CN102512756B - Method and equipment for processing biological cell in object - Google Patents
Method and equipment for processing biological cell in object Download PDFInfo
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- CN102512756B CN102512756B CN201110400731.1A CN201110400731A CN102512756B CN 102512756 B CN102512756 B CN 102512756B CN 201110400731 A CN201110400731 A CN 201110400731A CN 102512756 B CN102512756 B CN 102512756B
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- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M35/00—Means for application of stress for stimulating the growth of microorganisms or the generation of fermentation or metabolic products; Means for electroporation or cell fusion
- C12M35/02—Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
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Abstract
The invention discloses method and equipment for generating a high-voltage pulse induction current in an object. The equipment at least comprises a DC high-voltage power source capable of generating currents of desired intensity, a pulse shaping network formed by one or more capacitors capable of storing electric energy, at least one charge/discharge switch, and at least one induction coil or at least one group of induction coils. When the pulse shaping network releases high-voltage pulses of specified waveform and wave width, the induction coil group is allowed to generate a change in magnetic induction flux in the pulse form under the action of the high-voltage pulses, a high-intensity induction field in the pulse form is excited and generated by the change of magnetic induction flux in the space close to the induction coil group, a high-intensity induced electromotive force in the pulse form is generated in the inside of the to-be-treated object which is put in the induction field, and a DC high-intensity induced current in the pulse form is generated in a non-contact manner inside the object by the induced electromotive force.
Description
Technical field
The present invention relates to the method and apparatus that a kind of high-voltage pulse faradic current produces.
Background technology
High pressure (or claiming high strength) impulse electric field (Pulsed Electric Fields, PEF) is applied in a plurality of fields such as food processing, medical treatment and Pollutant Treatment.
Take food processing as example, it is a kind of novel non-thermal food sterilization technology that high-voltage pulse induction PEF processes, it is liquid, semi-solid food products to be processed, and can be formed the production line of continuous sterilizing and sterile filling with higher electric field intensity (10-50kV/cm), shorter pulse width (0-100 μ s) and higher pulse frequency (0-2000Hz).Its sterilizing mechanisms is by external electrical field and microbial cell film direct effect, thereby destroys the structure of cell membrane, forms " electroporation " and causes bacteria inactivation rate.Electroporation phenomenon is the phenomenon that phalangeal cell is exposed to the lower cell membrane unstability occurring of high-voltage pulse induction PEF effect and forms aperture on cell membrane.Because cytoplasma membrane permeability significantly increases, intracellular osmotic pressure, higher than extracellular, finally causes the breakage of cell membrane.Microbial cell film consists of the phospholipid bilayer of integral protein matter, and it has certain electric charge, has certain permeability, also has certain intensity.Between the surfaces externally and internally of film, have certain electric potential difference, on cell membrane during an additional electric field, this electric field will increase the electric potential difference inside and outside film.Because the heterocharge of cell membrane two surface sediments attracts each other, cause the extruding of film; When electric field intensity increases to a marginal value, the permeability of cell membrane increases severely, and occurs many apertures, and film strength is reduced; Further effect makes cell membrane produce the large perforation of unrepairable, makes breakdown of cellular tissue, collapse, causes microorganism deactivated.
The indicator microoraganism of high-voltage pulse induction PEF sterilization experiment comprises bacillus subtilis, Deshi Lactobacillus, Listeria Monocytogenes, fluorescent pseudomonas, beer yeast, staphylococcus aureus, streptococcus thermophilus, escherichia coli, Escherichia coli O 157, Molds and yeasts etc., result of study shows, high-pressure pulse electric PEF processes all has good killing action to the trophosome cell of these microorganisms, affect a lot of because have of high-voltage pulse induction PEF sterilization, they are having a strong impact on bactericidal effect, substantially be divided into: (1) processing factors: electric field intensity, processing time, pulse frequency, pulse width, pulse shape, sample flow rate and initial temperature.(2) product factors: product composition, electric conductivity, ionic strength, pH, water activity and viscosity.(3) microorganism characteristic factor: microbe species, growth conditions and growth period.
Current high-voltage pulse induction PEF technology has following shortcoming:
(1) impulse electric field can affect electrostatic interaction between protein group and the location of charged group, upsets Electric Field Distribution and electrostatic interaction between gal4 amino acid residue, causes separation of charge, thereby affects the structure (secondary and three grades) of protein.(2) electrode electrochemical reaction around can be on comprising that the food component of protein produces certain impact.(3) because electrochemical reaction can cause electrode corrosion, the metallicses such as the ferrum in electrode, chromium, nickel, manganese can be discharged in food.(4) product of electrode electro Chemical reaction, such as some free radicals, active chlorine, active oxygen etc. probably caused lipid by creating singlet oxygen by using, free radical and other oxidizing substance initiated oxidations reaction (chain reaction), produces the oxidation product of series of complex.(5) high-voltage pulse induction PEF is larger on the impact of food carbohydrate ingredient and vitamin.(6) major limitation of high-voltage pulse induction PEF technology is can only be for food liquid (as milk and fruit juice), and semisolid food effect is poor, and solid-state food cannot use substantially.Main cause is that electrode and processed food can not good contacts, and the heterogeneous texture of solid-state food inside and conductivity difference also affect sterilization effect.
High-voltage pulse induction PEF system equipment mainly comprises five parts: supply unit, pulse generating unit (comprising electric capacity and gauge tap), sample treatment chamber, cooling system and temperature measuring system.
High-voltage pulse induction PEF is applied to the electroporation (electroporation, EP) that medical domain mainly concentrates on tumor cell.By the perforation of cancer cell membrane, overcome the barrier action of film to medicine, improve curative effect of medication, reduce the drug resistance of tumor to medicine, be the oncotherapy new technique occurring in recent years, be also expected the gene therapy for tumor.The electric field intensity that this method adopts is not less than 600V/cm, makes cell produce reversibility perforation, can not really kill cancerous cell.If raising electric field intensity may bring disaster to surrounding normal cell when killing cancerous cell.The Medpulser electroporation treatment instrument that U.S. Genetronics company produces adopts square wave electric pulse, has 6 pieces of needle electrodes to insert tumor, produces the uniform electric field that is not less than 780V/cm.The limitation of this technology shows in the control of electric field scope, crosses conference and injures normal cell, too smallly can not kill completely cancerous cell.Even the cancerous issue between electrode, the uniformity of electric field is also difficult to reach.In addition, electrode need insert human body, belongs to traumatic treatment means.
High-voltage pulse induction PEF also can be applicable to the degraded of harmful substance in aqueous liquid foodstuff (as organophosphor) or the decomposing, purifying of dirty water pollutant.But appoint and so can not be applied to the processing of solid matter.
Utilizing high-voltage pulse electric field sterilization is the more active research field of Abroad in Recent Years, and existing more patent is open.Domestic main patent application is from each universities and colleges.The device that patent of invention (01130064) relates to is mainly comprised of high-voltage pulse electric generating means, parameter measurement, demonstration and regulation device, shielding and automatic safety device and high-voltage pulse electric field processing chamber.When material subject to sterilization is passed through to high-voltage pulse electromagnetic field, microorganism is subject to the effect of strong-electromagnetic field power at the utmost point in the short time, and its cellularity is destroyed due to the potential difference between cell membrane, causes the irreversible perforation polarization of cell membrane.Patent of invention (200310119299) discloses a kind of impulse electric field for the method for Nicotiana tabacum L. Pesticidal and sterilizing.The low frequency shock pulse effect that the method is 10～15Kv/cm by pulse amplitude is placed on the Nicotiana tabacum L. between electrode, after certain hour, can kill entomogenous fungi.Unidirectional positive pulse or unidirectional negative pulse, or bidirectional pulse all can.But this invention does not have to illustrate the method that how to allow electrode and Nicotiana tabacum L. keep even contact, and this point is most important in production technology.Patent of invention (200410011305) relates to a kind of device for food, beverage high voltage pulse electric field processing, by forming with joining two electrodes in controllable high-voltage pulse power the two poles of the earth respectively, two radial dimension differences and the identical hollow pipe of cross sectional shape, be coaxial shape suit together, port is opened two hollow pipe electrode isolation by insulator shading ring, and fixed closed, the annular gap forming between these two hollow pipe electrodes is the cavity volume of carrying material handling, is provided with the material import and export communicating with this cavity volume on outer pole plate.Patent of invention (200410077405) discloses a kind of Prepolarized pulse electric field disinfectant method,, before high-voltage pulse electric field sterilization, first material is carried out in electrostatic field to pre-polarization, and described electrostatic field field intensity is 100～1000V/cm; Prepolarized pulse electric field disinfectant equipment comprises material-storage jar, pump, vacuum degasser, high-voltage pulse electric generator, electric pulse process chamber and the electrode being connected with DC source.Patent of invention (200510041039) discloses a kind of method for producing sugar-free tea beverage that adopts high voltage pulsation electric-field sterilizing tech, and first by Folium Camelliae sinensis lixiviate in hot water, millet paste is cooling rapidly after screen filtration, the centrifugal precipitation of going; Millet paste is after micro-filtration membrane is further filtered, then through high-voltage pulse electric field sterilization.In tea beverage after processing, polyphenol content, flavor substance content and aberration have no significant change, and by its cryopreservation, after 9 months, safety and sensible quality are still good.Patent of invention (200710008847) relates to a kind of process method of sterilization, enzyme inhibitor for non-thermal fruit and vegetable concentrated juice, utilize high voltage pulsation electric-field sterilizing tech, in conjunction with technology for freeze concentration, produce fruit and vegerable concentrated juice simultaneously, processed step is: 1. at normal temperatures, make the fruit and vegetable juice electric field intensity >=10kv/cm that flows through, umber of pulse >=10, the high-pressure pulse electric of pulse width >=2 μ s ,≤100 μ s carries out sterilization treatment, and the enzyme in part passivation fruit and vegetable juice; 2. by the fruit and vegetable juice after processing in the temperature freeze concentration below 0 ℃, the activity that suppresses enzyme in fruit and vegetable juice, whole processing procedure is carried out at a lower temperature, thereby when realizing sterilization, enzyme inhibitor, solve the fruit juice quality decline problem causing because of thermal methods.Patent of invention (20071044498) relates to a kind of high-pressure pulse electric sterilization process device for liquid food.The control signal input of the pulse signal output end of its pulse signal generation circuit and pulse generating circuit is connected, two pulse signal output ends of pulse generating circuit are connected with two pulse control signal inputs of discharge circuit, the voltage signal input of discharge circuit and the voltage signal output end of booster circuit are connected, two pole plates of sterilizing electric capacity respectively with the discharge signal outfan of discharge circuit and power supply be connected; Process chamber is sealing cuboid space, and two pole plates of sterilizing electric capacity are separately fixed in the opposed inner walls of two area maximums in process chamber, and two pole plates are full of its fixing inwall, on the sidewall of the process chamber vertical with battery lead plate, have a charging aperture.It can be applied to liquid food sterilizing field.
The U.S. has ratified the patent that more than 200 relevant high-voltage pulse induction PEF process food from 1987 to 2002.Such as Dunn and Pearlman(1987) the patent apparatus and method of shelf life (extend food liquid), Morshuis(2002) patent (utilizing method and the instrument of impulse electric field preserve foods), patent Robbins(2001) (being reduced in process and the instrument of the micro organism quantity in electrical conductance medium with low voltage pulsed electrical energy) and Lelieveld and Volanschi(2001) patent (method of food preservation and instrument) etc.
Aspect non-food stuff processing, Chinese utility model patent (2003249380) relates to high-pressure pulse electric to be killed in liquid and has biology (as virus, antibacterial, the microorganisms such as algae) a kind of high-pressure rotary impulse electric field alga killing and sterilizing machine, it is characterized in that sterilizer is by least two high voltage electric field posts, a high-voltage switch gear and a coaxial Dynamic Water are processed cavity and are formed, it is the cylindrical shape that axis position is placed with wire that coaxial Dynamic Water is processed cavity, wire is anode, cylinder-shaped coat is negative electrode, cavity between anode and negative electrode is high voltage electric field sterilizing place, wire connects with high-voltage switch gear one end, cylinder-shaped coat connects with high voltage electric field column one end, high-voltage switch gear connects with the high voltage electric field post other end, each high voltage electric field post is comprised of the transformer group of bottom and the capacitor on top and diode group, the transformer group of multipath magnetic circuit stack generation high-tension electricity is carried out cophase stacking by 2-70 transformator and is formed, and the capacitor of stored charge and diode group are connected in series and form by 50-10000.Patent of invention (200810224305) relates to a kind of method that reduces organophosphorus pesticide in soymilk, the bean milk that contains organophosphorus pesticide is flowed into pretreatment chamber through peristaltic pump, adopt the method for evacuation to carry out degassed, pre-cooling to bean milk, set high-pressure pulse electric parameter, open peristaltic pump, bean milk is pumped into high-voltage pulse electric field processing chamber, bean milk is processed, organophosphorus pesticide concentration in bean milk is significantly declined.Patent of invention (200810003740) has disclosed a kind of method of biological sludge high-efficiency dehydration, and the sludge moisture content after processing is lower than 50%.Biological sludge after self enzyme catalysis is processed voltage be 25kV/cm-120kV/cm, frequency be 1000Hz-10000Hz high-pressure pulse electric and as the perforation concentrated sulphuric acid of agent or the synergism of sulfur trioxide under, in mud, microbial cell is destructurized.The calcium sulfate that the protein discharging from broken cell, nucleic acid and other biomacromolecule material are newly produced and the moon or cationic-type polyacrylamide cohesion dehydration form the bulk sludge coagulating body of compact structure, and the latter is put into press dewatering machinery and sloughs free moisture.United States Patent (USP) (
Held and Chauhan(2002) patent a kind of method of using high voltage molecule to destroy waste activated sludge is proposed.
Britain Standen Ltd. discloses a patent of invention (200680026027): it is effective that the electric field with certain characteristic has demonstrated in the growth course that stops cancerous cell (and other rapid somatoblast).But, when cancer is positioned at the target area under body surface, transmit described useful electric field very difficult to described target area.By placing biocompatible field guide, each side electrodes of leading on the scene and apply the alternating voltage with appropriate frequency and amplitude between body surface and described target area between described electrode, useful field can be directed into described target area.In alternative embodiment, one of described electrode be placed directly on field lead above.Obviously, this method is appointed so need to lead insertion human body by electrode and field, and the homogeneity question between electrode is appointed right existence.Patent of invention (1993102036) relates to a kind of auxiliary electrical therapeutic apparatus that coordinates Drug therapy cancer.By adjust blood pressure, boost, voltage multiplying rectifier obtains height and forces down unidirectional current (field), through relay, produces intermittent electric current (field), connects combination electrode plate, make the insulant polarization of combination electrode plate, produce a kind of safety and can make the interrupted UNIFORM ELECTROSTATIC FIELD existing of human body deep tumor tissue.Thereby interfere with cancer cells growth, guide drugs is gathered in tumor tissue, and performance coordinates the assosting effect of Drug therapy cancer.What the method adopted is low pressure non-pulse electric field, and the mechanism of electric field interfere with cancer cells is unclear.Therefore curative effect leaves a question open.
Summary of the invention
The foundation of high-pressure pulse electric must meet several conditions: (1) high electric field intensity (the minimum critical intensity scope of most of microbe deactivation is 4-14kv/cm); (2) must be direct current or extremely low frequency AC field (electric field that is added on surface of cell membrane preferably keeps a direction, if changed at a high speed back and forth, can not make perforate membrane); (3) there is pulse characteristic; (4) need certain processing time; (5) foundation of electric field need to arrange positive negative at least two electrodes in object being treated.
As previously mentioned, the use of electrode can bring series of problems.
The invention provides a kind of faradic method and apparatus of high-voltage pulse that produces in object, object meets exactly above 4 conditions and cancels electrode condition, make this technology have larger superiority than existing high-voltage pulse technology, the present invention can produce with cordless high-voltage pulse faradic current in pending object.
The technology proposing due to the present invention has adopted special induction field mode, therefore be called high-voltage pulse induction field technology (Pulsed Induction Electric Field), is called for short PIEF.The generation of high-voltage pulse induction field technology PIEF is from high-voltage pulse induction generator (PIEF generator).PIEF generator is responsible for providing waveform, persistent period and the desirable strength of high-voltage pulse.
For achieving the above object, the present invention adopts following technical scheme:
A method for the treatment of biological cell in object, comprises the following steps: the high direct voltage of (1) power generation institute desired strength; (2) utilize one or electric capacity in groups to carry out stored electric energy; (3) waveform and the wide release high-voltage pulse of ripple with regulation by pulse forming network; (4) high-voltage pulse makes induction coil group produce the magnetic induction variations of flux of impulse form; (5) near the space of the variation of magnetic induction flux induction coil group excites the high strength induction field that produces impulse form; (6) be positioned over the high strength induction electromotive force that interior of articles pending in induction field produces impulse form; (7) induction electromotive force forms the direct current high strength faradic current of impulse form at pending object, and the method can produce with cordless high-voltage pulse faradic current in pending object; (8) in induction coil and/or pending interior of articles or outside appropriate location, add and can strengthen induction coil group magnetic induction flux and very large to such an extent as to very little permeability magnetic material or the magnetic conduction construction part of eddy current effect of resistivity own, make to improve through the magnetic induction of this pending object, but can be at the permeability magnetic material adding or the significant eddy current of the inner generation of magnetic conduction construction part.
Described method, the permeability magnetic material that strengthens magnetic induction comprises ferrous alloy and ferrite; Or the permeability magnetic material that strengthens magnetic induction can be loop-like transformer core, also can make other magnetic conduction construction part, also can make microgranular; Permeability magnetic material can be positioned among induction coil, also can be placed on outside induction coil; Can be placed on outside pending object, also can be placed on pending interior of articles.
Described method, allows magnetic conduction construction part stretch in pending object depression, and magnetic force path by this pending interior of articles and density of line of magnetic force and magnetic induction are all increased; Or pending object is placed in one or more breach of opening on originally closed permeability magnetic material structural member, make the intensive magnetic line of force through pending object, portion produces very strong pulse induction electric current within it.
Described method, the permeability magnetic material adding at pending interior of articles, comprises metal powder, salt end, electrolyte, high conductivity liquid and their mixture.
Described method, the form of pending object can be solid-state, liquid state or gaseous state; From class although, can be metal, pottery, macromolecular material, food, medicine or articles for daily use; From kinestate, can maintain static and process, also can be and flow or mobile status, process incessantly.
Described method, pending object be possible by microorganism or/and food, medicine or the articles for daily use that Toxic pollutes, pending body surface or the inner faradic current producing are for the deactivation of microorganism and the decomposition of noxious substance.
For the treatment of an equipment for biological cell in object, which comprises at least a DC high-voltage power supply that can produce institute's desired strength, the electric capacity of one or more energy stored electric energies forms pulse forming network, at least one charge and discharge switch, at least one or one group of induction coil, after the waveform and ripple wide release high-voltage pulse of pulse forming network with regulation, high-voltage pulse makes induction coil group produce the magnetic induction variations of flux of impulse form, near the space of the variation of magnetic induction flux induction coil group excites the high strength induction field that produces impulse form, be positioned over the high strength induction electromotive force that interior of articles pending in induction field produces impulse form, induction electromotive force forms the direct current high strength faradic current of impulse form with cordless at pending interior of articles, this equipment can produce with cordless high-voltage pulse faradic current in pending object, in induction coil and/or pending interior of articles or outside appropriate location, add and can strengthen induction coil group magnetic induction flux and very large to such an extent as to very little permeability magnetic material or the magnetic conduction construction part of eddy current effect of resistivity own, make to improve through the magnetic induction of this pending object, but can be at the permeability magnetic material adding or the significant eddy current of the inner generation of magnetic conduction construction part.
Described equipment, the permeability magnetic material that strengthens magnetic induction comprises ferrous alloy and ferrite; Or the permeability magnetic material that strengthens magnetic induction can be loop-like transformer core, also can make other magnetic conduction construction part, also can make microgranular; Permeability magnetic material can be positioned among induction coil, also can be placed on outside induction coil; Can be placed on outside pending object, also can be placed on pending interior of articles.
Described equipment, allows magnetic conduction construction part stretch in pending object depression, and magnetic force path by this pending interior of articles and density of line of magnetic force and magnetic induction are all increased; Or pending object is placed in one or more breach of opening on originally closed permeability magnetic material structural member, make the intensive magnetic line of force through pending object, portion produces very strong pulse induction electric current within it.
Described equipment, the permeability magnetic material adding at pending interior of articles, comprises metal powder, salt end, electrolyte, high conductivity liquid and their mixture.
Described equipment, the form of pending object can be solid-state, liquid state or gaseous state; From class although, can be vivo biological tissue, inorganic matter, metal, pottery, macromolecular material, food, medicine or articles for daily use; From kinestate, can maintain static and process, also can be and flow or mobile status, process incessantly.
Described equipment, pending object be possible by microorganism or/and food, medicine or the articles for daily use that Toxic pollutes, pending body surface or the inner faradic current producing are for the deactivation of microorganism and the decomposition of noxious substance; Or pending object is human body or organism pathological tissues; the intensity controlled pulse induction electric current that pathological tissues inside or skin surface produce is for promoting the increase of organization internal or skin surface cell permeability, and the increase of permeability can realize by the reversible or irreversible perforation of cell membrane; Or pending object is tumor tissues, the reversible perforation of cell membrane is used for promoting medicine to enter tumor cell inside, the irreversible perforation of cell membrane or destroy for direct killing off tumor cells.
Described equipment, by injecting to pathological tissues or input medicine, inject or input simultaneously or only normal saline or other high conductivity liquid that contains high permeability material microgranule, make the projecting normal structure of density of line of magnetic force in pathological tissues, the pulse induction current ratio surrounding normal cell that sick cell is born is large; Or the reversible perforation of cell membrane is used for promoting outside gene to intracellular transfer; Or the increase of cell permeability is used for promoting that glucose in blood enters cell; The increase of skin surface cell or tissue permeability is used for promoting that medicine enters human body from skin; On organization internal or surface or skin appearance layer add the liquid containing high permeability material microgranule, comprise normal saline or other mixed liquid containing the ferrite nano microgranule of glucose parcel.
The difference of the present invention and existing high-voltage pulse induction PEF is: (1) does not need electrode can produce controlled high intensity pulses electric current; (2) pending object needs only in the space induction field that can conduct electricity and produce in induction coil group, can produce in inside required high intensity pulses electric current; (3) in pending interior of articles or outside interpolation, can strengthen the material of the magnetic induction flux (magnetic flux) of induction coil group, can strengthen the impulse form faradic current that induction electromotive force forms at interior of articles; Reach the object that improves killing microorganisms or cancerous cell effect.
The present invention can be applicable to food processing, food processing, medical treatment and Pollutant Treatment.
Accompanying drawing explanation
The faradic circuit diagram of Fig. 1 single index attenuation type high-voltage pulse.
The faradic circuit diagram of the bipolar exponential damping type of Fig. 2 high-voltage pulse.
Fig. 3 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment mono-.
Fig. 4 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment bis-.
Fig. 5 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment tri-.
Fig. 6 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment tetra-.
Fig. 7 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment five.
Fig. 8 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment six.
Fig. 9 high magnetic permeability, the schematic diagram of low eddy current effect structural member and pending object relative position embodiment seven.
The schematic diagram of Figure 10 fruit surface process for producing line.
The structural representation of Figure 11 sterilization fresh case.
Figure 12 cancerous issue external treatment principle schematic.
The specific embodiment
The present invention relates to the faradic method and apparatus of a kind of generation Unidirectional direct-current high-voltage pulse: high direct voltage pulse induction generator (PIEF generator).PIEF generator is responsible for providing waveform, persistent period and the desirable strength of high-voltage pulse.The normal work of equipment comprises following process: the high direct voltage of (1) power generation institute desired strength; (2) utilize one or electric capacity in groups to carry out stored electric energy; (3) waveform and the wide release high-voltage pulse of ripple with regulation by pulse forming network; (4) high-voltage pulse makes induction coil group produce the magnetic induction variations of flux of impulse form; (5) near the space of the variation of magnetic induction flux induction coil group excites the high strength induction field that produces impulse form; (6) be positioned over the inner high strength induction electromotive force that produces impulse form of conductive body pending in induction field; (7) induction electromotive force is at the inner high strength faradic current that forms impulse form of conductive body.(8) if added in the inner or outside appropriate location of induction coil and/or conductive body, can strengthen induction coil group magnetic induction flux and resistivity own is very large or very little magnetic conduction substance or the magnetic conduction construction part of eddy current effect, can make to improve through the magnetic flux increment of conductive body, and can not produce obvious eddy current and consume energy in substance or material internal; (9) if add the high material of conductivity at pending interior of articles, can improve the inner faradic intensity producing of handled thing, thereby improve, kill handled thing surface or the inner microorganism existing, cancerous cell and the efficiency of decomposing noxious substance.
Fig. 1 can produce the faradic circuit diagram of single index attenuation type high-voltage pulse.In figure, 1 is DC high-voltage power supply, can produce the high direct voltage that is not less than thousands of volts, and R1 is charging resistor, C1 is the capacitor for discharging and recharging, the 4th, transmission line resistance, the 5th, switch resistance, the 6th, induction coil resistance, the 7th, induction coil, the 8th, the one-way magnetic line that induction coil produces, the 9th, be positioned near the conductive body of induction coil, the 10th, at the inner unidirectional faradic current producing of conductive body, the 11st, charge and discharge switch, is called again electric brake.Electric brake 11 discharges electric energy in high-voltage pulse mode by pulse forming network, and it must be controlled the high voltage being present in capacitor 3 and act on the high electric current in shaping network.On market, there are two class high power electric brakees, i.e. ON electric brake and ON/OFF electric brake.The latter has the function of random switch.
Fig. 2 can produce the faradic circuit diagram of bipolar exponential damping type high-voltage pulse.In figure, 1 is DC high-voltage power supply, and R1, R2 and R3 are charging resistors; C1, C2 and C3 are the capacitors for discharging and recharging, the 4th, transmission line resistance, the 5th, switch resistance, the 11st, charge and discharge switch, the 6th, induction coil resistance, the 7th, induction coil, the 16th, high magnetic permeability structural member, the magnetic line of force direction that can guide induction coil to produce, increases density of line of magnetic force, the 9th, be positioned over the conductive body of high magnetic permeability structural member periphery, the 10th, at the inner unidirectional faradic current producing of conductive body.
Can strengthen induction coil group magnetic induction flux (magnetic flux), material or the material that itself can not produce again very strong eddy current effect have a lot, and selection principle is: pcrmeability is high and resistivity is large.Pure iron pcrmeability high (10000), but resistivity low (10m Ω .cm), in the alternating magnetic field producing, can produce very strong eddy current, so electromagnetism rate is very suitable with iron pan at induction coil.Aluminum is paramagnetics material, and susceptibility is very little, and relative permeability is a bit larger tham 1.Copper is diamagentic effect material, and relative permeability is less than 1.All can not strengthen the magnetic induction flux of induction coil, enable to strengthen, itself also can produce very strong eddy current effect.The ferritic maximum permeability μ of manganese-zinc (Mn-Zn)
rmaxreach 2500, resistivity reaches 2X10
6(m Ω .cm), so be desirable selection.As the silicon steel (4.00%Si) of transformator material, although pcrmeability μ
rmaxreach 7000, but resistivity only has 45-70 (m Ω .cm), so after need to laminating, form laminated construction, insulation between layers, makes eddy current effect because being confined to become very little in monolithic thin layer.In the present invention, will adopt this class material, material or structural member strengthen the magnetic induction flux of induction coil and pending interior of articles.On the other hand, these materials, the position that material or structural member are placed is also very important.Its design principle is: improve as far as possible the density of line of magnetic force through pending interior of articles.
What Fig. 3-Fig. 9 showed is the schematic diagram of 7 kinds of embodiment.In figure, 7 is induction coils; The 16th, high magnetic permeability, high resistivity material or high magnetic permeability, the structural member of low eddy current effect; The 17th, pending object; Dotted line represents the magnetic line of force.Embodiment mono-is shown in Figure 3, and in design, pending object is positioned over one end of strip permeability magnetic material structural member 16, the magnetic line of force sending from this end of structural member, only have part through the bottom of pending object, and density of line of magnetic force is low, magnetic induction is little.Thereby treatment effect is poor.Embodiment bis-is shown in Figure 4, and design and embodiment mono-design difference are in pending object, to add or embedded extra permeability magnetic material 18, makes to enter magnetic induction line in pending object and extends, and density increases, to improve treatment effect.Embodiment tri-is shown in Figure 5, design is the version of embodiment bis-designs, allow permeability magnetic material structural member stretch in the specially designed depression of pending object, magnetic force path by this interior of articles and density of line of magnetic force and magnetic induction are all increased.Embodiment tetra-is shown in Figure 6, design is to open (or a plurality of) breach on originally closed permeability magnetic material structural member (as loop-like transformer core), pending object is put into breach, make the intensive magnetic line of force through object, portion produces very strong unidirectional pulse faradic current within it.Embodiment five is shown in Figure 7, design and embodiment tetra-design differences are: the microgranule of a large amount of permeability magnetic materials is managed to inject a certain region 19 of pending interior of articles, make further to increase through the density of line of magnetic force in this region, the microorganism in this region or cancerous cell will bear larger single line pulse induction electric current.Embodiment six is shown in Figure 8, and the design of design is suitable for the pending object of flat, and induction coil 7 is designed to plate-like, is similar to the coil in Household induction cooker.Permeability magnetic material structural member is positioned over (or above) below coil, can be whole plate-like or is comprised of the strip structure part of a plurality of radial arrangement.Pending object is put in (or below) above coil, and magnetic power, through the larger area in object, produces the faradic current of distribution uniform.Embodiment seven is shown in Figure 9, and design is that induction coil and permeability magnetic material structural member are positioned over to pending object center, allows the magnetic power that structural member sends in handled object, walk longer distance, produces continuous faradic current on the way.
In the present invention, the form of pending object can be solid-state, liquid state or gaseous state.From class although, can be vivo biological tissue or inorganic matter, can be metal, pottery or macromolecular material, can be food, medicine, articles for daily use etc.From kinestate, can maintain static and process, also can be and flow or mobile status, continual processing.
In the present invention, the permeability magnetic material that strengthens magnetic induction can be made various structural members, also can make microgranular (as the powder of nano-scale).Permeability magnetic material can be positioned among induction coil (allow coil winding permeability magnetic material structural member), also can be placed on outside induction coil; Can in case be placed on outside pending object, also can be placed on pending interior of articles.
In the present invention, can carry out by increasing the measure of pending interior of articles material electrical conductivity the faradic current of enhancement process thing inside.Be included in the inner high material of electrical conductivity that adds of handled thing, comprise metal powder, salt end, electrolyte etc.
Figure 10 is the schematic diagram of a fruit surface process for producing line.The fruit 21 being positioned on transport tape 20 passes the breach of permeability magnetic material structural member 16 with certain speed, the intensive magnetic line of force of structural member indentation, there will, through fruit, make microorganism deactivation because high-intensity faradic current causes membrane perforation of fruit surface.The residual pesticide (as organophosphor) that fruit surface adheres to simultaneously also can, by decomposed, reach the object of killing two birds with one stone.
What Figure 11 showed is the structural representation of this sterilization fresh case.In figure, 1 is DC high-voltage power supply, can produce the high direct voltage that is not less than thousands of volts, and 22 are to provide the generator of high-pressure pulse direct current, the 7th, and induction coil, the 16th, there is the structural member of high permeability and low eddy current effect, the 23rd, pending food.The 24th, the container of packing foods.General Requirements aluminum, the paramagnetic materials such as macromolecule or pottery are made.If container is very shallow dish, and food fills very fullly.With ferrous material, also can.
Figure 12 is the principle schematic for the treatment of breast cancer tissue.In figure, 7 is induction coils, the 26th, there is high permeability, and the therapeutic apparatus of low eddy current effect, when induction coil passes into DC-pulse.On therapeutic apparatus, produce the magnetic circuit of base closed.But its indentation, there has leakage field.By ultrasonic or CT method, determine breast carcinoma position and size in advance, except injectable drug in cancerous tissue, also need injection containing normal saline or the solvent of high permeability material microgranule, also can the two inject together.If drug administration is only injected the latter.Then allow breast embed therapeutic apparatus breach, make the magnetic power that send at breach two ends pass breast carcinoma tissue 25.Due to the aggregation of high magnetic permeability microgranule to the magnetic line of force, make density of line of magnetic force in cancerous tissue far above normal surrounding tissue, again due to the high conductivity of normal saline, the unidirectional pulse faradic current that cancerous cell is born is more much bigger than surrounding normal cell.So the punching rate of cancer cell membrane is much larger than normal cell, medicine can enter wherein, plays efficient killing action.A clinical experiment example is that ferrite nano particles is wrapped up with glucose molecule, after dissolving, injects and suffers from Mus tumor locus in water, and cancerous cell is sealed by magnetic field completely.On the one hand, adopt the technology of the present invention, make the perforate membrane of the tumor cell that surrounded by magnetic particle and death.On the other hand, under impulse electric field continuous action, ferrite nano particles can be heated to 45 ℃ or higher, makes tumor cell bear high temperature and accelerates death.Owing to not having magnetic particle in normal structure around, therefore harmless.
Preliminary experiment has shown good result.Adopt circuit diagram shown in Fig. 1, use 220V alternating current power supply, by obtaining the high pressure of 25K after transformation, then be converted to direct current, charge and discharge capacitance can bear 30K high pressure.Induction coil adopts the spiral plate-like coil form in Fig. 8 design, and coil line is that multiply enamel covered wire gummed forms, and needs the above high pressure of resistance to 30K.The parts transformation of the way that its permeability magnetic material and winding wire are all pulled down in available Household induction cooker.Above hub of a spool, place milk box.Wherein milk is pasturising milk, under room temperature (20
oc) shelf-life is no more than 3 days.In contrast, outside coil, certain distance is placed same milk box.Capacitor charging at full capacity after, start to spark, produce the pulse current of approximate single index Decay Rate, make to produce in permeability magnetic material corresponding magnetic field impulse, the magnetic line of force is through milk box, make to produce unidirectional faradic current of moment in milk, this pulse current makes the microbial cell film in milk occur irreversible perforation and death.Automatically charging again after electric capacity is discharged, and then electric discharge, between discharging and recharging, interval is approximately 1.5 seconds.
Experiment shows, accepts to process the milk of 2 hours and can extend more than one times than the milk that the there is no processing shelf-life at room temperature.Experiment is demonstration further, if put into Ferrite Material in accepting the milk of processing, and can the significant prolongation shelf-life.
The present invention can be widely used in a plurality of fields, and instantiation is as follows: one. food processing: high-voltage pulse induction PEF technology is the bacteria inactivation rate of large-scale application on liquid state or part half flowable state food processing line.But so far, still can not be for solid-state, the processed of semisolid and powdery food.The high-voltage pulse induction field PIEF technology that the present invention proposes can be used in the bacteria inactivation rate of all form food processing lines.Figure 10 is the schematic diagram of a fruit surface process for producing line.The fruit 21 being positioned on transport tape 20 passes the breach of permeability magnetic material structural member 16 with certain speed, the intensive magnetic line of force of structural member indentation, there will, through fruit, make microorganism deactivation because high-intensity faradic current causes membrane perforation of fruit surface.The residual pesticide (as organophosphor) that fruit surface adheres to simultaneously also can, by decomposed, reach the object of killing two birds with one stone.
Two. food sterilizing is fresh-keeping: the high-voltage pulse induction field PIEF technology that the present invention proposes also can be used for the fresh-keeping and instant sterilization treatment of food.Owing to not needing heating, institute is very suitable for the sterilization of the instant food of raw food (as Sushi, oysters seafood).The sterilization fresh case of art designs can substitute conventional refrigerator or household freezer accordingly, it is with the obvious advantage: sterilizing is regardless of kind (refrigerator can not suppress Listerella etc. and not fear cold microorganism), can eliminate because microorganism does not have the food nitrite that deactivation causes to increase in refrigerator, can go deep into the inner thoroughly sterilizing of food, power and energy saving, noise is little, without freon, do not need insulation material, cost is low etc.But cold drink can not be provided and freeze, being unsuitable for preserving the easy food that melts under room temperature.What Figure 11 showed is the structural representation of this sterilization fresh case.In figure, 1 is DC high-voltage power supply, can produce the high direct voltage that is not less than thousands of volts, and 22 are to provide the generator of high-pressure pulse direct current, the 7th, and induction coil, the 16th, there is the structural member of high permeability and low eddy current effect, the 23rd, pending food.The 24th, the container of packing foods.General Requirements aluminum, the paramagnetic materials such as macromolecule or pottery are made.If container is very shallow dish, and food fills very fullly.With ferrous material, also can.
Three. the external electroporation of tumor cell: electroporation (EP) or reversibility electrical breakdown (REB) they are the oncotherapy technology that development in recent years is got up.It adopts the electrode needle transmitting high-voltage pulse current that inserts lesion region, make tumor cell membrane occur the electroporation that micropore or permeability increase sharply, allow cancer therapy drug can overcome cell membrane barrier, directly enter cell interior and kill cancerous cell, reach enhancing effect of drugs, reduce dosage and side effect, overcome the object of drug resistance.This method need to be inserted human body by electrode, and therapeutic process is simple, and effect is certain, and expense is few.The high-voltage pulse induction field PIEF technology that the present invention proposes can similarly be treated in vitro.And do not need electrode insertion.Figure 12 is the principle schematic for the treatment of breast cancer tissue.In figure, 7 is induction coils, the 26th, there is high permeability, and the therapeutic apparatus of low eddy current effect, when induction coil passes into DC-pulse.On therapeutic apparatus, produce the magnetic circuit of base closed.But its indentation, there has leakage field.By ultrasonic or CT method, determine breast carcinoma position and size in advance, except injectable drug in cancerous tissue, also need injection containing normal saline or the solvent of high permeability material microgranule, also can the two inject together.If drug administration is only injected the latter.Then allow breast embed therapeutic apparatus breach, make the magnetic power that send at breach two ends pass breast carcinoma tissue 25.Due to the aggregation of high magnetic permeability microgranule to the magnetic line of force, make density of line of magnetic force in cancerous tissue far above normal surrounding tissue, again due to the high conductivity of normal saline, the unidirectional pulse faradic current that cancerous cell is born is more much bigger than surrounding normal cell.So the punching rate of cancer cell membrane is much larger than normal cell, medicine can enter wherein, plays efficient killing action.A clinical experiment example is that ferrite nano particles is wrapped up with glucose molecule, after dissolving, injects and suffers from Mus tumor locus in water, and cancerous cell is sealed by magnetic field completely.On the one hand, adopt the technology of the present invention, make the perforate membrane of the tumor cell that surrounded by magnetic particle and death.On the other hand, under impulse electric field continuous action, ferrite nano particles can be heated to 45 ℃ or higher, makes tumor cell bear high temperature and accelerates death.Owing to not having magnetic particle in normal structure around, therefore harmless.
Four. Pulse Electric gene therapy: gene therapy is the new technique developing rapidly in recent years.It supplements or transforms by human genetic material is revised the object that reaches treatment disease.Wherein gene transfer technique is crucial.The essence of Pulse Electric gene therapy is: cell is under high-voltage pulse electro ultrafiltration, and hole appears in cell membrane, and genes of interest deforms and moves under electric field action, even if can pass less hole, enters in cell.Once the hole formation on film, gene subsequently is also easier to shift under weak electric field.After perforate membrane, in cell, still maintain complete shell system, it is active that cell still can keep, and can make the genes of interest effective expression entering.The technology of the present invention can complete the membrane perforation of pathological tissues in vitro, and allows gene transfer enter in sick cell, thereby has advantages of non-invasive therapy.
Five. the non-invasive therapy of cancer: if strengthened pulse strength and action time, optimize faradic current parameter, adopt said method and equipment, just can, without cancer therapy drug in the situation that, make cancer cell membrane produce irreversible perforation and death.Cancerous issue normal cell is around unaffected, or impact is very little.Reach the external non-invasive therapy of cancer.In recent years, people adopt magnetic in clinical experiment, and how rice microgranule is as pharmaceutical carrier, after taking, under additional introduction by magnetic field, arrives diseased region, and then drug release, kills cancerous cell.The technology of the present invention can further be hit cancerous cell in the pharmaceutically-active while, improved therapeutic effect.
Six. diabetes non-drug therapy: when the concentration of glucose in blood raises, have at least the influencing factor of two aspects that organism metabolism rate is improved.The one, concentration of glucose raises diffusion process is accelerated, and histiocyte is easy to obtain glucose, and it utilizes the metabolic process of glucose to will speed up and produce extra heat, and heat energy is the energy of minimum form.This is that physical action is main factor.The 2nd, the rapid secretion of insulin, impels each histiocytic membrane permeability to increase, and glucose enters in cell, produces oxidation heating, and this is that biochemical action is main factor.If insulin secretion reduces or insulin resistant occurs, only, under medicine helps, the glucose in blood can enter cell in a large number.Present device is positioned over to skin surface, at organization internal in a big way, produces intensity controlled pulse direct current faradism, can make the film of a large amount of cells produce small reversibility perforation, glucose in blood can be entered in cell and be utilized rapidly.Thereby reducing in time blood glucose, is complete noninvasive whole body therapeutic, is so far, just hypoglycemic unique method can not fall by medicine.
Seven. percutaneous dosing new method: " percutaneous dosing " is an ancient administering mode.Modern percutaneous dosing has been broken through traditional boundary far away, its development has reflected the last word of controlled release drug administration and target administration, it is applied to treat local skin or general disease (as cardiovascular disease, nervous system disease), than other dosage forms, have advantages of safer, effective, stable and patient compliance is good.But because skin is very low to the permeability of most drug, only have small part medicine to be applicable to percutaneous dosing.It is the horny layer (stratum corneum) of skin that medicine sees through the topmost barrier of skin, what most of transdermal administration was studied is to promote medicine to see through the various technical methods of keratodermatitis, comprise various transdermal enhancers, iontophoresis (iontophoresis), electroporation method (electroporation), phonophoresis (phonorphoresis, sononphoresis) and laser introductory technique etc.The technology of the present invention provides a kind of new thinking.Employing is positioned over the permeability magnetic material structural member of skin surface, and the intensity controlled pulse induction electricity producing in keratodermatitis, can puncture rapidly intercellular lipid.Because this lipid plays a major role at skin barrier, so skin barrier is removed immediately, the medicine of placing in advance skin surface just can enter in body in a large number.If medicine is electrolyte or the solution of high conductivity, can also play the effect that increases induction current intensity.
Claims (13)
1. for the treatment of a method for biological cell in object, comprise the following steps: the high direct voltage of (1) power generation institute desired strength; (2) utilize one or electric capacity in groups to carry out stored electric energy; (3) waveform and the wide release high-voltage pulse of ripple with regulation by pulse forming network; (4) high-voltage pulse makes induction coil group produce the magnetic induction variations of flux of impulse form; (5) near the space of the variation of magnetic induction flux induction coil group excites the high strength induction field that produces impulse form; (6) be positioned over the high strength induction electromotive force that interior of articles pending in induction field produces impulse form; (7) induction electromotive force forms the direct current high strength faradic current of impulse form at pending object, and the method can produce with cordless high-voltage pulse faradic current in pending object; (8) in induction coil and/or pending interior of articles or outside appropriate location, add and can strengthen induction coil group magnetic induction flux and very large to such an extent as to very little permeability magnetic material or the magnetic conduction construction part of eddy current effect of resistivity own, make to improve through the magnetic induction of this pending object, but can be at the permeability magnetic material adding or the significant eddy current of the inner generation of magnetic conduction construction part;
Described pending object does not comprise vivo biological tissue.
2. the method for claim 1, is characterized in that: the permeability magnetic material that strengthens magnetic induction comprises ferrous alloy and ferrite; Or the permeability magnetic material that strengthens magnetic induction can be loop-like transformer core, also can make other magnetic conduction construction part, also can make microgranular; Permeability magnetic material can be positioned among induction coil, also can be placed on outside induction coil; Can be placed on outside pending object, also can be placed on pending interior of articles.
3. method as claimed in claim 2, is characterized in that: allow magnetic conduction construction part stretch in pending object depression, magnetic force path by this pending interior of articles and density of line of magnetic force and magnetic induction are all increased; Or pending object is placed in one or more breach of opening on originally closed permeability magnetic material structural member, make the intensive magnetic line of force through pending object, portion produces very strong pulse induction electric current within it.
4. the method for claim 1, is characterized in that: the permeability magnetic material adding at pending interior of articles, comprises metal powder, salt end, electrolyte, high conductivity liquid and their mixture.
5. the method for claim 1, is characterized in that: the form of pending object can be solid-state, liquid state or gaseous state; From class although, can be metal, pottery, macromolecular material, food, medicine or articles for daily use; From kinestate, can maintain static and process, also can be and flow or mobile status, process incessantly.
6. the method for claim 1, it is characterized in that: pending object for may be by microorganism or/and food, medicine or the articles for daily use that Toxic pollutes, pending body surface or the inner faradic current producing are for the deactivation of microorganism and the decomposition of noxious substance.
7. for the treatment of an equipment for biological cell in object, which comprises at least a DC high-voltage power supply that can produce institute's desired strength, the electric capacity of one or more energy stored electric energies forms pulse forming network, at least one charge and discharge switch, at least one or one group of induction coil, after the waveform and ripple wide release high-voltage pulse of pulse forming network with regulation, high-voltage pulse makes induction coil group produce the magnetic induction variations of flux of impulse form, near the space of the variation of magnetic induction flux induction coil group excites the high strength induction field that produces impulse form, be positioned over the high strength induction electromotive force that interior of articles pending in induction field produces impulse form, induction electromotive force forms the direct current high strength faradic current of impulse form with cordless at pending interior of articles, this equipment can produce with cordless high-voltage pulse faradic current in pending object, in induction coil and/or pending interior of articles or outside appropriate location, add and can strengthen induction coil group magnetic induction flux and very large to such an extent as to very little permeability magnetic material or the magnetic conduction construction part of eddy current effect of resistivity own, make to improve through the magnetic induction of this pending object, but can be at the permeability magnetic material adding or the significant eddy current of the inner generation of magnetic conduction construction part.
8. equipment as claimed in claim 7, is characterized in that: the permeability magnetic material that strengthens magnetic induction comprises ferrous alloy and ferrite; Or the permeability magnetic material that strengthens magnetic induction can be loop-like transformer core, also can make other magnetic conduction construction part, also can make microgranular; Permeability magnetic material can be positioned among induction coil, also can be placed on outside induction coil; Can be placed on outside pending object, also can be placed on pending interior of articles.
9. equipment as claimed in claim 8, is characterized in that: allow magnetic conduction construction part stretch in pending object depression, magnetic force path by this pending interior of articles and density of line of magnetic force and magnetic induction are all increased; Or pending object is placed in one or more breach of opening on originally closed permeability magnetic material structural member, make the intensive magnetic line of force through pending object, portion produces very strong pulse induction electric current within it.
10. equipment as claimed in claim 7, is characterized in that: the permeability magnetic material adding at pending interior of articles, comprises metal powder, salt end, electrolyte, high conductivity liquid and their mixture.
11. equipment as claimed in claim 7, is characterized in that: the form of pending object can be solid-state, liquid state or gaseous state; From class although, can be vivo biological tissue, inorganic matter, metal, pottery, macromolecular material, food, medicine or articles for daily use; From kinestate, can maintain static and process, also can be and flow or mobile status, process incessantly.
12. equipment as claimed in claim 7, it is characterized in that: pending object for may be by microorganism or/and food, medicine or the articles for daily use that Toxic pollutes, pending body surface or the inner faradic current producing are for the deactivation of microorganism and the decomposition of noxious substance; Or pending object is human body or organism pathological tissues; the intensity controlled pulse induction electric current that pathological tissues inside or skin surface produce is for promoting the increase of organization internal or skin surface cell permeability, and the increase of permeability can realize by the reversible or irreversible perforation of cell membrane; Or pending object is tumor tissues, the reversible perforation of cell membrane is used for promoting medicine to enter tumor cell inside, the irreversible perforation of cell membrane or destroy for direct killing off tumor cells.
13. equipment as claimed in claim 12, it is characterized in that: by injecting to pathological tissues or input medicine, inject or input simultaneously or only normal saline or other high conductivity liquid that contains high permeability material microgranule, make the projecting normal structure of density of line of magnetic force in pathological tissues, the pulse induction current ratio surrounding normal cell that sick cell is born is large; Or the reversible perforation of cell membrane is used for promoting outside gene to intracellular transfer; Or the increase of cell permeability is used for promoting that glucose in blood enters cell; The increase of skin surface cell or tissue permeability is used for promoting that medicine enters human body from skin; On organization internal or surface or skin appearance layer add the liquid containing high permeability material microgranule, comprise normal saline or other mixed liquid containing the ferrite nano microgranule of glucose parcel.
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| EP4265278A1 (en) | 2022-04-21 | 2023-10-25 | Elbiotech Sp. z o.o. | Device for sterilization and disinfection of items |
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Effective date of registration: 20161207 Address after: Branch of Beijing economic and Technological Development Zone of Beijing City fourteen street 100176 No. 99 building 33 room 508 building B Patentee after: BEIJING YINHEZHIZHOU ENVIRONMENTAL PROTECTION SCIENCE & TECHNOLOGY CO.,LTD. Address before: 100021 Beijing city Chaoyang District No. 32 Xiaoyun Road, Concordia Plaza C block 701 Patentee before: He Zongyan |
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Granted publication date: 20141022 Termination date: 20211206 |
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| CF01 | Termination of patent right due to non-payment of annual fee |