CN111821563A - Method and device for controlling movement or position of substance in living body - Google Patents
Method and device for controlling movement or position of substance in living body Download PDFInfo
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- CN111821563A CN111821563A CN202010329306.7A CN202010329306A CN111821563A CN 111821563 A CN111821563 A CN 111821563A CN 202010329306 A CN202010329306 A CN 202010329306A CN 111821563 A CN111821563 A CN 111821563A
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- A—HUMAN NECESSITIES
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- 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
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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
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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
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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
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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Abstract
The invention provides a method for controlling the movement or position of a substance in a living body, which at least comprises the following steps: 1) placing the living body in an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the positions of the different electrodes are adjustable; 2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential; 3) the properties of the electric field are adjusted to control the movement of the at least one substance within the living body or to control the location of the at least one substance within the living body. The invention can act on the charged substance in vivo through the electric field, so that the charged substance moves or is discharged out of the body according to a preset mode, and can act on tumor cells, act on in-vivo drugs, act on in-vivo water, act on in-vivo nerves, act on in-vivo heavy metal ions, act on in-vivo ions, act on chemical reaction process control reaction sequence, catalyze, prevent partial substance reaction and the like.
Description
Technical Field
The invention relates to a method and a device for controlling the movement or position of a substance in a living body.
Background
Gravity, friction force, coulomb force and universal attraction are widely distributed and act around people, so that the magnetic field can generate magnetic force, the magnetic force can be easily displayed and seen by people by using two magnets, the electric field can generate acting force, and the acting force can be called as electric power. Since this power is only present between species with different electrical charges or between species with different electrical charges, it is hardly observed directly or frequently and is not noticed. It actually exists. Many things that are not normally accomplished with known forces can be accomplished with electrical power.
The external medicine can be applied in a positioning way, and is quick, convenient, efficient and low-toxicity. Oral or intravenous administration is generally systemic and cannot be targeted. The goal of administration is to treat and minimize the toxic side effects of the drug. Some diseases (such as cancer) can damage normal cells while being treated by drugs, causing great harm to human bodies, and when oral chemotherapy drugs are selected for treating cancer, various side effects of different degrees can occur, such as nausea, vomiting, dry mouth, anorexia, numbness of hands and feet, hair loss and the like, most chemotherapy drugs have different degrees of bone marrow suppression, and the bone marrow suppression is often the dose-limiting toxicity of the anti-tumor drugs. The bone marrow suppression can be manifested as leucopenia, especially granulocytopenia in the early stage, in severe cases, blood platelets, red blood cells and hemoglobin can be reduced, different medicines have different effects on bone marrow, such as different degrees of reaction, and patients can also have symptoms of fatigue, weakness, resistance reduction, susceptibility to infection, fever, bleeding and the like, so that the quality of life of the patients is generally reduced, and even the patients are forced to stop treatment due to intolerance. Meanwhile, chemotherapy drugs are usually immunosuppressive drugs, which have different degrees of inhibition on the immune function of the body, so that the immune system of the body plays an important role in eliminating residual tumor cells in the body, and when the immune function is low, the tumor is not easy to control, but rather, the relapse or metastasis process is accelerated.
Disclosure of Invention
In view of the above-mentioned disadvantages of the prior art, it is an object of the present invention to provide a method and apparatus for controlling the movement or position of a substance in a living body.
To achieve the above and other related objects, a first aspect of the present invention provides a method for controlling the movement or position of a substance in a living body, the method comprising at least the steps of:
1) placing the living body in an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the positions of the different electrodes are adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the properties of the electric field are adjusted to control the movement of the at least one substance within the living body or to control the location of the at least one substance within the living body.
A second invention provides a method of discharging a charged substance out of a living body, the method including at least the steps of:
1) placing a living body containing charged substances in the body into an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the position of the different electrode is adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the performance of the electric field is adjusted to control the charged substances in the living body so that the charged substances are discharged out of the living body.
The third invention provides an electric field positioning drug delivery device, which at least comprises:
a space electric field contact electrode;
the space electric field outer electrode is used for forming a space electric field with the space electric field contact electrode, comprises more than 2 different electrodes, and is adjustable in position and used for adjusting the coverage area of the space electric field;
and the regulating and controlling unit is used for regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the live preparation in the living body.
A fourth aspect of the invention provides the use of the aforementioned electric field localization drug delivery device in any one or more of: (1) positioning administration; (2) and enriching metal ions.
A fifth aspect of the present invention provides a method for controlling a movement trajectory of an ionic preparation in a living body, the method at least comprising the steps of:
1) connecting the space electric field contact electrodes of the living body to be detected to enable the living body to be detected and the space electric field contact electrodes to form an equipotential;
2) adjusting the position of each different electrode to adjust the coverage area of the space electric field;
3) regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the ionic preparation in the living body.
As described above, the method and apparatus for controlling the movement or position of a substance in vivo according to the present invention have the following advantageous effects:
the invention can act on the charged substance in vivo through the electric field, so that the charged substance moves or is discharged out of the body according to a preset mode, and can act on tumor cells, act on in-vivo drugs, act on in-vivo water, act on in-vivo nerves, act on in-vivo heavy metal ions, act on in-vivo ions, act on chemical reaction process control reaction sequence, catalyze, prevent partial substance reaction and the like. Can realize the auxiliary growth, treatment, administration, detumescence, modification and catalysis.
The invention is safe to human body, high field intensity requires high voltage, and the prevention of point discharge is the most difficult problem of high field intensity electrostatics, and the point discharge can be effectively prevented by adopting the equipotential electric field technology, so that the product equipment conforms to the national regulations. Need not worry about electrocuteeing, equipotential electric field technique is safer. The medicine is accurately positioned and gathered, the dosage of the medicine is greatly reduced, the administration efficiency in a local range is improved, the dosage of the medicine for intravenous injection can be reduced by several times to dozens of times, and the medicine is targeted and concentrated at a pathological change part under the action of an electric field, so that the medicine concentration of a target part is hundreds of times or even thousands of times higher than that of other parts, the medicine effect can be increased by dozens of times, the applicability is stronger, and the application is wider.
Drawings
FIG. 1 is a schematic view of the structure of the electric field positioning drug delivery device of the present invention.
Fig. 2 shows a schematic circuit diagram of the electric field positioning drug delivery device of the present invention.
Fig. 3 shows a flow chart of a verification experiment of the electric field positioning drug delivery device of the invention.
FIG. 4 is a schematic diagram of the electric field acting on the electronegative tissue in a living body according to the invention (the outer electrode is negatively charged).
FIG. 5 is a schematic diagram of the electric field acting on the electronegative tissue in a living body according to the invention (the outer electrode is positively charged).
Detailed Description
The following description of the embodiments of the present invention is provided for illustrative purposes, and other advantages and effects of the present invention will become apparent to those skilled in the art from the present disclosure.
Please refer to fig. 1 to 5. It should be understood that the structures, ratios, sizes, and the like shown in the drawings and described in the specification are only used for matching with the disclosure of the specification, so as to be understood and read by those skilled in the art, and are not used to limit the conditions under which the present invention can be implemented, so that the present invention has no technical significance, and any structural modification, ratio relationship change, or size adjustment should still fall within the scope of the present invention without affecting the efficacy and the achievable purpose of the present invention. In addition, the terms "upper", "lower", "left", "right", "middle" and "one" used in the present specification are for clarity of description, and are not intended to limit the scope of the present invention, and the relative relationship between the terms and the terms is not to be construed as a scope of the present invention.
Principle of positioning administration
(1) Principle of ionic medicine directional movement
The ionic drug is a charged body, and the coulomb force F borne by the charged body in an electric field
F＝EQ (i)
(i) In the formula
E: electric field intensity in newtons/coulombs
Q: the charge quantity of the charged body is positive and negative, and the unit is coulomb
If Q is a positive charge, the direction of F is the same as the direction of E; if Q is a negative charge, then F is in the opposite direction to E.
As can be seen from the formula (i), the charged drug is subjected to a force with a certain direction in the electric field, and when the force is larger than other forces applied to the drug molecules (or particles), the charged drug particles move directionally in the direction of the electric field.
(2) Principle for promoting efficient enrichment of drugs/medicaments in positioning manner
When the electric field irradiates the location administration part (such as sole), the charged ionic drug or medicament moves along the direction of the electric field, passes through epidermis and dermis, part of the medicament passes through the capillary vessel, and the rest of the medicament continuously permeates the capillary vessel and finally collects at the location part (sole). And the electric field barrier or boundary formed naturally by the space electric field coverage area and the uncovered area ensures that the ionic (charged) reagent is in the focus or the treatment field within the set condition, and the continuous treatment is implemented. The setting condition is a dose metering; the electric field strength; time of action, etc. The agent which is exchanged with the lesion tissue and loses charge activity or naturally inactivated agent is transported out of the electric field shield through blood vessels, is mainly metabolized by the kidney or the liver and is discharged out of the body, and is partially metabolized by sweat glands or feces.
The mode of administration of drug molecules from the capillaries into various tissues is called free diffusion administration. The theory of diffusion movement has been studied to make clear that the diffusion rate is proportional to the concentration difference.
V＝K×(C1-C2) (ii)
In the formula
V diffusion velocity
K is constant
C1Concentration of drug on inner wall of capillary vessel
C2Concentration of drug on outer wall of capillary vessel
Capillary diameter 6X 103～7×103nm, the diameter of the drug molecule is generally less than 100nm, and the diameter of the water molecule is 0.2 nm. In traditional free diffusion, the rate of diffusion is directly proportional to the difference in concentration, drug delivery is slow and systemic action is not targeted. And when the charged drug molecules move towards the outer wall of the capillary under the action of the electric field, the drug concentration of the target part is greatly increased (by more than 1000 times). Thus, C1Without increasing or even decreasing. The medicine absorption rate of the part is increased, and the concentration is greatly increased.
The invention provides a method for controlling the movement or position of a substance in a living body, which at least comprises the following steps:
1) placing the living body in an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the positions of the different electrodes are adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the properties of the electric field are adjusted to control the movement of the at least one substance within the living body or to control the location of the at least one substance within the living body.
Further, in step 3), the property of adjusting the electric field is selected from one or more of adjusting the position of the different electrode, the electric field intensity, the electric field direction, the electric field pulse frequency and the electric field range.
The living body is an animal living body. Further, it is a mammal. The mammal is preferably a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is preferably a monkey, ape or human.
In one embodiment, the contact electrode is grounded.
Further, the outer electrode is not in contact with the living body to be measured.
In one embodiment, the counter electrode is a point-like probe.
In the electric field, at least one substance in a living body is controlled to gather at the position acted by the electric field. The substance is charged.
Optionally, the substance is selected from one or more of a charged agent, an extraneous harmful charged substance, and an ion in a living organism.
In further embodiments, the charged pharmaceutical agent is one or more of a charged injectable pharmaceutical agent, a charged oral pharmaceutical agent, and a charged rectal pharmaceutical agent.
Optionally, the charged medicament includes, but is not limited to, charged medicaments suitable for various administration modes such as oral administration, sublingual injection, intravenous injection, acupoint injection, rectal instillation administration, intramuscular injection, subcutaneous injection and the like.
In one embodiment, the generating means further comprises:
the power supply is used for supplying electric energy to the generating device;
the contact electrode does not influence the position of the different electrode or the selection of the electrifying condition.
In one embodiment, the position of the counter electrode and/or the properties of the electric field are determined based on the target site, target concentration.
In one embodiment, the power supply is a high voltage output power supply.
In one embodiment, the power supply is a battery or a high-voltage output power formed by a direct current power supply DC through an oscillating circuit AC excitation step-up transformer.
In one embodiment, the voltage of the electric field is adjustable between 0.001kV and 120kV, the current output is adjustable between 0.001mA and 10000mA, and the working distance of the electric field is adjustable between 0.1cm and 100 cm.
In one embodiment, the voltage is based on the depth of action and the distance of the electric field; and/or the current is less than the limit that living tissue can tolerate.
The power supply of the electric field is direct current.
The positive electrode of the direct-current high-voltage power supply is equipotentially connected with the living body, the negative electrode of the direct-current high-voltage power supply is connected with the outer electrode, the direct-current power supply is started, so that an electric field is generated between the living body and the electrodes, electric power is generated simultaneously, the electric power acts on a substance with positive charges in the living body firstly, and the substance is pulled to approach the negative electrode firstly. The magnitude of the generated power depends on the voltage between the electrodes and the charge of the charged substance. By utilizing the charge difference in organisms, positively charged substances, positive ions, conductive substances and conductive substances with small friction force can be respectively pulled.
As shown in FIG. 4 and FIG. 5, if the electrodes are connected in reverse, the equipotential of the living body is used as the negative electrode, the external electrode is used as the positive electrode, the DC power supply is turned on, so that an electric field is generated between the living body and the electrodes, and electric power is generated simultaneously, the electric power acts on the substance with negative charges in the living body, and the substance is pulled to the positive electrode. The magnitude of the generated power depends on the voltage between the electrodes and the charge of the charged substance. By utilizing the charge difference in organisms, negatively charged substances, negative ions, conductive substances and conductive substances with small friction force can be respectively pulled.
The electric charges and the electric conduction capacities of substances in living organisms are different, the electric field attraction of an external electric field to the substances is different, and the attraction of the substances with high different electric potential and strong different electric potential guiding capacity is large; can be moved first or obtain a greater electric force. On the contrary, the substance is lagged to be acted by the electric field force; and the electric field force is relatively weak; if the substance is charged opposite to the external electrode, a difference in the repulsive force in the opposite direction also occurs.
The method for discharging charged substances from a living body according to the present invention at least comprises the steps of:
1) placing a living body containing charged substances in the body into an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the position of the different electrode is adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the performance of the electric field is adjusted to control the charged substances in the living body so that the charged substances are discharged out of the living body.
Further, in step 3), the property of adjusting the electric field is selected from one or more of adjusting the position of the different electrode, the electric field intensity, the electric field direction, the electric field pulse frequency and the electric field range.
The living body is an animal living body. Further, it is a mammal. The mammal is preferably a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is preferably a monkey, ape or human.
In one embodiment, the contact electrode is grounded.
Further, the outer electrode is not in contact with the living body to be measured.
In one embodiment, the counter electrode is a point-like probe.
In the electric field, at least one substance in a living body is controlled to gather at the position acted by the electric field. The substance is charged.
Optionally, the substance is selected from one or more of a foreign harmful charged substance and an ion in a living body.
In one embodiment, the generating means further comprises:
the power supply is used for supplying electric energy to the generating device;
the contact electrode does not influence the position of the different electrode or the selection of the electrifying condition.
In one embodiment, the position of the counter electrode and/or the properties of the electric field are determined based on the target site, target concentration.
In one embodiment, the power supply is a high voltage output power supply.
In one embodiment, the power supply is a battery or a high-voltage output power formed by a direct current power supply DC through an oscillating circuit AC excitation step-up transformer.
In one embodiment, the voltage of the electric field is adjustable between 0.001kV and 120kV, and the current output is adjustable between 0.001mA and 10000 mA.
In one embodiment, the voltage is based on the depth of action and the distance of the electric field; and/or the current is less than the limit that living tissue can tolerate.
The power supply of the electric field is direct current.
As shown in fig. 1 and 2, the present invention provides an electric field localization drug delivery device, at least comprising:
a space electric field contact electrode;
the space electric field outer electrode is used for forming a space electric field with the space electric field contact electrode, comprises more than 2 different electrodes, and is adjustable in position and used for adjusting the coverage area of the space electric field;
and the regulating and controlling unit is used for regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the live preparation in the living body.
Furthermore, the space electric field contact electrode is used for being connected with a living body to be detected, so that the living body to be detected and the space electric field contact electrode form an equipotential.
Further, the equipotential contact point may be the sole of a foot as shown in fig. 1, or may be another part of the living body to be measured, or may be water-wet or conductive grease.
The living body to be detected is an animal living body. Further, it is a mammal. The mammal is preferably a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is preferably a monkey, ape or human.
In one embodiment, the space electric field contact electrode is grounded.
Optionally, the external electrode of the space electric field may or may not contact with the living body to be measured.
In one embodiment, the counter electrode is a point-like probe.
In the space electric field, the charged agents gather at the site of the electric field. In one embodiment, the charged agent is a charged agent.
In further embodiments, the charged agent is one or more of an ionic injectable agent, an ionic oral agent, and an ionic rectal agent.
Optionally, the ionic medicament includes, but is not limited to, ionic medicaments suitable for various administration modes such as oral administration, sublingual injection, intravenous injection, acupoint injection, rectal instillation administration, intramuscular injection, subcutaneous injection and the like.
In one embodiment, the generating means further comprises:
the power supply is used for supplying electric energy to the generating device;
the space electric field contact electrode does not influence the position of the different electrode or the selection of the electrifying condition.
In one embodiment, the position of the counter electrode and/or the properties of the spatial electric field are determined based on the target site, target concentration and/or dose.
In one embodiment, the power supply is a high voltage output power supply.
In one embodiment, the power supply is a battery or a high-voltage output power formed by a direct current power supply DC through an oscillating circuit AC excitation step-up transformer.
In one embodiment, the voltage of the power supply is adjustable between 0.001kV and 120kV, the current output is adjustable between 0.001mA and 10000mA, and the working distance of an electric field is adjustable between 0.1cm and 100 cm; .
In one embodiment, the voltage is based on the depth of action and the distance of the electric field; and/or the current is adjusted according to the tolerable limit of the living body to be tested.
The invention also provides the use of the aforementioned electric field localization drug delivery device in any one or more of: (1) positioning administration; (2) and enriching metal ions.
Alternatively, in the use (1), the drug or medicament for localized administration includes, but is not limited to, ionic (cationic, anionic) reagents and neutral reagents (ion exchange or ionization treatment is performed before use).
The invention also provides a method for controlling the motion trail of the ionic preparation in the living body, which at least comprises the following steps:
1) connecting the space electric field contact electrodes of the living body to be detected to enable the living body to be detected and the space electric field contact electrodes to form an equipotential;
2) adjusting the position of each different electrode to adjust the coverage area of the space electric field;
3) regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the live preparation in vivo.
Further, the equipotential contact point may be the sole of a foot as shown in fig. 1, or may be another part of the living body to be measured, or may be water-wet or conductive grease.
The living body to be detected is an animal living body. Further, it is a mammal. The mammal is preferably a rodent, artiodactyla, perissodactyla, lagomorpha, primate, or the like. The primate is preferably a monkey, ape or human.
In one embodiment, the space electric field contact electrode is grounded.
Optionally, the external electrode of the space electric field may or may not contact with the living body to be measured.
In one embodiment, the counter electrode is a point-like probe.
In the space electric field, the charged agents gather at the site of the electric field. In one embodiment, the charged agent is a charged agent.
In further embodiments, the charged pharmaceutical agent is one or more of a charged injectable pharmaceutical agent, a charged oral pharmaceutical agent, and a charged rectal pharmaceutical agent.
Optionally, the charged medicament includes, but is not limited to, charged medicaments suitable for various administration modes such as oral administration, sublingual injection, intravenous injection, acupoint injection, rectal instillation administration, intramuscular injection, subcutaneous injection and the like.
In the space electric field, the ionic reagent moves towards the direction of the electrode outside the space electric field.
In one embodiment, the generating means further comprises:
the power supply is used for supplying electric energy to the generating device;
the space electric field contact electrode does not influence the position of the different electrode or the selection of the electrifying condition.
In one embodiment, the position of the counter electrode and/or the properties of the spatial electric field are determined based on the target site, target concentration and/or dose.
In one embodiment, the power supply is a high voltage output power supply.
In one embodiment, the power supply is a battery or a high-voltage output power formed by a direct current power supply DC through an oscillating circuit AC excitation step-up transformer.
In one embodiment, the voltage of the power supply is adjustable between 0.001kV and 120kV, the current output is adjustable between 0.001mA and 10000mA, and the working distance of the electric field is adjustable between 0.1cm and 100 cm.
In one embodiment, the voltage is based on the depth of action and the distance of the electric field; and/or the current is adjusted according to the tolerable limit of the living body to be tested, and the positioning administration range comprises a space electric field coverage area. But is not limited to, the spatial electric field coverage area.
In one embodiment, the method for controlling the movement or position of a substance in a living body or the method for discharging a charged substance from a living body according to the present invention, the electric field generating device is the above-mentioned electric field localization drug delivery device. At this time, the contact electrode refers to the space electric field contact electrode, and the outer electrode refers to a space electric field outer electrode.
Verification experiment
4.1 preparation of Experimental animals
70 rats with the age of 15-18 weeks are selected, and the weight is 250-320 g. The rats were housed by breeders and acclimatized to the new environment for 2 weeks prior to the start of the experiment. During this period, the weight of the animals was carefully observed and measured every week, and all animals were excluded from the study, which did not adapt to the environment, such as weight loss. The rats were randomly divided into 6 groups, each group was divided into 6 groups, and the rats were divided into 6 groups, i.e., a-F groups, based on the parameters and voltages selected by the apparatus, and subjected to drug administration verification at different electric field strengths of 0.1KV, 1KV, 3KV, 10KV, 30KV, and 120KV, respectively (n is 10). Another group of 1 and 10 rats was prepared as a control group, and direct cardiac injection was performed (without electric field localization administration).
Table 1: summary of electric field intensity parameters of animals tested in group and experimental precursors
| Grouping detail | A | B | C | D | E | F | G |
| Electric field intensity (kv) | 0.1 | 1 | 3 | 10 | 30 | 120 | None |
| Body weight (g) | 285±13.6 | 292±16.3 | 273±15.8 | 297±14.9 | 265±16.3 | 271±18.5 | 292±17.6 |
4.2 Experimental flow sheet
See figure 3 for details.
4.2.1 electrocardiographic examination
The rats were fixed on a plate in the supine position, and after observing that the rats had no orthotropic reaction, the weight of the rats was weighed, and the rats were anesthetized with 10% chloral hydrate in an amount of 0.3ml/100 g. The electrocardiogram is collected for 30 minutes by using the Powerlab system, which is 30 minutes before treatment for short. And then, carrying out sublingual intravenous injection of verapamil with the dose of 1.0mg/kg (about 300 mug/rat: the injection dose is 6 times of the normal dose of the human drug according to an equivalent dose coefficient folding algorithm in pharmacology experimental methodology compiled by professor of xu Tertiary cloud), arranging an external electrode of a space electric field of the positioning drug delivery device at or irradiating the chest part of the rat, connecting a contact electrode of the space electric field of the rat, connecting the contact electrode of the space electric field with the ground, and delivering the irradiation with different electric field strengths according to requirements. After 1 hour and 24 hours, the rats are subjected to electrocardiographic examination, and electrocardiographic signals are continuously acquired for 30 minutes again, which is 30 minutes after treatment for short.
4.2.2 blood Collection and Biochemical index detection
After 1 hour after the electrocardiographic examination, 10 rats were randomly selected from each group, fixed on an dissecting table, opened, the abdominal aorta was separated, and 2.5ml of blood was drawn from the abdominal aorta. After heat treatment at 37 ℃ for 30min, the mixture was centrifuged at 1000rpm for 2min to separate the serum. And detecting the content of verapamil in the serum.
Table 2: electric field intensity parameter and verapamil dosage of experimental animals
4.2.3 tissue harvesting
After blood withdrawal, the rats were sacrificed and the rat heart, liver and kidney were removed and snap frozen in liquid nitrogen for use (for measurement of verapamil concentration).
4.2.4 tissue verapamil concentration measurement
(1) Preparation of tissue homogenate
Taking out lung and heart intermediate tissue from-80 deg.C refrigerator, cutting tissue into small pieces, stirring, adding 2 times of methanol-water (1: 1, v/v) mixed solution, and homogenizing for 5 min.
(2) Centrifugation
The setting rotation speed is 1000rpm, the working temperature is 4 ℃, and the centrifugation time is 10 min. Centrifuging, collecting supernatant, storing in liquid nitrogen or refrigerator at-80 deg.C, and testing.
(3) Liquid chromatography-tandem mass spectrometer drug configuration
Preparing verapamil standard into standard series solutions with concentrations of 1, 3, 10, 30, 100 and 300 ng/mL. A control of 10mg oxcarbazepine was weighed and dissolved in acetonitrile-water (50:50, v/v) to prepare a stock solution of oxcarbazepine at 1mg/mL, which was diluted to 1000ng/mL with acetonitrile (50:50, v/v) and used as an internal standard.
(4) Chromatographic conditions
Chromatographic column Poroshell 120 SB-C18 column (4.6X 50mm I.D., 2.7 μm); mobile phase: phase A was a 5mM ammonium acetate in 0.2% formic acid aqueous phase; phase B is acetonitrile, and gradient elution is carried out for 2min and 60% of phase B; flow rate: 0.8 mL/min; column temperature: 40 ℃; sample introduction amount: 10 μ L.
4.6.5 sample introduction
17 μ L, vortex mixed for 40s, centrifuged for 5min (15000rpm), injected 5-10 μ L, LC-MS/MS analyzed.
4.3 statistical methods
Performing data analysis by using SPSS17.0 software, wherein experimental data are expressed by mean +/-standard deviation, t test is used when each group of baseline data is normally distributed, independent sample t test is adopted for comparison among groups, and paired sample t test is adopted for comparison in groups; and when the data are not normally distributed, the data are compared by adopting a rank sum test method. The difference is statistically significant when P is less than 0.05.
Table 3: distribution of verapamil cationic agent 1hr after administration
| Grouping detail | A | B | C | D | E | F | G |
| Electric field intensity (kv) | 0.1 | 1 | 3 | 10 | 30 | 120 | None |
| Blood (mug) | None | None | 1.2±1.1 | 6.3±1.1 | 20.1±11.2 | 12.3±5.6 | 120.3±13.8 |
| Heart (mug) | None | None | 6.5±2.1 | 31.5±2.1 | 125.2±15.8 | 205.2±6.8 | 105.2±15.8 |
| Liver (mug) | None | None | 0.9±0.5 | 1.3±0.6 | 3.3±0.9 | 7.3±2.1 | 5.3±1.5 |
| Kidney (ug) | None | None | 1.5±0.3 | 6.3±2.3 | 15.2±7.2 | 15.5±3.8 | 21.5±5.3 |
Before the administration starts, the administration box is electrified with positive charges for 15 minutes, so that the positive charges are added to the medicament, and the administration box is always connected with the positive charges during the administration period of the electric field. After 1 hour of electric field administration, each group of experimental animals (5 animals each) was euthanized and blood was collected, and the heart, liver and kidney were removed. Detection was performed using HPLC liquid phase analysis techniques. And respectively counting the verapamil content in each tissue after the weight and the blood volume of each organ tissue and blood are corrected. Group G (control group) was administered without applying an electric field, and the drug was directly injected into the heart, and 1hr after the start of administration, about 1/3 doses remained in the heart, 1/3 remained in blood components via blood, and the remainder was mainly excreted to the outside of the body via renal excretion.
When the electric field intensity of the electric field administration group reaches 3KV, the administration effect begins to appear. When the electric field strength reaches 30KV, the administration effect reaches the effect of direct injection of the heart. When the electric field is increased to 120KV, the administration effect is about twice of the direct injection dosage of the heart, and the residual function mainly excreted by the kidney is kept unchanged. This result suggests that the cationic formulation is expected to replace the conventional administration mode of direct injection into the vein or affected part by using the electric field administration mode described in the patent. The medical expenditure and the medical insurance cost of medical resources and the burden of the patient are saved along with the reduction of the dosage of the medicament while the additional pain of the patient caused by physical puncture is avoided.
Neutral or cationic agents as described above can significantly increase the revenue population. Can negative ion preparations widely used in clinical practice bring the same benefits? To solve this puzzle, we energized the chamber with a negative charge for 15 minutes before the start of dosing, which made the drug add a negative charge and ensured that the chamber was always connected to the negative charge during the electric field dosing period.
Table 4: distribution of verapamil anionic agent 1hr after administration
| Grouping detail | A | B | C | D | E | F | G |
| Electric field intensity (kv) | 0.1 | 1 | 3 | 10 | 30 | 120 | None |
| Blood (mug) | None | None | 1.1±1.3 | 5.3±1.7 | 18.3±9.2 | 11.3±7.5 | 114.6±15.8 |
| Heart (mug) | None | None | 7.2±1.8 | 28.5±2.4 | 113.2±23.1 | 195.7±7.2 | 112.3±21.7 |
| Liver (mug) | None | None | 1.2±0.8 | 1.5±0.8 | 5.1±2.1 | 9.3±1.9 | 6.5±2.7 |
| Kidney (ug) | None | None | 1.8±1.2 | 5.3±1.7 | 18.3±5.8 | 21.5±1.8 | 19.3±6.1 |
After 1 hour of electric field administration, each group of experimental animals (5 animals each) was euthanized and blood was collected, and the heart, liver and kidney were removed. Detection was performed using HPLC liquid phase analysis techniques. And respectively counting the verapamil content in each tissue after the weight and the blood volume of each organ tissue and blood are corrected. Group G (control group) was administered without applying an electric field, and the drug was directly injected into the heart, and 1hr after the start of administration, about 1/3 doses remained in the heart, 1/3 remained in blood components via blood, and the remainder was mainly excreted to the outside of the body via renal excretion.
Similar effects to those of cationic agents are demonstrated in anionic agents. When the electric field intensity of the electric field administration group reaches 3KV, the administration effect begins to appear. When the electric field strength reaches 30KV, the administration effect reaches the effect of direct injection of the heart. When the electric field is increased to 120KV, the administration effect is about twice of the direct injection dose of the heart. This result suggests that the cationic formulation is expected to replace the conventional administration mode of direct injection into the vein or affected part by using the electric field administration mode described in the patent. The physical puncture is avoided to bring additional pain to the patient, and the medical expenditure and the medical insurance cost of medical resources and the burden of the patient can be saved along with the reduction of the dosage of the medicament.
It is noted that, as a general knowledge of electric field operation, when it is necessary to administer a cationic reagent in an electric field administration mode, it is necessary to secure a positive charge for the reagent, and a negative electrode is added to an administration port box, and when it is necessary to administer an anionic reagent, it is necessary to administer a counter electrode.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (21)
1. A method for controlling the movement or position of a substance in a living body, the method comprising at least the steps of:
1) placing the living body in an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the positions of the different electrodes are adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the properties of the electric field are adjusted to control the movement of the at least one substance within the living body or to control the location of the at least one substance within the living body.
2. The method according to claim 1, wherein in step 3), the property of the electric field is adjusted by one or more selected from the group consisting of adjusting the position of the counter 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.
3. The method for controlling the movement or position of a substance in a living body according to claim 1, wherein in the step 3), the substance is a substance with difference electrons or a substance generating difference electrons by external electricity.
4. The method of claim 1, wherein the substance is selected from one or more of a group consisting of a charged agent, a foreign harmful charged substance, and an ion in a living body.
5. The method of claim 1, further comprising one or more of the following features:
a. the contact electrode is grounded;
b. the different electrode is a point-shaped probe;
c. the outer electrode is not in contact with the living body;
d. the voltage of the electric field is adjustable between 0.001kV and 120kV, and the current output is adjustable between 0.001mA and 10000 mA; the working distance of the electric field is adjustable between 0.1cm and 100 cm;
e. the performance of the electric field is confirmed according to the target site and/or the target concentration;
f. the power supply of the electric field is direct current.
6. The method according to claim 5, wherein when the feature d is included, the voltage is set according to the depth of action and the distance of the electric field; and/or the current is less than the limit that living tissue can tolerate.
7. A method for discharging charged substances out of a living body, characterized in that the method comprises at least the steps of:
1) placing a living body containing charged substances in the body into an electric field generating device, wherein the electric field generating device comprises a contact electrode and an outer electrode, the outer electrode comprises more than 1 different electrode, and the position of the different electrode is adjustable;
2) contacting the living body with a contact electrode to make the living body and the contact electrode form an equipotential;
3) the performance of the electric field is adjusted to control the charged substances in the living body so that the charged substances are discharged out of the living body.
8. The method for discharging charged substances from a living body according to claim 7, wherein in step 3), the property of adjusting the electric field is selected from one or more of adjusting the position of the counter 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.
9. The method of causing charged species to be expelled from a living body according to claim 7, wherein the control method further comprises one or more of the following features:
a. the contact electrode is grounded;
b. the different electrode is a point-shaped probe;
c. the outer electrode is not contacted with the living body to be measured;
d. the voltage of the electric field is adjustable between 0.001kV and 120kV, and the current output is adjustable between 0.001mA and 10000 mA;
e. the position of the different electrode and/or the performance of the electric field are confirmed according to the target site and/or the target concentration;
f. the power supply of the electric field is direct current.
10. The method for discharging charged substances from a living body according to claim 9, wherein the voltage is a value according to an action depth and an electric field distance when the feature d is included; and/or the current is less than the limit that living tissue can tolerate.
11. An electric field positioning drug delivery device, characterized in that it comprises at least:
a space electric field contact electrode;
the space electric field outer electrode is used for forming a space electric field with the space electric field contact electrode, comprises more than 2 different electrodes, and is adjustable in position and used for adjusting the coverage area of the space electric field;
and the regulating and controlling unit is used for regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the live preparation in the living body.
12. The electric field positioning drug delivery device of claim 11, wherein: further comprising one or more of the following features:
a. the space electric field contact electrode is used for being connected with a living body to be detected, so that the living body to be detected and the space electric field contact electrode form an equipotential;
b. the space electric field contact electrode is grounded;
c. the different electrode is a point-shaped probe;
d. the position of the counter electrode and/or the performance of the space electric field is confirmed according to the target site, the target concentration and/or the dosage.
13. The electric field positioning drug delivery device of claim 11, wherein the generating device further comprises:
and the power supply is used for supplying electric energy to the generating device.
14. The electric field positioning drug delivery device of claim 13, wherein the power supply is a high voltage output power supply; preferably, the power supply is a battery or a high-voltage output power formed by a direct-current power supply DC through an oscillating circuit AC excitation step-up transformer.
15. The electric field positioning drug delivery device of claim 14, wherein the voltage of the power supply is adjustable, the voltage of the power supply is 0.001kV to 120kV, the current output is adjustable, and the working distance of the electric field is adjustable, wherein the working distance of the electric field is adjustable, and the working distance of the electric field is adjustable.
16. The electric field positioning drug delivery device of claim 15, wherein: in the characteristic 2), the voltage is taken according to the action depth and the electric field distance; and/or the current is adjusted according to the tolerable limit of the living body to be tested.
17. Use of the electric field positioning administration device of any of claims 11-16 in any one or more of: (1) positioning administration; (2) and enriching metal ions.
18. Use according to claim 17, wherein in use (1) the drug or agent to be administered locally is selected from an ionic agent or a neutral agent.
19. A method for controlling the trajectory of a movement of an ionic agent in vivo, the method comprising at least the steps of:
1) connecting the space electric field contact electrodes of the living body to be detected to enable the living body to be detected and the space electric field contact electrodes to form an equipotential;
2) adjusting the position of each different electrode to adjust the coverage area of the space electric field;
3) regulating and controlling the performance of the space electric field, including one or more of electric field intensity, electric field direction, electric field pulse frequency and electric field range, and controlling the motion track of the live preparation in vivo.
20. The method of claim 19, wherein the method of using further comprises one or more of the following features:
a. the space electric field contact electrode is grounded;
b. the different electrode is a point-shaped probe;
c. the voltage of the power supply is adjustable, the voltage of the power supply is adjustable and ranges from 0.001kV to 120kV, the current output is adjustable and ranges from 0.001mA to 10000mA, and the working distance of an electric field is adjustable and ranges from 0.1cm to 100 cm;
d. in the space electric field, the ionic reagent moves towards the direction of an electrode outside the space electric field;
e. the position of the counter electrode and/or the performance of the space electric field is confirmed according to the target site, the target concentration and/or the dosage.
21. The method according to claim 20, wherein in the characteristic d, the voltage is set according to the depth of action and the distance of the electric field; and/or the current is adjusted according to the tolerable limit of the living tissues to be tested, and the positioning administration range comprises a space electric field coverage area.
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| CN106823125A (en) * | 2017-03-24 | 2017-06-13 | 长沙利星医药科技开发有限公司 | A kind of device of use amplitude modulation electric-field enhancing curative effect of medication |
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| 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 |
| CN208405772U (en) * | 2017-10-10 | 2019-01-22 | 无锡健寿医疗科技有限公司 | A kind of field energy health instrument for simulating the earth's electric field |
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2020
- 2020-04-23 CN CN202010329306.7A patent/CN111821563A/en active Pending
- 2020-04-23 WO PCT/CN2020/086399 patent/WO2020216290A1/en active Application Filing
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| EP0378132A2 (en) * | 1989-01-09 | 1990-07-18 | S.L. Cit Ionofor | A device for the administration of medication by iontopheresis for local - regional treatment. |
| CN1206353A (en) * | 1995-11-21 | 1999-01-27 | E·N·勒纳 | Device for enhanced delivery of biologically active substances and compounds in organism |
| CN1608691A (en) * | 2004-11-25 | 2005-04-27 | 杨世升 | Locating and medicating instrument |
| CN1824341A (en) * | 2004-12-17 | 2006-08-30 | 株式会社白寿生科学研究所 | Methods and apparatus of treating disorders with electric fields |
| US20110137381A1 (en) * | 2006-07-05 | 2011-06-09 | Harry Lee | Treatment of neurological disorders via electrical stimulation, and methods related thereto |
| CN101318054A (en) * | 2008-07-18 | 2008-12-10 | 圣太科医疗科技（上海）有限公司 | Microelectro field net guided transfer apparatus for medicament in hepar target cell |
| CN106823125A (en) * | 2017-03-24 | 2017-06-13 | 长沙利星医药科技开发有限公司 | A kind of device of use amplitude modulation electric-field enhancing curative effect of medication |
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