 inhibitor CMKRL1, dual-specific tyrosine phosphorylation-regulated kinase 3, regulatory erythroid Kinase (long form), DYRK3 protein, Ig lambda chain V-VII region (Mot) - human.
  • composition according to the application can be used prophylactically and therapeutically as well as for supporting biological activities.
  • composition in particular in the form
  • a combination of composition and pharmaceutically acceptable carrier can be used as a pharmaceutical agent to treat chronic infections, septic infections, atopic eczema, atopic dermatitis, psoriasis, and other of the above immune disorders.
  • a prophylactic indication of the composition is spielnem the administration of the composition in a Patien ⁇ th, which is treated with a radiotherapy or chemotherapy with cytostatics to prevent or mitigate the immune suppression, which is initiated by the type of therapy.
  • prophylactic administration of the composition of the invention is useful, for example, when a blood transfusion has led to a cellular intolerance that adversely affects the immune status of the patient.
  • composition according to the invention can also be used prophylactically in order to stabilize the condition of the patient so that the injuries or pathogenic changes can be causally treated.
  • the composition can be used to optimize the poliferation and differentiation of different cell types at different stages of their maturation. If the release of CD 4 or CDe and IF-gamma is to be increased or if the activity of T-lymphocytes is to be improved.
  • Th 1 thymocyte populations
  • Cytokines and interleukins Another use is the activation of thymocyte populations (Th 1) or the release of Cytokines and interleukins. Furthermore, it is possible to activate the calcium ion transport through the cell membrane or to improve the oxidative metabolism in cells of important metabolic organs such as the liver or the kidneys. However, regulatory suppression mechanisms of immunological cascades can also be activated.
  • the composition according to the invention comprises customary auxiliaries, preferably carriers, adjuvants and / or vehicles.
  • the carriers may be, for example, fillers, extenders, binders, humectants, disintegrants, dissolution inhibitors, absorption accelerators, wetting agents, adsorbents and / or lubricants.
  • the composition is referred to in particular as a drug or pharmaceutical agent.
  • the agent according to the invention is used as gel, powder, powder, tablet, sustained-release tablet, premix, emulsion, pour-on formulation, drops, concentrate, granules, syrup, pellet, fluid, capsule, aerosol, spray and or inhalant prepared and / or used in this form.
  • the tablets, dragees, capsules, pills and granules may be provided with the usual, optionally opacifying, containing coatings and shells and also be composed so that they deliver the active substance or only optionally delayed in a certain part of the intestinal tract, where as embedding masses, for example, polymer substances and waxes can be used.
  • compositions of this invention may be for oral administration in any orally acceptable manner, for example
  • Dosage form used the capsules, tablets and aqueous suspensions and solutions, but is not limited thereto.
  • carriers which are commonly used include lactose and corn starch.
  • Lubricants such as magnesium stearate, can typically be added.
  • usable diluents such as lactose and dried corn starch are used.
  • aqueous suspensions are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and / or flavoring and / or coloring agents may be added.
  • the active substance (s) may optionally also be present in microencapsulated form with one or more of the abovementioned excipients.
  • Suppositories may in addition to the active substance contain the customary water-soluble or water-insoluble excipients, for example polyethylene glycols, fats, for example cocoa fat and higher esters (for example Ci 4 -Aiko- hol with cis-fatty acid) or mixtures of these substances.
  • customary water-soluble or water-insoluble excipients for example polyethylene glycols, fats, for example cocoa fat and higher esters (for example Ci 4 -Aiko- hol with cis-fatty acid) or mixtures of these substances.
  • Ointments, pastes, creams and gels may in addition to the active ingredients or the usual excipients contain, for example, animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances.
  • Powders and sprays may contain, in addition to the active substance (s), the usual excipients, for example lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances.
  • Sprays may additionally contain the usual propellants, for example chlorine fluorocarbons, contained.
  • Solutions and emulsions may, in addition to the active ingredients, that is to say the composition according to the invention, the customary carriers such as solvents, solubilizers and emulsifiers, for example water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-Butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.
  • the solutions and emulsions may also be present in sterile and blood isotonic form.
  • Suspensions may, in addition to the active ingredients, the usual carriers such as liquid diluents, for example water, ethyl alcohol, propylene glycol, suspending agents, for example ethoxylated Isostearylalkohole, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures contain these substances.
  • liquid diluents for example water, ethyl alcohol, propylene glycol
  • suspending agents for example ethoxylated Isostearylalkohole, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures contain these substances.
  • the pharmaceutical compositions may be in the form of a lyophilized sterile injectable preparation, for example as a sterile injectable aqueous or oily suspension.
  • This suspension may also be formulated by methods known in the art using suitable dispersing or wetting agents (such as Tween 80) and suspending agents.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example a solution in 1,3-butanediol.
  • Compatible vehicles and solvents that can be used include mannitol, water, Ringer's Solution and isotonic sodium chloride solution.
  • sterile non-volatile oils are commonly used as the solvent or suspending medium.
  • Any mild non-volatile oil including synthetic mono- or diglycerides may be used for this purpose.
  • Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated forms.
  • These oil solutions or suspensions may also contain a long-chain alcohol or similar alcohol as a diluent or dispersant.
  • compositions mentioned may also contain colorants, preservatives and odour- and taste-improved additives, for example peppermint oil and eucalyptus oil and sweeteners, for example saccharin.
  • the composition according to the invention should preferably be present in the listed pharmaceutical preparations in a concentration of from about 0.01 to 99.9, preferably from about 0.05 to 99,% by weight of the total mixture.
  • the listed pharmaceutical preparations may contain other active pharmaceutical ingredients; but in addition to other pharmaceutical agents also salts, buffers, vitamins, sugar derivatives, in particular Saccaride, enzymes, plant extracts and others.
  • the buffers and sugar derivatives advantageously reduce the pain on subcutaneous administration, and enzymes such as hyaluronase increase the efficacy.
  • the preparation of the abovementioned pharmaceutical preparations is usually carried out by known methods, for example by mixing the active substance (s) with the carrier (s).
  • the preparations mentioned can be administered either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously) in humans and animals, intracisternally, intravaginally, intraperitoneally, locally (powder, ointment, drops) and for the therapy of the diseases mentioned below.
  • Injection solutions, solutions and suspensions for oral therapy, gels, infusion formulations, emulsions, ointments or drops are suitable as suitable preparation.
  • ophthalmic and dermatological formulations, silver and other salts, ear drops, eye ointments, powders or solutions may be used.
  • uptake may also take place via the feed or drinking water in suitable formulations.
  • the medicaments can be incorporated into other carrier materials such as, for example, plastics-plastic chains for local therapy-collagen or bone cement.
  • the composition is incorporated in a concentration of from 0.1 to 99.5, preferably from 0.5 to 95, particularly preferably from 20 to 80,% by weight in a pharmaceutical preparation. That is, the composition is present in the abovementioned pharmaceutical preparations, for example tablets, pills, granules and others, preferably in a concentration of from 0.1 to 99.5% by weight of the total mixture.
  • the amount of active ingredient that is to say the amount of a composition according to the invention which is combined with the carrier materials in order to produce a single dosage form, will be able to vary by the skilled person depending on the patient to be treated and the particular mode of administration.
  • the proportion of active compound in the preparation may be changed to provide a maintenance dose that arrests the disease. Subsequently, the dose or frequency of administration or both are reduced as a function of the symptoms to a level at which the improved condition is maintained. When the symptoms have been alleviated to the desired level, treatment should cease. However, patients may require discontinuous treatment on a long-term basis after any recurrence of disease symptoms. Accordingly, the proportion of the composition, that is to say its concentration, in the overall mixture of the pharmaceutical preparation as well as its composition or combination is variable and can be modified and adapted by the person skilled in the art on the basis of his specialist knowledge.
  • composition according to the invention can be brought into contact with an organism, preferably a human or an animal, in various ways. Furthermore, it is known to the person skilled in the art that in particular the pharmaceutical agents in various
  • Dosages can be applied.
  • the application should be carried out in such a way that the disease is combated as effectively as possible or the onset of a disease in a prophylactic administration is prevented.
  • concentration and the type of application can be determined by a person skilled in the art by routine tests.
  • Preferred applications of the compounds according to the invention are oral administration in the form of powders, tablets, juice, drops, capsules or the like, rectal administration in the form of suppositories, solutions and the like, parenterally in the form of injections, infusions and Solutions as well as locally in the form of ointments, patches, envelopes, rinses and the like.
  • the contacting of the composition according to the invention preferably takes place prophylactically or therapeutically.
  • the suitability of the chosen administration forms as well as the dose, the application scheme, the adjuvant choice and the like can be determined, for example, by taking serum allergy. quotas from the patient, that is, the human or animal, and testing for the presence of disease indicators during the course of the treatment protocol. Alternatively and concomitantly, the condition of the kidneys, the liver or the like, but also the amount of T cells or other cells of the immune system, can be determined concomitantly in a conventional manner in order to obtain a general overview of the immunological constitution of the patient and, in particular, the constitution of metabolically important organs. In addition, the patient's clinical condition can be monitored for the desired effect.
  • the patient may be treated with agents according to the invention modified, if appropriate, with other known medicaments, from which an improvement in the overall constitution can be expected.
  • agents according to the invention modified, if appropriate, with other known medicaments, from which an improvement in the overall constitution can be expected.
  • injections for example intramuscularly or subcutaneously or into the blood vessels, are another preferred route for the therapeutic administration of the composition according to the invention.
  • the delivery via catheters or surgical tubes can be used; For example, via catheters that lead directly to bestimm ⁇ th organs such as the kidneys, liver, spleen, intestine, lungs, etc.
  • composition of the invention can be used in a preferred embodiment in a total amount of preferably 0.05 to 500 mg / kg body weight per 24 hours, preferably from 5 to 100 mg / kg body weight. in this connection it is advantageously a therapeutic amount used to prevent or ameliorate the symptoms of a disorder or responsive, pathologically physiological condition.
  • the dose will depend on the age, the health and weight of the recipient, the degree of the disease, the nature of a necessary concomitant treatment, the frequency of treatment, and the nature of the desired effects and side effects.
  • the daily dose of 0.05 to 500 mg / kg of body weight can be applied once or several times in order to obtain the desired results.
  • pharmaceutical agents for about 1 to 10 times daily administration or alternatively or additionally as used continuous infusion.
  • Such administrations can be used as a chronic or acute therapy.
  • the quantities of active compound which are combined with the carrier materials in order to produce a single dosage form may, of course, vary depending on the host to be treated and the particular mode of administration.
  • the target dose it is preferred to distribute the target dose to 2 to 5 applications, wherein for each application, for example, 1 to 2 tablets are administered with an active ingredient content of 0.05 to 500 mg / kg body weight.
  • the active ingredient content it is possible to choose the active ingredient content also higher, for example up to a concentration of up to 5000 mg / kg.
  • the tablets may also be retarded, whereby the number of Appli ⁇ cation per day reduced to 1 to 3.
  • the active ingredient content of the sustained-release tablets may be 3 to 3,000 mg. If, as stated, the active ingredient is administered by an injection, it is preferred to bring the host into contact with the composition according to the invention 1 to 10 times a day or by continuous infusion, quantities of 1 to 4000 mg per day are preferred.
  • the preferred ones Total amounts per day have proven beneficial in human and veterinary medicine. It may be necessary to deviate from the stated dosages, depending on the type and body weight of the host to be treated, the nature and severity of the disease, the method of preparation of the application of the
  • the pharmaceutical agent is used in a single dose of from 1 to 100, in particular from 2 to 50 mg / kg of body weight.
  • the amount of the single dose per application can also be varied by the person skilled in the art on the basis of his specialist knowledge.
  • the compounds used according to the invention can also be used in veterinary medicine in the individual concentrations and preparations mentioned together with the feed or with feed preparations or with the drinking water.
  • a single dose preferably contains the amount of active ingredient which is administered in an application and which usually corresponds to a whole, a half daily dose or a third or a quarter of a daily dose.
  • the dosage units may preferably contain 1, 2, 3 or 4 or more single doses or 0.5, 0.3 or 0.25 of a single dose.
  • the daily dose of the compounds according to the invention is preferably distributed over 2 to 10 applications, preferably 2 to 7, more preferably 3 to 5 applications.
  • a permanent infusion of the agents according to the invention possible.
  • 1 to 2 tablets are given for each oral application of the compounds according to the invention.
  • the tablets according to the invention may be provided with coatings and shells known to the person skilled in the art and may also be combined in such a way that they release the active substance (s) only in preferred part of the host.
  • the individual constituents of the composition are optionally associated with one another or bound in a liposome with a carrier, wherein the inclusion in liposomes in the sense of the invention need not necessarily mean that the composition is present inside the liposomes.
  • An inclusion in the sense of the invention may also mean that the composition is associated with the membrane of the liposomes, for example, so that they are anchored on the outer membrane.
  • Such a representation of the composition according to the invention in or on the liposomes is advantageous if the person skilled in the art selects the liposomes in such a way that they have an immunostimulating action.
  • DE 198 51 2 82 discloses various possibilities for modifying the immunostimulating action of liposomes.
  • the lipids may be simple lipids such as esters and amides or complex lipids such as glycolipids such as cerebrosides or gangliosides, sphingolipids or phospholipids.
  • the invention also relates to a process for the preparation of a composition which can be used for said prophylactic and therapeutic indications and for therapy-accompanying improvements of the biologic genetic efficiency, especially of the cellular immune system.
  • the method according to the invention consists in collecting and homogenizing blood, plasma or serum constituents which as far as possible do not cause any immunological tolerance problems.
  • the homogenization can be carried out, for example, mechanically and / or by freeze-thaw cycles or by other homogenization methods known to those skilled in the art.
  • homogenisations are all processes which can induce or support cell lysis.
  • the homogenization makes possible the intimate mixing of components of a system, which are inherently immiscible or difficult to mix, over the entire volume, so that the material obtained is substantially independent of the number of constituents essentially only in a few phases, in particular in a single component , occurs.
  • the homogenization causes a reduction of the particle size of the disperse phase, a deagglomerization of particle aggregates and leads to dispersions with increased sedimentation stability.
  • the homogenization can be carried out with dynamic apparatuses but also with static apparatuses, that is to say in mixers without moving parts.
  • Preferred starting material are blood cells, preferably white blood cells.
  • the blood cells can be prepared, for example, as a buffy coat preserve, which is rich in thrombocytes and erythrocytes, the skilled person being familiar with standard processes for the preparation of these preserves.
  • a buffy coat preserve which is rich in thrombocytes and erythrocytes
  • the starting material for example red and / or white blood cells, first as a buffy coat preserve in order to homogenize the biologically active components, for example by a freeze-thaw cycle. That is, the exact sequence of the individual process steps in the context of the invention is interchangeable.
  • cellular blood components such as leukocytes
  • lyophilization it may be advantageous to prepare a solution which is initially prefiltered, then ultrafiltered and subsequently sterile filtered.
  • the recovered filtrate can be pasteurized, for example, in a water bath. After this process, the pasteurized material can be sterilized and lyophilized again. Of course, other sterilization methods can also be used, for example treatment with high-energy radiation, for example UV or X-radiation. Each of these individual steps can be accompanied by quality controls. These are possible, for example, by taking aliquots from the sample which are for the presence of Microorganisms, viruses or other undesirable components.
  • the preparation of the blood cell concentration, in particular of the leucocyte concentrate takes place by freeze-thaw cycles or by ultrasound treatment of the cells or as a combination of these two methods.
  • the freeze-thaw cycle makes it possible to obtain stable and reproducible fragments of said proteins and peptides of the cellular constituents of the blood.
  • the composition according to the invention represents the lyophilisable, sterilizable, filterable and dialyzable homogenates from blood cells, in particular white blood cells, which have passed through a freeze-thaw cycle several times and were sterilized at temperatures around 100 ° C.
  • the freeze-thaw cycle can in this case be designed so that the frozen material is cut, z. B. with a microtome, then thaw it and optionally freeze again.
  • the freeze-thaw cycle is preferably a freeze-thaw-cut cycle. The process conditions were chosen so that only the stable fragments of the peptides and proteins are present in the recovered composition.
  • the dialysis of the homogenate is carried out so that low molecular weight particles of colloids or macromolecules penetrate by diffusion from the homogenate into the preferably continuously pure solvent through semipermeable membrane, wherein the large molecules are retained.
  • the rate of dialysis can be increased by raising the temperature or applying an electrical voltage, for example in electrodialysis.
  • Dialysis can, of course, lent also be carried out with dialysis columns, wherein molecules are separated with a molecular weight of about 10 kDa.
  • the freeze-drying serves in particular for the concentration of the dialysate.
  • Freeze-drying in the sense of the invention is a term for the drying of a deep frozen material in a high vacuum by freezing the solvent, which then evaporates in the frozen state by the sublimation drying.
  • the freeze-drying according to the invention can also be carried out as dehydration, in particular using solutions; preferably with the addition of solutions such as, for example, serum, milk, carbohydrates, amino acids, enzymes, buffer solutions, salts and / or vitamins. In order to bring the lyophilized material back into solution for use, it is possible to dissolve it, for example, in distilled water or in other solvents.
  • the ultraviolet spectrum of the material in particular in the range of 2000 nm and 400 nm. If the material is free of undesirable constituents or largely free of such constituents, prefiltration is required
  • Example by a Millipore membrane advantageous.
  • a porous medium such as the Millipore membrane RA (1.2 / im) with a prefilter AP15, flows through the continuous phase of the liquid, at the same time retaining the dispersed phase on the surface of the porous medium or in its interior ,
  • an ultrafiltration material By means of an ultrafiltration material can be separated with a limit of 10 kDa.
  • the recovered material can be replaced by another filtration step sterilized, for example with the aid of the sterilization filter Millipore GS (0.22 microns).
  • the ultrafiltration can be effected by membrane microfiltration but also by reverse osmosis.
  • For the ultrafiltration predominantly asymmetrically structured, porous membranes of various organic and inorganic materials are used
  • polysulphone or ceramic in the form of tubes, capillaries, hollow fibers and surface membranes.
  • the pasteurization tion for example, in a water bath at a temperature of 60 Tempe ⁇ 0 C for several hours done.
  • the pasteurization may but at any temperature below 100 0 C in certain cases, but also preferably be carried out above 100 0 C for an arbitrary time. That is, a sterilization of more than 100 0 C is a preferred pasteurization in the context of the invention.
  • Sterilization or pasteurization of more than 100 ° C. advantageously results in reproducible, stable, readily usable denaturation products and cleavage products which do not have the disadvantages of the composition of the prior art. This is especially true if the cellular parent compounds are human leukocytes. It was completely surprising that the combination of the features: (i) human leukocytes as starting materials, (ii) those treated by the process according to the invention and / or (iii) pasteurization above 100 ° C. achieved the abovementioned surprising advantages can. It is particularly advantageous to subject the starting compounds to no papain hydrolysis or alcohol denaturation. Even the abandonment of drastic
  • Cleaning steps as for example in the ion exchange chromatography or paper electrophoresis occur, is advantageous because they cause other products that can hardly be used in therapy. Furthermore, the absence of red blood cells is advantageous. It is surprising that minor modifications of the process, such as initial denaturation with organic solvents, would lead to completely different process products which can not be used to solve the problem of the invention. Also leucocytes from the non-human area can be used only to a limited extent to achieve the object of the invention. Furthermore, it is advantageous to separate all components that are greater than 3,000 Da.
  • the invention also relates to the use of the composition according to the invention and / or of the pharmaceutical agent according to the invention for the treatment of diseases which are associated with a deficiency of cellular immunity, for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity, for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity, for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity, for example in the defect according to ICDIO code: D.84.4.
  • diseases which are associated with a deficiency of cellular immunity
  • Inflammations in the sense of the invention are the reaction of the organism, carried on the connective tissue and the blood vessels, to an externally or internally induced inflammatory stimulus with the purpose of eliminating or inactivating it and of repairing irritation-induced tissue damage. These are triggered by mechanical stimuli (foreign bodies, pressure, injury) and other physical factors (ionizing radiation, UV light, heat, cold), chemical substances (alkalis, acids, heavy metals, bacterial toxins, allergens and immune complexes) and pathogens (Microorganisms, worms, insects) or pathological metabolic products, derailed enzymes, malignant tumors.
  • mechanical stimuli foreign bodies, pressure, injury
  • other physical factors ionizing radiation, UV light, heat, cold
  • chemical substances alkalis, acids, heavy metals, bacterial toxins, allergens and immune complexes
  • pathogens Microorganisms, worms, insects
  • the process is complemented by disruption of the electrolyte balance (transmineralization), immigration of neutrophilic granulocytes and monocytes through the vessel walls (see also leukotaxis), the latter with the purpose of eliminating the Entzündungs ⁇ irritation and damaged to necrotic cells (phagocytosis); Furthermore, lymphocyte effector cells migrate, which lead to the formation of specific antibodies against the inflammatory stimulus (immune reaction), as well as eosinophils (in the healing phase or, very early in the case of allergic hyperergic events).
  • fragments (C3a and C5a) of this system are released which, like the histamine and bradykinin, act as mediators of the inflammation, in the sense of stimulating the chemotaxis of the cited
  • inflammations in the sense of the invention are the purulent, the exudative tive, fibrinous, gangrenous, granulomatous, haemorrhagic, catarrhal, necrotizing, proliferative or productive, pseudomembranous, serous, specific and / or ulcerous inflammations.
  • Autoimmune diseases in the sense of the invention are diseases which are wholly or partly due to the formation of autoantibodies and their damaging effect on the entire organism or organ systems, that is to say on auto-aggression. Classification is possible as organ-specific, intermediate and / or systemic autoimmune disease.
  • organ-specific autoimmune diseases are HASHIMOTO thyroiditis, primary myxedema, thyrotoxicosis (BASEDOW disease), pernicious anemia, ADDISON disease, myasthenia gravis and / or juvenile diabetes mellitus.
  • Preferred intermediate autoimmune diseases are GOODPASTURE syndrome, autoimmune hemolytic anemia, autoimmune leukopenia, idiopathic thrombocytopenia, pemphigus vulgaris, sympathetic ophthalmia, primary biliary cirrhosis, autoimmune hepatitis, ulcerative colitis and / or SJ ⁇ GREN syndrome.
  • Preferred systemic autoimmune diseases are rheumatoid arthritis, rheumatic fever, systemic lupus erythematosus, dermatomyositis / polymyositis, progressive systemic sclerosis, WEGENER granulomatosis, panarteritis nodosa and / or hypersensitivity angiitis.
  • the basis for this is an aggressive immune reaction as a result of collapse of the immune tolerance to self-determinants and a decrease in the activity of the T-suppressor cells (with lymphocyte marker T 8) or a top weight of the T-hepatic cells (with lymphocyte marker T 4) over the Suppressor cells; furthermore, the formation of autoantigens is possible, for example, by linking host proteins with haptens (for example drugs), ontogenetic tissue developing only after development of self-tolerance, and protein components unmasked by changes in the conformation of the proteins in connection with, for example, infection by viruses or bacteria; also for neoplasia-derived new proteins.
  • haptens for example drugs
  • sepsis disorders are diseases as a result of continuous or periodic penetration of pathogenic bacteria and / or their poisons from a pathogen and their spread on the lymph-blood route to general or local infection.
  • Sepsis in the sense of the invention are preferably wound sepsis (phlegmon, thrombophlebitis, lymphangitis), puerperal sepsis (in case of puerperal fever), otogenic sepsis (in otitis media), tonsillogenic sepsis (in angina, peritonsillitis), cholangiotic sepsis (in case of purulent cholecystitis, cholangitis) , pylephlebitic sepsis (in pylephlebitis) umbilical sepsis (in case of omphalitis etc.), urosepsis and tooth granuloma.
  • sepsis may be acute to very severe (foudroyant), subacute (for example as endocarditis lenta) or chronic, but of course also as neonatal sepsis.
  • Sepsis within the meaning of the invention are thus all pathogenic changes in a patient, which may be associated with intermittent fever and chills and with splenic tumor, with toxic reactions or damage to the bone marrow or the blood (polynuclear leukocytosis, anemia, hemolysis, thrombocytopenia) or with pathogenic Reactions to the heart and the nerves of the nerves (tachycardia, central circulation, edema, oligarchy, possibly shock) or the digestive tract (dry, covered tongue, diarrhea) or septicopyemia (pyemia with formation of septic infarcts and metastatic infarction) Abscess).
  • preferred diseases which are associated with a deficiency of the cellular immune system are furthermore: AIDS, acne, albuminuria (proteinuria), alcohol withdrawal syndrome, allergies, alopecia (hair loss), ALS (amyotrophic lateral sclerosis), Alzheimer's disease , AMD (age-related macular degeneration), anemia, anxiety disorders, anthrax (anthrax), aortic sclerosis, arterial
  • Occlusive disease arteriosclerosis, arterial occlusion, temporal arteritis, arteriosclerosis, arteriovenous fistulas, arthritis, osteoarthritis, asthma, respiratory insufficiency, autoimmune disease, AV block, acidosis, herniated disc, peritonitis, pancreatic cancer, Becker muscular dystrophy, benign prostatic hyperplasia (BPH), bladder carcinoma, hemophilia Hemophilia), bronchial carcinoma, breast cancer, BSE, Budd-Chiari syndrome, bulimia nervosa, bursitis (bursitis), Byler syndrome, bypass, chlamydial infection, chronic pain, Cirrhosis, Commotio cerebri (concussion),
  • Lymphocytic cancer Hodgkin's disease
  • lymphogranulomatosis lymphoma
  • Lyssa gastric carcinoma
  • breast carcinoma breast carcinoma
  • meningitis anthrax
  • cystic fibrosis multiple sclerosis (MS)
  • myocardial infarction myocardial infarction
  • atopic dermatitis neurofibromatosis
  • neural tumors kidney cancer
  • the cancer or tumor being treated or prevented is selected from the group of cancers or tumoral diseases of the ear, nose and throat, lungs, mediastinum, gastrointestinal tract, genitourinary system, gynecological system, breast, endocrine system, skin, bones and soft tissue sarcomas, mesotheliomas, melanomas, neoplasms of the central nervous system, cancers or childhood tumors, lymphomas, leukemias, paraneoplastic syndromes, metastases without a known primary tumor (CUP syndrome), peritoneal carcinoma cancers, immunosuppression-related malignancies and / or tumor metastases.
  • CUP syndrome primary tumor
  • peritoneal carcinoma cancers immunosuppression-related malignancies and / or tumor metastases.
  • the tumors may be of the following types of cancer: adenocarcinoma of the breast, the prostate and the large intestine; all forms of lung cancer emanating from the bronchi; Bone marrow cancer, melanoma, hepatoma, neuroblastoma; the papilloma; Apudom, Choristom, Branchioma; the malignant carcinoid syndrome; carcinoid heart disease; the carcinoma (for example, Walker carcinoma, basal cell carcinoma, basosquamous carcinoma, Brown-Pearce carcinoma, ductal carcinoma, Ehrlich tumor, in situ carcinoma, cancer 2 carcinoma, Merkel cell carcinoma, mucous carcinoma not small cell lung carcinoma, oat cell carcinoma, papillary carcinoma, cirrhotic carcinoma, bronchiolo-alveolar carcinoma, bronchial carcinoma, squamous cell carcinoma and transitional cell carcinoma); histiocytic dysfunction; Leukemia (for example in connection with B cell leukemia, mixed cell leukemia, null cell leukemia,
  • the cancer or tumor being treated or prevented is selected from the group consisting of tumors of the ear, nose and throat, including tumors of the inner nose, paranasal sinuses, nasopharynx, lips , the oral cavity, the oropharynx, the larynx, the hypopharynx, the Ear, salivary and paraganglion, tumors of the lung comprising non-small cell lung carcinomas, small cell lung carcinomas, tumors of the mediastinum, tumors of the gastrointestinal tract comprising tumors of the esophagus, stomach, pancreas, liver, gallbladder and biliary tract, small intestine , Colon and rectal carcinomas and anal carcinomas, urogenital tumors comprising tumors of the kidneys, the ureter, the bladder, the prostate, the urethra, the penis and the testicles, gynecologic tumors comprising tumors of the cervix, vagina, vulva,
  • Lymphomas comprising non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, primary lymphomas of the central nervous system, Hodgkin's disease, leukemias comprising acute leukemias, chronic myeloid and lymphatic leukemias, plasma cell neoplasms, myelodysplastic syndromes, paraneoplastic syndromes, metastases without known Primary tumor (CUP syndrome), peritoneal carcinomatosis, immunosuppression-related malignancy, including AIDS-related malignancies such as Kaposi's sarcoma, AIDS-associated lymphomas, AIDS-associated central nervous system lymphomas, AIDS-associated malignancies
  • Hodgkin and AIDS-associated anogenital tumors transplant-related malignancies, metastatic tumors including brain metastases, lung metastases, liver metastases, bone metastases, pleural and pericardial metastases. tases and malignant ascites.
  • the cancer or tumor being treated or prevented is selected from the group consisting of cancers or tumors of mammal carcinomas, gastrointestinal tumors including colon carcinomas, gastric carcinomas, pancreatic carcinomas, colon cancer, small bowel cancer Ovarian carcinomas, cervical carcinomas, lung cancer, prostate cancer, renal cell carcinomas and / or liver metastases.
  • the invention also relates to the use of the composition according to the invention in methods for the prophylaxis and / or therapy of persons, animals and / or patients with pathogenic modifications and / or defects of cellular immunity, in particular cancer, sepsis, allergic reactions in connection with a cytostatic, chemo- and / or radiotherapy and / or as a prophylaxis and / or therapy in connection with accidents involving atomic, biological, chemical and / or radioactive substances and / or materials.
  • the invention also relates to a kit and its use in medicine. It is preferred to use the compounds according to the invention or the kit comprising them in a combination therapy, in particular for the treatment of tumors. It is particularly preferred here that the combination therapy comprises chemotherapy, a cytostatic treatment and / or radiation therapy. In a particularly preferred embodiment of the invention, the combination therapy is an adjuvant, biologically-specified form of therapy. It is very particularly preferred that this form of therapy is an immunotherapy. Furthermore, it is particularly preferred that the combination therapy comprises a gene therapy and / or a therapy with an inventive corresponding compound. The person skilled in the art is familiar with various combination therapies, in particular for the treatment of tumors.
  • a cytostatic treatment is carried out within a combination therapy or, for example, an irradiation of a specific tumor area, this treatment being combined with a gene therapy, wherein the compounds according to the invention are used as anticancer agents.
  • the compounds according to the invention may be very particularly preferred that the compounds according to the invention be used to increase the sensitivity of tumor cells to cytostatic agents and / or radiation.
  • the compounds according to the invention are used for the inhibition of vitality, the proliferation rate of cells and / or for the induction of apoptosis and of a cell cycle arrest.
  • a Concentrate Containing Cellular Blood Components e.g. Leukocytes or erytrocytes, includes:
  • a homogenate of selected cells is prepared, for example by a repeated freeze-thaw cycle or by means of ultrasound treatment of the cells or by a combination of the two processes. Subsequently, the individual volumes are pooled. 2. Dialysis of the homogenate:
  • Dialysis is performed as a column or membrane dialysis in which all particles larger than 10 kDa are separated.
  • the dialysate is concentrated by lyophilization, the lyophilization being carried out by standard procedures.
  • the lyophilisate is made up with 2 ml of Aqua.
  • the intermediate control is performed by absorption measurement in the spectrum from 260 to 280nm.
  • the ultrafiltration is carried out by a PTGC membrane in a Millipore cassette system with an exclusion limit of 10 KDa.
  • the sterilization by filtration is carried out by means of a Millipore GS filter of (0.22 microns).
  • the solution according to the invention is pasteurized in individual vessels in a water bath at a temperature of 60 ° C. for 10 hours.
  • the liquid composition is automatically aliquoted under sterile conditions (from 2 liters of total solution to 5ml vials).
  • the lyophilization is carried out by standard methods. The filling of the individual aliquots takes place under nitrogen atmosphere and cooling.
  • composition of the invention has also been tested in vivo in various animal systems. With the help of
  • T-lymphocytes In rosette tests in guinea pig T-lymphocytes, the status of cellular immunity under the influence of the composition of the invention in combination with oxoplatin, campto, taxol and eloxatin was investigated. The improvement of the T-lymphocyte status in immunosuppressed guinea pigs after administration of the composition according to the invention was tested in each case. Before the experiments, the amount of T lymphocytes was determined by the rosette test in guinea pigs, and then the decrease in the amount of T lymphocytes was determined by the immunosuppressive agent azathioprine. A second determination of T lymphocytes was made seven Days after the application of azathioprine. This was followed by subcutaneous administration of the composition according to the invention into the laboratory animals. The last determination of the number of T-lymphocytes in guinea pigs was carried out 14 to 19 days after administration of the composition according to the invention.
  • composition according to the invention has been studied in human patients who have studied psoriasis vulgaria and arthritis due to psoriasis. Patients were given three doses of the composition of the invention at weekly intervals, one dose comprising 4 mg of composition in 2 ml. Six months after the initiation of therapy, three out of eight patients showed complete disappearance of the syndromes of the two diseases mentioned above. In five other cases, a significant improvement in the clinical picture was observed. The immunological improvement of the overall situation was associated with an improvement in the entirety of the relevant clinical data. The median level of rosette cells was 33% in patients prior to therapy initiation and increased to 67% at the end of therapy.
  • composition of the invention was used in female patients diagnosed with Systemic Lupus Erythematosus (SLE). In the patients one could not affect SLE.
  • SLE Systemic Lupus Erythematosus
  • composition according to the invention was further tested with the composition according to the invention, with individual dilution steps starting at 500 ⁇ g / ml being investigated. The best effects were determined at a concentration of 30 ⁇ g / ml.
  • composition of the invention has an antiproliferative effect on most cell lines, particularly MIAPaCa-2 pancreatic cancer cells and LNCaP hormone-sensitive prostate cancer cell lines.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Zoology (AREA)
  • Virology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Rolling Contact Bearings (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne une composition constituée de protéines, de peptides et/ou de constituants peptidiques, un produit pharmaceutique comprenant cette composition, un procédé pour produire cette composition, ainsi que l'utilisation de cette composition pour protéger ou traiter des personnes, des animaux et/ou des patients présentant des modifications et/ou des défauts pathogènes de l'immunité cellulaire, notamment un cancer, une septicémie ou des réactions allergiques, en relation avec une thérapie par cytostatiques, une chimiothérapie et/ou une radiothérapie.
EP05800702A 2004-09-24 2005-09-26 Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire Withdrawn EP1796695A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP05800702A EP1796695A2 (fr) 2004-09-24 2005-09-26 Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP04090376A EP1640012A1 (fr) 2004-09-24 2004-09-24 Agents pharmaceutiques comprenant des constituants du sang 10 kDa et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire
US10/948,753 US20060067942A1 (en) 2004-09-24 2004-09-24 Pharmaceutical agent comprising amino acids, peptides, proteins and/or fractions and fragments thereof and the use of same in the prophylaxis and treatment of immune system deficiency in humans and animals
EP05800702A EP1796695A2 (fr) 2004-09-24 2005-09-26 Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire
PCT/DE2005/001729 WO2006032269A2 (fr) 2004-09-24 2005-09-26 Produit pharmaceutique comprenant des acides amines, des peptides, des proteines et/ou leurs fractions et fragments et son utilisation pour la prevention et le traitement de defauts du systeme immunitaire chez l'homme et chez les animaux

Publications (1)

Publication Number Publication Date
EP1796695A2 true EP1796695A2 (fr) 2007-06-20

Family

ID=36051574

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05800702A Withdrawn EP1796695A2 (fr) 2004-09-24 2005-09-26 Agents pharmaceutiques comprenant des constituants du sang <10 kda et l'utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire

Country Status (8)

Country Link
EP (1) EP1796695A2 (fr)
JP (1) JP2008514556A (fr)
AU (1) AU2005287727A1 (fr)
BR (1) BRPI0517349A (fr)
CA (1) CA2580192A1 (fr)
DE (1) DE112005002912A5 (fr)
MX (1) MX2007003489A (fr)
WO (1) WO2006032269A2 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1507215A (en) * 1975-08-19 1978-04-12 Green Cross Corp Processes for producing immunoregulatory preparations
HU182087B (en) * 1980-01-15 1983-12-28 Mta Kiserleti Orvostudomanyi K Process for preparing an active substance for the selective inhibition of the multiplication of normal cells and of cells in myeloide leukemia
ZA847349B (en) * 1983-10-05 1985-04-24 Solco Basel Ag Process for the preparation of a biologically active extract
RU2055589C1 (ru) * 1992-08-21 1996-03-10 Левон Никитович Мкртчян Способ получения биологически активного вещества, обладающего противоопухолевой, иммуномодулирующей и интерфероногенной активностью

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006032269A2 *

Also Published As

Publication number Publication date
WO2006032269A2 (fr) 2006-03-30
WO2006032269A3 (fr) 2006-06-15
MX2007003489A (es) 2007-05-18
DE112005002912A5 (de) 2007-08-30
BRPI0517349A (pt) 2008-10-07
AU2005287727A1 (en) 2006-03-30
CA2580192A1 (fr) 2006-03-30
JP2008514556A (ja) 2008-05-08

Similar Documents

Publication Publication Date Title
EP0178624B1 (fr) Liposomes à partir de lipides synthétiques
DE69528258T2 (de) Haiknorpelextrakte mit antiangiogenischer wirkung und einem effekt auf tumorregression und verfahren zur herstellung derselben
DE3833319C2 (fr)
US5466455A (en) Polyphase fluid-extraction process, resulting products and methods of use
DE3852221T2 (de) Tierische Zelle mit darin eingeführtem antigenem Protein.
CH668554A5 (de) Liposomen welche polypeptide mit interleukin-2-aktivitaet enthalten sowie verfahren zu ihrer herstellung.
WO1987003480A2 (fr) Medicament a effet anti-tumoral contenant de l&#39;hexadecylphosphocholine
EP0109993B1 (fr) Méthode d&#39;extraction de la propolis, poudre sèche de propolis soluble dans l&#39;eau ainsi obtenue et préparations cosmétiques et pharmaceutiques la contenant
DE69104362T2 (de) Autobiotika sowie deren verwendung bei der in vivo eliminierung körperfremder zellen.
CN1197552C (zh) 应用抗炎剂的制剂
PT1289535E (pt) Entidades apoptóticas para utilização no tratamento de desordens neurodegenerativas e de outras desordens neurológicas
US20080220083A1 (en) Pharmaceutical Agent Comprising Blood Components &lt;10 Kda And Their Use For Prophylaxis And Treatment Of Defects Of The Immune System
EP0213523A2 (fr) Compositions pharmaceutiques contenant des phospholipides acylés
DE19961141A1 (de) Pharmazeutische Zusammensetzung aus Spinnengiften sowie deren Herstellung und Verwendung zur Behandlung von Tumorerkrankungen
US5260067A (en) Cytotropic heterogeneous molecular lipids (CHML) and process for preparing the same
EP0381823B1 (fr) Lipides moléculaires hétérogènes cytotropiques et leur procédé de préparation
EP1796695A2 (fr) Agents pharmaceutiques comprenant des constituants du sang &lt;10 kda et l&#39;utilisation dans la prophylaxe et dans le traitement des troubles du système immunitaire
WO2006032268A1 (fr) Produit pharmaceutique comprenant des produits sanguins et son utilisation comme produit a injecter ou a perfuser pour la prevention et le traitement de defauts du systeme immunitaire chez l&#39;homme
US20060067942A1 (en) Pharmaceutical agent comprising amino acids, peptides, proteins and/or fractions and fragments thereof and the use of same in the prophylaxis and treatment of immune system deficiency in humans and animals
EP4248964A1 (fr) Composition pharmaceutique destinée au traitement du sepsis, et utilisation associée
KR20060038387A (ko) 화학요법을 받고 있는 암 환자를 치료하는 방법
DE2714443C3 (de) Hersteilung einer parenteral zu applizierenden Lösung für die Behandlung von Krebs und schwer heilbaren Hauterkrankungen
RU2118533C1 (ru) Средство для лечения облученных млекопитающих
EP0423262A1 (fr) Fraction proteinique de l&#39;appareil de photosynthese vegetal utile comme substance active de dissolution selective de cellules cancereuses et pour le traitement ulterieur de cicatrices, de cheloides et de processus inflammatoires; substances pharmaceutiques contenant cette fraction proteinique.
EP1448220B1 (fr) Agent pharmaceutique contenant un agent antiphlogistique et un hydrolysat de lactalbumin et son utilisation

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20070424

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

DAX Request for extension of the european patent (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RTI1 Title (correction)

Free format text: PHARMACEUTICALS AGENTS COMPRISING BLOOD COMPONENTS LOWER 10 KDA AND THEIR USE FOR PROPHYLAXIS AND TREATMENT OF DEFECTS OF THE IMMUNE SYSTEM

RTI1 Title (correction)

Free format text: PHARMACEUTICALS AGENTS COMPRISING BLOOD COMPONENTS LOWER 10 KDA FOR PROPHYLAXIS AND TREATMENT OF DEFECTS OF THE IMMUNE SYSTEM

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: RIEMSER ARZNEIMITTEL AG

RIN1 Information on inventor provided before grant (corrected)

Inventor name: RIEMSER ARZNEIMITTEL AG

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20081112