CN110975134A - Laser ultrasonic device for transdermal drug delivery and manufacturing method - Google Patents
Laser ultrasonic device for transdermal drug delivery and manufacturing method Download PDFInfo
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- CN110975134A CN110975134A CN201911376216.7A CN201911376216A CN110975134A CN 110975134 A CN110975134 A CN 110975134A CN 201911376216 A CN201911376216 A CN 201911376216A CN 110975134 A CN110975134 A CN 110975134A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M2037/0007—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
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- Dermatology (AREA)
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Abstract
The invention relates to a laser ultrasonic device for transdermal drug delivery and a manufacturing method thereof, comprising a Q-switched frequency-doubled laser generator and a laser ultrasonic transducer, wherein the Q-switched frequency-doubled laser generator is used for generating laser Q-switched pulses with 532nm wavelength, 10nS pulse width and adjustable instantaneous power of 2-50 MW; the laser ultrasonic transducer generates ultrasonic pulses under the excitation of pulse laser, the ultrasonic frequency reaches 100MHz, and the instantaneous power of the ultrasonic pulses is 20 KW-500 KW. The invention generates ultrasonic pulse with frequency of 100MHz and power over 100KW by laser ultrasonic technology, can break through special barrier of skin, promotes drug to enter dermis through cuticle and epidermis, diffuse to capillary vessel, transfer to systemic circulation, and realizes efficient, noninvasive and uniform transdermal administration effect; solves the problems of easy infection, uneven administration, strong pain and low percutaneous absorption efficiency in the existing transdermal administration mode.
Description
Technical Field
The invention relates to laser ultrasonic equipment, in particular to a laser ultrasonic device for transdermal drug delivery and a manufacturing method thereof.
Background
The skin is a main route for effectively treating diseases, particularly skin diseases, and the transdermal administration mode has many advantages that ① drugs directly act on lesion tissues, ② reduces the degradation of the liver, ③ plasma concentration is stable, ④ cannot be degraded by digestive tracts (such as insulin in polypeptide drugs), but the skin has a special barrier function and can effectively limit the exchange with the external environment and the permeation of exogenous compounds.
Disclosure of Invention
The invention aims to provide a laser ultrasonic device for transdermal drug delivery and a manufacturing method thereof, ultrasonic pulses with the frequency of 100MHz and the power of over 100KW are generated by a laser ultrasonic technology, so that a special barrier of skin can be broken through, drugs are promoted to enter dermis through cuticle and epidermis, diffuse to capillary vessels and transfer to systemic circulation, and the effect of efficient, noninvasive and uniform transdermal drug delivery is realized; solves the problems of easy infection, uneven administration, strong pain and low percutaneous absorption efficiency in the existing transdermal administration mode.
In order to achieve the purpose, the invention has the following technical scheme:
the laser ultrasonic device for transdermal drug delivery comprises a Q-switched frequency-doubled laser generator and a laser ultrasonic transducer, wherein the Q-switched frequency-doubled laser generator is used for generating laser Q-switched pulses with 532nm wavelength, 10nS pulse width and 2-50 MW instantaneous power; the laser ultrasonic transducer generates ultrasonic pulses under the excitation of pulse laser, the ultrasonic frequency reaches 100MHz, and the instantaneous power of the ultrasonic pulses is 20 KW-500 KW.
YAG solid laser is adopted in the Q-switching frequency-doubling laser generator, the laser wavelength of 1064nm laser after Q-switching and frequency doubling output is 532nm, the laser pulse width is 10nS, and the power of the laser pulse is 2 MW-50 MW adjustable.
The laser ultrasonic transducer comprises a laser ultrasonic transducer sheet and a circular sheet prepared by mixing graphite powder and epoxy resin, wherein one surface of the circular sheet is used as a laser receiving surface, and the other surface of the circular sheet is plated with chrome and used as an ultrasonic output surface.
The invention relates to a method for manufacturing a laser ultrasonic device for transdermal drug delivery, wherein a laser ultrasonic transducer piece is prepared by mixing and uniformly stirring 4 parts of graphite powder and 6 parts of epoxy resin by weight, pouring the mixture into a mold, naturally curing the mixture into a semi-finished product at the temperature of 20-30 ℃ for 24 hours, and plating chromium on the surface of one side of the semi-finished product to form a finished product.
When the invention is used, the transdermal drug delivery method of the laser ultrasonic device for transdermal drug delivery comprises the following steps:
1) setting the output frequency and single pulse energy of laser Q-switching pulse, and enabling a pump source lamp in the solid laser to generate light energy required for exciting Nd, YAG (neodymium-doped yttrium aluminum garnet) solid laser substances under the action of a pump power supply according to the set working parameters, generating 1064nm laser by the solid laser, and generating and outputting 532nm laser Q-switching pulse by a laser generator after Q-switching and frequency doubling;
2) laser Q-switched pulses output by a laser generator are directly and vertically incident to a laser receiving surface of a laser ultrasonic energy conversion sheet, so that the transient temperature of the surface of the laser Q-switched pulses rapidly exceeds the melting point of a material, plasma is generated on the surface of an irradiated energy converter, a small part of substances on the surface of the irradiated energy converter can be sprayed out at a high speed, a vertical reaction force is generated on the surface of the energy converter, a compression pulse is generated on the surface irradiated by the laser, a normal impulsive force is generated on the energy converter, and therefore high-intensity ultrasonic pulses with the ultrasonic frequency of 100MHz and the instantaneous power of 20 KW-500 KW are excited and output from an ultrasonic output surface;
3) the output end face of the laser ultrasonic transducer is arranged on the skin coated with the medicine, so that the pulse ultrasonic wave generated by the laser ultrasonic transducer vertically acts on the medicine on the surface of the skin, the medicine is promoted to effectively break through the special barrier function of the skin, the medicine is efficiently promoted to penetrate through the cuticle and the epidermis to enter the dermis, and then is diffused to the capillary vessel and transferred to the systemic circulation, and the transdermal administration is realized.
The invention has the advantages that:
the pulse ultrasonic wave generated by the laser ultrasonic technology breaks through the capability of a special barrier of the skin, and overcomes the defects of invasive wound pain, high infection risk and uneven administration of the traditional subcutaneous injection and microneedle transdermal administration modes; compared with the traditional electroacoustic conversion ultrasonic transdermal administration, the frequency and the power of the ultrasonic wave are over thousand times, and the ultrasonic wave exceeds the threshold value required by transdermal administration, thereby fundamentally overcoming the defect of low transdermal administration permeation efficiency of the electroacoustic conversion ultrasonic transdermal administration. The transdermal drug delivery method of laser ultrasound is safe and painless, and can efficiently promote the drug to enter the dermis through the cuticle and the epidermis, diffuse to the capillary vessel and transfer to systemic circulation. The comprehensive performance of the laser ultrasonic transdermal drug delivery method is superior to that of other transdermal drug delivery methods.
Drawings
FIG. 1 is a block schematic diagram of the apparatus of the present invention;
FIG. 2 is a schematic diagram of a laser ultrasonic transducer;
FIG. 3 is a schematic diagram of a laser ultrasonic excitation mechanism;
wherein: 1 is a laser receiving surface, 2 is an ultrasonic output surface, 3 is a laser pulse, 4 is a vertical reaction force, and 5 is an ultrasonic wave.
Detailed Description
The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.
As shown in the figures 1-3 of the drawings,
the invention relates to a laser ultrasonic device for transdermal drug delivery, which comprises a Q-switching frequency-doubling laser generator and a laser ultrasonic transducer. YAG (neodymium-doped yttrium aluminum garnet) solid laser is pumped to generate 1064nm laser, the laser is instantly in a high Q value state through a Q switch to generate avalanche type laser oscillation, laser wavelength is converted into 532nm from 1064nm after the frequency is doubled by a KTP nonlinear crystal, and laser pulse with 10nS pulse width and 50MW instantaneous power is output; when a laser receiving surface of the laser ultrasonic transducer is irradiated by a laser Q-switching pulse, the transient temperature of the surface rapidly exceeds the melting point of a material, so that plasma is generated on the irradiated surface, at the moment, a substance is sprayed out, a vertical reaction force is generated on the surface of the irradiated surface, a compression pulse is generated at the same time, a normal impulse force is generated on the laser ultrasonic transducer, and therefore ultrasonic waves are excited, the pulse width of the ultrasonic waves and the pulse width of a laser beam are in the same order of magnitude, and the frequency of the ultrasonic waves excited by the laser can reach 100 MHz; the opto-acoustic conversion efficiency is 1%, so the instantaneous power of the ultrasonic pulse can reach 500 KW.
The order of magnitude refers to a number of dimensions or levels of size, with a fixed ratio maintained between each level. The ratios typically used are 10, 2, 1000, 1024, e (euler number, approximately equal to 2.71828182846 transcendental numbers, i.e., the base of the natural logarithm). In real life, the order of magnitude is generally based on 10 (to what powers of 10) unless otherwise noted.
The Q-switching frequency-doubling laser generator consists of an Nd: YAG (neodymium-doped yttrium aluminum garnet) solid laser, a Q switch, a KTP nonlinear crystal, a control circuit, a pumping power supply and a cooling water circuit. The Q-switching frequency-doubling laser generator adopts an ML-3080Q type Q switch Nd-YAG laser therapeutic machine produced by Wuhanqizhi laser technology limited company.
The laser ultrasonic transducer comprises a laser ultrasonic transducer sheet and a circular sheet prepared by mixing graphite powder and epoxy resin, wherein one surface of the circular sheet is used as a laser receiving surface, and the other surface of the circular sheet is plated with chrome and used as an ultrasonic output surface.
The invention relates to a method for manufacturing a laser ultrasonic device for transdermal drug delivery, wherein a laser ultrasonic transducer piece is prepared by mixing and uniformly stirring 4 parts of graphite powder and 6 parts of epoxy resin by weight, pouring the mixture into a mold, naturally curing the mixture into a semi-finished product at the temperature of 20-30 ℃ for 24 hours, and plating chromium on the surface of one side of the semi-finished product to form a finished product.
The Q-switching frequency-doubling laser generator can set the output frequency range of 532nm laser pulses to be 1-10 Hz and the output single pulse energy range to be 20-500 mJ according to actual needs. (corresponding to instantaneous laser power in the range of 2MW to 50 MW); the control circuit automatically adjusts the internal working voltage and current and controls the pump power supply charging and discharging circuit according to the set parameters; YAG laser works under the excitation of pump source, produce 1064nm long pulse laser, and under Q switch and KTP nonlinear crystal function, convert to 532nm laser and transfer Q pulse to output; the single pulse width was 10 nS.
The laser ultrasonic transducer is assembled on a laser output interface in advance, 532nm laser Q-switched pulses output by the Q-switched frequency doubling laser generator are directly and vertically incident to a laser receiving surface of a laser ultrasonic transducer piece, each laser pulse excites a normal force source on the receiving surface of the laser ultrasonic transducer piece, and therefore an ultrasonic pulse with the frequency of 100MHz and the power of 20 KW-500 KW is generated on an output surface.
The output end face of the laser ultrasonic transducer is arranged on the skin coated with the medicine, so that the ultrasonic pulse generated by the laser ultrasonic transducer acts on the medicine on the surface of the skin, the medicine is promoted to effectively break through the special barrier function of the skin, the medicine is efficiently promoted to enter the dermis through the cuticle and the epidermis, and is diffused to the capillary vessel and transferred to the systemic circulation, and the transdermal administration is realized.
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. Not all embodiments are exhaustive. All obvious changes and modifications which are obvious to the technical scheme of the invention are covered by the protection scope of the invention.
Claims (4)
1. A laser ultrasound device for transdermal drug delivery, characterized by: the device comprises a Q-switched frequency-doubled laser generator and a laser ultrasonic transducer, wherein the Q-switched frequency-doubled laser generator is used for generating adjustable laser Q-switched pulses with the wavelength of 532nm, the pulse width of 10nS and the instantaneous power of 2 MW-50 MW; the laser ultrasonic transducer has the laser-excited ultrasonic frequency up to 100MHz and the instantaneous power of ultrasonic pulse of 20-500 KW.
2. The laser ultrasound device for transdermal drug delivery according to claim 1, characterized in that: YAG solid laser is adopted in the Q-switched frequency-doubled laser generator, the laser wavelength of 1064nm laser after Q-switched and frequency-doubled output is 532nm, the laser pulse width is 10nS, and the power of the laser pulse is 2 MW-50 MW adjustable.
3. The laser ultrasound device for transdermal drug delivery according to claim 1, characterized in that: the laser ultrasonic transducer comprises a laser ultrasonic transducer piece and a circular sheet made of graphite powder and epoxy resin through mixing, wherein one surface of the circular sheet is used as a laser receiving surface, and the other surface of the circular sheet is plated with chrome and is used as an ultrasonic output surface.
4. The method of claim 1, wherein the laser ultrasound device comprises: the laser ultrasonic transducer is prepared by mixing and stirring 4 parts by weight of graphite powder and 6 parts by weight of epoxy resin uniformly, pouring the mixture into a mold, naturally curing the mixture at 20-30 ℃ for 24 hours to form a semi-finished product, and plating chromium on the surface of one side of the semi-finished product to form a finished product as an ultrasonic output surface.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201911376216.7A CN110975134A (en) | 2019-12-27 | 2019-12-27 | Laser ultrasonic device for transdermal drug delivery and manufacturing method |
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| CN201911376216.7A CN110975134A (en) | 2019-12-27 | 2019-12-27 | Laser ultrasonic device for transdermal drug delivery and manufacturing method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796842A (en) * | 2022-05-30 | 2022-07-29 | 深圳高性能医疗器械国家研究院有限公司 | Transdermal drug delivery structure, method for producing same, and transdermal drug delivery system |
| CN114832228A (en) * | 2022-07-04 | 2022-08-02 | 中国科学院长春光学精密机械与物理研究所 | Multi-wavelength laser promotes transdermal device of dosing |
Citations (5)
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| US20010055435A1 (en) * | 2000-08-02 | 2001-12-27 | Elena Biagi | Opto-acoustic generator of ultrasound waves from laser energy supplied via optical fiber |
| CN1787849A (en) * | 2003-06-13 | 2006-06-14 | 宝洁公司 | Ultrasonic sonophoresis skin care device |
| CN101174754A (en) * | 2007-10-29 | 2008-05-07 | 山东科技大学 | Laser based on lunate harmonic reflection mirror |
| CN102908720A (en) * | 2012-10-22 | 2013-02-06 | 李复生 | Uremia skin dialysis curer |
| CN207886521U (en) * | 2017-06-14 | 2018-09-21 | 青岛尤尼科技有限公司 | Transdermal medicine for treating instrument |
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2019
- 2019-12-27 CN CN201911376216.7A patent/CN110975134A/en active Pending
Patent Citations (5)
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| US20010055435A1 (en) * | 2000-08-02 | 2001-12-27 | Elena Biagi | Opto-acoustic generator of ultrasound waves from laser energy supplied via optical fiber |
| CN1787849A (en) * | 2003-06-13 | 2006-06-14 | 宝洁公司 | Ultrasonic sonophoresis skin care device |
| CN101174754A (en) * | 2007-10-29 | 2008-05-07 | 山东科技大学 | Laser based on lunate harmonic reflection mirror |
| CN102908720A (en) * | 2012-10-22 | 2013-02-06 | 李复生 | Uremia skin dialysis curer |
| CN207886521U (en) * | 2017-06-14 | 2018-09-21 | 青岛尤尼科技有限公司 | Transdermal medicine for treating instrument |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114796842A (en) * | 2022-05-30 | 2022-07-29 | 深圳高性能医疗器械国家研究院有限公司 | Transdermal drug delivery structure, method for producing same, and transdermal drug delivery system |
| CN114796842B (en) * | 2022-05-30 | 2024-03-29 | 深圳高性能医疗器械国家研究院有限公司 | Percutaneous medicine introduction structure, preparation method thereof and percutaneous medicine introduction system |
| CN114832228A (en) * | 2022-07-04 | 2022-08-02 | 中国科学院长春光学精密机械与物理研究所 | Multi-wavelength laser promotes transdermal device of dosing |
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Application publication date: 20200410 |