An apparatus for regulating testosterone levels in male mammals

Abstract

The present invention relates to a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, which comprises a low-intensity ultrasonic wave generating / producing device.

Description

Technical Field

[0001] The present invention relates to a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, which comprises a low-intensity ultrasonic wave generating / producing device. Background Art

[0002] Male hormones, also known as "male hormones," are hormones that promote the maturation of male accessory organs and the appearance of secondary sexual characteristics, maintaining normal libido and reproductive function. Testosterone, secreted by the testicles, is the primary male hormone and belongs to the steroid hormone class. Testosterone is inactivated in the liver, and its derivatives are excreted in the urine.

[0003] The main functions of testosterone include stimulating the male accessory sexual organs to mature, maintaining normal sexual desire, and promoting sperm maturation. It is also closely related to other important physiological indicators of mammals, such as promoting protein synthesis and skeletal muscle growth, inhibiting the increase of body fat, stimulating the production of red blood cells and the growth of long bones, insulin production, and cognitive ability.

[0004] Testosterone, a mammalian male hormone, plays an important role in the life cycle of male mammals and is widely involved in various physiological metabolisms of male mammals. Although some synthetic male hormone-like substances, such as testosterone-like substances, have been developed to address various symptoms or diseases caused by abnormal or reduced male hormone levels in mammals, long-term use of exogenous male hormone substances can lead to risks such as metabolic and cardiovascular diseases. Therefore, it is highly desirable to find non-drug and / or non-exogenous means to improve or treat various symptoms or diseases associated with abnormal or reduced male hormone levels, such as testosterone, in male mammals, such as male humans. Summary of the Invention

[0005] The present invention aims to provide a device for improving or regulating abnormal or reduced levels of male hormones, such as testosterone, in male mammals through non-drug means, thereby improving or treating symptoms or diseases associated with abnormal or reduced levels of male hormones in male mammals. The present inventors unexpectedly discovered that local application of ultrasound within a certain safe frequency range to the sexual organs of male mammals can effectively activate and proliferate Leydig cells, thereby increasing the concentration of endogenous serum testosterone in the body, thereby improving or treating various symptoms or diseases associated with abnormal or reduced levels of male hormones, such as testosterone. The present invention is based on the above discovery and has now been completed.

[0006] The first aspect of the present invention relates to a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, comprising:

[0007] Power supply, ultrasonic generating component, which generates an intensity of 5-500mW / cm 2 Ultrasound.

[0008] The second aspect of the present invention relates to a device for improving or treating various symptoms or diseases related to abnormal or decreased male hormones such as testosterone, which comprises: a power source, an ultrasonic generating component, which generates an intensity of 5-500mW / cm 2 Ultrasound.

[0009] Another aspect of the present invention relates to a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, comprising:

[0010] Isolation transformer, switching power supply, ultrasonic excitation source, ultrasonic generating device, optional control module, optional touch screen, as well as optional water pump, liquid storage and water pipe.

[0011] Another aspect of the present invention relates to a device for improving or treating various symptoms or diseases related to abnormal or decreased male hormones such as testosterone, which includes an isolation transformer, a switching power supply, an ultrasonic excitation source, an ultrasonic generating device, an optional water pump, a liquid storage device, a water pipe, an optional control module and an optional touch screen.

[0012] The present invention also relates to an ultrasonic generator for use in preparing or producing a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, wherein the ultrasonic generator generates ultrasonic waves with a frequency in the range of 1-3 MHz and an intensity of 5-500 mW / cm 2 Ultrasound.

[0013] The present invention also relates to an ultrasonic generator for use in preparing or producing a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones such as testosterone, wherein the ultrasonic generator generates ultrasonic waves with a frequency in the range of 1-3 MHz and an intensity of 5-500 mW / cm 2 Ultrasound.

[0014] According to the present invention, "optional" means that it may be present or not, or may contain or include, or does not contain or include.

[0015] According to the present invention, the isolation transformer and the switching power supply are the power supply part of the device, which are used to provide power to the entire device, and are electrically connected to the ultrasonic excitation source and the optional control module;

[0016] The ultrasonic excitation source can generate a driving voltage of a specific frequency to drive the ultrasonic generating device to generate ultrasonic waves of a specific frequency and intensity, and the two are electrically connected;

[0017] The ultrasonic generator can generate ultrasonic waves of specific frequency and intensity. It can be unmodulated continuous ultrasonic waves or modulated low-intensity pulsed ultrasonic waves. The component can generate an intensity of 5-500mW / cm 2 , ultrasound with a frequency of 1-3 MHz, preferably 10-200 mW / cm 2 The frequency is preferably 1.7 MHz, or modulated low-intensity pulsed ultrasound, the modulation frequency is preferably 1 KHz, and the ultrasonic sound intensity is preferably 10-200 mW / cm 2 , the frequency is preferably 1.7MHz.

[0018] According to the present invention, the isolation transformer and the switching power supply are the power supply part of the device, which are used to provide power to the entire device and are electrically connected to the ultrasonic excitation source and the optional control module;

[0019] The ultrasonic excitation source can generate a driving voltage of a specific frequency to drive the ultrasonic generating device to generate ultrasonic waves of a specific frequency and intensity, and the two are electrically connected;

[0020] Furthermore, the ultrasonic generator can be with or without liquid coupling agent, which can generate ultrasonic waves of a specific frequency and intensity, which can be unmodulated continuous ultrasonic waves or modulated low-intensity pulsed ultrasonic waves. The component can generate an intensity of 5-500mW / cm 2 Ultrasonic waves with a frequency of 1-3 MHz, or modulated low-intensity pulsed ultrasonic waves, with a modulation frequency of preferably 1 KHz and an ultrasonic intensity of preferably 10-200 mW / cm 2 The frequency is preferably 1.7 MHz. It comprises a housing, a piezoelectric transducer, a coupling membrane disposed in a fixed groove between the front end of the ultrasonic generator and the application site, and a cavity formed between the piezoelectric transducer and the coupling membrane. The cavity can be filled with a liquid coupling agent or other non-liquid coupling agent.

[0021] The liquid coupling agent is water (preferably purified water) or other liquid solutions that can couple ultrasonic wave conduction.

[0022] The non-liquid coupling agent is an ultrasound gel (such as Ultrasound Gel Pad, Shenzhen Minhao Technology Co., Ltd.) or other solid materials that can match the ultrasonic transmission (such as medical B-ultrasound probe).

[0023] The coupling membrane is a soft elastic membrane that can be concave inward or protruded outward, and can be well combined with the action site.

[0024] According to the present invention, "symptoms or diseases related to abnormal or decreased androgen such as testosterone in male mammals" include, but are not limited to: sexual dysfunction, physical weakness, menopausal symptoms, abnormal body metabolism, cardio-cerebral system disorders, abnormal blood sugar, cognitive function, etc.

[0025] According to the present invention, the piezoelectric transducer can generate the following types of ultrasonic waves, for example, emitting focused ultrasonic waves, emitting trend-focused ultrasonic waves, emitting collimated ultrasonic waves, or emitting divergent ultrasonic waves.

[0026] The touch screen can display the operation interface and parameters in the control module, and can also be used to operate and control the device, such as selecting the power size, etc. It is electrically connected and communicated with the control module, which can be wired signal transmission or wireless signal transmission;

[0027] The control module and the touch screen module are optional modules. The ultrasonic output can be achieved without these two modules. The control module and the touch screen module can help the user to better control the device.

[0028] The water pump, water pipe, and liquid storage device constitute the liquid couplant circulation module of the present invention. This module is optional. It is required if an ultrasonic generator with liquid couplant is selected. It is not required if an ultrasonic generator without liquid couplant is selected.

[0029] According to the present invention, by applying low-intensity pulsed ultrasound with a frequency of 1-3 MHz to the sexual organs of male mammals, such as male testicles, Leydig cells can be effectively activated and proliferated, thereby increasing serum testosterone concentration. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1The schematic diagram of the structure of a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention is shown. 01 is an isolation transformer, 02 is a switching power supply, 03 is an ultrasonic excitation source, 04 is an ultrasonic generator, 05 is a control module, 06 is a touch screen, 07 is a water pump, 08 is a liquid reservoir, and 09 is a water pipe. The isolation transformer and switching power supply constitute the device's power module, providing power to the entire device and electrically connected to the ultrasonic excitation source and the control module. The ultrasonic excitation source is electrically connected to the ultrasonic generator, which is in communication with the control module. The control module is electrically and communicatively connected to the touch screen. The water pump is electrically connected to the ultrasonic excitation source, connected to the liquid reservoir via a water pipe, connected to the ultrasonic generator via a water pipe, and connected to the liquid reservoir via a water pipe. The water pump, liquid reservoir, water pipe, and ultrasonic generator constitute a liquid circulation system. Components within the dashed box are some or all non-essential components.

[0031] Figure 2A A schematic diagram of the appearance of an ultrasonic generator in a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention is shown. 10 is a coupling membrane, 11 is a housing, and the coupling membrane and housing are connected by a mechanical structure.

[0032] Figure 2B A schematic cross-sectional view of an ultrasonic generator device of the present invention, used to improve or treat various symptoms or diseases associated with abnormal or decreased androgen levels, such as testosterone, is shown. Reference numeral 10 represents a coupling membrane, reference numeral 13 represents a piezoelectric transducer, reference numeral 14 represents a housing, reference numeral 15 represents a cavity, and reference numeral 16 represents an inlet and outlet for a liquid coupling agent. The piezoelectric transducer, coupling membrane, and housing are mechanically connected, forming a cavity between the coupling membrane and the piezoelectric transducer. This cavity can be filled with either a liquid coupling agent or a non-liquid coupling agent.

[0033] Figure 2C A schematic diagram of another ultrasonic generator device of the present invention is shown, which is used to improve or treat various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone. Reference numeral 17 represents a housing, reference numeral 18 represents two coupling membranes, and reference numeral 19 represents an application site securing groove. The coupling membranes are mechanically connected to the housing, forming an application site securing groove between the two coupling membranes.

[0034] Figure 2D A cross-sectional schematic diagram of another ultrasonic generator of the present invention is shown, which is used to improve or treat various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone. 20 is an application site fixing groove, 21 is two coupling membranes, 22 is a piezoelectric transducer, and 23 and 24 are the inlet and outlet of the liquid coupling agent.

[0035] Figure 2A and 2B 2C and 2D show the appearance and structural schematic diagrams of two ultrasonic wave generating devices of a device for improving or treating various symptoms or diseases related to abnormal or decreased male hormones such as testosterone according to the present invention, which can emit focused ultrasonic waves, trended focused ultrasonic waves, collimated ultrasonic waves or divergent ultrasonic waves;

[0036] Figure 3 A schematic diagram illustrating the morphology of focused ultrasonic waves emitted by an ultrasonic wave generator of a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention. Such waves converge at a focal point, where the energy density is the highest.

[0037] Figure 4 A schematic diagram illustrating the morphology of focused ultrasound waves emitted by an ultrasound generator of a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention. This type of wave is a type of focused ultrasound wave, except that the focal point is farther away, and the energy density is less than that of focused ultrasound waves and greater than that of collimated ultrasound waves.

[0038] Figure 5 A schematic diagram shows the collimated ultrasonic wave emitted by an ultrasonic wave generator of a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention. This wave is a straight line, neither converging nor diverging. The energy density is uniform along the entire line. At the same ultrasonic wave intensity, the energy density is less than that of a focused wave and greater than that of a diverging wave.

[0039] Figure 6 A schematic diagram shows the divergent ultrasonic wave morphology emitted by an ultrasonic wave generator of a device for improving or treating various symptoms or diseases associated with abnormal or decreased male hormones, such as testosterone, according to the present invention. This wave radiates outward in a trumpet-like shape and has the lowest energy density compared to other waves at the same sound intensity.

[0040] Figure 7 The figure shows the damage to testicular tissue after ultrasound treatment at different intensities, L1 to L6. Observations in the safe intensity range screening group revealed that low-intensity pulsed ultrasound at energy levels L5 and L6 can cause slight bleeding in the testicles.

[0041] Figure 8 The results of the experiment show the effects of low-intensity pulsed ultrasound of different intensities on serum testosterone concentration in adult male Sprague-Dawley rats.

[0042] Figure 9The effect of low-intensity pulsed ultrasound on the proliferation of Leydig cells in the testes of adult male Sprague-Dawley rats is shown. The number of Leydig cells increased, with the LIPUS-1 group showing the greatest increase.

[0043] Detailed description and specific implementation methods

[0044] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, rather than all the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present invention and its application or use. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0045] The present invention relates to a device for improving or regulating abnormal or reduced levels of male hormones such as testosterone in male mammals, comprising:

[0046] An isolation transformer (01), a switching power supply (02), an ultrasonic excitation source (03), an ultrasonic generating device (04), a water pump (07), a liquid storage device (08), a water pipe (09), a control module (05) and a touch screen (06).

[0047] The isolation transformer (01) and the switching power supply (02) are the power supply parts of the device, which are used to provide power to the entire device and are electrically connected to the ultrasonic excitation source (03) and the control module (05);

[0048] The ultrasonic excitation source (03) can generate a driving voltage of a specific frequency to drive the ultrasonic generating device (04) to generate ultrasonic waves of a specific frequency and intensity, and the two are electrically connected;

[0049] The ultrasonic generating device (04) can be with or without liquid coupling agent, and can generate ultrasonic waves of a specific frequency and intensity, which can be unmodulated continuous ultrasonic waves or modulated low-intensity pulsed ultrasonic waves. The component can generate an intensity of 5-500mW / cm 2 , ultrasonic waves with a frequency of 1-3 MHz, or modulated low-intensity pulsed ultrasonic waves, the modulation frequency is preferably 1 KHz, and the ultrasonic sound intensity is preferably 10-200 mW / cm 2The frequency is preferably 1.7 MHz. It comprises a housing (11, 14, 17), a piezoelectric transducer (13, 22), a coupling membrane (10, 12, 18, 21) arranged at the front end of an ultrasonic generator (04) and in a fixing groove (18, 20) at an application site, and a cavity (15) formed between the piezoelectric transducer (13, 22) and the coupling membrane (10, 12, 18, 21). The cavity (15) can be filled with a liquid coupling agent or other non-liquid coupling agents.

[0050] The coupling membrane (10, 12, 18, 21) is a soft elastic membrane that can be concave inward or protruded outward, and can be well combined with the action part.

[0051] According to the present invention, the piezoelectric transducer (13, 22) can generate the following types of ultrasonic waves, for example, emit focused ultrasonic waves, emit trend-focused ultrasonic waves, emit collimated ultrasonic waves, or emit divergent ultrasonic waves.

[0052] The ultrasonic wave generating device (04) of the present invention has two forms, namely a circular ultrasonic wave generating device (04) and an elongated ultrasonic wave generating device (04), respectively. Figure 2A and Figure 2C As shown, the circular ultrasonic generator (04) can be used by hand or connected to a bracket with a universal shaft, which is convenient for fixing the position of the ultrasonic generator (04) and the direction of action of the ultrasonic generator (04), and when the device is used for treatment, the subject can sit on a special treatment chair for treatment;

[0053] A long ultrasonic generator (04) includes an ultrasonic generator housing (11, 14, 17), an application site fixing groove (18, 20), an ultrasonic generator coupling membrane (2) (18, 21), and a piezoelectric transducer (2 identical) (22). The long ultrasonic generator (04) can be used by hand or connected to a bracket with a universal shaft, which is convenient for fixing the position of the ultrasonic generator (04) and the action direction of the ultrasonic generator (04). When the device is used for treatment, the subject can lie on a special treatment bed for treatment. During treatment, the subject can lie on the treatment bed, and then the doctor will operate to place one of the subject's testicles into the application site fixing groove (18, 20) of the ultrasonic generator, or both testicles can be placed into the application site fixing groove (18, 20) at the same time, and then start the power for treatment. The two piezoelectric transducers (22) of the ultrasonic generator can output simultaneously or individually and alternately, and the output time and method can be selected as needed.

[0054] The touch screen (06) can display the operation interface, parameters, etc. in the control module (05), and can also be used to operate and control the device, such as selecting the power size, etc. It is electrically connected and communicated with the control module (05), which can be wired signal transmission or wireless signal transmission.

[0055] The control module (05) and the touch screen (06) are non-essential modules. The output of ultrasonic waves can be achieved even without these two modules. The control module (05) and the touch screen (06) can help the user better control the device.

[0056] The water pump (07), the water pipe (09), and the liquid storage (08) constitute the liquid coupling agent circulation module of the present invention. This module is a non-essential module. If an ultrasonic generator with a liquid coupling agent is selected, this module is required. If an ultrasonic generator without a liquid coupling agent is selected, this module is not required. Specific embodiments

[0057] Example 1

[0058] The transmission frequency is 1.7MHz and the ultrasonic intensity is 67±10% mW / cm 2 (L1), the device of the present invention with collimated low-intensity pulsed ultrasound with a modulation frequency of 1KHz and corresponding pulsed ultrasound of other intensities.

[0059] The specific implementation plan is as follows:

[0060] AC220V grid power is connected to the isolation transformer component (withstand voltage 4000V, 500W, 1:1 output) and connected to the terminal block to output AC220V;

[0061] A Lenovo IdeaPad S410 laptop computer was selected as the control module component. It was connected to the ultrasonic excitation source via a USB cable. The touch screen display function was completed by the laptop display, and the touch function of the touch screen was completed by the laptop mouse. The power supply was connected to the terminal block by an adapter (CPA-AO65).

[0062] Select a switching power supply (Mingwei: LRS-200-24) that outputs DC24V after connecting to the terminal block as the power supply component of the excitation source;

[0063] The power management chip 1 (LM5118, commercially available) in the ultrasonic excitation source adjusts the voltage by increasing or decreasing the voltage through the control module to realize the output L1. The power management chip 2 (LT3509EMSE) supplies power to other components of the entire ultrasonic excitation source.

[0064] The ultrasonic excitation source component uses an MCU (single-chip microcomputer, MSP430F5529, commercially available) to output: a 1KHz square wave modulating a 1.7MHz square wave, with a positive duty cycle of 20% for the 1KHz frequency and a positive duty cycle of 50% for the 1.7MHz frequency;

[0065] A field effect tube (IRFP250N, commercially available) is selected as a class E amplifier circuit and connected to the ultrasonic generator through a coaxial cable (impedance characteristic 50Ω). The MCU provides a frequency driving signal and the power management chip 1 provides power.

[0066] The ultrasonic generator consists of an ABS plastic shell, a silicone coupling membrane (disc-shaped, 0.3mm thick, hardness: 60 degrees Shore, convex), a piezoelectric transducer (resonant frequency 1.7MHZ), and silicone rings on both sides of the piezoelectric transducer. The upper and lower edges are fixed with ABS plastic by screw extrusion. The coupling membrane is fixed to the ABS plastic that fixes the piezoelectric transducer through another ABS plastic part. The piezoelectric transducer and the silicone coupling membrane form a cavity. A water pump (EIDEC: 00H220H12, commercially available) is selected for water circulation and exhaust. The liquid storage device (a self-made 200mm×200mm×150mm organic glass water tank) is filled with purified water. After the cavity is filled with water and exhausted with a water pump, the control module is used to select the output of ultrasonic waves of different intensities to the target.

[0067] according to Figure 1 The assembly shown has a transmission frequency of 1.7 MHz and an ultrasonic intensity of 67 ± 10% mW / cm 2 (L1) is a device of the present invention for collimated low-intensity pulsed ultrasound with a modulation frequency of 1 kHz.

[0068] With the other components above unchanged, the control module can be used to select different energy levels to obtain the following different ultrasonic energy devices: L2: 86±10% mW / cm 2 , L3: 106±10% mW / cm 2 , L4: 126±10% mW / cm 2 , L5: 146±10% mW / cm 2 , L6: 166±10% mW / cm 2 .

[0069] Example 2

[0070] The device of Example 1 was used to test and observe 12-week-old male Sprague-Dawley rats, and the effects on serum testosterone concentration and testicular Leydig cells were observed.

[0071] Experimental methods

[0072] Fourteen 12-week-old male Sprague-Dawley rats were selected and all rats were housed under a 12-hour light and 12-hour dark cycle. The 14 12-week-old male Sprague-Dawley rats were divided into 4 groups:

[0073] The first group was the blank control group, consisting of 3 rats, numbered ctrl-1, which did not receive any treatment and were kept under the same conditions as the other groups;

[0074] The second group was a safe intensity range screening group, consisting of three rats, designated ctrl-2. Three rats and six testicles were divided into six groups, each receiving one testicle. Each group received six treatment settings, with each setting treating one testicle for two minutes. Forty-eight hours after treatment, the rats were sacrificed and tissue specimens collected for testing.

[0075] Through observation of the safe intensity range screening group, it was found that low-intensity pulsed ultrasound at L5 and L6 energy levels can cause slight bleeding in the testicles (see Appendix Figure 7 ), in order not to damage the tissue, the lower energy levels L1 and L2 were selected for the experiment in the following treatment;

[0076] The third group is treatment group 1, which consists of 4 rats and is numbered LIPUS-1. The above-mentioned device for regulating low testosterone in male mammals is used to apply ultrasound to the rats in this group. The intensity of ultrasound L1 is 67±10% mW / cm 2 , treatment twice a week, 2 minutes each time, for 3 consecutive weeks;

[0077] The fourth group is treatment group 2, which consists of 4 rats and is numbered LIPUS-2. The above-mentioned device for regulating low testosterone in male mammals is used to apply ultrasound to the rats in this group. The intensity of ultrasound L2 is 86±10% mW / cm 2 , treat twice a week, 2 minutes each time, for 3 consecutive weeks.

[0078] Treatment group 1 (LIPUS-1) and treatment group 2 (LIPUS-2) were irradiated using a collimated LIPUS device, the ultrasonic generator (04) was directly applied to the scrotum of the rats to cover the testicles, and a medical ultrasonic coupling agent ( Medical ultrasonic coupling agent, Beijing China Resources Kangtai High-tech Development Institute). The energy flux density of treatment group 1 and treatment group 2 was L1 (67±10% mW / cm 2 ) and L2(86±10%mW / cm 2) for 2 minutes. Rats in treatment groups 1 and 2 were treated twice weekly for 3 consecutive weeks. One week after the last LIPUS treatment, the rats were sacrificed and serum and organs were collected. Serum testosterone concentrations were measured, and testicular tissue was histologically examined.

[0079] Whole blood was drawn from each rat into separate collection tubes and allowed to clot for 30 minutes. The clotted blood was then centrifuged at 1000 rpm for 15 minutes (Eppendorf 5414 microcentrifuge, Enfield, CT, USA). Serum was removed from the collection tubes and stored at −80°C until use. Serum testosterone levels were measured in 11 randomly selected rats from the blank control group (ctrl-1) and treatment groups 1 and 2 using a parametric testosterone assay kit (R&D Systems, Minneapolis, MN, USA) according to the manufacturer's instructions.

[0080] No abnormal behavior was observed in any rat during the study. No blood was observed in the urine or stool. No signs of pain were observed in general appearance, activity, or observation of the treatment site. Monitoring revealed normal activity, good response to irritating lipid treatment, adequate motor activity, satisfactory food and water intake, normal social interactions, and normal use of cage accessories. No clinical signs of irritation or injury were observed.

[0081] Experimental results

[0082] 1. Effect of LIPUS on serum testosterone concentration

[0083] The average serum testosterone concentrations in the blank control group, LIPUS-1 group, and LIPUS-2 group were 2.2175±0.21ng / ml, 7.1033±0.61ng / ml, and 5.4516±0.475ng / ml, respectively. Ultrasound stimulation significantly increased serum testosterone levels (220% for level 1 and 145% for level 2). (See Appendix Figure 8 and Table 1 ).

[0084]

[0085] Table 1 Effect of LIPUS on serum testosterone concentration

[0086] 2. Effects of LIPUS on Leydig cells

[0087] Leydig cells, also known as intermedial cells of leydig, are located near the seminiferous tubules of the testicles. They produce testosterone in response to luteinizing hormone (LH).

[0088] The number of interstitial cells was determined as follows:

[0089] One rat was randomly selected from the control group crrl-1 and the treatment groups LIUPS-1 and LIPUS-2 for testicular section observation.

[0090] Testicular tissue was fixed in 2% paraformaldehyde and 0.002% saturated picric acid for 24 hours, placed in 0.1 M phosphate buffer (pH 8.0) for 4 hours, and then soaked in a buffer containing 30% sucrose overnight. The specimens were placed in OCT compound (Sakura Finetic USA, Torrance, CA) and stored at -70°C until use. Fixed, frozen tissue specimens were cut at a thickness of 10 μm, mounted on charged slides (Fisher Scientific, Pittsburgh, PA), and air-dried for 5 minutes. The tissues were then stained with EdU, immunostained, or immunofluorescently stained.

[0091] Testicular cryosections were prepared, and immunofluorescence was performed as previously described. Briefly, the tissue was rehydrated with PBS for 5 minutes and treated with hydrogen peroxide / methanol to quench endogenous peroxidase activity. After rinsing with water, the sections were rinsed twice with PBS for 5 minutes each and then incubated with 3% horse serum / PBS / 0.3% triton X-100 for 30 minutes. Excess fluid was drained and the sections were incubated overnight at 4°C with primary antibodies including anti-stAR to identify Leydig cells (StAR; 1:500; Santa Cruz Biotechnology, Santa Cruz, CA, USA); anti-DDX4 to identify spermatocytes (1:500; Millipore Corporation, Bedford, MA, USA); and anti-smooth muscle (a-sma) to define the outline of seminiferous tubules (1:1000; Sigma-Aldrich, St. Louis, MO, USA). Secondary antibodies included Alexa-488- and Alexa-594-conjugated antibodies (1:500; Invitrogen). Cell nuclei were stained with 4',6-diamidino-2-phenylindole (DAPI).For image analysis, four randomly selected fields of view from each tissue section of each animal in each group were photographed and recorded using a Retiga Q image digital static camera and ACT-1 software (Nikon Instruments Inc., Melville, NY, USA).

[0092] LIPUS treatment significantly increased the number of interstitial cells in L1 and L2 groups ( Figure 3 ). Leydig cells were activated and proliferated under LIPUS treatment (see Appendix Figure 9 and Table 2 ).

[0093] Table 2 LIPUS promotes the proliferation of mesenchymal cells in vivo

[0094]

[0095] The data obtained show that low-intensity pulsed ultrasound can significantly increase serum testosterone concentration by activating interstitial cells and causing them to proliferate.

[0096] The above are merely exemplary embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Use of an ultrasonic generator for the preparation or production of a device for improving or regulating abnormal or reduced testosterone levels in adult male mammals, wherein the ultrasonic generator generates ultrasonic waves with a frequency range of 1.7-3 MHz and an intensity of 60.3-500 mW / cm 2 The ultrasonic wave generating device further comprises: A piezoelectric transducer and a coupling membrane arranged at the front end of the piezoelectric transducer. The coupling membrane is a soft elastic membrane that is concave inward or protrudes outward and can be well combined with the action site. The device also includes an ultrasonic excitation source connected to the ultrasonic generating device for controlling the operation of the ultrasonic generating device; as well as an optional water pump, a liquid storage device and a water pipe; and a control module that is communicatively connected to the ultrasonic excitation source.

2. The application according to claim 1, wherein the ultrasonic wave generating device emits one of focused ultrasonic waves, trend-focused ultrasonic waves, collimated ultrasonic waves, or divergent ultrasonic waves.

3. The use according to claim 1 or 2, wherein the device comprises a power supply, wherein the power supply comprises: An isolation transformer including input and output terminals for connecting to mains power; A switching power supply is connected to the output terminal of the isolation transformer and is electrically connected to the ultrasonic generating device, a control module, an optional touch screen, and an optional water pump, a liquid storage device and a water pipe.

4. The application according to claim 3, wherein the device further comprises a touch screen communicatively and electrically connected to the control module.

5. The application according to claim 1, wherein the ultrasonic generator generates an ultrasonic wave with a frequency of 1.7 MHz and an intensity of 67 ± 10% mW / cm 2 ultrasound.

6. The application according to claim 1, wherein the ultrasonic generator generates an ultrasonic wave with a frequency of 1.7 MHz and an intensity of 86 ± 10% mW / cm 2 ultrasound.

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