Heat-emitting biocompatible ceramic materials
SUBSTANCE: ingredients are hardened in situ to produce solid biocompatible material capable of left in organism for a long time.
EFFECT: enhanced effectiveness in recovering mechanical strength of skeleton after cancer diseases; reduced risk of complications.
27 cl, 1 dwg
The invention relates to biocompatible ceramic compositions which, before curing possess a high degree of formemost or pressuemosti and ineterest and which harden or otverzhdajutsja in situ, generating elevated temperatures, the levels of which can be controlled. Compositions according to the present invention and they generate higher temperatures can be used, for example, for therapeutic purposes in vivo, as for example, for the treatment of tumors, the treatment of pain, treatment of vessels etc.
Prerequisites to the creation of inventions
Malignant tumors are traditionally treated by any of three methods: surgery, radiation therapy or chemotherapy. Often requires a combination of these three methods. The surgical method can be removed larger tumors in the appropriate places. However, a surgical method is often insufficient due to residual malignant tissue and paired tumors. Radiation therapy is used for smaller tumors, especially in hard to reach places. When using radiation therapy may require surgical intervention. Chemotherapy suffers from disadvantages associated with the occurrence of other side effects, including necrotic effects on non-cancerous cells.
Therapeu the practical technique studied in some areas of surgery, is the heat generation in vivo in certain places of the body and the use of this heat for therapeutic purposes, such as for the treatment of cancer cells. Local heating can be achieved in different ways, for example via a catheter equipped with elements that generates heat due to electrical resistance, which can be controlled in the desired locations through the vascular system.
An alternative way to achieve heating in vivo is the use of small volumes of slurries or pastes of the fuel material in the desired locations, for example by injection needles. The material injected into the body, cures due to exothermic chemical reactions and thereby generates the desired temperature. With increasing temperature there is a local therapeutic effects. In the ideal case, after completion of the reaction utverjdenie substance should form a biocompatible solid material that can remain in the body for long periods of time without any negative effects on health. At present, they are only slightly therapies using fuel materials; fuel material is a bone cement based on PMMA (polymethylmethacrylate), despite from OUTSTA he biocompatibility.
Therapy of malignant cancer tumors and metastases, myeloma, various cysts and so on, with the involvement of local application of fuel materials in vivo, is used to some extent, although it is still rarely used treatment method. This method is in local thermal necrosis, or limiting the supply or blood flow or oxygenation of tumors or cells.
The use of injectable fuel materials for cancer treatment is particularly suitable in respect of tumors in the skeleton. This method may include direct injection of cement, destroy cells, or, alternatively, removal of the tumor by surgery followed by filling the remaining cavity material curable in situ. The first method provides at least two advantages. One of them is that elevated temperatures during curing and reduce the activity of the remaining malignant tissue or kill her. Another result is that the cement restores the mechanical properties of the skeleton and, therefore, reduces the risk of fractures due to weak bones.
In addition, injectable pastes used in combination with radiation therapy, for example, when the vertebrae of the vertebral column is initially filled with bone cement based on PMMA, injecor the subject in trabecular inner portion through the feeding legs to provide mechanical strength, and after that perform radiation therapy of the same vertebra.
Similarly injectable paste is used to treat destroyed osteoporotic vertebrae. Filling destroyed vertebral bone cement reduces pain, you can restore the dimensions of the vertebrae. In this case, the heat, in addition to the mechanical stabilization of the vertebrae, reduces the pain in the spine.
Locally released heat can be used for local destruction of the nerves to reduce pain, disorders of the blood vessels and to initiate local action of drugs.
To date, there is no biocompatible cement industrial production, specially developed for therapeutic purposes for therapy by heat. Use only standard bone cement based on polymethylmethacrylate (PMMA). This material allows to obtain a sufficient temperature, but it does not provide sufficient biocompatibility. However, due to the lack of better alternatives, the bone cement based on PMMA is common in surgery.
The shortcomings of existing materials
Modern bone cements based on PMMA designed for orthopedic purposes, mainly for fixing implants bedri of the knee joint in the skeleton. Despite the many disadvantages of these materials are now common in orthopedics after several decades of their use. However, the search continues for a better, more biocompatible bone cement.
Bone cements based on PMMA are not biocompatible materials. They have a clear toxic effects caused by leakage components, such as solvent and unpolymerized monomer. These leaks are particularly large in low-viscosity compositions (injectable) with a high content of solvents and monomers.
In the ideal case of cell therapy with fuel pastes volume of the cured material remaining after treatment, will cause minimum adverse reactions in tissues. It requires a high degree of chemical resistance and biocompatibility.
In the treatment of bone cancer cured material remaining in the skeleton, in the ideal case has mechanical properties similar to the mechanical properties of natural bone. In particular, insufficient strength or rigidity unfavorable for load-bearing parts of the skeleton. Orthopedic cement preferably will have a modulus of elasticity of about 10-20 GPA. Modern bone cements based on PMMA have an elastic modulus of about 3 GPA.
Modern bone cements on cos the ve PMMA utverjdayut heat in amounts considered excessive for normal orthopedic applications. According to some, in vertebroplastic temperature rise can be useful because it can help reduce pain. However, modern bone cements do not provide the surgeon any opportunities for regulation of the generated temperature or provide them to a very limited extent.
In addition, interest cements, which during curing causes a small increase of temperature. Low bone cement-based hydraulic ceramics described in pending Swedish patent application "Ceramic material and method of manufacture" (SE-0104441-1)filed 27.12.2001, In the referenced patent application temperature rise due to hydration reactions keep adding suitable inert, non phases, which, in addition, favorable mechanical properties and biocompatibility. However, these ceramic materials do not provide the possibility to control the heat through well-controlled phase compositions hydrating ceramics or temperature control by means of accelerators and retarders.
Summary of the invention
In view of the disadvantages associated with injectable pastoors the diversified compositions known from the prior art, when used for cell therapy, pain relief, treatment of the blood vessels and so on, there is a need for curing in situ pasty material which can be injected through a thin needle into the areas in the human body and which is cured during a controlled period of time with the release of a regulated amount of heat, providing a variety of therapeutic effects on target tissues and organs and forming a stable, non-toxic and biocompatible solid volume. When used for the skeleton of the cured material should preferably have mechanical properties similar to the mechanical properties of bone.
To meet these needs, the present invention uses hydraulic cements, especially calcium aluminates, which otverzhdajutsja exothermically as a result of chemical reactions with water, forming a hard ceramic materials with high biocompatibility and suitable mechanical properties.
The aim of the present invention is to provide injectable ceramic fuel biochemistry compositions based hydraulic oxide ceramics, mainly calcium aluminates, the curing time and temperature increase which can be adjusted in accordance with clinicianscientists. After curing is formed of biocompatible material, which, remaining in the body for long periods of time, does not cause any negative health effects.
Another objective of the present invention is to provide compositions that can act as a carrying load, implantable bone material, restoring the mechanical properties of the skeleton after removal or radiation therapy of tumors, and as a consequence, reducing the risk of fractures due to weakening of bones.
Another objective of the present invention is the use of biocompatible ceramic composition for therapeutic treatment of heat generated by these compositions.
More specifically, the injectable biocompatible cement composition according to the present invention can be suitably used for therapeutic purposes in vivo, for example, to treat cancer, pain, treatment of blood vessels, bone repair and activation of drugs by heat that they emit when cured in situ in the body.
In addition, biocompatible cement composition according to the present invention can be used for the manufacture of medical implants, orthopedic implants, dental implant, or used as a dental filling material is.
In addition, the present invention can be used for manufacturing media pharmaceuticals for delivery of the drug in the patient's body.
These biocompatible ceramic composition mainly composed of a hydraulic powder raw material, mainly containing phase aluminate calcium: less than 50 vol.%, preferably, less than 10 vol.%, CA2calculated on the total volume of phases of calcium aluminate; more than 50 vol.%, preferably more than 90 vol.%, SA and C12And7calculated on the total volume of phases of calcium aluminate; and less than 10 vol.%, preferably, less than 3 vol.%, With3And calculated on the total volume of phases of calcium aluminate. The composition according to the present invention may optionally contain suitable additives. The sum of all components is 100%, and the amount of SA phase is at least 50%, preferably at least 70%, most preferably at least 90%.
Hydraulic powder raw material according to the present invention, furthermore, may contain hydraulic powdered calcium silicate and/or calcium sulfate in the amount of less than 50 vol.% of the total hydraulic ingredients.
Compositions according to the present invention, furthermore, may contain negitave the ical filler, containing calcium titanate or any other ternary oxide of perovskite structure according to the formula ABO3where O is oxygen and a and b are metals, or any mixture of these ternary oxides. In the perovskite structure And is chosen from the group consisting of Mg, Ca, Sr or Ba, and in the perovskite structure is chosen from the group consisting of Ti, Zr or Hf. Non-filler must be present in an amount of less than 30 vol.%, preferably, less than 10% vol. of the total volume of the ceramic ingredients.
In order to increase the biological activity of the compositions according to the present invention, they also may contain particles or powder of one or more biocompatible materials selected from the group consisting of calcium carbonate, calcium phosphate, Apatite, florouracil, carbonate-Apatite and hydroxyapatite, the total number of which shall be less than 30 vol.% of the total volume of the ceramic ingredients.
The particle size of powdered/crushed raw material is preferably less than 20 microns, preferably less than 10 microns, and most preferably less than 3 microns.
Curing of the compositions according to the present invention can be implemented in various ways, as for example, processing of biocompatible ceramic composition, a hardening agent, as for example, the CTE is redusa liquid water, or steam, or by the preparation of suspensions of the specified curing liquid and biocompatible ceramic composition.
The hardener may contain additives to enhance the heat by adjusting the curing time. These additives can be selected from plasticizers (agents that reduce the amount of water needed to maintain high yield and to control viscosity or machinability of the suspension of the ceramic powder without adding excessive amounts of water), such as, for example, polycarboxylic acids, polyacrylic acids and sverkhplasticheskogo, as for example, Conpac 30®. In addition, the additive according to the present invention can be selected from accelerators, which accelerate the process of solidification and which are selected from the group including lithium chloride, lithium hydroxide, lithium carbonate, lithium sulfate, lithium nitrate, lithium citrate, calcium hydroxide, potassium hydroxide, potassium carbonate, sodium hydroxide, sodium carbonate, sodium sulfate and sulfuric acid. In a preferred embodiment of the present invention accelerator is LiCl, and in a more preferred embodiment of the present invention LiCl is present in an amount of 10-500 mg per 100 g of the curing liquid. Even among the additives according to the present invention are moderators, notoriousness the process of hardening and which is selected from the group including polysaccharides, glycerol, sugars, starches and thickeners based on cellulose.
When the compositions according to the present invention is used in particular as a dental material or implants, the compositions can also contain additives to control the expansion, as for example, colloidal silicon dioxide and/or calcium silicate. During the curing material expansion is ≤0,8%.
Being injected or otherwise introduced into the body of a patient, the composition according to the present invention can during curing to generate temperature of 30-150°C.
After curing the composition according to the present invention has a compressive strength of at least 100 MPa.
The present invention also relates to a curable biocompatible ceramic composition according to the above and also to the medical device containing the specified curable biocompatible ceramic composition.
The present invention also relates to a method of manufacturing the above-described chemically bound, biocompatible ceramic composition, which includes the preparation of the calcium aluminate powder mixture with the selected phase composition and particle size and curing the above-mentioned mixture by processing of biocompatible ceramics is practical composition hardener, as for example, curing the liquid on the basis of water or steam, or preparation of the suspension from the specified curing liquid and biocompatible ceramic composition. Furthermore, the method may include the stage of removing any residual water or organic contamination of the powder mixture prior to curing.
The present invention also relates to a therapeutic method involving the introduction phase biocompatible ceramic composition into the patient and curing the specified composition, whereby heat.
In a preferred embodiment of the invention a method of heat release in vivo in the patient's body for therapeutic purposes (e.g. for cancer treatment, treatment of the blood vessels, relieving pain, and activation of drugs) includes the following stages:
preparing a powder mixture of calcium aluminates containing less than 50 vol.%, preferably, less than 10 vol.%, CA2calculated on the total volume of phases of calcium aluminate, more than 50 vol.%, preferably more than 90 vol.% SA and C12And7calculated on the total volume of phases of calcium aluminate, less than 10 vol.%, preferably, less than 3 vol.%, With3And calculated on the total volume of phases of calcium aluminate, and the number of SA phase is at least 50%, preferably, less is th least 70% and most preferably at least 90%, and the optional addition of calcium silicate and/or calcium sulphate in a quantity less than 50% vol. of the total hydraulic ingredients.
A preferred variant of the method according to the present invention includes the optional addition of non-filler in the amount of less than 30 vol.%, preferably, less than 10% vol. of the total volume of the ceramic ingredients; optional addition of particles or powder of one or more biocompatible materials, the total amount of which should be less than 30 vol.% of the total volume of the ceramic ingredients; optional reduction of particle size of powdered/crushed material to less than 20 microns, preferably less than 10 microns, and most preferably less than 3 microns; optional removal of any residual water and organic impurities from the powder mixture; optional introduction of additives to control viscosity and workability, such as, plasticizers, additives for regulating the expansion, accelerators and retarders curing.
A preferred variant of the method according to the present invention, also includes the introduction of the above composition in the body defined in nnom place therapeutic treatment and curing of the composition in situ in a patient's body.
When the above-mentioned method stage curing may, before the introduction of the composition into the patient to include mixing a biocompatible ceramic composition with a curing agent to obtain thereby the suspension and the subsequent introduction of the suspension into the desired location in the body of the specified patient. In addition, the stage of curing can be accomplished by the introduction of biocompatible ceramic composition into the patient and then in situ in the desired place by the processing composition, a hardening agent, as for example, an aqueous solution or water vapor.
Brief description of drawings
The present invention will become clearer from the detailed description below and the accompanying drawings, which are given only as an illustration and in no way limit the present invention, and in which:
figure 1 - graph showing the change with time of the temperature generated by the composition according to the present invention, having a concentration of 0.4 wt.% LiCl in hydraulic mortar,
figure 2 is a graph showing the change with time of the temperature generated by the composition according to the present invention, having a concentration of 0.05 wt.% LiCl in the hydraulic solution.
Detailed description of the invention
The present invention relates to materials which otverzhdajutsja exothermically with vyd the population controlled amounts of heat, leading to higher temperatures. Fuel materials can be used for therapeutic purposes related to local heating of cells, cellular systems and organs. The material applied in the form of suspensions, pastes or pastes in the desired place, for example, by injection, where it cures into a solid, creating a sufficient temperature to achieve the desired results, for example, treatment of a tumor, pain relief or treatment vessels. The materials according to the present invention offers an alternative to conventional bone cements based on PMMA.
The material according to the invention cures as a result of hydration reactions between the ceramic oxide powders and water. Due to the hydration of a new, durable binder phase consisting of hydrates. Ceramic materials, cured due to hydration, called hydraulic cements. In the number of hydraulic materials include concrete based on Portland cement, and special ceramics used in dentistry and orthopedics. The amount of heat released during hydration depends on several factors, as described below.
The most suitable hydraulic cement according to the present invention is calcium aluminate. This material consists of phases in the system Cao-Al2O3. In l the literature describes several phases, mainly, C3A, C12A7CA and CA2(C=CaO, A=Al2O3), all of which relate to the present invention. According to the invention as an alternative implementation can be used a calcium silicate.
There are several reasons for the use of calcium aluminates as the primary substance for injectable biochemists. Compared to other aqueous binder systems, for example, phosphates, carbonates and sulfates of calcium aluminates have a high chemical resistance, high strength and variable speed curing. However, the silicates have properties similar to the properties of aluminates, and can also be used according to the present invention. In addition, chemical curing, water-based, makes the process relatively unaffected by body fluids based on water. Prior to curing the material has good machinability; it can be used as suspensions and pastes. In addition, the temperature generated by the aluminates of calcium, can be adjusted by selection of the phase composition.
Biochemistry a composition based on calcium aluminate, which relate to the present invention, is described in pending Swedish patent application "Ceramic material and the way it is made is I" (SE-0104441-1), submitted 27.12.2001, and in PCT/SE99/01803 "Binder system with dimensional stability", submitted 08.10.1999, All the additives described in these patent applications relate to the present invention.
If the powder of the calcium aluminate is mixed with water or an aqueous solution, it begins a process that involves the stages of dissolution of calcium aluminate in water and formation of a solution containing calcium ions and aluminium. When a sufficient concentration of ions begins deposition in the liquid crystalline hydrates of calcium aluminate. These hydrates form a new durable binder phase in the cured solid material.
The temperature achieved during the curing of hydraulic cement, depend on several factors, most important of which are: phase composition of the starting powder of calcium aluminate, the particle size of the initial powder material, the dissolution rate, the rate of hydration, adjustable additives of accelerators or retarders, the number of inert, non-phase in the composition, the total amount of hydrated material and the heat transfer to the environment.
Hydration of calcium aluminates and calcium silicates is a staged process. Originally formed hydrates for several stages become more stable hydrate phase. At room temperature the initial hydrate the phase is CaO· Al2O3·10H2O, abbreviated - CAH10(C=CaO, A=Al2O3H=H2O). The most stable hydrate phase is3EN6. The following reactions identified for hydration SA:
All stages of the reaction are exothermic with heat. Education CAH10(stage 1) creates 245±5 j/g2EN8(the next stage) - 2280±5 j/g, and C3AH6(stage 3) - 120±5 j/g When the amount of the several stages of hydration, the total amount of heat emitted from the standard cement from calcium aluminate, consisting mainly of the phases of the SA and CA2ranges from 450 to 500 j/, the Principles of hydration are similar to cement from calcium silicate.
Particular stages of hydration temperature dependent. The higher the temperature, the more reaction stages can occur for a certain period of time. At room temperature, the hydrate SAN10formed quickly, but the transformation in C3EN6occurs very slowly, i.e. over a period of several months. At body temperature (37°C)3EN6formed within a few hours. At 60°With a stable hydrate forms in minutes. If during the initial hydration quickly occur several reaction stages, the generating system is raised higher temperature. When a slower hydration generated a lower temperature.
In addition, there are other phases of calcium aluminate, mainly With3A, C12And7and CA2that hydratious result in similar reactions. As established, the rate of hydration depends on the stoichiometry of the initial phase. The greater the amount of Ca in the source powder, the faster hydration. Thus, C3A and C12And7otverzhdajutsja faster than SA and SA2. The most likely explanation of this phenomenon is found in the mechanisms of hydration, which include the initial dissolution of calcium aluminate in water and subsequent precipitation of hydrates when the concentration of CA - and Al-ions in solution reach sufficient levels. To initiate precipitation of hydrates require a higher concentration of Ca-ions than the concentration of Al ions.
Any cement from calcium aluminate is a mixture of phases. In General, commercially available cements consist of CA and CA2. Phase3A, C12And7do not use in commercially sold cements. However, higher content of these bystrovozvodyaschihsya phases of calcium aluminate cause more rapid hydration and thus higher temperatures. Supplements of these phases can be used for temperature control, with slaveboy in hydraulic ceramics based on calcium aluminate.
The temperature generated by hydraulic cements based on calcium aluminate according to the present invention, can be adjusted approximately to the interval between 30 and 150°C. All this interval refers to therapeutic applications. Cell death occurs at a temperature of from about 45°depending on the time of exposure. The volume used for the treatment of osteoporotic vertebrae ranges from 3 to 8 ml For treatment of tumors in the spine is usually required 1-5 ml In vascular therapy usually requires about 0.5-2 ml
Regulation of the temperature rise during curing
To generate the high temperatures during curing injectable bio-cement it is necessary to consider at least the following factors:
The choice of the phase composition in the hydraulic source powder and hydrates that are formed during the initial stage of curing. Phase calcium aluminate, rich Sa, hydratious faster. For example, when a larger number With3And increases the rate of hydration compared to a net SA and, thus, achieve high temperature. The addition of CA2to SA reduces the rate of hydration. Except for CA and CA2for the present invention of particular interest are compositions of fuel materials with3and With 12And7.
For the present invention of particular interest are the powder composition with small amounts of CA2(which utverjdaet very slowly) or without it. The number of CA2must be less than 50 vol.%, preferably, less than 10 vol.%, in the calculation of the total number of phases of calcium aluminate; most of the aluminates of calcium is CA and12And7(with average speeds curing), forming together more than 50 vol.%, preferably more than 90 vol.%. In addition, the desirable lower part With3And acting as an accelerator or a curing initiator. Number3And should be less than 10 vol.%, preferably, less than 3 vol.% of the total number of phases of calcium aluminate. For the present invention is unique regulation of generating temperatures in the respective volumes of material by selecting the phase compositions at specified intervals.
The particle size of the original powder. Smaller particles dissolve and hydratious faster and thereby generate higher temperatures. The particle size regulate pre-treatment powder hydraulic cement methods of reducing particle size, for example, by grinding. The particle size of the powder, preferably less than 10 microns, more before occhialino, less than 3 micron.
The rate of hydration regulate the addition of accelerators and/or moderators. There are several accelerating additives known in this technical field, for example, lithium salts such as lithium chloride, as well as moderators, such as sugars and various hydrocarbons. Through combinations of accelerators and retarders can be achieved certain results in curing different period of very slow curing or without him, followed by a delayed stage of rapid hydration; the curing cycle has an exponential character.
In the present invention accelerators and retarders are used, mainly, not to regulate the curing time, as it is known in the field of technology, but rather to regulate the generation of temperatures.
Of particular interest are compositions, curable LiCl solutions with a content of about 10-500 mg of LiCl in 100 g of water, and composition, curing solutions containing combinations of accelerators and retarders, for example LiCl, respectively, and sugar.
Examples of other salts that can be used as accelerators according to the present invention are: lithium hydroxide, lithium carbonate, lithium sulfate, lithium nitrate, lithium citrate, calcium hydroxide, potassium hydroxide, potassium carbonate, hydroxide hydroxide is I, sodium carbonate, sodium sulfate and sulfuric acid.
Examples of retarders that can be used according to the present invention are glycerol, polysaccharides, sugars, starches and thickeners based on cellulose.
Ceramic composition according to the present invention, in addition, contain a component which is a plasticizer-based compounds selected from the group comprising polycarboxylic acid, polyacrylic acid and surplusldeficit, as for example, Conpac 30®.
The amount of inert, non phases in the cement composition. Non-phase, for example dehydration oxides, other ceramic materials or metals, may be added for such purposes as increasing the mechanical strength and dimensional stability during hydration. However, to generate high temperatures the number of non phases should be maintained small. For the invention are suitable concentration of non phases is less than 30 vol.%; their number should be preferably less than 10 vol.% of the total number of ceramic ingredients. In addition, non-additives can also affect the rate of hydration.
In addition, the total amount of hydrated material and the heat transfer to the environment have an effect on the temperature, the which can be achieved. Therefore, to achieve the same temperature specific volume heat should be higher for smaller volumes biochemist. Conversely, large amounts of cement useful for generating high temperatures.
This example describes the procedure for manufacturing a ceramic cement, consisting of hydrated calcium aluminate without fillers, and this example serves to illustrate the impact of the speed of hydration on the generated temperature. It should be noted that the achieved temperature also depend on other factors, such as the volume of the cured material and the heat transfer to the environment.
As the raw material used to market the product Ternal White® from Lafarge Aluminates. He is a calcium aluminate with a ratio of Al2O3/CaO equal to about 70/30.
The first stage of the preparation was reducing the particle size of the powder. This was achieved by grinding in a ball mill. Crushed in a rotating cylindrical plastic container, which is 1/3 of their volume was filled with powder Ternal White and another 1/3 - inert grinding balls made of silicon nitride having a diameter of 10 mm Fluid used during grinding was isopropanol; the total grinding time is 72 hours. When the reduction rate of 90% h the CI decreased to less than 10 microns.
After the grinding process of grinding beads were removed by sieving, and the alcohol evaporated. After that, the crushed powder was progulivali at 400°C for 4 hours to remove residual water and organic pollution.
The second stage was the preparation of a solution for hydration. The solution consisted of deionized water to which was added a plasticizer and an accelerator. The plasticizer was selected from a group of commercially available, so-called sverkhplasticheskogo Conpac 30® from Perstorp AB, known in the field of technology, but also would act any such agent. Surplusldeficit was added in water to a concentration of 1 wt.%. Accelerator LiCl was added at concentrations of 0.05, and 0.08, 0.2 or 0.4 wt.%.
The prepared powder Ternal White and aqueous solutions were mixed so that the ratio of mass of water to mass of the crushed powder Ternal White® was 0,35. The mixture of powder and liquid were utverjdali on the air in 10-ml plastic container, and the temperature rise recorded by thermocouple is introduced into the center of the volume of cement.
The results are shown in figure 1 and 2. Figure 1 shows that at a concentration of 0.4 wt.% LiCl in the hydrating solution creates a temperature over 90°during curing in an environment with a room temperature, while figure 2 illustrates a much smaller temperature achieved by the LiCl concentration of 0.05 wt.%, and t is the train slower rate of hydration.
This example serves only to illustrate the influence on the temperature the rate of cure achieved by adding a curing accelerators, in this case LiCl.
This example describes the different speeds curing typical of aluminates of calcium from different phases of calcium aluminate.
As raw materials use three different powder of calcium aluminate containing 99% pure phases of CA12And7and CA3.
The powder particles of size less than 10 μm, was obtained by grinding as described in example 1. Milled powders were also progulivali at 400°C for 4 hours to remove any residue.
As fluids for hydration used deionized water without any additives.
The prepared powders were mixed with water, maintaining the mass ratio of water to the powder constant at the level of 0.35. The mixture of powder and water utverjdali in 10-ml plastic containers in air at room temperature.
The rate of hydration for phases of CA12And7, CA3measured as the time until solidification, respectively 4-6 hours, 5-10 2-4 minutes and seconds.
1. Biocompatible ceramic hydraulic powder composition consisting of phases of calcium aluminate with the following structure:
less than 50 vol.%, p is edocfile less than 10% vol. CA 2calculated on the total volume of phases of calcium aluminate,
more than 50 vol.%, preferably more than 90 vol.% SA and C12And7calculated on the total volume of phases of calcium aluminate,
less than 10 vol.%, preferably less than 3 vol.% With3And calculated on the total volume of phases of calcium aluminate, and
optionally, suitable additives, where the sum of all components is 100% and in which the SA phase is at least 50%, preferably at least 70%, most preferably at least 90%.
2. Biocompatible ceramic composition according to claim 1, characterized in that it further comprises a hydraulic powdered calcium silicate and/or calcium sulfate in the amount of less than 50% of the total volume of hydraulic ingredients.
3. Biocompatible ceramic composition according to claim 1, characterized in that it further comprises a non-filler containing calcium titanate or any other ternary oxide of perovskite structure according to the formula ABO3where O is oxygen and a and b are metals, or any mixture of these ternary oxides, with specified filler is present in amounts of less than 30 vol.%, preferably less than 10 vol.% of the total volume of the ceramic ingredients.
4. Biocompatible ceramic comp the position according to claim 3, characterized in that in the perovskite structure selected from the group comprising Mg, Ca, Sr or BA, or that in the perovskite structure selected from the group comprising Ti, Zr or Hf.
5. Biocompatible ceramic composition according to claim 1, characterized in that it further contains particles or powder of one or more biocompatible materials selected from the group including calcium carbonate, calcium phosphate, Apatite, florouracil, carbonate-Apatite and hydroxyapatite, the total number of which shall be less than 30 vol.% of the total volume of the ceramic ingredients.
6. Biocompatible ceramic composition according to claim 1, characterized in that it further comprises a component that is a plasticizer-based compounds selected from the group consisting of polycarboxylic acid, polyacrylic acid and surplusldeficit, as, for example, Conpac 30®.
7. Biocompatible ceramic composition according to claim 1, characterized in that it further contains an additive for regulating the expansion, as, for example, colloidal silicon dioxide and/or calcium silicate.
8. Biocompatible ceramic composition according to claim 1, characterized in that it further comprises curing the liquid is water-based.
9. Biocompatible ceramic composition according to claim 8, wherein curing the liquid more the tion contains accelerator, which speeds up the process of hardening and which is selected from the group including lithium chloride, lithium hydroxide, lithium carbonate, lithium sulfate, lithium nitrate, lithium citrate, calcium hydroxide, potassium hydroxide, potassium carbonate, sodium hydroxide, sodium carbonate, sodium sulfate and sulfuric acid.
10. Biocompatible ceramic composition according to claim 9, characterized in that LiCl is present in an amount of 10-500 mg per 100 g of the curing liquid.
11. Biocompatible ceramic composition according to claim 8, wherein curing the liquid further comprises a retarder that slows down the process of hardening and which is selected from the group comprising polysaccharides, glycerol, sugars, starches and thickeners based on cellulose.
12. Biocompatible ceramic composition according to claim 1, characterized in that the particle size used powdered/crushed raw material is mostly less than 20 microns, preferably less than 10 μm, and most preferably less than 3 microns.
13. Biocompatible ceramic composition according to claim 1, characterized in that the biocompatible ceramic composition during curing in a living human body generates temperature of 30-150°C.
14. Biocompatible ceramic composition according to claim 1, characterized in that the expansion during curing of the composition and is ≤ 0,8%.
15. Curable biocompatible ceramic material, characterized in that the material is based on biocompatible ceramic powder composition according to claims 1 to 14 and is in hydrated form.
16. Biocompatible ceramic material according to item 15, characterized in that it has a compressive strength of at least 100 MPa.
17. A method of manufacturing a biocompatible ceramic material according to item 15 or 16, which includes a step of curing biocompatible ceramic powder composition according to claims 1-14 by mixing the specified composition with a hydrating fluid.
18. The method of manufacturing according to 17, characterized in that it further includes a step of removing any residual water or organic contamination of the powder mixture prior to curing.
19. Medical implant containing biocompatible ceramic composition according to any one of claims 1 to 14.
20. Orthopedic implant containing biocompatible ceramic composition according to any one of claims 1 to 14.
21. Dental filling material or dental implant containing biocompatible ceramic composition according to any one of claims 1 to 14.
22. Media drugs for delivery of the drug in the patient's body containing biocompatible ceramic composition according to any one of claims 1 to 14.
23. The use of biozones the ima ceramic composition according to any one of claims 1 to 14 for therapeutic treatment of warm, stand out from the specified composition in the curing.
24. Method heat release in vivo in the patient's body for therapeutic purposes (for example, cancer treatment, treatment of the blood vessels, relieving pain, and activation of medicines), including the stage of introduction of biocompatible ceramic powder composition according to claims 1 to 14 in the patient's body and curing the specified composition, whereby heat.
25. The method according to paragraph 24, wherein the biocompatible ceramic powder composition prior to introduction into the patient mixed with hardener to obtain thereby the suspension.
26. The method according to paragraph 24, wherein the biocompatible ceramic composition is introduced into the patient, is treated with a hardener in situ.
27. The method according to p. 25 or 26, characterized in that the hardener is used an aqueous solution or water vapor.
SUBSTANCE: method has stages for manufacturing medical device and introducing effective dose of Linezolid.
EFFECT: improved infection prophylaxis in medical purpose devices.
17 dwg, 11 dwg, 6 tbl
FIELD: medical equipment.
SUBSTANCE: when treating surface of implant intended for implantation into bone tissue, microscopic roughness is provided, which roughness has pores and peaks. Diameter of pores is smaller or equal to 1 micron, depth of pores equals to 500 nm maximum, width of peak at level of half of pores equals to 15-150% diameter of pores.
EFFECT: higher reliability of attachment of implant.
21 cl, 3 tbl, 10 dwg, 2 ex
SUBSTANCE: the present innovation deals with a medicinal prosthesis that contains metallic material, such as titanium or its alloy, in which surface parts of metallic material area covered with the layer of the corresponding hydroxide material, such as titanium hydroxide. Preferably, hydroxide layer contains one or more biomolecular substances being connected with it. Also, the innovation in question refers to electrolytic process for obtaining a medicinal prosthesis. Metallic prostheses are of improved biological compatibility.
EFFECT: higher efficiency.
24 cl, 8 ex, 3 tbl
SUBSTANCE: method involves introducing proper mesenchyme stem cells separated from marrow and cultivated in vitro. The cells are implanted on a carrier into cerebral cortex region planned in advance. To do it, the mesenchyme stem cells are preliminarily introduced into modified resorbable stent (carrier). The number of cells to be introduced is equal to 7-12 mln per one Brodman zone selected for transplanting autologic mesenchyme stem cells. Marked anatomical changes in brain regions being the case, the same quantity of cells are inravascularly (intravenously or intra-arterially) introduced. The treatment is carried out in particular cases in concurrently introducing the mesenchyme stem cells in intraperenchymatous or intravenous way.
EFFECT: enhanced effectiveness of treatment in cognitive-mnestic function disorder cases.
SUBSTANCE: transplant mixture has liophylized allogenic bone tissue and allogenic hydroxyapatite and patient autoblood platelets gel with Metronidazole, taken in the following components proportions (%): liophylized allogenic bone tissue - 65; allogenic hydroxyapatite - 10; patient autoblood platelets gel - 20; Metronidazole - 5.
EFFECT: enhanced effectiveness of treatment; no clamps required; reliably and tightly closed bone tissue defect; accelerated regenerate reorganization; improved antiseptic and immunomodulating action.
FIELD: medicine, in particular tubular polyurethane articles (guides, suction drainages, catheters) having aseptic coat.
SUBSTANCE: claimed articles are produced by providing of article elements followed by assembly thereof and application of aseptic coat by impregnation of catheter surface with chlorohexidine and/or salts thereof (e.g., dihydrochloride, or diacetate, or bigluconate, etc.), by article treatment for 14-180 min with aqueous-alcohol solutions of chlorohexidine and/or salts thereof at 20-60°C, containing (mass %): chlorohexidine and/or salts thereof 1-5; ethanol or methanol 75-85; water 15-25.
EFFECT: prolonged anti-microbial activity; protection against body contamination during catheterizing.
5 cl, 1 tbl
SUBSTANCE: bone-and-mineral product contains porous bone mineral particles produced from natural bone and having crystalline structure practically corresponding to natural bone structure and practically containing no endogenous organic material. The particles have fibers of physiologically compatible type II resorbable collagen at least on their surface. Mass proportion of type II collagen fibers and porous bone mineral is at least equal to approximately 1:40.
EFFECT: enhanced effectiveness in recovering combined injuries of cartilage and bone tissue in articulations having defects.
8 cl, 6 dwg
FIELD: medicine; therapeutic dentistry.
SUBSTANCE: new biological material for layer has low antigeny properties and keeps physical and mechanical properties of initial donor tissue. Biological laying has powder-like modified dentine with unblocked chemical bonds among collagen, chondrointin sulfates and mineral salts and Alloplant biological materials which have to be osteogeny stimulator, vasculogeny stimulator, phagocytosis stimulator at definite content of components. Laying for curing pulpitis has biological active matters to stimulate angiogenesis, dentinogenesis which matters activate phagocytosis.
EFFECT: improved efficiency of treatment.
1 dwg, 2 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes implant prepared by mixing a carrier material with components of the preparation antibiotic/antibiotics with delayed release of an active substance (aminoglycoside, lincosamide antibiotics, 4-quinolone antibiotics and tetracyclines), and a method for preparing the implant. Release of an active substance from implant during from some days to some weeks doesn't dependent from a carrier material and adsorption effects of a carrier-material surface.
EFFECT: improved and valuable properties of preparation.
13 cl, 1 tbl, 6 ex
FIELD: medical engineering.
SUBSTANCE: method involves boiling reinforcing fabric in mixture of 10% aqueous solution of detergent powder Lotus or others, 5% aqueous solution of KOH or NaOH alkali during 45-60 min with following neutralization, removing saponated fats, activating superficial threads with 10% aqueous solution of oxalic acid, washing in running water and drying the reinforcing fabric at 25-60°C to reach humidity of 1.5-2.5%.
EFFECT: improved adhesive-cohesive reinforcing fabric properties; avoided delamination; high strength; reduced article weight.
FIELD: medicine, gel composition.
SUBSTANCE: claimed composition contains calcium sulfate and viscous biopolymers and can be easily introduced into defect part of damaged bone. Composition of present invention is capable of penetration into adjacent organs and is useful as physiologically acceptable filling material for bone concretion.
EFFECT: composition to prevent growth of undesired conjunctive tissues and to induce blood vessel growth and bone osteoblast development in earlier stage.
7 ex, 9 dwg, 1 tbl, 6 cl
FIELD: stomatologic techniques and materials.
SUBSTANCE: proposed membrane comprises at least two porous polytetrafluoroethylene layers: one adjusting parodentium tissues and the other being outside layer, the two having different porous structure. Layer adjusting parodentium tissues is characterized by volume portion of hollow space equal to 78-94%, specific surface of hollow space 0.5-0.9 mcm2/mcm3, average distance between hollows 20.0-50.0 mcm, and average volumetric chord 20.0-30.0 mcm. Outside layer is characterized by volume portion of hollow space equal to 30-60%, specific surface of hollow space 0.1-0.5 mcm2/mcm3, average distance between hollows 1.8-15.0 mcm, and average volumetric chord 1.0-15.0 mcm.
EFFECT: increased regenerative activity and simplified use.
7 cl, 7 dwg, 1 tbl, 6 ex
FIELD: composite materials for stomatology.
SUBSTANCE: proposed composite material has porous inorganic nonmetallic matrix and second material. Bending strength of matrix is no less than 40 Mpa as determined according to ISO 6 872; second material is just organic material which at least partially fills pores of matrix; elasticity modulus E of composite material is equal to or exceeds 25 Gpa determined according to ISO 10 477. Properties of proposed composite are between properties of ceramic and plastic materials, for example, friability is below that of ceramic materials but attrition resistance is higher as compared with that of polymers filled with inorganic materials. Specification describes method of production and application of material.
EFFECT: enhanced efficiency and reliability.
13 cl, 4 ex