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WO2020216290A1 - 活体内物质的运动或位置的控制方法及装置 - Google Patents

活体内物质的运动或位置的控制方法及装置 Download PDF

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Publication number
WO2020216290A1
WO2020216290A1 PCT/CN2020/086399 CN2020086399W WO2020216290A1 WO 2020216290 A1 WO2020216290 A1 WO 2020216290A1 CN 2020086399 W CN2020086399 W CN 2020086399W WO 2020216290 A1 WO2020216290 A1 WO 2020216290A1
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Prior art keywords
electric field
living body
electrode
substance
adjustable
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PCT/CN2020/086399
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English (en)
French (fr)
Inventor
乐飚
王丽江
唐万福
奚勇
Original Assignee
上海必修福企业管理有限公司
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Publication of WO2020216290A1 publication Critical patent/WO2020216290A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/205—Applying electric currents by contact electrodes continuous direct currents for promoting a biological process
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents

Definitions

  • the invention relates to a method and device for controlling the movement or position of a substance in a living body.
  • External medicine can be administered in a targeted manner, which is fast, convenient, efficient and low-toxic.
  • Oral or intravenous injection and other internal medications are generally systemic and cannot be administered locally.
  • the goal of administration is to treat and minimize the side effects of the drug.
  • Some diseases such as cancer
  • oral chemotherapy drugs for cancer treatment, various side effects such as nausea and vomiting will occur. , Dry mouth, lack of appetite, numb hands and feet, hair loss, etc., most chemotherapy drugs have different degrees of bone marrow suppression, and bone marrow suppression is often the dose-limiting toxicity of anti-tumor drugs.
  • Bone marrow suppression can be manifested as a reduction of white blood cells, especially granulocytes in the early stage. In severe cases, platelets, red blood cells, and hemoglobin can be reduced. Different drugs have different effects on the bone marrow, so the degree of response is different, and patients can also There are manifestations of fatigue, weakness, decreased resistance, susceptibility to infection, fever, bleeding, etc., resulting in a general decline in the quality of life of patients, and even being forced to stop treatment due to intolerance. At the same time, chemotherapeutic drugs are generally immunosuppressive drugs, which inhibit the immune function of the body to varying degrees. The immune system of the body plays an important role in destroying the remaining tumor cells in the body. When the immune function is low, the tumor is not easy to be controlled. , But accelerate the process of recurrence or metastasis.
  • the purpose of the present invention is to provide a method and device for controlling the movement or position of a substance in a living body.
  • the first invention provides a method for controlling the movement or position of a substance in a living body.
  • the method at least includes the following steps:
  • the electric field generating device includes a contact electrode and an external electrode, the external electrode includes more than one different electrode, and the position of the different electrode is adjustable;
  • the second invention provides a method for expelling charged substances from a living body.
  • the method at least includes the following steps:
  • the electric field generating device includes a contact electrode and an external electrode, the external electrode includes more than one different electrode, and the position of the different electrode is adjustable;
  • the third invention provides an electric field positioning drug delivery device, which at least includes:
  • the space electric field outer electrode is used to form a space electric field between the space electric field contact electrode, including more than two different electrodes, the position of each different electrode is adjustable, and is used to adjust the coverage area of the space electric field;
  • the regulating unit is used to regulate and control the performance of the space electric field, including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field range, and control the movement trajectory of the charged agent in the living body.
  • the fourth invention provides the use of the aforementioned electric field positioning drug delivery device in any one or more of the following: (1) positioning drug delivery; (2) enriching metal ions.
  • the fifth invention provides a method for controlling the movement trajectory of an ionic preparation in vivo.
  • the method at least includes the following steps:
  • Adjust and control the performance of the spatial electric field including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field range, and control the trajectory of the ionic agent in vivo.
  • the method and device for controlling the movement or position of a substance in a living body of the present invention has the following beneficial effects:
  • the invention can act on the charged substances in the living body through the electric field, make it move or excrete in a predetermined way, can act on tumor cells, act on drugs in the organism, act on water in the organism, act on the nerves in the organism, and act on heavy metals in the organism. Ions, acting on ions in organisms, acting on chemical reaction processes, controlling the sequence of reactions, catalyzing, and preventing reactions of some substances. It can achieve assisted growth, treatment, drug delivery, swelling, modification, and catalysis.
  • the invention is safe for the human body, high field strength requires high voltage, and preventing tip discharge is a sophisticated problem in high field strength electrostatics.
  • Equipotential electric field technology is adopted to effectively prevent tip discharge and make product equipment comply with national regulations. No need to worry about electric shock, the equipotential electric field technology is safer.
  • Precise positioning and aggregation of drugs can greatly reduce the dosage and improve the efficiency of local administration.
  • the amount of intravenous drugs can be reduced several to ten times. Under the action of an electric field, the drugs can be targeted to focus on the lesion. In this way, the target
  • the concentration of the drug in the site is hundreds or even thousands of times higher than that in other sites, the drug effect can be increased dozens of times, the applicability is stronger, and the application is wider.
  • Figure 1 shows a schematic diagram of the structure of the electric field positioning drug delivery device of the present invention.
  • Figure 2 is a schematic circuit diagram of the electric field positioning drug delivery device of the present invention.
  • Figure 3 shows a flow chart of the verification experiment of the electric field positioning drug delivery device of the present invention.
  • Figure 4 is a schematic diagram of the force of the present invention on the negatively charged tissues in the organism (the external electrode is negative).
  • Figure 5 is a schematic diagram of the force of the present invention on the negatively charged tissues in the organism (the external electrode is positive).
  • Ionic drugs are charged bodies, and the Coulomb force F received by charged bodies in an electric field
  • the charged drug is subjected to a force with a certain direction in the electric field.
  • this force is greater than other forces on the drug molecule (or particle)
  • the charged drug particle will Do directional movement in the direction of the electric field.
  • the charged ionic drug or drug When the electric field is irradiated to the localized drug delivery site (such as the sole of the foot), the charged ionic drug or drug will move in the direction of the electric field and pass through the epidermis and dermis. Part of the drug will pass through the capillaries, and the rest will continue to penetrate the capillaries and eventually gather At the location (foot).
  • the natural electric field barrier or boundary formed between the area covered by the spatial electric field and the uncovered area ensures that the ionic (charged) reagent is in the focus or treatment area within the set conditions, and continuous treatment is implemented.
  • the setting conditions refer to parameters such as pharmaceutical measurement; electric field strength; action time. Reagents that exchange with the lesion tissue and lose their charge activity or naturally inactivate reagents are transported out of the electric field shield through blood vessels, and are mainly excreted through kidney or liver metabolism, and partly through sweat glands or feces.
  • the method of drug delivery from capillaries into various tissues is called free diffusion drug delivery.
  • the theory of diffusion movement has been clearly studied, and the diffusion rate is directly proportional to the concentration difference.
  • V K ⁇ (C 1 -C 2 ) (ii)
  • the diameter of capillaries is 6 ⁇ 10 3 to 7 ⁇ 10 3 nm, the diameter of drug molecules is generally less than 100 nm, and the diameter of water molecules is 0.2 nm.
  • the diffusion rate is proportional to the concentration difference, the drug delivery is slow and the systemic effect cannot be directed.
  • the charged drug molecule is under the action of an electric field, the drug molecule moves toward the outer wall of the capillary under the action of the electric field, which greatly increases the concentration of the drug at the target site (more than 1000 times). In this way, C 1 does not increase or even decrease.
  • the absorption rate of the drug in this part is improved, and the concentration is greatly increased.
  • the method for controlling the movement or position of a substance in a living body at least includes the following steps:
  • the electric field generating device includes a contact electrode and an external electrode, the external electrode includes more than one different electrode, and the position of the different electrode is adjustable;
  • the performance of adjusting the electric field is selected from one or more of adjusting the position of the different electrode, the intensity of the electric field, the direction of the electric field, the pulse frequency of the electric field, and the range of the electric field.
  • the living body is a living animal body. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the contact electrode is grounded.
  • the external electrode is not in contact with the living body to be tested.
  • the different electrode is a point probe.
  • At least one substance in the living body is controlled to gather at the position where the electric field acts.
  • the substance is charged.
  • the substance is selected from one or more of charged medicaments, foreign harmful charged substances, and ions in organisms.
  • the charged medicament is one or more of charged injection medicament, charged oral medicament and charged rectal administration medicament.
  • it includes, but is not limited to, charged medicaments suitable for oral administration, sublingual injection, intravenous injection, acupoint injection, rectal drip administration, intramuscular injection, subcutaneous injection, etc.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the contact electrode does not affect the selection of the position of the different electrode or the electrification condition.
  • the position of the different electrode and/or the performance of the electric field are confirmed according to the target site and target concentration.
  • the power supply is a high-voltage output power supply.
  • the power supply is a high-voltage output power supply formed by a battery or a direct current power supply DC through an AC excitation step-up transformer of an oscillating circuit.
  • the voltage of the electric field is adjustable from 0.001 kV to 120 kV
  • the current output is adjustable from 0.001 mA to 10000 mA
  • the working distance of the electric field is adjustable from 0.1 cm to 100 cm.
  • the voltage is taken according to the depth of action and the distance of the electric field; and/or the current is less than the limit that the living tissue can tolerate.
  • the power source of the electric field is direct current.
  • the positive pole of the DC high voltage power supply is connected to the living body at the same potential, the negative pole is connected to the external electrode, and the DC power supply is turned on to generate an electric field between the living body and the electrode. Electricity is generated at the same time. This electric power first acts on the positively charged substance in the living body. Negative electrode. The amount of electricity generated depends on the voltage between the electrodes and the amount of charged material. Utilizing the charge difference in the organism, it can pull positively charged materials, positive ions, conductive materials, and conductive materials with low friction.
  • the living body's equipotential is used as the negative electrode, and the external electrode is used as the positive electrode.
  • Turn on the DC power supply to generate an electric field between the living body and the electrode. Electricity is generated at the same time.
  • This electric power first acts on the living body. A negatively charged substance, this substance is first pulled towards the positive electrode. The amount of electricity generated depends on the voltage between the electrodes and the amount of charged material. Utilizing the charge difference in the organism, it can pull negatively charged materials, negative ions, conductive materials, and conductive materials with low friction.
  • the method for expelling charged substances from a living body at least includes the following steps:
  • the electric field generating device includes a contact electrode and an external electrode, the external electrode includes more than one different electrode, and the position of the different electrode is adjustable;
  • the performance of adjusting the electric field is selected from one or more of adjusting the position of the different electrode, electric field intensity, electric field direction, electric field pulse frequency, and electric field range.
  • the living body is a living animal body. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the contact electrode is grounded.
  • the external electrode is not in contact with the living body to be tested.
  • the different electrode is a point probe.
  • At least one substance in the living body is controlled to gather at the position where the electric field acts.
  • the substance is charged.
  • the substance is selected from one or more of harmful externally charged substances and ions in organisms.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the contact electrode does not affect the selection of the position of the different electrode or the electrification condition.
  • the position of the different electrode and/or the performance of the electric field are confirmed according to the target site and target concentration.
  • the power supply is a high-voltage output power supply.
  • the power supply is a high-voltage output power supply formed by a battery or a direct current power supply DC through an AC excitation step-up transformer of an oscillating circuit.
  • the voltage of the electric field is adjustable from 0.001 kV to 120 kV, and the current output is adjustable from 0.001 mA to 10000 mA.
  • the voltage is taken according to the depth of action and the distance of the electric field; and/or the current is less than the limit that the living tissue can tolerate.
  • the power source of the electric field is direct current.
  • the present invention provides an electric field positioning drug delivery device, which at least includes:
  • the space electric field outer electrode is used to form a space electric field between the space electric field contact electrode, including more than two different electrodes, the position of each different electrode is adjustable, and is used to adjust the coverage area of the space electric field;
  • the regulating unit is used to regulate and control the performance of the space electric field, including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field range, and control the movement trajectory of the charged agent in the living body.
  • the spatial electric field contact electrode is used to connect with the living body to be measured, so that the living body to be measured and the spatial electric field contact electrode form an equipotential.
  • equipotential contact point may be the sole of the foot as shown in FIG. 1, or may be other parts of the living body to be tested, or be moisturizing, conductive grease, or the like.
  • the living body to be tested is a living animal body. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the spatial electric field contact electrode is grounded.
  • the external electrode of the spatial electric field may be in contact with the living body to be measured, or may not be in contact with the living body to be measured.
  • the different electrode is a point probe.
  • the charged agent is concentrated at the position where the electric field acts.
  • the charged agent is a charged agent.
  • the charged medicament is one or more of ionic injection medicaments, ionic oral medicaments and ionic rectal administration medicaments.
  • ionic agents suitable for various administration modes such as oral administration, sublingual injection, intravenous injection, acupoint injection, rectal drip administration, intramuscular injection, and subcutaneous injection.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the spatial electric field contacting the electrode does not affect the selection of the position of the different electrode or the electrification situation.
  • the position of the different electrode and/or the performance of the spatial electric field are confirmed according to the target site, target concentration and/or dosage.
  • the power supply is a high-voltage output power supply.
  • the power supply is a high-voltage output power supply formed by a battery or a direct current power supply DC through an AC excitation step-up transformer of an oscillating circuit.
  • the voltage of the power supply is adjustable from 0.001kV to 120kV
  • the current output is from 0.001mA to 10000mA
  • the working distance of the electric field is from 0.1cm to 100cm.
  • the voltage is taken according to the depth of action and the distance of the electric field; and/or the current is adjusted according to the limit that the living body to be tested can tolerate.
  • the present invention also provides the use of the aforementioned electric field positioning drug delivery device in any one or more of the following: (1) positioning drug delivery; (2) enriching metal ions.
  • the drugs or medicaments for targeted administration include but are not limited to ionic (cationic, anionic) reagents and neutral reagents (ion exchange or ionization treatment before use).
  • the present invention also provides a method for controlling the movement trajectory of the ionic preparation in vivo.
  • the method at least includes the following steps:
  • Adjust and control the performance of the space electric field including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field range, and control the movement trajectory of the charged agent in the living body.
  • equipotential contact point may be the sole of the foot as shown in FIG. 1, or may be other parts of the living body to be tested, or be moisturizing, conductive grease, or the like.
  • the living body to be tested is a living animal body. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the spatial electric field contact electrode is grounded.
  • the external electrode of the spatial electric field may be in contact with the living body to be measured, or may not be in contact with the living body to be measured.
  • the different electrode is a point probe.
  • the charged agent is concentrated at the position where the electric field acts.
  • the charged agent is a charged agent.
  • the charged medicament is one or more of charged injection medicament, charged oral medicament and charged rectal administration medicament.
  • it includes, but is not limited to, charged medicaments suitable for oral administration, sublingual injection, intravenous injection, acupoint injection, rectal drip administration, intramuscular injection, subcutaneous injection, etc.
  • the ionic reagent moves in the direction of the outer electrode of the spatial electric field.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the spatial electric field contacting the electrode does not affect the selection of the position of the different electrode or the electrification situation.
  • the position of the different electrode and/or the performance of the spatial electric field are confirmed according to the target site, target concentration and/or dosage.
  • the power supply is a high-voltage output power supply.
  • the power supply is a high-voltage output power supply formed by a battery or a direct current power supply DC through an AC excitation step-up transformer of an oscillating circuit.
  • the voltage of the power supply is adjustable from 0.001 kV to 120 kV
  • the current output is adjustable from 0.001 mA to 10000 mA
  • the working distance of the electric field is adjustable from 0.1 cm to 100 cm.
  • the voltage is selected according to the depth of action and the distance of the electric field; and/or the current is adjusted according to the limit that the living body to be tested can tolerate, and the range of positioning and administration includes the area covered by the spatial electric field. But it is not limited to the area covered by the spatial electric field.
  • the electric field generating device is the aforementioned electric field positioning drug delivery device.
  • the contact electrode refers to the spatial electric field contact electrode
  • the external electrode refers to the spatial electric field external electrode.
  • Table 1 Summary of electric field intensity parameters and pre-experimental weights of experimental animals
  • the rat was fixed on a flat plate in the supine position, and after observing that the rat had no righting reaction, the rat was weighed, and 10% chloral hydrate was taken to anesthetize the rat in an amount of 0.3ml/100g.
  • sublingual intravenous injection of verapamil was performed at a dose of 1.0 mg/kg (about 300 ⁇ g/rat: according to the equivalent dose coefficient conversion algorithm in "Pharmacological Experiment Methodology" edited by Professor Xu Shuyun, the injection dose was 6 times the normal human dose.
  • Table 2 Electric field intensity parameters and verapamil dosage of experimental animals in the group
  • the rats were sacrificed, and the heart, liver and kidneys of the rats were taken out, quick-frozen with liquid nitrogen, and then reserved for use (for measuring the concentration of verapamil).
  • verapamil standards were made into standard series solutions with concentrations of 1, 3, 10, 30, 100, and 300 ng/mL.
  • Phase A is 5mM ammonium acetate 0.2% formic acid aqueous phase
  • Phase B is acetonitrile, 2min 60% B isocratic elution
  • flow rate 0.8mL/min
  • Column temperature 40°C
  • Injection volume 10 ⁇ L.
  • SPSS17.0 software was used for data analysis.
  • the experimental data are expressed as mean ⁇ standard deviation.
  • the t test is used, the independent sample t test is used for comparison between groups, and the paired sample t test is used for comparison within groups ;
  • the rank sum test is used for comparison. P ⁇ 0.05 was considered as statistically significant.
  • the dosing box Before the start of administration, the dosing box should be positively charged for 15 minutes to add positive charges to the drug, and to ensure that the dosing box is always connected to the positive charge during the electric field administration period.
  • the experimental animals (5 in each group) were euthanized and blood was collected, and the heart, liver and kidney were taken out.
  • the content of verapamil in each tissue was counted.
  • Group G did not implement electric field administration, and injected the drug directly into the heart. 1 hr after the start of administration, about 1/3 of the dose remained in the heart, 1/3 of the menstrual blood remained in the blood components, and the rest was mainly excreted through the kidneys Excreted from the body.
  • the cationic preparation adopts the electric field administration mode described in the patent, which is expected to replace the existing traditional administration mode of intravenous or direct injection into the affected area. While avoiding the additional pain caused by the physical puncture to the patient, with the reduction of the dosage of the medicine, the medical resources and the medical expenditure and medical insurance cost of the patient's own burden are saved.
  • Table 4 Distribution of anionic agents of verapamil after 1 hr of administration

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Abstract

本发明提供一种活体内物质的运动或位置的控制方法，所述方法至少包括如下步骤：1)将活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；3)调节电场的性能，以控制活体内的至少一种物质运动或控制活体内至少一种物质的位置。本发明通过电场，可以对活体内的带电物质产生作用，使其按照预定的方式运动或排出体外，可以作用肿瘤细胞、作用生物体内药物、作用生物体内水、作用生物体内神经、作用生物体内重金属离子、作用生物体内离子、作用化学反应过程控制反应顺序、催化、阻止部分物质反应等。

Description

活体内物质的运动或位置的控制方法及装置 技术领域
本发明涉及一种活体内物质的运动或位置的控制方法及装置。
背景技术
重力、摩擦力、库伦力、万有引力广泛分布作用在我们周围，很容易理解和观察到，包括磁场会产生磁力，用两块磁铁就很容易展示给我们看到、感觉到，电场也会产生作用力，我们可以把它称为电力。由于这个电力只表现在带不同电性物质间或有差异电荷物质间，我们几乎不能直接或经常观察到，并不引起注意。但它实际存在。利用电力可以完成很多通常已知作用力无法完成的很多事情。
外用药可以定位给药，快速、方便、高效且低毒。口服或静脉注射等内用药一般是全身作用，不能定位给药。给药的目标是治疗且尽量降低药物的毒副作用。一些病(比如癌症)在药物治疗的同时，也会损害正常细胞，对人体造成极大的伤害，在选择口服化疗药物用于癌症治疗的时候，会出现各种不同程度的副作用，诸如恶心呕吐、口干舌燥、食欲缺乏、手脚麻木、毛发脱落等等，大多数化疗药物均有不同程度的骨髓抑制，而骨髓抑制又常为抗肿瘤药物的剂量限制性毒性。骨髓抑制在早期可表现为白细胞尤其是粒细胞减少，严重时血小板、红细胞、血红蛋白均可降低，不同的药物对骨髓作用的强弱、快慢和长短不同，所以反应程度也不同，同时患者还可有疲乏无力、抵抗力下降、易感染、发热、出血等表现，导致患者生存质量普遍下降，甚至因不能耐受而被迫中止治疗。同时，化疗药物一般多是免疫抑制药，对机体的免疫功能有不同程度的抑制作用，机体免疫系统在消灭体内残存肿瘤细胞上起着很重要的作用，当免疫功能低下时，肿瘤不易被控制，反而加快复发或转移进程。
发明内容
鉴于以上所述现有技术的缺点，本发明的目的在于提供一种活体内物质的运动或位置的控制方法及装置。
为实现上述目的及其他相关目的，第一本发明提供一种活体内物质的运动或位置的控制方法，所述方法至少包括如下步骤：
1)将活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
3)调节电场的性能，以控制活体内的至少一种物质运动或控制活体内至少一种物质的位置。
第二本发明提供一种使带电物质排出活体的方法，所述方法至少包括如下步骤：
1)将体内含有带电物质的活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
3)调节电场的性能，以控制活体体内的带电物质，使带电物质排出活体。
第三本发明提供一种电场定位给药装置，所述电场定位给药装置至少包括：
空间电场接触电极；
空间电场外电极，用于与所述空间电场接触电极之间形成空间电场，包括2个以上异电极，各个异电极的位置可调，用于调整空间电场的覆盖面积；
调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内带电制剂的运动轨迹。
第四本发明提供前述电场定位给药装置在以下任一项或多项中的用途：(1)定位给药；(2)富集金属离子。
第五本发明提供活体内离子型制剂的运动轨迹的控制方法，所述方法至少包括如下步骤：
1)将所述待测活体空间电场接触电极连接，使待测活体与所述空间电场接触电极形成等电位；
2)调整各个异电极的位置，以调整空间电场的覆盖面积；
3)调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内离子型制剂的运动轨迹。
如上所述，本发明的活体内物质的运动或位置的控制方法及装置，具有以下有益效果：
本发明通过电场，可以对活体内的带电物质产生作用，使其按照预定的方式运动或排出体外，可以作用肿瘤细胞、作用生物体内药物、作用生物体内水、作用生物体内神经、作用生物体内重金属离子、作用生物体内离子、作用化学反应过程控制反应顺序、催化、阻止部分物质反应等。可以实现辅助生长、治疗、给药、消肿、改性、催化。
本发明对人体安全，高场强需要高电压，而防止尖端放电是高场强静电学的尖端难题，采用等位电场技术，可以有效防止尖端放电，使产品设备符合国家规定。无需担心触电，等电位电场技术更安全。药物精确定位聚集，大大降低给药用量，提高局部范围给药效率，可以将静注药物量降低几倍至十几倍，在电场作用下，使药物靶向集中于病变处，这样，目标 部位的药物浓度比其它部位高几百倍乃至上千倍，药物效果可以增大几十倍，适用性更强，应用更广泛。
附图说明
图1显示为本发明电场定位给药装置结构示意图。
图2显示为本发明电场定位给药装置电路原理图。
图3显示为本发明电场定位给药装置验证实验流程图。
图4显示为本发明电场对生物体内负电性组织作用力示意图(外电极为负电)。
图5显示为本发明电场对生物体内负电性组织作用力示意图(外电极为正电)。
具体实施方式
以下由特定的具体实施例说明本发明的实施方式，熟悉此技术的人士可由本说明书所揭露的内容轻易地了解本发明的其他优点及功效。
请参阅图1至图5。须知，本说明书所附图式所绘示的结构、比例、大小等，均仅用以配合说明书所揭示的内容，以供熟悉此技术的人士了解与阅读，并非用以限定本发明可实施的限定条件，故不具技术上的实质意义，任何结构的修饰、比例关系的改变或大小的调整，在不影响本发明所能产生的功效及所能达成的目的下，均应仍落在本发明所揭示的技术内容能涵盖的范围内。同时，本说明书中所引用的如“上”、“下”、“左”、“右”、“中间”及“一”等的用语，亦仅为便于叙述的明了，而非用以限定本发明可实施的范围，其相对关系的改变或调整，在无实质变更技术内容下，当亦视为本发明可实施的范畴。
定位给药的原理
(1)离子型药物定向运动的原理
离子型药物是带电体，带电体在电场中受到的库仑力F
F＝EQ    (i)
(i)式中
E：电场强度，单位为牛顿/库伦
Q：带电体的电荷量，有正负两种，其单位为库伦
若Q为正电荷，则F的方向与E的方向相同；若Q为负电荷，则F的方向与E的方向相反。
从(i)式可以看出，带有电荷的药物在电场中受到一个具有确定方向的力，当此力大于药物分子(或粒子)所受的其它的力时，带有电荷的药物粒子会按电场的方向做定向运动。
(2)定位促进药物/药剂高效富集的原理
当电场照射到定位给药部位(如脚掌)，带电荷的离子型药物或药剂就会按电场的方向运动，穿过表皮，真皮，部分药剂经由毛细血管，其余药剂继续渗透毛细血管，最终汇集在定位部位(脚掌)。而空间电场覆盖区域与未覆盖区域自然形成的电场屏障或界限，在设定条件内确保离子型(带电荷)试剂处于病灶或治疗领域内，实施持续治疗。设定条件是指药剂计量；电场强度；作用时间等参数。与病灶组织交换而失去电荷活性的试剂或自然失活的试剂通过血管输送出电场屏蔽，主要经肾或肝脏代谢排出体外，部分通过汗腺或粪便代谢。
药物分子从毛细血管进入各种组织的给药方式叫做自由扩散给药。扩散运动的理论已研究清楚，扩散速度与浓度差成正比。
V＝K×(C 1-C 2)     (ii)
式中
V:扩散速度
K:常数
C 1:毛细血管内壁药物浓度
C 2:毛细血管外壁药物浓度
毛细血管的直径6×10 3～7×10 3nm，药物分子直径一般小于100nm，水分子的直径为0.2nm。在传统自由扩散中，扩散速度与浓度差成正比，药物传递慢且全身作用无法定向。而当带电药物分子在电场作用下，药物分子在电场作用下向毛细血管外壁的方向运动，使得目标部位药物浓度大大增加(1000倍以上)。这样，C 1在不增加甚至减少的条件下。该部位药物吸收速度提高、浓度大大增加。
本发明提供的活体内物质的运动或位置的控制方法，至少包括如下步骤：
1)将活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
3)调节电场的性能，以控制活体内的至少一种物质运动或控制活体内至少一种物质的位置。
进一步的，步骤3)中，调节电场的性能选自调整异电极的位置、电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种。
所述活体为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
在一种实施方式中，所述接触电极接地。
进一步的，所述外电极不与待测活体接触。
在一种实施方式中，所述异电极为点状探头。
在电场中，控制活体内的至少一种物质聚集于电场作用的位置。所述物质带电。
可选的，所述物质选自带电药剂、外来有害带电物质和生物体内离子中的一种或多种。
在进一步的实施方式中，所述带电药剂为带电注射药剂、带电口服药剂和带电直肠给药药剂中的一种或多种。
可选的，包括但不限于适用于口服给药、舌下注射，静脉注射，穴位注射，直肠滴入给药，肌肉注射，皮下注射等各种给药方式的带电药剂。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或电场的性能根据目标位点、目标浓度确认。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源为电池或直流电源DC通过震荡电路AC励磁升压变压器形成的高压输出电源。
在一种实施方式中，所述电场的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
在一种实施方式中，电压根据作用深度以及电场距离取值；和/或，电流小于活体组织能够忍受的极限。
所述电场的电源为直流电。
直流高压电源正极等电位接通活体，负极接外电极，开启直流电源，使活体和电极间产生电场，电力同时产生，这个电力首先作用在生物体内带正电荷物质，这个物质首先被拉动，趋向负电极。产生电力大小取决电极间电压高低以及带电荷物质电量。利用生物体内带电差异，可以分别拉动带正电物质、正离子、导电物质、摩擦力小的导电物质。
如图4和图5所示，如果将电极反接，活体等电位作为负极，外电极作为正极，开启直流电源，使活体和电极间产生电场，电力同时产生，这个电力首先作用在活体内带负电荷物质，这个物质首先被拉动，趋向正电极。产生电力大小取决电极间电压高低以及带电荷物质电量。利用生物体内带电差异，可以分别拉动带负电物质、负离子、导电物质、摩擦力小的导电物质。
活体生物体内物质所带电荷以及导电能力存在差异，外加电场对这些物质电场引力就存在差异，带异电位高和导异电位能力强的物质引力大；可以先被移动或获得更大的电场力。反之物质滞后被电场力作用；且电场力相对弱；如果物质所带电荷与外电极相反，同样会出现反向斥力差异。
本发明提供的使带电物质排出活体的方法，至少包括如下步骤：
1)将体内含有带电物质的活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
3)调节电场的性能，以控制活体体内的带电物质，使带电物质排出活体。
进一步的，步骤3)中，所述调节电场的性能选自调整异电极的位置、电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种。
所述活体为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
在一种实施方式中，所述接触电极接地。
进一步的，所述外电极不与待测活体接触。
在一种实施方式中，所述异电极为点状探头。
在电场中，控制活体内的至少一种物质聚集于电场作用的位置。所述物质带电。
可选的，所述物质选自外来有害带电物质和生物体内离子中的一种或多种。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或电场的性能根据目标位点、目标浓度确认。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源为电池或直流电源DC通过震荡电路AC励磁升压变压器形成的高压输出电源。
在一种实施方式中，所述电场的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA。
在一种实施方式中，电压根据作用深度以及电场距离取值；和/或，电流小于活体组织能够忍受的极限。
所述电场的电源为直流电。
如图1和图2所示，本发明提供一种电场定位给药装置，至少包括：
空间电场接触电极；
空间电场外电极，用于与所述空间电场接触电极之间形成空间电场，包括2个以上异电极，各个异电极的位置可调，用于调整空间电场的覆盖面积；
调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内带电制剂的运动轨迹。
进一步的，所述空间电场接触电极用于与待测活体相连接，使待测活体与所述空间电场接触电极形成等电位。
进一步的，等电位接触点可以是如图1所示的脚掌，也可以是待测活体的其他部位或者是水润、导电脂等。
所述待测活体为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
在一种实施方式中，所述空间电场接触电极接地。
可选的，所述空间电场外电极可以与待测活体接触，也可以不与测活体接触。
在一种实施方式中，所述异电极为点状探头。
在所述空间电场中，所述带电制剂聚集于电场作用的位置。在一种实施方式中，所述带电制剂为带电药剂。
在进一步的实施方式中，所述带电药剂为离子型注射药剂、离子型口服药剂和离子型直肠给药药剂中的一种或多种。
可选的，包括但不限于适用于口服给药、舌下注射，静脉注射，穴位注射，直肠滴入给药，肌肉注射，皮下注射等各种给药方式的离子型药剂。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
空间电场接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或空间电场的性能根据目标位点、目标浓度和/或用量确认。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源为电池或直流电源DC通过震荡电路AC励磁升压变压器形成的高压输出电源。
在一种实施方式中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的 0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm；。
在一种实施方式中，电压根据作用深度以及电场距离取值；和/或，电流根据待测活体能够忍受的极限调整。
本发明还提供前述电场定位给药装置在以下任一项或多项中的用途：(1)定位给药；(2)富集金属离子。
可选的，用途(1)中，进行定位给药的药物或药剂包括但并不仅限于离子型(阳离子，阴离子)试剂与中性试剂(使用前实施离子交换或离子化处理)。
本发明还提供活体内离子型制剂的运动轨迹的控制方法，所述方法至少包括如下步骤：
1)将所述待测活体空间电场接触电极连接，使待测活体与所述空间电场接触电极形成等电位；
2)调整各个异电极的位置，以调整空间电场的覆盖面积；
3)调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内带电制剂的运动轨迹。
进一步的，等电位接触点可以是如图1所示的脚掌，也可以是待测活体的其他部位或者是水润、导电脂等。
所述待测活体为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
在一种实施方式中，所述空间电场接触电极接地。
可选的，所述空间电场外电极可以与待测活体接触，也可以不与测活体接触。
在一种实施方式中，所述异电极为点状探头。
在所述空间电场中，所述带电制剂聚集于电场作用的位置。在一种实施方式中，所述带电制剂为带电药剂。
在进一步的实施方式中，所述带电药剂为带电注射药剂、带电口服药剂和带电直肠给药药剂中的一种或多种。
可选的，包括但不限于适用于口服给药、舌下注射，静脉注射，穴位注射，直肠滴入给药，肌肉注射，皮下注射等各种给药方式的带电药剂。
在所述空间电场中，所述离子型试剂向空间电场外电极的方向运动。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
空间电场接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或空间电场的性能根据目标位点、目标浓度和/或用量确认。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源为电池或直流电源DC通过震荡电路AC励磁升压变压器形成的高压输出电源。
在一种实施方式中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
在一种实施方式中，电压根据作用深度以及电场距离取值；和/或，电流根据待测活体能够忍受的极限调整，定位给药范围包括空间电场覆盖区域。但不仅限于空间电场覆盖区域。
在一种实施方式中，本发明所述的活体内物质的运动或位置的控制方法或一种使带电物质排出活体的方法中，所述电场发生装置为前述的电场定位给药装置。此时，所述接触电极是指所述空间电场接触电极，所述外电极是指空间电场外电极。
验证实验
4.1实验动物的准备
选择月龄15-18周的大鼠70只，体重250-320克。由饲养员饲养，大鼠在开始试验前适应新环境2周。在此期间每周仔细观察与测量动物体重，所有入选动物均排除体重减轻等不适应环境者。随机分为6组，每组各10只大鼠，根据仪器所选参数电压不同分为A-F组共6组，分别实施0.1KV、1KV、3KV、10KV、30KV、120KV不同电场强度下的给药验证(n＝10)。另行准备1组10只大鼠为对照组，实施心脏直接注射(不实施电场定位给药)。
表1：入组实验动物的电场强度参数与实验前体重汇总
分组明细 A B C D E F G
实施电场强度(kv) 0.1 1 3 10 30 120 None
体重(g) 285±13.6 292±16.3 273±15.8 297±14.9 265±16.3 271±18.5 292±17.6
4.2实验流程图
详见图3。
4.2.1心电图检查
仰卧位将鼠固定于平板上，观察大鼠无翻正反应后，称量大鼠重量，取10％水合氯醛按0.3ml/100g的量麻醉大鼠。利用Powerlab系统采集心电图30分钟，简称治疗前30分钟。然后进行舌下静脉注射维拉帕米，剂量为1.0mg/kg(约300μg/大鼠：根据徐叔云教授主编《药理实验方法学》中等效剂量系数折算法，该注射剂量为人正常用药剂量的6倍)将定位给药 装置的空间电场外电极安置于或照射大鼠的胸前部位，大鼠本身空间电场接触电极相连，且空间电场接触电极与大地相连，按要求给予不同电场强度的照射。1小时及24小时候后对大鼠行心电图检查，再次连续采集心电图信号30分钟，简称治疗后30分钟。
4.2.2血液采集和生化指标检测
1小时后心电图检查完毕后，各实施组随机选取10只大鼠，固定于解剖台上，开腹，分离腹主动脉，于腹主动脉抽血2.5ml。37°加热处理30min后，1000rpm离心2min，分离血清。检测血清中维拉帕米含量。
表2：入组实验动物的电场强度参数与维拉帕米给药量
Figure PCTCN2020086399-appb-000001
4.2.3组织采集
抽取血液后，处死大鼠，取出大鼠心脏，肝脏与肾脏，液氮速冻后备用(用于测量维拉帕米浓度测定)。
4.2.4组织维拉帕米浓度测量
(1)组织匀浆液的制备
将肺、心脏中间组织从-80℃冰箱取出，将组织剪成小块并搅拌均匀，加入2倍重量的甲醇-水(1：1，v/v)混合溶液，匀浆5min。
(2)离心
设置转速1000rpm，工作温度4℃，离心时间10min。离心后取上清液，液氮或－80℃冰箱保存，待测。
(3)液相色谱-串联质谱仪药品配置
将维拉帕米标准品制成浓度为1、3、10、30、100，300ng/mL的标准系列溶液。称取10mg奥卡西平的对照品，用乙腈-水溶液(50:50，v/v)溶解，配成1mg/mL的奥卡西平储备液，用时加入乙腈水(50:50，v/v)稀释至浓度为1000ng/mL作为内标使用。
(4)色谱条件
色谱柱:Poroshell 120 SB-C18柱(4.6×50mm I.D.，2.7μm)；流动相：A相为5mM乙酸铵的0.2％甲酸水相；B相为乙腈，2min 60％B等梯度洗脱；流速：0.8mL/min；柱温：40℃；进样量：10μL。
4.6.5进样
17μL，涡流混合40s，离心5min(15000rpm)，进样5-10μL，LC-MS/MS分析。
4.3统计方法
应用SPSS17.0软件进行数据分析，实验数据以均数±标准差表示，当各组基线数据呈正态分布时使用t检验，组间比较采用独立样本t检验，组内比较采用配对样本t检验；当数据不呈正态分布时采用秩和检验法比较。均以P＜0.05为差异存在统计学意义。
表3：给药1hr后维拉帕米阳离子型试剂的分布情况
分组明细 A B C D E F G
实施电场强度(kv) 0.1 1 3 10 30 120 None
血液中(μg) None None 1.2±1.1 6.3±1.1 20.1±11.2 12.3±5.6 120.3±13.8
心脏(μg) None None 6.5±2.1 31.5±2.1 125.2±15.8 205.2±6.8 105.2±15.8
肝脏(μg) None None 0.9±0.5 1.3±0.6 3.3±0.9 7.3±2.1 5.3±1.5
肾脏(μg) None None 1.5±0.3 6.3±2.3 15.2±7.2 15.5±3.8 21.5±5.3
给药开始前，给药箱通阳性电荷15分钟，使药剂附加阳性电荷，并确保电场给药期间，给药箱始终连接阳性电荷。电场给药1小时后，各组实验动物(各5只)安乐死后采血，取出心脏，肝脏与肾脏后。使用HPLC液相分析技术实施检测。各器官组织与血液通过重量与血液体积补正后分别统计各组织中维拉帕米含量。G组(对照组)不实施电场给药，直接将药物注射到心脏，给药开始1hr后，约1/3剂量残存于心脏，1/3经血行残存于血液组分，剩余主要经肾排泄排出体外。
电场给药组当电场强度达到3KV时，开始出现给药效果。电场强度达到30KV时，给药效果已达到心脏直接注射效果。继续加大电场到120KV时，给药效果达到心脏直接注射剂量的约两倍，且剩余主要经肾排泄的功能维持不变。这一验证结果暗示阳离子型制剂采用专利所述电场给药模式下，有望代替现有静脉或患部直接注射的传统给药模式。避免了物理穿刺给患者带来附加痛苦的同时，伴随药剂用量的减少，医疗资源与患者自身负担的医疗支出与医保费用节俭。
如上所述中性试剂或阳离子型试剂可以显著的增加收益人群。广泛应用于临床的阴性离子制剂是否可以带来同样的恩惠？为解开这个谜团，我们在给药开始前，给药箱通阴性电荷15分钟，使药剂附加阴性电荷，并确保电场给药期间，给药箱始终连接阴性电荷。
表4：给药1hr后维拉帕米阴离子型试剂的分布情况
分组明细 A B C D E F G
实施电场强度(kv) 0.1 1 3 10 30 120 None
血液中(μg) None None 1.1±1.3 5.3±1.7 18.3±9.2 11.3±7.5 114.6±15.8
心脏(μg) None None 7.2±1.8 28.5±2.4 113.2±23.1 195.7±7.2 112.3±21.7
肝脏(μg) None None 1.2±0.8 1.5±0.8 5.1±2.1 9.3±1.9 6.5±2.7
肾脏(μg) None None 1.8±1.2 5.3±1.7 18.3±5.8 21.5±1.8 19.3±6.1
电场给药1小时后，各组实验动物(各5只)安乐死后采血，取出心脏，肝脏与肾脏后。 使用HPLC液相分析技术实施检测。各器官组织与血液通过重量与血液体积补正后分别统计各组织中维拉帕米含量。G组(对照组)不实施电场给药，直接将药物注射到心脏，给药开始1hr后，约1/3剂量残存于心脏，1/3经血行残存于血液组分，剩余主要经肾排泄排出体外。
与阳离子型试剂类似的效应在阴离子型试剂中得到证实。电场给药组当电场强度达到3KV时，开始出现给药效果。电场强度达到30KV时，给药效果已达到心脏直接注射效果。继续加大电场到120KV时，给药效果达到心脏直接注射剂量的约两倍。这一验证结果暗示阳离子型制剂采用专利所述电场给药模式下，有望代替现有静脉或患部直接注射的传统给药模式。避免了物理穿刺给患者带来附加痛苦的同时，伴随药剂用量的减少，能够节约医疗资源与患者自身负担的医疗支出与医保费用。
需要各位同业或同行参与人员注意的是，作为电场作业的常识，当需要通过电场给药模式实施阳离子型试剂给药时，药剂需要确保阳性电荷，同时在给药端箱添加负电极，而负离子试剂给药时，则需要实施反向电极。
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下，对上述实施例进行修饰或改变。因此，举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变，仍应由本发明的权利要求所涵盖。

Claims (21)

  1. 一种活体内物质的运动或位置的控制方法，其特征在于，所述方法至少包括如下步骤：
    1)将活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
    2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
    3)调节电场的性能，以控制活体内的至少一种物质运动或控制活体内至少一种物质的位置。
  2. 如权利要求1所述的活体内物质的运动或位置的控制方法，其特征在于，步骤3)中，调节电场的性能选自调整异电极的位置、电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种。
  3. 如权利要求1所述的活体内物质的运动或位置的控制方法，其特征在于，步骤3)中，所述物质是带差异电子或通过外加电产生差异电子。
  4. 如权利要求1所述的活体内物质的运动或位置的控制方法，其特征在于，所述物质选自带电药剂、外来有害带电物质和生物体内离子中的一种或多种。
  5. 根据权利要求1所述的活体内物质的运动或位置的控制方法，其特征在于，所述控制方法还包括以下特征中的一个或多个：
    a.所述接触电极接地；
    b.所述异电极为点状探头；
    c.所述外电极不与活体接触；
    d.电场的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA；，电场的工作距离为可调的0.1cm-100cm；
    e.所述电场的性能根据目标位点和/或目标浓度确认；
    f.所述电场的电源为直流电。
  6. 根据权利要求5所述的活体内物质的运动或位置的控制方法，其特征在于，当包括特征d时，电压根据作用深度以及电场距离取值；和/或，电流小于活体组织能够忍受的极限。
  7. 一种使带电物质排出活体的方法，其特征在于，所述方法至少包括如下步骤：
    1)将体内含有带电物质的活体置于电场发生装置中，所述电场发生装置包括接触电极和外电极，所述外电极包括1个以上异电极，异电极的位置可调；
    2)将所述活体与接触电极接触，使所述活体与所述接触电极形成等电位；
    3)调节电场的性能，以控制活体体内的带电物质，使带电物质排出活体。
  8. 根据权利要求7所述的使带电物质排出活体的方法，其特征在于，步骤3)中，所述调节 电场的性能选自调整异电极的位置、电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种。
  9. 根据权利要求7所述的使带电物质排出活体的方法，其特征在于，所述控制方法还包括以下特征中的一个或多个：
    a.所述接触电极接地；
    b.所述异电极为点状探头；
    c.所述外电极不与待测活体接触；
    d.电场的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA；
    e.所述异电极的位置和/或电场的性能根据目标位点和/或目标浓度确认；
    f.所述电场的电源为直流电。
  10. 根据权利要求9所述的使带电物质排出活体的方法，其特征在于，当包括特征d时，电压根据作用深度以及电场距离取值；和/或，电流小于活体组织能够忍受的极限。
  11. 一种电场定位给药装置，其特征在于，所述电场定位给药装置至少包括：
    空间电场接触电极；
    空间电场外电极，用于与所述空间电场接触电极之间形成空间电场，包括2个以上异电极，各个异电极的位置可调，用于调整空间电场的覆盖面积；
    调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内带电制剂的运动轨迹。
  12. 根据权利要求11所述的电场定位给药装置，其特征在于：还包括以下特征中的一项或多项：
    a.所述空间电场接触电极用于与待测活体相连接，使待测活体与所述空间电场接触电极形成等电位；
    b.所述空间电场接触电极接地；
    c.所述异电极为点状探头；
    d.所述异电极的位置和/或空间电场的性能根据目标位点、目标浓度和/或用量确认。
  13. 根据权利要求11所述的电场定位给药装置，其特征在于，所述发生装置还包括：
    供电电源，用于给所述发生装置提供电能。
  14. 根据权利要求13所述的电场定位给药装置，其特征在于，所述供电电源为高压输出电源；优选的，所述供电电源为电池或直流电源DC通过震荡电路AC励磁升压变压器形成的高压输出电源。
  15. 根据权利要求14所述的电场定位给药装置，其特征在于，所述供电电源的电压为可调的所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
  16. 根据权利要求15所述的电场定位给药装置，其特征在于：特征2)中，电压根据作用深度以及电场距离取值；和/或，电流根据待测活体能够忍受的极限调整。
  17. 如权利要求11-16任一所述的电场定位给药装置在以下任一项或多项中的用途：(1)定位给药；(2)富集金属离子。
  18. 如权利要求17所述的用途，其特征在于，用途(1)中，进行定位给药的药物或药剂选自离子型试剂或中性试剂。
  19. 一种活体内离子型制剂的运动轨迹的控制方法，其特征在于，所述方法至少包括如下步骤：
    1)将所述待测活体空间电场接触电极连接，使待测活体与所述空间电场接触电极形成等电位；
    2)调整各个异电极的位置，以调整空间电场的覆盖面积；
    3)调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种，并控制活体内带电制剂的运动轨迹。
  20. 根据权利要求19所述的活体内离子型制剂的运动轨迹的控制方法，其特征在于，所述使用方法还包括以下特征中的一个或多个：
    a.所述空间电场接触电极接地；
    b.所述异电极为点状探头；
    c.供电电源的电压为可调的所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm；
    d.在所述空间电场中，所述离子型试剂向空间电场外电极的方向运动；
    e.所述异电极的位置和/或空间电场的性能根据目标位点、目标浓度和/或用量确认。
  21. 根据权利要求20所述的活体内离子型制剂的运动轨迹的控制方法，其特征在于，特征d中，电压根据作用深度以及电场距离取值；和/或，电流根据待测活体组织能够忍受的极限调整，定位给药范围包括空间电场覆盖区域。
PCT/CN2020/086399 2019-04-23 2020-04-23 活体内物质的运动或位置的控制方法及装置 WO2020216290A1 (zh)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4094322A (en) * 1976-06-18 1978-06-13 Hakuju Institute For Health Science Co., Ltd. Therapeutical apparatus using electric field
CN1608691A (zh) * 2004-11-25 2005-04-27 杨世升 定位给药仪
CN1824341A (zh) * 2004-12-17 2006-08-30 株式会社白寿生科学研究所 用电场治疗疾病的方法和装置
CN208405772U (zh) * 2017-10-10 2019-01-22 无锡健寿医疗科技有限公司 一种模拟地球电场的场能健康仪

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2012944A6 (es) * 1989-01-09 1990-04-16 Tomas Justribo Jose Ramon Procedimiento y su dispositivo para la admionistracion de farmacos mediante ionoforesis, para tratamiento loco-regionales.
CN1206353A (zh) * 1995-11-21 1999-01-27 E·N·勒纳 提高有机体内生物活性物质和化合物释放的装置
ES2664415T3 (es) * 2006-07-05 2018-04-19 Precisis Ag Sistema para el tratamiento de trastornos neurológicos mediante estimulación eléctrica
CN101318054B (zh) * 2008-07-18 2012-01-25 圣太科医疗科技（上海）有限公司 微电场网引导的肝脏靶向性细胞内药物传递装置
CN106823125A (zh) * 2017-03-24 2017-06-13 长沙利星医药科技开发有限公司 一种采用调幅电场增强药物疗效的装置

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4094322A (en) * 1976-06-18 1978-06-13 Hakuju Institute For Health Science Co., Ltd. Therapeutical apparatus using electric field
CN1608691A (zh) * 2004-11-25 2005-04-27 杨世升 定位给药仪
CN1824341A (zh) * 2004-12-17 2006-08-30 株式会社白寿生科学研究所 用电场治疗疾病的方法和装置
CN208405772U (zh) * 2017-10-10 2019-01-22 无锡健寿医疗科技有限公司 一种模拟地球电场的场能健康仪

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