Implanted products, containing nanoparticles

FIELD: medicine.

SUBSTANCE: invention relates to the application of a solid medicinal product, which is heated under the impact of an alternating magnetic field, for further therapeutic treatment after surgical ablation of tumours and cancerous ulcers. The medicinal product represents a surgical implant, presented in the form of a physiologically acceptable fabric, sponge or film. The medicinal product contains magnetic particles, which generate heat when excited by an impact of the alternating magnetic field, and in this way, heat the medicinal product.

EFFECT: invention ensures considerable improvement of further treatment after operation on cancerous tumour in comparison with chemotherapy.

21 cl, 14 ex

 

The present invention relates to implantable products containing nanoparticles, and their use in medicine, in particular, for subsequent thermal therapeutic treatment after surgical removal of tumors and cancerous ulcers.

After surgical removal of tumor tissue, almost always the problems associated with the fact that the body is still preserved tumor cells (incomplete resection). After wound closure, these tumor cells will be able to grow and form larger tumors and/or metastases. For this reason, carry out subsequent chemotherapy treatment, which is for the patient to serious stress. Thus it is necessary to remove the minimum number of healthy tissue, and the surgeon must compromise between, preferably, the complete resection of the tumor and removing the minimum number of healthy tissue.

The purpose of the present invention is to provide products and methods for more effective follow-up treatment after surgery for cancer.

Goal is achieved by the independent claims. Additional preferred embodiments of follow from the independent claims, examples and descriptions.

Surprisingly, it was found that implantable medical products is s, containing nanoparticles, heated in an alternating magnetic field, have the potential to significantly improve further treatment after surgery for cancer compared with chemotherapy, if these medical products are implanted or placed in the area of operations.

Therefore, the present invention relates to a solid or gel-like medical products, heating in an alternating magnetic field in which the medical product is present in the form of a physiologically acceptable cloth, sponge, film or gel, where the magnetic particles contained in the medical product form heat when excited by an alternating magnetic field and, thus, heat of the medical product.

For patentable medical product it is crucially important that these particles, i.e. particles excited by an alternating magnetic field, were stationary embedded in medical product or glued to it.

Aqueous solutions of magnetic particles typically receive or to send particles loaded with pharmacological drugs at a specific target location using a static magnetic field, or aqueous solutions of particles induced by an alternating magnetic field, is injected directly into the tumor, so that the particles accumulated in swollen the left cells and destroy tumor cells using the generated heat. First of all, heat is generated due to the energy dissipation of hysteretic heating of the particles.

Patentable medical products are not water or physiological aqueous solutions or suspensions of magnetic particles, and are solid or gel-like media, such as cloth or film, in which a stationary embedded particles. Provided that this does not apply to biorazlagaemykh medical products, particles will always remain inside of a medical product, medical product will remain in implantirovannomu place, like a dental implant or an artificial knee joint.

Because particles, constantly remaining in a medical product, will not be washed away due to diffusion, and will only be freed at the expense of degradation in the case of biorazlagaemykh medical products, the area in which you have placed the implanted medical device, will still be able to heat up after a desired period of time, i.e. one week after implantation, one month after implantation, one year after implantation, and ten years after implantation.

Preferred embodiments of the present invention relate to biorazlagaemykh medical products that are consumed by humans the animals at different speeds depending on the indications. However, particles are released from this medical product is not by diffusion, but only in the framework of biological destruction. Thus, this biorelativity medical product will be exposed to the dissolution, at which the remaining fragments of the medical product, undergoing dissolution, and can then be heated under the action of an alternating magnetic field.

However, for patentable medical products is fundamentally important that they are flexible or deformable and were able to repeat the outlines of the surface of the tissue or organ or the operating area after surgical removal of the tumor. Thus, patentable medical products presented in the form of fabrics that can be placed on the tissue or organs or in the operating area and that will repeat uneven surfaces easily, or in the form of a gel, film-forming composition or film-forming spray, properties which allow you to apply them on any uneven surface.

In this document, the operating region refers to the area that is limited to the outer edges of the surgical wound. In other words, the operating region is a transitional region or the boundary region between the tumor and healthy tissue. Subsequent treatment of this area plays very well the ü important role in preventing relapses.

Medical products described in this document are superimposed, is applied in the form of a coating on the operating region and, in the case of spray, sprayed on the area of operations and, thus, may be provided for further treatment of surgical wounds after tumor surgery.

Thus, patentable medical products not originally intended for systemic use, and for implantation into the operating region. As patentable medical products will remain in the operating area, preferably during subsequent chemotherapy, patentable medical products are biorazlagaemykh in accordance with the time frames scheduled therapy sessions and undergo biological resorption over a longer period of time or are not destructible.

It is important that patentable medical products, preferably biorstwami or slowly biorstwami medical products, were not presented in a stiff form, and could quickly take the shape of the surface of the operating region, which should be covered.

Thus, preferred, in particular, flexible, highly elastic, easily accepting other forms or formless medical products or carriers for nagrevaemykh the particles.

Thus, all medical products according to the invention are elastic and non-metallic carriers who accept the specified form of the surface and the maximum cover it, and, moreover, suitable for introduction of magnetic particles, in particular, super-paramagnetic nanoparticles. Preferred biorazlagaemykh patentable medical products are medical cellulose, dressings placed in the wound devices, surgical suture material, wraps, sponges, medical fabrics, ointments, gels or film-forming sprays.

Medical cellulose and medical fabric preferably form a two-dimensional structure with a low density that inegrirovanny particles. Magnetic particles are attached to the fibrous structure of this medical product, which after the operation is placed into the wound in the operating region in a dry or pre-moistened form.

Sponge or biorstwami porous three-dimensional structure, which, in General, may contain magnetic particles on the surface and in the cavities inside the porous structure, but also in the spongy material, represent another kind of patentable medical products. After surgery, these sponges are placed inside the wound, where they will fill the area of operations fully or tol is to partially. Magnetic particles can be released from these spongy structures in which these particles may also be present in a tightly bound form. May release only weakly bound particles by diffusion from the cavities of the porous structure, and by birthrate spongy structure, if the particles are embedded or embedded in the material with a spongy structure.

Patentable medical foods are intended for implantation in the human and animal body and must be physiologically acceptable. It is important that patentable medical products was present in liquid form in the form of a solution or suspension, and in the form of a viscous or dense or film-forming or solid composition, so that after implantation of the medical product must remain in the desired position.

It is also important that medical product suitable for any surfaces, so that he repeated the contours of the surface.

Herein, a carrier of magnetic particles is referred to as "medical product", and tissue, pulp, gels, film-forming compositions and so on, is described in detail in this document serve as "carriers"that can be biorazlagaemykh or biostability and do not possess magnetic properties and, thus, no magnetic particles not on the such speed in an alternating magnetic field. Carriers made of inanimate matter, may contain x-ray labels or contrast medium and to bind the particles, preferably by bonding and/or covalent bonds. However, mainly particles, which biorazlagaemykh will dissipate heat through the excitation of an alternating magnetic field and, therefore, will be not only to warm themselves, but also the media, that is, in other words the entire medical product as a whole, as well as the surrounding tissue. In addition, pharmacological drugs, such as drugs, can be incorporated into a medical device, as described below, and be released under the action of diffusion and/or birthrate media and/or generation of heat and/or alternating magnetic field to first to fight tumor cells.

In this document, any used medically tissue or pulp is referred to as "fabric", which produce dressings placed in the wound devices, bandages or other medical fabric or cloth.

The phrase "birthdaaay medical product" explicitly applies only to the matrix for the magnetic particles, but not to the magnetic particles, which are usually not biorazlagaemykh. Therefore, biorazlagaemykh are medical cellulose, Perevoz CNY material, placed in the wound devices, surgical suture material, wraps, sponges, medical fabrics, ointments, gels or film-forming sprays, embed or causing magnetic particles. Thus, the matrix for the magnetic particles destructible medical product with magnetic particles, i.e. medical product without magnetic particles is biorstwami, and magnetic particles usually remain or accumulate in tumor tissue or malignant cells, respectively, and they almost will not be subjected to biological degradation or coating will be subjected to biological degradation in part, and the magnetic core generally will not be subject to biological degradation.

The region, which was attended by a remote tumor or remote cancerous tissue, is designated as area of operations.

Other preferred alternatives patentable medical products are liquid or gel-like compositions in the form of ointments, creams, gels and sprays, in particular, film-forming sprays. These formulations contain magnetic particles and should be applied or sprayed on the operating region after removal of the tumor.

Except the magnetic particles patentable medical products preferably are meorazreen the mi and, hence, it will be completely dissolved, preferably within one to twelve months, more preferably from one to six months, thus containing magnetic particles will also be released.

The principle of operation of patentable medical products is that they must cover the area of operations to the maximum extent possible to ensure that the magnetic particles were so close to surviving malignant cells or retained by cancerous tissue as possible. Magnetic particles and, preferably, super-paramagnetic particles can be heated in an alternating magnetic field, and still surviving cancer cells will be destroyed by thermotherapy. In this paper the magnetic particles contained in patentable medical product, will heat the medical product as a whole, and magnetic particles, diffusing beyond the medical product will heat the cancer cells to which they will adhere or in which they will penetrate.

In addition, thermal therapeutic treatment can complement conventional chemotherapy or radiation therapy, since thermal therapeutic treatment leads to a relatively small adverse effects and may exercise the I at the same time with homeotherapeutics treatment. As patentable medical products must cover the operating area or must complete operating region to the maximum extent possible, then, accordingly, patentable medical products are preferably in direct contact with the still surviving malignant cells and still surviving cancer tissue, which can be killed in a particularly effective way in the immediate proximity of the magnetic particles. Therefore, thermal therapeutic treatment patentable medical products is significantly more selective and sparing than chemotherapy and radiation therapy.

In one of the preferred embodiments of the present invention, at least one pharmacologically active compound, preferably an anticancer drug, is associated with the specified magnetic particles. Examples of suitable anti-cancer drugs include: actinomycin, aminoglutethimide, amsacrine, anastrozole, antagonists of purine or pyrimidine bases, anthracyclin, aromatase inhibitors, asparaginase, antiestrogens, bexarotene, bleomycin, buserelin, busulfan, derivatives camptothecin, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine (itineraries), alkylating cytostatic agents, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin (adriamycin), epirubicin, estramustine, etoposide, exemestane, fludarabine, fluorouracil, folic acid antagonists, formestane, gemcitabine, glucocorticoids, goserelin, hormones and hormone antagonists, Cosmegen, hydroxyurea, idarubitsin, ifosfamide, imatinib, irinotecan, letrozole, leiprorelina, lomustin, melphalan, mercapto-purine, methotrexate, miltefosine, mitomycin, inhibitors of mitosis, mitoxantrone, nimustine, oxaliplatin, paclitaxel, pentostatin, procarbazine, tamoxifen, temozolomide, teniposide, testolactone, thiotepa, tioguanin, topoisomerase inhibitors, topotecan, treosulfan, tretinoin, triptorelin, trofosfamide, vinblastine, vincristine, vindesine, vinorelbine, antibiotics with cytostatic activity.

Separating at least one therapeutically active drug from the particles can additionally be achieved or initiated using alternating magnetic fields. Thus, it is possible to make thermal therapeutic treatment was supplemented antiproliferative drug directly into the operating area, which again will increase the efficiency. Of course, in this document it is also possible to carry out additional chemotherapy or radiation therapy day is in parallel or separately in time.

At least one pharmacological drug should not be attached to the particles, preferably nanoparticles. It can optionally contain patentable in medical product or applied to its surface without binding to the particles.

Linking drugs with particles has the advantage of that is that will be preferred aimed at the target release, because the medicine together with particles can penetrate into malignant cells or can join malignant cells, and the release can be induced by a magnetic field.

In this context, "caused" or "magnetic-field-induced" means, in relation to a certain object, an alternating magnetic field or pulse causes directly the release or the Department, or the Department of drugs is mediated, for example, under the action of enzymes or heat generated.

Thus, containing nanoparticles of medical products in the form of medical cellulose, dressing material, placed in the wound devices, surgical suture material, compresses, medical sponges, medical fabrics, ointments, gels or film-forming sprays can updat the further contain at least one pharmaceutical drug, preferably an anti-cancer substance. Appropriate medicines, as well as the binding of particles, described in detail below.

These implants and implantable medical products are heated in an alternating magnetic field through the application of an external alternating magnetic field after application of medical products or biorazlagaemykh medical products operating in the field.

Heating the particles in an alternating magnetic field, the intensity of the alternating magnetic field is preferably in the range from 1 to 25 kA/m, more preferably in the range of from 2 to 18 kA/m and the frequency is preferably in the range of from 5 to 5000 kHz, more preferably in the range from 10 to 1000 kHz.

Under the action of heat released magnetic particles, preferably super-paramagnetic nanoparticles, and optionally present medicines, which will then join malignant cells and kill them. Specified sparing therapy, including therapy, applies, in particular, in combination with other treatments, such as radiotherapy and/or chemotherapy.

Magnetic particles

According to the invention, any magnetic particles may be used provided that they are heated under the action of premanagement field.

Thus, the preferred microparticles and, in particular, nanoparticles, and super-paramagnetic microparticles and, in particular, nanoparticles.

These nanoparticles preferably have magnetic, more preferably superparamagnetic particles, nuclei. The preferred materials are maghemite, magnetite, Nickel alloys, nicolemarie alloys or cobaltocene alloys such as FeNi, or CoNi.

To improve the magnetic characteristics, the magnetic core can also be used in the second layer. This will lead to a stronger result of the coercive field compared to nanoparticles with a single-layer core. The first layer of the core can be made of super-paramagnetic substance, and the second layer of the core may be made of a substance different from the substance of the first layer of the kernel. This core can be coated with additional layers, for example, will carry medicines. Multilayered particles to investirovanie tumor cells with conjugates of particles and medicines described in the application WO 98/58673 A.

The core or cores themselves are composed of magnetic material, preferably ferromagnetic, antiferromagnetic, ferrimagnetic, antiferromagnitnogo or super-paramagnetic substances, preferably made of iron oxide, the company and superparamagnetic particles of iron oxide or of pure iron, provided with an oxide film. These nanoparticles can be heated under the action of an alternating magnetic field, preferably with the magnetic field strength in the range from 2 to 25 kA/m and frequency, which preferably is in the range from 5 to 5000 kHz. Using this method, you can heat tissue containing nanoparticles, more than 50°C. Such high temperatures can be achieved if a tumor cell will be absorbed up to 800 PG of iron in the form of nanoparticles or more. Therefore, nanoparticles can not leave the target area for a longer period of time, and thus, heat may be applied to the tumor, moreover, repeatedly, with high precision and without interaction with the external environment. Heating based on heat dissipation at the translational and rotational motion in magnetic relaxation, and hysteresis losses of heat.

The nanoparticles preferably are composed of iron oxide and, in particular, magnetite (Fe3O4), maghemite (γ-Fe2O3or mixtures of the two oxides. Basically, the preferred nanoparticles can be determined by using the formula FeOxwhere x is a rational number from 1 to 2. The nanoparticles are characterized by a diameter preferably less than 500 nm. The nanoparticles preferably who have an average diameter of 15 nm or preferably the diameter is in the range from 1 to 200 nm, and in particular, preferably in the range of from 5 to 30 nm.

Obtaining nanoparticles without drugs and without coating, is described in detail in DE 4428851 A.

According to the invention, in addition to the magnetic substances of the formula FeOxwhere x is a rational number in the range from 1.0 to 2.0, you can use substances with the General formula MFe2O4where M = Co, Ni, Mn, Zn, Cd, Ba, or other ferrites.

It is also possible configuration nanoparticles with other metal core instead of iron oxide. This document should include such metals as gold, silver, platinum, copper, cobalt, Nickel, iron, manganese, samarium, neodymium, iridium, osmium, ruthenium, rhodium, palladium or alloys of the above metals.

However, it is also possible to obtain nanoparticles of the non-magnetic substance, such as silicon dioxide (SiO2). Moreover, also suitable particles of silicon dioxide or polymer, in which is embedded and/or attached to a magnetic substance such as the above-mentioned magnetic substance.

In addition, it is possible to obtain the magnetic particles on the surface which has the chemical structure, such as antibodies, nucleic acids, peptides, aptamers, or other molecules that are capable of selective binding to a target that will increase the affinity of the particles to Vero uchimsya cells. Such surface modification increases the affinity of malignant cells through the recognition of specific surface structures on the degenerated cells. Preferred chemical structures, which provide magnetic particles the ability to selective binding to the target, which represents, for example, polyclonal antibodies, monoclonal antibodies, humanized antibodies, human antibodies, chimeric antibodies, recombinant antibodies, bespecifically antibodies, antibody fragments, aptamers, Fab fragments, Fc fragments, peptides, peptidomimetics, oligomers with omissions, ribozymes, CpG oligomers, deoxyribozyme, RNA switches, and lipids.

In a preferred embodiment of the present invention between the nanoparticles and therapeutically active substances may not necessarily be formed connection. May be the formation of links with drug due predominantly covalent or covalent bonds and/or sufficiently strong ionic bonds, connections enable or education complex connections, so that an uncontrolled release of drugs will be largely prevented. The release of drugs not under the influence of an alternating magnetic field is considered uncontrolled the s release.

As therapeutically active substances can be selected from antiproliferative, protivoerozionnye, antiangiogenic, antithrombine, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic, anticoagulant, antibacterial, antiviral and/or antifungal medicines, where preferred are antiproliferative, protivoerozionnye, antiangiogenic, cytostatic and/or cytotoxic drugs, as well as nucleic acids, amino acids, peptides, proteins, carbohydrates, lipids, glycoproteins, glikana or lipoproteins with antiproliferative, protivoerozionnye, antiangiogenic, antithrombine, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic, anticoagulant, antibacterial, antiviral and/or antifungal properties. In addition, these substances may be a radio-sensitizing tools or sensitizing means or reinforcing means for the other, combined, conventional methods of treatment of malignant tumors, or contain such sensitizing tools.

Alkylating funds antibiotics with cytotoxic properties, antimetabolites, inhibitors of microtubules and topoisomerase inhibitors containing platinum is soedineniya and cytotoxic other means such as asparaginase, tretinoin, alkaloids, toxins pedofile, taxanes and Miltefosine®, hormones, immunomodulators, monoclonal antibodies, transductor signals (signal transduction molecules and cytokines, among others, can be used as cytotoxic and/or cytostatic compounds, i.e. chemical compounds with cytotoxic and/or cytostatic properties.

As examples of alkylating means among other things, you can call harachaman, cyclophosphamide, trofosfamide, ifosfamide, melphalan, chlorambucil, busulfan, thiotepa, carmustin, lomustin, dacarbazine, procarbazine, temozolomide, treosulfan, estramustin, nimustine.

Examples of antibiotics and cytostatic properties are daunorubicin, doxorubicin (adriamycin), dactinomycin, mitomycin C, bleomycin, epirubicin (4-EPI-adriamycin), idarubitsin, mitoxantrone and amsacrine.

Methotrexate, 5-fluorouracil, 6-tioguanin, 6-mercaptopurine, fludarabine, cladribine, pentostatin, gemcitabine, azathioprine, raltitrexed, capecitabine, cytosine arabinoside, tioguanin and mercaptopurine can be cited as examples of antimetabolites (antimetabolites drugs).

Vincristine, vinblastine, vindesine, etoposide, and teniposide among others belong to the class of alkaloids and toxins of pedophila. In addition, the image is meniu can be used containing platinum compounds. For example, as containing platinum compounds mentioned cisplatin, carboplatin, oxiplatin. For example, alkaloids such as Vinca alkaloids (vincristine, vinblastine, vindesine, vinorelbine) and taxanes (paclitaxel/Taxol®, paclitaxel and docetaxel), and derivatives of paclitaxel are inhibitors of microtubules. Toxins of pedophila (etoposide, teniposide) and alkaloids camptothecin (camptothecin, topotecan and irinotecan) can be described as inhibitors of topoisomerase.

For example, hydrocarbide (hydroxyurea), imatinib, Miltefosine®, amsacrine, pentostatin, bexarotene, tretinoin and asparaginase can be considered as other cytotoxic drugs (cytotoxic other means). Representatives of the class of monoclonal antibodies include trastuzumab (also known as Herceptin®), alemtuzumab (also known as Mabcampath®) and rituximab (also known as MabThera®).

According to the invention, also hormones such as glucocorticoids (prednisone), estrogens (fosfestrol, estramustin), LHRH (buserelin, goserelin, leiprorelina, triptorelin), flutamide, tsiproteronatsetat, tamoxifen, toremifene, aminoglutethimide, formestane, exemestane, letrozole and anastrozole can be used. Interleukin-2, interferon-α, interferon-γ, erythropoietin, G-CSF, trastuzumab (Herceptin®), R is taximan (MabThera®), gefitinib (Iressa®), ibritumomab (Zevalin®), levamisole, and retinoids belong to classes of immunomodulators, cytokines, antibodies and transduction signals.

The above medicines may be contained together with the magnetic particles in patentable medical product or applied to its surface. In the case where the medicinal product is due to covalent or ionic bonds are connected with magnetic particles or medical product or biorazlagaemykh medical product, binding of drugs occurs, for example, with the participation of hydroxyl groups, amino groups, carbonyl groups, thiol groups or carboxyl groups, depending on what functional group is an appropriate remedy.

With the participation of hydroxyl groups is preferably formed esters, acetals or ketals, with the participation of thiol groups preferably are formed thiol esters, thiol acetals or a thiol ketals, with the participation of amino groups preferably are formed amides and partly imine (shiftby Foundation), with the participation of the carboxyl groups is preferably formed esters or amides, and with the participation of the carbonyl groups is preferably formed ketals.

In addition, it is preferable that the drug or drug is yli associated with nanoparticles or with medical product or biorazlagaemykh medical product is not directly and in immobilized form by using a linker molecule. In addition, known methods of functionalization of the surface of the nanoparticles, so that amino groups, hydroxy-group, carboxyl group or a carbonyl group can be formed on the surface of nanoparticles by known methods.

Therapeutically active substances associated with nanoparticles and/or medical product or biorazlagaemykh medical product directly or through a linker molecule, preferably via an amide bond or an ether bond.

Preferred linkers that contain pH-degradable acetal, ether, gidrazonami or minovia group and can be cleaved by reaction in an acidic environment or enzymatic reaction.

Amide group must be named as enzymatic degradable group of the linker molecule or around it. The group split under the action of heat or acid, contain, for example, phosphate groups, thiophosphate groups, sulfate groups, phosphamide group, urethane group or aminogroup.

It is not necessary that the drug was covalently linked to a linker or biorazlagaemykh medical product, it can be associated with ionic or hydrogen bonds, or may be present in intercalated or coordinate form is.

As described above, in patentable medical products you can use any magnetic particles. Examples of such magnetic particles described in WO 2005 070471 A2, WO 02/43708 A2, US 5411730 A1, WO 2005 042142 A2, WO 03/026618 A1, WO 2005 065282 A2, WO 2006 108405 A2 and WO 2007 019845 A2.

Biorstwami medical products

After an operation for cancer surgeon leaves inside the patient's body patentable biorstwami medical products in the form of implants, gels, tissues, fabrics, coverings for wounds or film-forming drugs, and then closes the wound.

Patentable biorstwami medical products are, in particular, for the subsequent treatment of the operating region using the heat produced by thermotherapy to destroy remaining tumor cells and to prevent recurrence.

Thus, patentable biorstwami medical products consist of physiologically acceptable material and/or split into a physiologically acceptable degradation products and components.

Materials for patentable medical products selected from the group consisting of, or consisting of: polyacrylic acid, polyacrylate, polymethylmethacrylate, polybutylmethacrylate, polyisobutylene, polyacrylamide, polyacrylonitrile, polyamide, polyetherimide, polyethylenimine, polyimide, polycarbona is, polycarbonate, polyvinylacetal, polivinilhlorid, polyvinylidenechloride, simple, polyvinyl ether, polyvinyl aromatic compounds, complex, polyvinyl ether, polyvinylpyrrolidone, Polyoxymethylene, polyethylene, polypropylene, polytetrafluoroethylene, polyurethane, polyolefin elastomer, polyisobutylene, EPDM resins, porcelian, carboxymethylchitosan, polyethylene terephthalate, polyvalent, carboxymethylcellulose, cellulose, rayon, triacetate, rayon, cellulose nitrate, cellulose acetate, hydroxyethyl cellulose, cellulose butyrate, acetate-butyrate cellulose, ethylvinylacetate copolymer, polysulfone, polyethersulfone, epoxy resin, ABS resin,EPDM resin, silicone prepolymer, silicone, polysiloxane, polivinilhlorid, simple cellulose ether, cellulose triacetate, chitosan, derivatives of chitosan, the polymerized oil, polivalente, poly-ε-decalactone, polylactide, polyglycolide, copolymers of polylactide and polyglycolide, poly-ε-caprolacton, polyhydroxyalkane acid, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxybutyrate-co-valerate, poly(1,4-dioxane-2,3-dione), poly(1,3-dioxane-2-one), poly-para-dioxanone, polyanhydrides, anhydride polimolekuly acid, polyhydroxybutyrate, polycyanoacrylate, polycaprolactones, poly-β-maleic acid, polycaprolactone is relat, multiblock copolymers derived from oligosaprogenic and oligodeoxynucleotide, polyetheramine multiblock copolymers derived from PEG and poly(utilityrelated), politisation, trimethylarsine polyglycolic acid, polycaprolactone-glycolide, poly(γ-Atrpatakan), poly(DTH-aminocarbonyl), poly(DTE-co-DT-carbonate), poly(bisphenol a-aminocarbonyl), polychaetes, trimethylarsine polyglycolic acid, polytrimethylene, polyaminocarboxylic, polyvinyl alcohols, polyetherimide, glycosidation polyesters, polyphosphatase, polyphosphazene, poly[p-carboxyphenoxy)propane], polyhydroxyvalerate acid, polyethylene oxide-propylene oxide, soft polyurethanes, polyurethanes with amino acid residues in the backbone, polyetherether, polyethylene oxide, polyalkylacrylate, polyarteritis, carrageenan, starch, collagen, polymers albumen, polyaminoamide, synthetic polyaminoamide, Zein, modified Zein, polyhydroxyalkanoates, pectic acid, actin acid, fibrin, modified fibrin, casein, modified casein, carboxymethylchitin, albumin, hyaluronic acid, heparansulfate, heparin, chondroitin sulfate, dextran, cyclodextrin, copolymers derived from PEG and polypropylenglycol, Arabian gum, guar or other Kameda-resin, gelatin, to the lagen, collagen-N-hydroxysuccinimide, lipids, lipids, polymerized oils and their modifications, copolymers and mixtures of the above substances.

The above polymers are biorazlagaemykh and you can get them with such degree of polymerization and cross-links that can be biretrosteel.

The term "birthdaaay" or "bioassays" I understand that these materials were destroyed or will be destroyed 90 percent by weight in the period from 1 month to 12 months, preferably 6 months, under physiological conditions.

Preferred biorazlagaemykh polymers include polylactide, polyglycolides, copolymers of polylactide and polyglycolides, polyhydroxybutyrates, polyhydroxybutyrate, polyarteritis, picolylamine polyesters, polyvinyl alcohols, polyvinylpyrrolidone, copolymers of acrylamide and acrylic acid, hyaluronic acid, heparansulfate, heparin, chondroitin sulfate, dextran, β-cyclodextrin, hydrophilic cross-linked dextrins, alginates, phospholipids, carbomer, cross-linked peptides and proteins, silicones, polyethylene glycol (PEG), polypropyleneglycol (BCP), copolymers of PEG and BCPs, collagen, polymerized oils and waxes and their mixtures and copolymers.

In addition, preferred are polyesters, polylactide and copolymers of diols and esters or diols and l is tidow. For example, the diols used in ethane-1,2-diol, propane-1,3-diol or butane-1,4-diol.

According to the invention, in particular, the polyesters used for the polymer layer. Preferred are such polymers from the group of polyesters, which are distinguished by the presence of the following monomers:

In the depicted monomers R, R', R" and R"' represent alkyl groups containing from 1 to 5 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, or cyclopentyl, and preferably methyl or ethyl. Y is an integer from 1 to 9, and x denotes the degree of polymerization. In particular, preferred are polymers of the representative monomers:

As additional representatives of absorbable polymers should be called Resomer®, poly(L-lactides) with the General formula -(C6H8About4)nis, for example, L 210, 210 L S, L 207 S, L 209 S, poly(L-lactide-co-D,L-lactide)s with the General formula -(C6H8About4)n-for example, LR 706, LR 708, L 214 S, LR 704, poly(L-lactide-co-trimethylarsine)s with the General formula -[(C6H8About4)x-(C4H6About3)y]n-for example, LT 706, poly(L-lactide-co-glycolide)s with the General formula -[(C6H8About4)x- ( 4H4About4)y]n-for example, LG 824, LG 857, poly(L-lactide-co-ε-caprolactone)s with the General formula -[(C6H8O4)x-(C6H10O2)y]nis, for example, LC 703, poly(D,L-lactide-co-glycolide)s with the General formula -[(C6H8O4)x-(C4H4O4)y]n-for example, RG 509 S, RG 502 H, RG 503 H, RG 504 H, RG 502, RG 503, RG 504, poly(D,L-lactide)s with the General formula -[(C6H8O4)nis, for example, R 202 S, R 202 H, R 203 S and R 203 H. In this document Resomer® 203 S represents an alternative to a particularly preferred polymer Resomer® R 203. Name Resomer® denotes a high-tech product company Boehringer Ingelheim.

Basically, in the present invention the use of absorbable polymers is particularly preferred. In addition, preferred are homopolymers of lactic acid (polylactide), and polymers derived from lactic and glycolic acids.

Bistabile medical products

Patentable biostable or beyond biretrosteel medical products in the form of gels, sponges and, in particular, film-forming compositions, film-forming sprays or substance, tissue, pulp, coverings for wounds, etc. obtained from beyond biretrosteel or bad birthrelease materials.

Materials the La patentable biolabeling medical products selected from the group containing or consisting of: polyacrylic acid and polyacrylate, for example, polymethylmethacrylate, polybutylmethacrylate, polyacrylamide, polyacrylonitrile, polyamides, polyetherimide, polyethylenimine, polyimides, polycarbonates, polycarbonate, polyvinyledene, poly(vinylchloride)s, poly(vinylidenechloride)s, simple, polyvinyl ethers, polyvinyl aromatics, complex, polyvinyl ethers, polyvinylpyrrolidone, polyoxymethylenes, polyethylene, polypropylene, polytetrafluoroethylene, polyurethanes, polyolefin elastomers, polyisobutylene, EPDM resins, Versiliana, carboxymethyl chitosan, polyethylene terephthalate, polyvalent, carboxymethylcellulose, cellulose, viscose, triacetate viscose, cellulose nitrate, acetate cellulose, hydroxyethyl cellulose, cellulose butyrate, acetate-butyrate cellulose, ethylvanillin acetate copolymers, polysulfones, epoxy resin, ABS resin, EPDM resins, silicones, such as polysiloxane, polyvinyl halides and copolymers, simple cellulose ether, cellulose triacetate, chitosan and their copolymers and/or mixtures.

Preferred biostable polymers used in medical engineering and for biolabeling implants are polyethersulfone, substituted polyethersulfone, polyphenylsulfone, substituted polyphenylsulfone, block copolymers is of resultone, block copolymers of perfluorinated polysulfone, block copolymers poliftorirovannykh polysulfone, block copolymers of substituted polysulfone and/or mixtures of the above polymers.

Gels

Patentable nanoparticles can be embedded in gels or hydrogels, or may be components of a film-forming sprays, which preferably also be biretrosteel. To improve the stabilization of the film-forming gels or sprays, patentable nanoparticles described herein can be combined with gel-forming or film-forming means.

Suitable gel-forming or film-forming means preferably represent materials based on cellulose, such as cellulose nitrate or ethylcellulose or their physiologically acceptable polymers, polyvinyl acetate, partially saponified polyvinyl acetate, polymer mixtures of vinyl acetate and of acrylic acid or crotonic acid or monoalkyl ester of maleic acid, ternary polymer mixtures of vinyl acetate and crotonic acid and ventilationthe, or crotonic acid and finalproject, polymer mixture metilfenidato ether and monoalkyl ester of maleic acid, in particular, in the form of monobutyl ester of maleic acid, polymer mixtures of vinyl ether fatty to the slots and acrylic acid or methacrylic acid, a polymeric mixture of N-vinylpyrrolidone, methacrylic acid and alkylboron of methacrylic acid, a polymer of a mixture of acrylic acid and methacrylic acid or alkylboron ester of acrylic acid or alkylboron of methacrylic acid, in particular with a content of Quaternary ammonium groups, or polymers, copolymers or mixtures containing acrylate, methacrylate or the ammonium utilityrelated, or polyvinylacetal and polyvinylbutyral, alkyl-substituted poly-N-vinylpyrrolidone, alkilany ether polymer mixtures of olefins and maleic anhydride, reaction products of rosin with acrylic acid and benzoin resin, chitosan, Luvimer 100®, aluminum stearate, carbomer, cocamide IEA, carboxymethylation, carboxymethyl hydroxypropyl guar or carrageenan red algae.

The alkyl radicals of the above esters usually have a short circuit and, for the most part, do not contain more than four carbon. Such compounds are referred to herein as polymeropoulos or gel-forming means.

In addition, water-soluble polymers, for example, ion polyamides, polyurethanes and polyesters, as well as Homo - and copolymers of ethylene unsaturated monomers belong to gelling and film forming means, respectively. Such compounds, e.g. the measures are supplied under the brand names Acronal®, Acudyne®, Amerhold®, Amphome®, Eastman AQ®, Ladival®, Lovocryl®, Luviflex VBM®, Luvimer®, Luviset P. U. R. ®, Luviskol®, Luviskol Plus®, Stepanhold®, Ultrahold®, Ultrahold Strong® or Versatyl®. Luvimer® is a polyacrylate.

Additional components patentable gels may be the most natural polymers. Among them are albumin, collagen, hyaluronan, chitosan, and chitin. Copolymer or a block copolymer of polyethylene oxide with terminal α-hydroxy acid or poly-α-hydroxy acid is a particularly preferred non-natural polymer.

In addition, glycosaminoglycans, such as aggrecan, decorin, biglycan and fibronodular are normal components bioabsorbable gels or film-forming solutions or sprays.

Also in the gels, solutions and sprays you can use the salt solutions such as saline solution (0.9 percent), PBS (phosphate-saline buffer, i.e. the solution of phosphate-saline buffer), DMEM (modified Dulbecco Wednesday Needle).

When using super-paramagnetic particles with a core of iron oxide, it is preferable content of iron oxide 3-30% by weight of 200 mg of gel, more preferred is a content of iron oxide is 5 to 25 percent by weight of 200 mg of gel, and most preferred is a content of iron oxide 10-20 percent by weight is 200 mg of gel.

Polymeric carriers

Magnetic particles can be added is already in the process of obtaining polymers and then will be introduced in bioassays polymer structure.

Examples for biorazlagaemykh medical products according to the invention are polymeric beads containing magnetic particles. Polymer beads preferably consist of polyhydroxybutyrate, polylactide, polyglycolide or copolymers of polylactic-to-glycolide. Alginate and Eudragit®are other especially preferred materials. The content of magnetic particles in these polymer beads is up to 20 percent by weight.

The polymer beads can be used by themselves or they can be embedded in gels or pastes, and they can be mobilitat medical cellulose.

The polymer beads can be heated up to a temperature of 50°C in an alternating magnetic field.

Medical cellulose

Covered medical implantable products that can be applied to the nanoparticles preferably are bioreserves. That is, they can be completely dissolved in the body or at least can be physiologically well-tolerated.

Medical implants containing nanoparticles, among others, are medical cellulose, dressings, placed aemia in wounds fixtures, surgical thread, compresses and medical fabrics.

Polyhydroxybutyrate and cellulose derivatives, derivatives of chitosan and collagen, polyethylene glycol, polyethylene oxide and polylactide are the preferred materials for medical pulp and matter. The products of the calcium alginate is woven with carboxymethylcellulose sodium is preferably used, if alginates are used as a covering for wounds. As an example you need to bring SeaSorb Soft from the company Coloplast.

If the nanoparticles applied to dressings and/or placed in the wound devices, it should be noted, in particular, products Tabotamp® and Spongostan® Johnson & Johnson. These products are obtained from regenerated cellulose by controlled oxidation.

If surgical thread should be impregnated with nanoparticles, the use of surgical thread, which consists of polyglycolic acid, polycaprolactone-to-glycolide or poly-p-dioxanone. Examples are products Marlin®, PCL and Marisorb® Catgut GmbH.

If the compresses should be impregnated with nanoparticles, in this document, in particular, it is necessary to use sterile gauze swabs made from 100% cotton. Examples are product lines Stericomp® or Askina®.

If you use medical cellulose, it is preferable that sumerianrecords it was more than 90%.

If you use medical fabrics, products Trevira® are preferred.

Medical fabrics and cellulose is sprayed with a solution of magnetic particles in water, ethanol or a mixture of water and ethanol or coated by dipping in the solution. The process of coating by dipping or spraying can be repeated several times after drying of the medical product.

One cm2the surface of the medical product is applied from 10 MK to 100 mg of magnetic particles.

For every gram of medical product is applied from 100 μg to 2 g of the coating of the magnetic particles.

Sponge

Medical sponges are bioreserves implants with spongy porous structure.

The preferred materials for medical sponges are collagen, oxidized cellulose, chitosan, thrombin, fibrin, chitin, alginate, hyaluronic acid, PLGA, PGA, PLA, polysaccharides and globin.

If you use medical sponge, it is preferable that the content of collagen was more than 90%.

For every gram of medical product is applied from 100 μg to 2 g of the magnetic particles.

Ointments and pastes

If the nanoparticles embedded in the ointment, you should use a basis for ointments that contains purified water in an amount of preferably 5-50 percent by weight, more preferably 10-40% by mass and most preferably 20-30% by weight. In addition, the ointment also contains liquid paraffin in an amount of preferably 40-90% by weight, more preferably 50-80% by weight and most preferably 20-60% by weight. In addition, the ointment may contain a viscous paraffin in an amount of preferably 5-50 percent by weight, more preferably 10-40% by weight and most preferably 20-30% by weight.

In addition, you can use the gelling and/or film-forming means, which are described in this document, you can add up to 30 percent by weight. In addition, polymers such as cellulose, chitosan, thrombin, fibrin, chitin, alginates, albumin, hyaluronic acid, hyaluronan, polysaccharides, globin, polylactide, polyglycolide, polylactide-to-glycolid, polyhydroxybutyrate, derivatives, cellulose derivatives, chitosan, polyethylene glycol and polyethylene oxide in amounts up to 30 percent by weight.

Film-forming sprays

The nanoparticles according to the invention can be implemented in sprayable solutions or can be components of a film-forming sprays. Magnetic particles or nanoparticles containing the drug, which are described in this document can be used in combination with gel-forming or film-forming means and for better stabilization of the film-forming sprays. Film-forming sprays contain at least one or more film-forming means.

Suitable film-forming means preferably are compounds based on cellulose, such as cellulose nitrate or ethylcellulose or their physiologically acceptable polymers, polyvinyl acetate, partially saponified polyvinyl acetate, polymer mixtures of vinyl acetate and of acrylic acid or crotonic acid or monoalkyl ester of maleic acid, ternary polymer mixtures of vinyl acetate and crotonic acid and ventilationthe, or crotonic acid and finalproject, polymer mixture metilfenidato ether and monoalkyl ester of maleic acid, in particular in the form of monobutyl ester of maleic acid, polymer mixtures of vinyl ester of fatty acid and of acrylic acid or methacrylic acid, a polymer of a mixture of N-vinylpyrrolidone, methacrylic acid and alkylboron of methacrylic acid, a polymer of a mixture of acrylic acid and methacrylic acid or alkylboron ester of acrylic acid or alkylboron of methacrylic acid, in particular with a content of Quaternary ammonium groups, or polymers, copolymers or mixtures containing acrylate, methacrylate or the ammonium ethyl methacrylate chloride, or polyvinyl acetals and polivinil the Raleigh, alkyl-substituted poly-N-vinylpyrrolidone, alkilany ether polymer mixtures of olefins and maleic anhydride, reaction products of rosin with acrylic acid and benzoin resin, chitosan, Luvimer 100®, aluminum stearate, carbomer, cocamide IEA, carboxymethylation, carboxymethyl hydroxypropyl guar or carrageenan red algae.

The alkyl radicals of the above esters usually have short chains and mostly do not contain more than four carbon atoms.

In addition, water-soluble polymers, such as ion polyamides, polyurethanes and polyesters, as well as Homo - and copolymers of ethylene unsaturated monomers belong to the gel-forming and film-forming means, respectively. Such compounds are available, for example, under the brand names Acronal®, Acudyne®, Amerhold®, Amphome®, Eastman AQ®, Ladival®, Lovocryl®, Luviflex VBM®, Luvimer®, Luviset P. U. R. ®, Luviskol®, Luviskol Plus®, Stepanhold®, Ultrahold®, Ultrahold Strong® or Versatyl®. Luvimer® is a polyacrylate, which was developed as a polymer for hair styling by BASF AG.

The preferred solvent is water, ethanol or a mixture of water and ethanol.

To use super-paramagnetic particles with a core of iron oxide, it is preferable content of iron oxide 3-30% by weight of 200 mg of gel, more preferred is a content of the oxide of W is found 5-25 percent by weight of 200 mg gel and the most preferred is a content of iron oxide 10-20 percent by weight of 200 mg of gel.

For every gram of medical product is applied from 100 μg to 2 g of the magnetic particles.

The production of implants containing nanoparticles occurs through a process of dipping or spraying. In this document, products, subject implantation dip in containing nanoparticles solution or suspension or spray containing nanoparticles solution. Products are then dried and placed in aseptic packaging. Gels, ointments, solutions and sprays produced by the desired pharmaceutical preparation in accordance with standard procedures, and the desired number of magnetic particles added is preferably in the last stage.

Received patentable biorstwami medical products used for the treatment and prevention of tumors, carcinomas and cancers, and also they serve, in particular, for the subsequent treatment of the operating area after an operation for cancer and, in particular, after the removal of a solid tumor.

Examples of cancer and tumors, for which you can use patentable medical products are: adenocarcinoma, choroidal melanoma, acute leukemia, acoustic neuroma, ampullary carcinoma, anal carcinoma, astrocytoma,basal cell carcinoma, pancreatic carcinoma, a tumor of the connective tissue, bladder cancer, bronchial carcinoma, non-small cell bronchial carcinoma, breast cancer, Burkitt's lymphoma, carcinoma of the body of the uterus, carcinoma of unknown primary localization of tumor, colon cancer, cancer of the small intestine, the small intestine tumor, ovarian cancer, endometrial carcinoma, ependymoma, epithelial cancers, Ewing Sarcoma, tumors of the gastrointestinal tract, cancer of the gallbladder, biliary carcinoma, uterine cancer, cervical cancer, glioblastomas, gynecologic tumors, ENT tumors, tumors of the hematopoietic system, cancer of the urethra, cancer of the skin, brain tumors (gliomas), metastases in the brain, cancer of the testis, pituitary tumor, carcinoids, Kaposi's sarcoma, cancer of the larynx, germinoma, bone cancer, colorectal carcinoma, head and neck tumors (tumors in the neck, nose and eyes), carcinoma of the colon, craniopharyngioma, cancer of the mouth and lips, liver cancer, liver metastases, tumor century, lung cancer, cancer of the lymph nodes (hopkinsi/nehodgkinski), lymphomas, stomach cancer, malignant melanoma, malignant neoplasia, malignoma gastrointestinal tract, carcinoma breast cancer, colorectal cancer, Protocol, melanoma, meningiomas, Hodgkin's disease, mushroom avium, cancer of the nose, n is urinoma, neuroblastoma, kidney cancer, pochernkletocny carcinoma, non-Hodgkin lymphoma, oligodendroglioma, carcinoma of the esophagus, carcinoma and osteolytic osteoplastic carcinoma, osteosarcoma, carcinoma of the ovary, pancreatic cancer, penile cancer, squamous cell carcinoma of the head and neck, prostate cancer, pharynx cancer, carcinoma of the rectum, retinoblastoma, cancer of the vagina, cancer of the thyroid gland, disease of Sneberger, esophageal cancer, spinaloga, T-cell lymphoma (mushroom mycosis fungoides), thymoma, tubular carcinoma, eye tumors, cancer of the urethra, prostate tumor, urothelial carcinoma, vulvar cancer, the lesion mastoid bone, soft tissue tumors, soft tissue sarcoma, Wilms ' tumor, cervical carcinoma and tongue cancer.

In particular, preferred are solid tumors. In addition, preferred are carcinoma of the prostate, brain tumor, sarcoma, cervical carcinoma, carcinoma of the ovary, breast carcinoma, bronchial carcinoma, melanoma, head and neck tumors, carcinoma of the esophagus, carcinoma of the rectum, pancreatic carcinoma, carcinoma of the bladder, carcinoma of the kidney, liver metastases, brain and lymph nodes.

In addition, the use and application patentable bioassays medical product which is particularly preferred in the field of medicine, preferably, in combination with radiation therapy and/or together with conventional chemotherapy.

This gentle way thermotherapy includes locally limited use of anti-cancer drugs and, thus, reduces drug burden and adverse effects on the patient. In addition, the likelihood of recurrence of metastases is significantly reduced, because the fight against tumor cells remaining after incomplete resection, is locally and selectively. In addition, medicines, not necessarily located on patentable implant or medical product can be released from the nanoparticles under the action of an alternating magnetic field applied from the outside, and will have a stronger selective action in the actions pane. This makes possible a more accurate dosing of drugs, because the drug will not be lost in the delivery process through the body because of the local nature of the method of treatment. Also the above method can effectively implement against malignant cells using nanoparticles without attached drugs. Herein, the nanoparticles are attached to malignant cells or infiltrating malignant cells and destroy cancer cells is the od action of an externally applied magnetic field, which heats the magnetic particles.

Additionally, molecules with the ability of the selective binding of, for example, monoclonal antibodies and/or aptamers, can be connected with the surface of the nanoparticles or the outer layer or shell nanoparticles to further increase the affinity to specific cell types.

In a preferred embodiment of the present invention the core of magnetic nanoparticles consists of magnetite (Fe3O4), maghemite (γ-Fe2O3) or mixtures of both oxides and preferably is of superparamagnetic particles. In addition, cores are stabilized with protective colloid shells, which make it possible to attach a therapeutically effective tools.

EXAMPLES

Example 1A:

General instructions regarding the receipt of the suspension/solution of nanoparticles for impregnating or coating on the carrier by spraying or dipping

A solution of 0.23 mol FeCl2and 0.46 mol FeCl3in 1 l of water was degirolami nitrogen. After that he added so much 5 M NaOH for 20 minutes to achieve a pH of 11.5. The precipitate was heated to 65°C for ten minutes and then cooled to room temperature for five minutes. After that, the residue suspended in deionized and degassed water up until the pH of the solution to prom is of no was 9. Sediment suspended in water and the pH of the suspension is brought to 6 by using glacial acetic acid. In the resulting suspension were added 10% by volume of a 30% by weight aqueous solution which is then stirred until then, until I run out of gas. After that, the suspension was diluted with water to a solid concentration of iron oxide 5 percent by weight.

Example 1B (without oxidation/aeration air):

In order to obtain nanoparticles of iron oxide in ethylene glycol, in 900 ml of ethylene glycol was dissolved in 0.1 mol FeCl3H 6N2About 0.2 mol FeCl3(anhydrous), 50 g of sodium acetate and 195 g of diaminohexane and was heated at 60°C for 1 hour. Then the solution was heated to boiling point for 30 minutes. The boiling temperature was maintained for six hours. The resulting dispersion was slowly cooled to room temperature.

The particles were washed three times with a mixture of ethanol and water.

Then the particles resuspendable in 900 ml of ethylene glycol and aziraphale atmospheric oxygen. The suspension was heated to the boiling point of ethylene glycol and maintained at this temperature for 24 hours.

After cooling, the particles were washed with water/ethanol and suspended in the water.

These particles were covered with a method similar to that shown in example 1G.

Example 1C (oxidation/p and the aeration air):

In order to obtain nanoparticles of iron oxide in ethylene glycol, in 900 ml of ethylene glycol was dissolved in 0.1 mol FeCl3H 6N2About 0.2 mol FeCl3(anhydrous), 50 g of sodium acetate and 195 g of diaminohexane and was heated at 60°C for 1 hour. Then the solution was heated to boiling point for 30 minutes. The boiling temperature was maintained for six hours. The resulting dispersion was slowly cooled to room temperature.

The particles were washed three times with a mixture of ethanol and water.

Then the particles resuspendable in 900 ml of ethylene glycol and aziraphale atmospheric oxygen. The suspension was heated to the boiling point of ethylene glycol and maintained at this temperature for 24 hours.

After cooling, the particles were washed with water/ethanol and suspended in 900 ml of 1 M HNO3. Then was added 450 ml of a 0.7 M solution of iron nitrate (Fe(NO3)3H 9H2O) and boiled under reflux for one hour (100°C). The particles were washed three times, each time with 500 ml of water.

These particles were covered with a method similar to that shown in example 1G.

Example 1D (without oxidation/without gassing air):

In order to obtain nanoparticles of iron oxide in ethylene glycol, in 900 ml of ethylene glycol was dissolved in 0.1 mol FeCl3H 6N2About 0.2 mol FeCl3(anhydrous), 50 g of sodium acetate and 195 g of diaminohexane and n is gravely at 60°C for 1 hour.

Then the solution was heated to boiling point for 30 minutes. The boiling temperature was maintained for six hours. The resulting dispersion was slowly cooled to room temperature.

The particles were washed three times with a mixture of ethanol and water.

Then the particles resuspendable in 900 ml of ethylene glycol.

The suspension was heated to the boiling point of ethylene glycol and maintained at this temperature for 24 hours.

After cooling, the particles were washed with water/ethanol and suspended in the water.

These particles were covered with a method similar to that shown in example 1G.

Example 1E (oxidation/without gassing air):

In order to obtain nanoparticles of iron oxide in ethylene glycol, in 900 ml of ethylene glycol was dissolved in 0.1 mol FeCl3H 6N2About 0.2 mol FeCl3(anhydrous), 50 g of sodium acetate and 195 g of diaminohexane and was heated at 60°C for 1 hour.

Then the solution was heated to boiling point for 30 minutes. The boiling temperature was maintained for six hours. The resulting dispersion was slowly cooled to room temperature.

The particles were washed three times with a mixture of ethanol and water.

Then the particles resuspendable in 900 ml of ethylene glycol. The suspension was heated to the boiling point of ethylene glycol and maintained at this temperature for 24 hours.

After the cooling gap is placed particles were washed with water/ethanol and suspended in 900 ml of 1 M HNO 3. Then was added 450 ml of a 0.7 M solution of iron nitrate (Fe(NO3)3H 9H2O) and boiled under reflux for one hour (100°C). The particles were washed three times, each time with 500 ml of water.

These particles were covered with a method similar to that shown in example 1G.

Example 1F:

In order to obtain nanoparticles of iron oxide, a solution of 96 g of sodium hydroxide and 680 ml of butyric acid in 2000 ml of methanol was added to a solution of 216 g setevogo iron oxide (III) in 500 ml of methanol. The obtained solid was washed with methanol and dissolved in diethyl ether. Then it was extracted several times with water. The solid is precipitated with acetone, washed and dried under vacuum.

75 g of this solid was dissolved in 250 ml of trioctylamine and was heated at 120°C for one hour.

Then the solution was heated to 380°C for 30 minutes in an autoclave. This temperature was maintained for 4 hours. The resulting dispersion was slowly cooled to room temperature.

The particles were washed three times with a mixture of ethanol and water.

Then the particles suspended in 300 ml dibutylamino ether of diethylene glycol and aziraphale atmospheric oxygen. The suspension was heated at 300°C in an autoclave and maintained at this temperature for 24 hours.

These particles were oxidized as in example 1C, and then covered way, similar to cnym shown in example 1G.

Example 1G:

Particles of examples 1B-1F were collected by centrifugation at high centrifugal force and washed with ethanol. 500 mg of the washed product was weighed into the extraction cartridge (603 g, Whatman) and placed in the to conventional Soxhlet extractions. 200 ml of ethanol were placed in a alembic of to conventional Soxhlet extractions as extractant. The extractant was heated to boiling. Continuous extraction was carried out for 8 hours, which included approximately 16 cycles of extraction. During this process, an ethanol solution acquired a yellowish color. The extraction cartridge after was removed, and the powder was transferred into a unit Slinka and dried under vacuum for 1 hour.

0.5 g of a powder of nanoparticles from example 4 are suspended in 20 ml of 0.01 M HCl for dispersing particles after extraction. Then the nanoparticles were treated with ultrasound for 30 minutes. Then 0.5 g) was added solid sodium oleate.

of 3.3 ml of a dispersion of particles according to example 5 (0.97 mol/l Fe) and 2.14 ml of tetraethoxysilane was added to 120 ml of a mixture of water/ethanol (3:1) and 1.5% by weight of ammonium. In the process of adding the dispersion was stirred and then treated with ultrasound for six hours. The dispersion was purified by centrifugation and re-dispersion in water.

Example 2: Sponge

Placed in the wound device, impregn is consistent nanoparticles

Commercially available sponge Tabotamp® dipped in a suspension of the nanoparticles obtained in accordance with example 1, for 6 minutes. The process of dipping was repeated twice after drying. Alternatively, the suspension can be applied with a pipette. This process can be repeated several times until, until it reaches the desired degree of loading of the sponge.

Example 3: Medical cellulose

Medical cellulose coated nanoparticles

On a piece of a covering for a wound, a width of 3 cm and 6 cm in length, for example, SeaSorb of the company Coloplast composed of calcium alginate and carboxymethylcellulose sodium, five times sprayed approximately 1 ml of the suspension of the nanoparticles according to example 1 and was dried in air for approximately 20 minutes after each round of spraying.

Alternatively, the suspension can be applied with a pipette. This process can be repeated several times until, until it reaches the desired degree of loading of the coating for wounds.

Example 4: Medical pulp with drug

Medical cellulose, impregnated with nanoparticles and cytostatic

Commercially available medical pulp made from carboxymethylcellulose sodium, poly-N-vinylpyrrolidone and polyethylene oxide (5 cm2), for five minutes, dipped in a suspension of the nanoparticles obtained according to p is the iMER 1, which contained a solution of paclitaxel 0.3 mg/ml Medical product is ready to use after drying and sterilization.

Example 5: gel

Preparation of a gel according to the invention

4 g of a mixture of collagen type I and collagen type II was dissolved in a liter of 50 mm acetic acid solution. A solution of collagen was centrifuged at a speed of 9500 rpm and 4°C for 45 minutes. The supernatant decantation, was placed in a dialysis tube and were dialyzed against 25 liters of 1 M solution of acetic acid for two days, and then were dialyzed against water for an additional four days.

After this, the solution of collagen is concentrated in a dialysis tube to a concentration of 20 mg/ml (2% wt./vol.).

To obtain a gel, 10 ml collagen were incubated with 0.1 ml of 1 N NaOH and 1 ml of DMEM (modified Dulbecco Wednesday Needle 10H) at 37°C for one hour.

After this was added 1.5 g of lyophilized nanoparticles with a size distribution of 1-100 nm.

The gel was applied to the area of operations to the extent possible after surgical removal of a solid tumor of the small intestine.

Successful treatment with thermotherapy in an alternating magnetic field was shown when heated to the operating region to 53°C.

Example 6: Gel drug

0.1 g CIT what static means, temosolomida, was added to 10 g of the gel obtained according to example 5, and then well mixed.

The application of the gel was carried out as described in example 5.

Example 7: Sponge

2 g of globin powder was obtained as described in US 2007031474 A.

Sponge implant was obtained by lyophilization of 1% aqueous suspension of oxidized cellulose 1.5% by weight of the powder globin at pH values of 7.2. Oxidized cellulose can be used in the form of fibers and in the form of two - or three-dimensional structure.

Received spongy structure consisted of approximately 100 mg of oxidized cellulose and 40-200 mg globin and had a volume of approximately 10 cm3and a thickness of approximately 3 mm.

The spongy structure sterilized with ethylene oxide and Packed.

Example 8A: Particles with drug

Obtaining nanoparticles with attached mitomycin

First of all, synthesized conjugate of mitomycin and functionalized with aldehyde groups alkoxysilane (for example, triethoxysilylpropyl) in order to connect the cytotoxic agent mitomycin with nanoparticles of iron oxide, stabilized aminosilanes. Thus, the drug was added through education kinoway communication. When mixing this conjugate was added to the aqueous dispersion of the particles, Stabi is yserowanej aminosilanes, for example, from WO 97/38058 A. the mixture was added ethylene glycol, and water was removed by distillation. In the conjugate drugs and silane was added (are condensed) to the already present shell-based aminosilane. Purification was carried out by dialysis against water ultra pure. A detailed description of the reactions included in WO 2006108405 A2.

Example 8B:

Obtaining nanoparticles associated with doxorubicin via aydinbey bridge, was carried out as described in WO 2006108405 A2.

Example 8C:

Obtaining nanoparticles associated with doxorubicin via the nucleotide sequence was carried out as described in WO 2006108405 A2.

Example 9: Sponge

A sponge-like structure was obtained as described in example 7, where instead of the oxidized cellulose used a mixture of collagen type I, collagen type II and chitosan (25:25:50 percent by weight).

After that, the resulting sponge was impregnated with an aqueous suspension of nanoparticles, United with doxorubicin according to example 8B or 8C, and dried.

Instead of subsequent impregnation, the suspension according to example 7 can also be added to a suspension of nanoparticles according to examples 8A, 8B or 8C and liofilizirovanny together with other components.

Example 10: Medical cellulose

Medical cellulose chitosan-based, uronic acid and carboxymethylcysteine (4 cm2, approximately 20 mg) was placed layer in the Cup for the cultivation and dropwise inflicted on her aqueous suspension containing nanoparticles with mitomycin attached according to example 8A, up until the loading of cellulose has not reached 50 mg nanoparticles.

Example 11: the Gel nanoparticles

23.5 percent by weight of UN-hydrated lecithin, 20.0% by mass of propylene glycol, 10.0 percent by weight of ethanol, 2.5% by weight of sorbitol, of 0.05 M phosphate buffer (up to 100.0%) was stirred at room temperature for 16 hours.

The resulting gel was stirred with a suspension of nanoparticles of example 1 for 4 hours to obtain a gel with nanoparticles.

Example 12: film-Forming spray with nanoparticles

172 g of diethyl ether maleic acid (inlet 1), 98 g of maleic anhydride (inlet 2, the heating separating funnel), 200 g minimizebutton ether (inlet 3) and 12 g of tert-butyl of pereodichnost (inlet 4) were placed in the appropriate dimensional vessels. First 111 ml of inlet 1, 10 ml of the inlet 3 and 3 ml of intake 4 was applied in 2 l mixing vessel equipped with a stirrer, heating, reflux and prepared dispensers, as well as inlet and outlet for gas, and was heated to 60°C. the Residue from the inlet 1, the remainder of the inlet 3 and vpus the 2 additive was added in 3 hours, and the remainder of the inlet 4 for 4 hours at this temperature. Then stirred for a further 1 hour at 80°C. the Obtained colorless melt, high viscosity, which was mixed with 18 g of water at this temperature and was stirred for 1 hour. After cooling to 75°C, 480 g of ethanol additive was added within 15 minutes and was stirred for 1 hour at this temperature. After cooling to 25°C obtained transparent viscous polymer solution with a solids content of 48.1 percent by weight.

Thus obtained viscous solution of the polymer was stirred with a suspension of nanoparticles of example 1 for 2 hours to obtain a film-forming spray with nanoparticles.

Example 13: film-Forming spray with nanoparticles and drug

10 ml of the polymer solution, which was obtained according to example 12 was mixed with 100 mg carboplatin and 1000 mg of lyophilized nanoparticles according to example 1.

Example 14: the Treatment of tumors of the cervical, thoracic wall, ear, nose and throat

The carrier material impregnated with a solution of nanoparticles according to example 1A (2 M and 3 M)was applied to the bone. The bone was placed in therapeutic device and subjected to the influence of an alternating magnetic field. The temperature increase measured at the upper part of the bone was determined at a constant temperature environment is Reda, how it was possible. This experiment shows that cervical tumors, chest wall, ear, nose and throat can be treated in an alternating magnetic field through the coated nanoparticles carriers that use bone-in or close to the bone.

Materials

Equipment:

- Therapeutic device MFH-12TS,

- Recirculation cooler (Julabo; FC600S) pipe connection

Clamp (for rats) with pipe connection

- Polytec Luxtron (model: LAB. KIT) with two sensors measuring temperature,

Device for measuring the field strength (with sensor),

- Water baths (37°C),

- Calibration sensor (calibrated to 11/09)

Material:

- 2 M or 3 M suspension of the nanoparticles according to example 1A: each was treated with ultrasound for 15 minutes

- Material media:

1: powder SPONGOSTAN (1 g, absorbable gelatin powder, styptic; Johnson & Johnson)

2: SPONGOSTAN Special (CC,1 cm, absorbable hemostatic gelatin sponge; Johnson & Johnson)

3: Gelita tampon (CC cm, sponge, made of hardened gelatin, obtained from pigs, bioreserve Antihemorrhagics means; B. Braun Melsungen AG)

4: Lyostypt® (3-5 cm, moisture-proof wrap of natural collagen derived from cows, localized bleeding, absorbable; B. Bran Melsungen AG)

- Bones ("pork ribs"),

- Tweezers,

- Clay mass,

Medical plaster (Durapore™; 3 M; 2.5 cm H 9.14 m)

- Cold/warm compress (Pharma-Depot GmbH; CI cm)

- A syringe for injection of tuberculin (Omnifix®-F; Braun; 0.01 ml/1 ml),

- disposable needle for injection (Sterican®; Braun; 27G11/2”, 0,CH mm)

- With a Vernier caliper (DialMax. Calibrated to 08/09; MS150-4/Atl)

The scalpel blade (No. 11),

- Cups,

- Camera

Reagents:

- Hydrogen peroxide (H2O2; 30%),

- Alginate (sodium salt of alginic acid),

Experiment

Suitable latch was brought to 55°C using a recirculating chiller. Conduct leak testing.

1. A retainer disposed in the hole in therapeutic device.

2. Pre-heated (37°C) cold/warm compress placed in the "head" of the latch (decreased volume of air in the device and slightly "smoothed out" temperature fluctuations).

3. Bone:

- bone was separated from pork ribs and quickly freed from meat,

placed in a glass of H2O2,

then the bone "purified" with a scalpel,

is the bone shared with saws convenient for experiment part.

4. Field strength:

the measure was aimed at measuring the field strength,

measuring head for change is abrazandote field was placed in that position in the retainer, which later made measurements, clay served the function of auxiliary labels

- analyzed following 3 field strength (appropriate for clinical use): 3,0 kA/m, and 3.5 kA/m to 4.0 kA/m,

with these measurements we obtained the following values:

% field strength is a tuning device that corresponds to a given field strength in kA/m

5. The temperature of the air in the inner space and the temperature of the lower part of the applicator defined in the lock.

Example 14A: Lyostypt®

Particles: Suspension of the nanoparticles according to example 1A (0.5 ml, 2 M).

Media: Lyostypt®, size: (19,C,C,4) mm

Bone: size: 44,C,C,9) mm

Measurements of bone fragment [linear dimensions: (44,C,C,9) mm] and cut off a portion of the medium size [size dimensions: (19,C,C,4) mm]. The carrier was placed on the bone and soaked particles (0.5 ml, 2 M according to example 1A). Loaded bone was placed in the applicator [sensor 1 (red): perpendicular on top of the impregnated carrier; sensor 2 (blue): the original value ("empty" bone)], and determine the values for media:

The sensor is located between the carrier and bone.

MP↑: Alternating magnetic field is included.

MP↓: Alternating magnetic field is switched off.

In tilator↑: Fan is enabled.

Fan↓: the Fan is off.

Sensor 1↓: Sensor is not functioning.

Example 14B: SPONGOSTAN

Particles: Suspension of the nanoparticles according to example 1A (1.5 ml, 2 M).

Media: powder Spongostan, weight: 0,3,

Bone: size: 44,C,C,9) mm

1.08 g of the powder (carrier) was soaked in 1.5 ml particles (2 M according to example 1A) and well stirred, and part number m=0,46 g impregnated carrier was applied to the bone.

Measuring head for measuring the field strength was placed in position in the clamp, which later made measurements; clay served the function of auxiliary labels. Analyzed the following 3 field strength (appropriate for clinical use): 3,0 kA/m, and 3.5 kA/m to 4.0 kA/m

Example 14C: SPONGOSTAN

Particles: Suspension of the nanoparticles according to example 1A (1.6 ml, 2 M)

Carrier: the Carrier is impregnated according to example 14B, weight: approximately 0.8,

Bone: size: 44,C,C,9) mm

The remaining amount of approximately 0.8 grams of the impregnated carrier from example 14B was mixed with 1.6 ml of particles (2 M according to example 1A) and applied to a bone, purified according to example 14. The sensor was again placed between the bone and the media. Again measured following 3 field strength: 3,0 kA/m, and 3.5 kA/m to 4.0 kA/m

Example 14D: SPONGOSTAN Special

Particles is: Suspension of the nanoparticles according to example 1A (1.0 ml, 2 M)

Carrier: the Carrier is impregnated according to example 14B, size: (10,C,C,0) mm

Bone: size: 44,C,C,9) mm

The media should be soaked in a suspension of particles (15 minutes) for medium to absorb particles (1.0 ml, 2 M according to example 1A). 1 ml of the suspension of particles was injected into a carrier inside the package [m=0,00]; ashlar absorbs high and is applied to the bone.

The measurements were carried out as described in example 14A.

Example 14E: Gelita tampon

Particles: Suspension of the nanoparticles according to example 1A (1.0 ml, 2 M).

Media: Gelita tampon, size: (CC), see

Bone: size: 44,C,C,9) mm

The media should be soaked in a suspension of particles (15 minutes) to ensure that the media has absorbed a suspension of nanoparticles (1.0 ml, 2 M according to example 1a). 1 ml of the suspension of particles was injected into the packing media of Gelita tampon; cube absorbs maximum (Gelita tampon [m=0,00] a suspension of nanoparticles: m=0.45 g) and placed on the bone.

1. The use of solid medical product, the heating under the action of alternating magnetic field for thermal therapeutic follow-up treatment after surgical removal of tumors and cancerous ulcers, where the medical device is a surgical implant is provided in the form of a physiologically acceptable tissue, hubc is or film, and where in the medical product contains magnetic particles, which will form the heat when excited by an alternating magnetic field and, thus, will heat the medical product.

2. The use of the medical product according to claim 1, where the particles are still embedded or attached to the medical product.

3. The use of the medical product according to claim 1, where the particles will remain in the medical product will not be released by diffusion, and will be released only if biorazlagaemykh medical products because of the destruction process.

4. The use of the medical product according to claim 1, where the medical device is deformable and can adapt to the contours of the surface tissue, or organ, or the operating area after surgical removal of the tumor.

5. The use of the medical product according to claim 1, where the medical product is biorazlagaemykh.

6. The use of the medical product according to claim 1 where the particles are microparticles or nanoparticles.

7. The use of the medical product according to claim 1 where the particles are paramagnetic or superparamagnetic particles.

8. The use of the medical product according to claim 1, where the medical product impregnated, coated or impregnated with magnetic particles.

9. The use of the medical product according to claim 1, where health is pool cue product can be bioassaying within one to twelve months.

10. The use of the medical product according to claim 1, where the medical product is physiologically acceptable and falls into a physiologically acceptable components.

11. The use of the medical product according to claim 1, where the medical product is flexible and does not consist of metal or metal alloy, and where the medical product is not available in the form of an aqueous solution of particles.

12. The use of the medical product according to claim 5, where birthdaaay medical product releases magnetic particles and/or delivers them into the surrounding tumor tissue or tumor cells.

13. The use of the medical product according to claim 1, where the magnetic particles are provided in a concentration of from 10 to 100 milligrams per square centimeter of the surface of the medical product.

14. The use of the medical product according to claim 1, where the magnetic particles are provided in a concentration of from 100 micrograms to 2 grams per gram of the medical product.

15. The use of the medical product according to claim 1, which additionally contains at least one therapeutically effective agent selected from the group consisting of antiproliferative, protivoerozionnye, antiangiogenic, antithrombine, anti-inflammatory, antiphlogistic, cytostatic, cytotoxic, anticoagulant, antibacterial, antiviral and/or the antifungal drugs.

16. The use of the medical product according to clause 15, where at least one therapeutically active substance selected from the group consisting of actinomycin S, aminoglutethimide, amsacrine, anastrozole, antagonists of purine or pyrimidine bases, anthracyclin, aromatase inhibitors, asparaginase, antiestrogens, bexarotene, bleomycin, bullerin, busulfan, derivatives camptothecin, capecitabine, carboplatin, carmustine, chlorambucil, cisplatin, cladribine, cyclophosphamide, cytarabine, cytosine arabinoside, alkylating cytostatic tools, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, epirubicin, estramustine, etoposide, exemestane, fludarabine, fluorouracil, antagonists folic acid, formestane, gemcitabine, glucocorticoids, goserelin, hormones and hormone antagonists, Cosmegen, hydroxyurea, idarubitsin, ifosfamide, imatinib, irinotecan, letrozole, leiprorelina, lomustin, melphalan, mercaptopurine, methotrexate, miltefosine, mitomycin, inhibitors of mitosis, mitoxantrone, nimustine, oxaliplatin, paclitaxel, pentostatin, procarbazine, tamoxifen, temozolomide, teniposide, testolactone, thiotepa, tioguanin, topoisomerase inhibitors, topotecan, treosulfan, tretinoin, triptorelin, trofosfamide, vinblastine, vincristine, vindesine, vinorelbine, antibiotics with cytostatic activity.

17. Prima is giving medical product according to item 15, where at least one drug is associated with a particle with adhesion, ionic, and covalent bonds or through a linker.

18. The use of the medical product according to clause 15, where the separation of at least one drug from the carrier is initiated by an alternating magnetic field.

19. The use of the medical product according to claim 1, where the medical device is selected from the group of the following materials:
polyacrylic acid, polyacrylate, polymethylmethacrylate, polybutylmethacrylate, polyisobutylene, polyacrylamide, polyacrylonitrile, polyamide, polyetherimide, polyethylenimine, polyimide, polycarbonate, polycarbonate, polyvinylacetal, polivinilhlorid, polyvinylidenechloride, simple, polyvinyl ether, polyvinyl aromatic compounds, complex, polyvinyl ether, polyvinylpyrrolidone, Polyoxymethylene, polyethylene, polypropylene, polytetrafluoroethylene, polyurethane, polyolefin elastomer, polyisobutylene, EPDM resins, porcelian, carboxymethylchitosan, polyethylene terephthalate, polyvalent, carboxymethylcellulose, cellulose, rayon, triacetate viscose, cellulose nitrate, cellulose acetate, hydroxyethyl cellulose, cellulose butyrate, acetate-butyrate cellulose, copolymer ethylvinylacetate, polysulfone, polyethersulfone, epoxy resin, ABS resin, EPDM resin, silicone prepolymer, forces the con, polysiloxane, polyvinyl halogen, a simple ester of cellulose, triacetate cellulose, chitosan, derivatives of chitosan, the polymerized oil, polivalente, poly-ε-decalactone, polylactide, polyglycolide, copolymers of polylactide and polyglycolide, poly-ε-caprolacton, polyhydroxyalkane acid, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxybutyrate-co-valerate, poly(1,4-dioxane-2,3-dione), poly(1,3-dioxane-2-one), poly-para-dioxanone, polyanhydrides, anhydride polimolekuly acid, polyhydroxybutyrate, polycyanoacrylate, polycaprolactone, poly-β-maleic acid, polycaprolactone, multiblock polymers made from oligosaprogenic and oligodeoxynucleotide, polyetherether-multiblock copolymers derived from PEG and poly(utilityrelated), politisation, trimethylarsine polyglycolic acid, polycaprolactone-glycolide, poly(y-Atrpatakan), poly(DTH-aminocarbonyl), poly(DTE-co-DT-carbonate), poly(bisphenol a-aminocarbonyl), polychaetes, trimethylarsine polyglycolic acid, polytrimethylene, polyaminocarboxylic, polyvinyl alcohols, polyetherimide, glycosidation polyesters, polyphosphatase, polyphosphazene, poly[p-carboxyphenoxy)propane], polyhydroxyvalerate acid, polyethylene oxide-propylene oxide, soft polyurethanes, polyurethanes with statementinvalid in hull, esters of polyethers, polyethylene oxide, polyalkylacrylate, polyarteritis, carrageenan, starch, collagen, polymers albumen, polyaminoamide, synthetic polyaminoamide, Zein, modified Zein, polyhydroxyalkanoates, pectic acid, actin acid, fibrin, modified fibrin, casein, modified casein, carboxymethylchitin, albumin, hyaluronic acid, heparan sulfate, heparin, chondroitin sulfate, dextran, cyclodextrin, copolymers derived from PEG and polypropylenglycol, Arabian gum, guar or other Kameda-resin, gelatin, collagen, collagen-n-hydroxysuccinimide, lipids, lipids, polymerized oils and their modifications, copolymers and mixtures of the aforementioned substances.

20. The use of the medical product according to claim 1, where the cancer, tumor or proliferative disease selected from the group comprising: adenocarcinoma, choroidal melanoma, acute leukemia, acoustic neuroma, ampullary carcinoma, anal carcinoma, astrocytoma, basal cell carcinoma, pancreatic carcinoma, a tumor of the connective tissue, bladder cancer, bronchial carcinoma, non-small cell bronchial carcinoma, breast cancer, Burkitt's lymphoma, carcinoma of the body of the uterus, carcinoma of unknown primary localization of tumor, colon cancer, cancer of the thin Kish and, tumors of the small intestine, ovarian cancer, endometrial carcinoma, ependymoma, epithelial cancers, Ewing sarcoma, tumors of the gastrointestinal tract, cancer of the gallbladder, biliary carcinoma, uterine cancer, cervical cancer, glioblastomas, gynecologic tumors, ENT tumors, tumors of the hematopoietic system, cancer of the urethra, skin cancer, brain tumors (gliomas), metastases in the brain, cancer of the testis, pituitary tumor, carcinoids, Kaposi's sarcoma, cancer of the larynx, germinoma, bone cancer, colorectal carcinoma, head and neck tumors (tumors in the neck, nose and ear), carcinoma of the colon, craniopharyngioma, cancer of the mouth and lips, liver cancer, liver metastases, tumor century, lung cancer, cancer of the lymph nodes (jackinsky/nehodgkinski), lymphomas, stomach cancer, malignant melanoma, malignant neoplasia, malignoma gastrointestinal tract, carcinoma, breast cancer, colorectal cancer, Protocol, melanoma, meningiomas, Hodgkin's disease, mushroom avium, cancer of the nose, neurinoma, neuroblastoma, kidney cancer, pochernkletocny carcinoma, non-Hodgkin lymphoma, oligodendroglioma, carcinoma of the esophagus, carcinoma and osteolytic osteoplastic carcinoma, osteosarcoma, carcinoma of the ovary, pancreatic cancer, penile cancer, squamous cell carcinoma of the head and neck, cancer of predstatelnoy gland, cancer of the pharynx, cancer of the rectum, retinoblastoma, cancer of the vagina, cancer of the thyroid gland, disease of Sneberger, esophageal cancer, spinaloga, T-cell lymphoma (mushroom mycosis fungoides), thymoma, tubular carcinoma, eye tumors, cancer of the urethra, prostate tumor, urothelial carcinoma, vulvar cancer, the lesion mastoid, soft tissue tumors, soft tissue sarcoma, Wilms ' tumor, cervical carcinoma and tongue cancer.

21. The use of the medical product according to any one of claims 1 to 20, where thermal therapeutic treatment after surgical removal of tumors and cancerous ulcers is to prevent recurrence.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: initial composition, consisting of the following components, wt %, is prepared: C-60 or C-70 fullerenes - 30-50; heat-conducting component - 10-60; binding agent - the remaining part. The heat-conducting component is selected from the group: wurtzide boron nitride, cubic boron nitride, diamond or their mixtures. The binding agent is selected from elements of the group IVa of the Periodic system or their alloy with copper. The heat-conducting element can be preliminarily covered with the binding agent. The obtained composition is subjected to impact of static pressure from 8 to 13 GPa with heating to 900-2000°C for not less than 20 seconds. A superhard composite material with heat-conductivity to 330 W/m·K, a ratio of microhardness to an elasticity coefficient 0.12 is obtained.

EFFECT: high wear resistance of the material.

2 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: plasmochemical reactions are initiated by pulse microwave discharge, influencing initial reagents, as the latter used is a mixture of titanium and boron powders in a nitrogen atmosphere, as initial reagents used is a powder of amorphous boron with a particle size of 1 mcm-100 mcm and a titanium powder with a particle size of 1 mcm - 100 mcm, the used microwave discharge has the power from 50 kW to 500 kW and a pulse duration from 100·10-6 s to 100·10-3 s, the working pressure of nitrogen constitutes from 0.1 to 1 atmosphere.

EFFECT: plasmochemical reactions result in co-formation of two target products - nanodisperse powders of titanium diboride and boron nitride of various shapes and sizes.

2 cl, 8 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining secondary amines, in particular to a novel method of imine hydration, which makes it possible to obtain secondary amines of the general formula where R1=C6H5: R2=cyclo-C6H11, cyclo-C5H9, -CH2C6H5, (CH3)2CHCH2(CH3)CH-; R1=-CH2C6H5: R2=cyclo-C6H11, R1= -C6H4OCH3: R2=cyclo-C5H9. Compounds are widely applied in the organic synthesis as semi-products. The method lies in hydration of imines by gaseous hydrogen in the presence of a catalyst. As imines, used are benzalaniline, benzalcyclohexylimine, cyclohexylidene phenylimine, 4-methylpent-2-ylidene phenylimine, cyclopentylidene-4-methoxyphenylimine, cyclopentylidene phenylimine, and as the catalyst, used are nickel nanoparticles, obtained in situ by reduction of nickel (II) chloride with sodium borohydride in a ratio 1:2, respectively. The process is carried out under atmospheric pressure of hydrogen in a medium of isopropanol or tert-butanol at a temperature of 60-70°C for 8-12 hours.

EFFECT: simplification of the method of obtaining compounds of the claimed structural formula.

7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining mineral silicic water (MSW), intended for application for medical purposes. The method of obtaining includes hydrolysis of tetraethoxysilane in the TEOS mixture: ethanol: water, acidified by HCl. Nanosol is obtained at a temperature of 55-65°C for 1.5 hours with evaporation of ethanol to the volume reduction by 1/3, then, dilution of the obtained nanosol with a physiological solution NaCl is carried out in 2 steps with equal portions of the physiological solution, preliminarily heated to 40-50 in a ratio of volumes of the initial nanosol: physiological solution 1:7 with 15-minute interval. After each dilution a temperature of the solution is kept in the range of 55-65°C.

EFFECT: increase of the compound application efficiency.

1 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to compositions and polymeric materials for biomedical use, comprising silver nanoparticles (0.0005-0.02 wt %) stabilised by amphiphilic copolymers of maleic acid (0.0008-0.05 wt %), low molecular weight organic amines (0.0002-0.04 wt %) and water. In addition, the said composition may additionally comprise the polymeric structure-forming agent.

EFFECT: introduction to the composition of the polymer structure-forming agent enables to obtain the macroporous structured hydrogel materials having prolonged bactericidal and antifungal action.

3 cl, 2 tbl, 9 ex

FIELD: metallurgy.

SUBSTANCE: proposed method comprises mixing of cryolite and the mix of nano-dispersed powder of oxides of niobium, titanium, zirconium, tantalum with mixing agent and further compaction of said mix. Cross-linking agent represents aqueous solution of glyoxal (40%). Note here that obtained pasty mix is compacted by screw pelletiser to cylindrical pellets to be dried for 3 hours at 80°C at the following ratio of components, in wt %: cryolite - 79-81, niobium oxide - 3-4, titanium oxide - 3-4, zirconium oxide - 4-3, tantalum oxide - 1-2, aqueous solution of glyoxal (40%) - 5-7.

EFFECT: higher physical and mechanical properties, decreased amount of cast rejects.

2 ex, 1 tbl, 1 dwg

FIELD: electricity.

SUBSTANCE: invention refers to electrical engineering, particularly to methods of conductive layer formation used in wide range of technics, including electronics or electrical equipment, and can be applied to form conductive links in microcircuits. Method of conductive layer formation on carbon nanotube base involves application of suspension of carbon nanotubes and carboxymethyl cellulose in water onto substrate, with the following component ratio, wt %: carboxymethyl cellulose 1-10, carbon nanotubes 1-10, drying at 20 to 150°C, pyrolysis at temperature over 250°C.

EFFECT: enhanced electric conductivity of layers formed.

4 cl, 1 tbl

FIELD: process engineering.

SUBSTANCE: invention relates to metallurgy. Parts are processed by quenching at 920-940°C, subjected to negative hardening with heating to 600-650°C for 2-10 hours and removal of decarbonised ply. Then, ion-plasma nitration is performed at 500-570°C, cathode voltage of 300-320 V, and current density of 0.20-0.23 mA/cm2. Ammonia with dissociation of 0-80% is used as a gas medium. Ammonia flow rate makes up to 20 dm3/h. Pressure in the chamber at cathode spraying makes 1.3-1.35 Pa and, at saturation, 5-8 GPa. This nitration is performed at cyclic temperature and ammonia dissociation variation. Note here that at the first half of described cycle temperature makes 570°C at maximum nitrogen potential. During second half, temperature decreases to 500°C while nitrogen potential is decreased owing to increase in ammonia dissociation to 40-80%. Note also that the number of said cycles should make at least 10. Nitrated part has surface ply containing diffusion ply with α-phase with nanosized incoherent alloying element nitrides that makes soft matrix. Besides, it has surface ply with hard inclusions composed by nanoparticles of ε-phase iron nitrides formed by local phase recrystallisation of iron nitride lattices. This results from cyclic temperature and ammonia dissociation variation.

EFFECT: higher wear resistance, longer life of kinetic friction parts made from above described material.

2 cl, 1 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: method of forming epitaxial copper nanostructures on the surface of semiconductor substrates includes formation of a monoatomic layer of copper silicide Cu2Si on a preliminarily prepared atomically clean surface of Si(111)7×7 at a temperature of 550-600°C under conditions of superhigh vacuum, further precipitation of copper on it at a temperature of 500-550°C with efficient copper thickness from 0.4 to 2.5 nm. With efficient copper thickness from 0.4 to 0.8 nm islands of epitaxial copper nanostructures of a triangular and polygonal shape are formed, and if copper thickness is in the range from 0.8 to 2.5 nm, in addition to copper islands of the triangular and polygonal shapes ideally even copper wires are formed. The formed epitaxial copper nanostructures possess faceting, are oriented along crystallographic directions <110>Cu||<112>Si.

EFFECT: invention provides a possibility of controlled formation of epitaxial copper nanostructures with a specified shape and dimensions on the surface of semiconductor substrates.

2 cl, 6 dwg

FIELD: nanotechnology.

SUBSTANCE: invention relates to nanotechnology equipment and designed for closed cycle of production and measurement of new products of nanoelectronics. The nanotechnological complex comprises a robot-distributor with the ability of axial rotation, coupled with the chamber of loading samples and the module of local influence, as well as the measuring module comprising a scanning probe microscope, an analytical chamber, a monochromator and an x-ray source. The measuring module and the analytical chamber are coupled with the robot-dispenser, the monochromator is coupled with the analytical chamber, and the x-ray source - with the monochromator. The module of local influence comprises a module of focused ion beams and the first scanning electron microscope.

EFFECT: enhanced functional capabilities of the nanotechnological complex.

6 cl, 6 dwg

FIELD: chemistry.

SUBSTANCE: memristor devices are nonvolatile memory devices and can be used to design computer systems based on an artificial neural network architecture. The present device consists of an active layer situated between two current-conducting layers with which it is in electrical contact. The active layer has a resistive switching property and is a double-layer oxide structure HfAlxOy/HfO2. The HfAlxOy layer has high solubility and high equilibrium concentration of oxygen vacancies, and HfO2 is a layer with low solubility of vacancies. The current-conducting layers are made of titanium nitride or tungsten nitride. A super-thin layer of ruthenium oxide with thickness of not less than 0.5 nm is deposited on the HfO2/TiN boundary surface.

EFFECT: high stability of modes of switching resistance to a low- and high-ohmic state, low switching voltage, high technological compatibility with existing silicon-based microcircuit manufacturing processes.

3 cl, 2 dwg

FIELD: biotechnology.

SUBSTANCE: as the present invention the method for production of polyfunctional magnetic nanoparticles based on bacterial magnetosomes and the hybrid protein MGG is provided, which enables to obtain magnetosomes binding immunoglobulins of the IgG class on the fragment Fc. The result is achieved in that in the lipid membrane of bacterial magnetosomes by ultrasonic treatment the hybrid protein MGG is integrated, which amino acid sequence comprises the transmembrane domain and the binding area of immunoglobulins.

EFFECT: obtaining polyfunctional magnetic sorbent bearing on the surface of magnetic nanoparticles of ligand, that enable to connect to the particles the immunoglobulins of IgG class.

4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining mineral silicic water (MSW), intended for application for medical purposes. The method of obtaining includes hydrolysis of tetraethoxysilane in the TEOS mixture: ethanol: water, acidified by HCl. Nanosol is obtained at a temperature of 55-65°C for 1.5 hours with evaporation of ethanol to the volume reduction by 1/3, then, dilution of the obtained nanosol with a physiological solution NaCl is carried out in 2 steps with equal portions of the physiological solution, preliminarily heated to 40-50 in a ratio of volumes of the initial nanosol: physiological solution 1:7 with 15-minute interval. After each dilution a temperature of the solution is kept in the range of 55-65°C.

EFFECT: increase of the compound application efficiency.

1 ex

FIELD: medicine.

SUBSTANCE: what is described is a method for preparing a nanostructured calcium-phosphate coating for medical implants consisting in sputtering a target of stoichiometric hydroxyapatite Ca10(PO4)6(OH)2 in high-frequency magnetron discharge plasma in the argon environment under pressure of 0.1-1 Pa and target power density of 0.1-1 W/cm2 for 15-180 min at a distance from the target to a carrier within the range of 40 to 50 cm, wherein the nanostructure is formed after a coating procedure in the process of the controlled thermal annealing at a temperature of 700-750°C for 15-30 min.

EFFECT: higher post-coating effectiveness of the production process.

4 dwg

FIELD: biotechnology.

SUBSTANCE: invention relates to compositions and polymeric materials for biomedical use, comprising silver nanoparticles (0.0005-0.02 wt %) stabilised by amphiphilic copolymers of maleic acid (0.0008-0.05 wt %), low molecular weight organic amines (0.0002-0.04 wt %) and water. In addition, the said composition may additionally comprise the polymeric structure-forming agent.

EFFECT: introduction to the composition of the polymer structure-forming agent enables to obtain the macroporous structured hydrogel materials having prolonged bactericidal and antifungal action.

3 cl, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for the delivery of a pharmaceutical agent to a focus of a disease. The composition contains a water-insoluble pharmaceutical agent which is paclitaxel, a pharmaceutically acceptable carrier which is albumin, preferentially human serum albumin. The relation (wt/wt) of albumin to paclitaxel makes 9:1. The pharmaceutical composition contains nanoparticles containing paclitaxel and albumin wherein the nanoparticles have a size of less than 200 nm.

EFFECT: administering the pharmaceutical composition according to the invention provides enhanced characteristics of the delivery of paclitaxel to the site of the disease and reduced adverse side effects.

24 cl, 5 tbl, 51 ex

FIELD: medicine.

SUBSTANCE: what is described is an umbrella device (occluder) with a modified coating layer for the left atrial appendage occlusion. The umbrella device (occluder) with the modified coating layer is made from a titanium nickelide alloy. It has the coating modified layer having a thickness of 80-95 nm which consists of at least two sub-layers: an external sub-layer having a thickness of 20-25 nm contains oxygen, carbon, silicone and titanium in the following ratio, at %: oxygen 25-65, carbon 1-5, silicone 1-10, titanium - the rest; an intermediate sub-layer having a thickness of 60-70 nm contains oxygen, carbon, silicone, titanium and nickel in the following ratio, at %: oxygen 5-30, carbon 1-5, silicone 10-30, nickel 1-50, titanium - the rest, with silicone reaching its maximum concentration at a depth of 30-35 nm from the surface. The modified coating layer of the umbrella device (occluder) has no evident interface of the sub-layers specific for a deposited layer.

EFFECT: umbrella device with the modified coating layer possesses biocompatibility, corrosive resistance and no toxicity.

9 cl, 2 dwg

FIELD: metallurgy.

SUBSTANCE: initial components represent SiO2 or titaniferous magnetite and SiO2 to be mixed with carbonate Li(Li2CO3) at the ratio of 55-70 mol. % initial components, Li2CO3 and FeCO3 making the rest in equal amounts of cathode materials LixFeyMzSiO4/C. Then, powder is fused at 1180±5°C. After cooling, obtained alloy is ground to introduce therein, as high-molecular compound, polymethyl methacrylate or soot in amount of 2-5% of alloy. Then, thermal treatment is performed in cycling mode. For this it is heated to ≥600°C and held for 55-65 minutes. Now, it is cooled to room temperature in 5-10 cycles along with powder surface modification by carbon at heating.

EFFECT: storage battery higher discharge capacity.

5 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: membrane is made of a tetrafluoroethylene copolymer with functional perfluorinated comonomers of the general structural formula: where R: (D), (E), (K), M-H, Li, K, Na; a=24.75-18.38 mol.%; b=78.62-81.12 mol.%; c=5.0-0.5 mol.%; and is from 10 mcm and higher thick, density is 1.93-2.10 g/cm3, mechanical strength is 16-22 MPa and a coefficient of gas permeability by hydrogen (K) is 1-3.7×10-16 m3m m-2Pa-1s-1 at 20-90°C. A method of obtaining consists in combination of a porous polytetrafluoroethylene film with a perfluorosulphocationite polymer in a medium of an organic or a water-organic solvent in the presence of a modifier. The modifier is represented by hydrocarbon polymers, fluoropolymers, perfluoropolymers or their mixtures, inorganic compounds or their mixtures.

EFFECT: high drops of pressure, high current density and efficiency of an electrolysis cell exploitation.

13 cl, 3 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: asphalt-concrete mixture containing oil viscous bitumen, a filling agent, sand with fraction to 5 mm, crushed stone and an additive contains as crushed stone crushed granite with fraction 5-15 mm, as sand - sweepings of rock crushing, as the filling agent - sludge of HES water preparation and as the additive - a homogeneous short-fibre cellulose fibre and an organomineral modifier, containing sludge of HES water preparation, Portland cement, a polymer additive Butonal NS 198 and sodium pyrophosphate, with the following component ratio, wt %: oil viscous bitumen 6.3-6.9, crushed granite with fraction 5-15 mm 62.8-67.5, sweepings of rock crushing with fraction 0-5 mm 13.5-17.6, homogeneous short-fibre cellulose fibre 0.2, filling agent - sludge of HES water preparation 12.47-12.48, sludge of HES water preparation 0.0158-0.0238, Portland cement 0.0016-0.00235, polymer additive Butonal NS 198 0.0024-0.00357, sodium pyrophosphate 0.0002-0.00028.

EFFECT: increased water resistance of asphalt-concrete mixtures.

2 tbl

FIELD: medicine.

SUBSTANCE: method involves teletherapy combined with a local electromagnetic hyperthermia, chemotherapy with cisplatin and bleomycin, metronidazole as an ingredient of a composite mixture introduced through rectum. Teletherapy is conducted with using a continuous course of 3D and IMRT planning with photons 6-18 MeV covering the tumour and regional metastases in a single basic dose of 1.6 to 1.8 Gy daily 5 times a week, 27-30 fractions, in a total radiation dose of 48.0-48.6 Gy. At the same time, the tumour is exposed to teletherapy with using a simultaneous integrated boost in a single basic dose of 2.0 to 2.2 Gy, 27-30 fractions, in a total radiation dose of 59.4-60.0 Gy.

EFFECT: method enables reducing a radiation exposure, a teletherapeutic dose on the surrounding critical structure, saving the time and conducting a fewer sessions of teletherapy, ensuring lower intensity and the number of toxic reactions, the total length of treatment, eliminating early recurrences.

2 ex

Up!