JP2005304918A - Wound treatment device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To promote recovery of a wounded area, which enables to shorten a period for a conservative treatment or to avoid a treatment or an operation for a case unresponsive to the conservative treatment. <P>SOLUTION: A wound treatment device comprises an ultrasonic treatment head module having an ultrasonic transducer therein and a controlling means to control its ultrasound radiation, from which an ultrasonic pulse is irradiated to the wounded area. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a cell proliferation inducing action by a physical / mechanical stimulus load on a wound site. More specifically, ultrasonic treatment of the wound site promotes cell growth at the wound site, promotes repair of the wound site such as pressure ulcers and ulcers, shortens the treatment period, or avoids invasive surgery It is related with the apparatus which performs.

  Pressure sores are necrosis of the skin / subcutaneous tissue caused by pressure applied continuously for a long time, and are likely to occur in elderly people and patients with motor paralysis who have reduced exercise capacity. In addition, blood circulation disorders after trauma may lead to skin ulcers. Each is a wound disease, and the onset factors are clear epidemiologically, but each disease occurs easily and requires a long time to heal, so rehabilitation and care are necessary. Current treatments for pressure ulcers and skin ulcers include prostaglandin-containing ointments, angiogenic factors, direct application of basic fibroblast growth factor (bFGF), autologous bone marrow cell transplantation for the purpose of inducing angiogenesis, Hepatocyte growth factor (HGF) gene transfer is also performed.

Ultrasound irradiation has long been used in the rehabilitation field for the purpose of enhancing the effect of heat on tissues and promoting blood flow, and has been applied to the treatment of pressure ulcers and skin ulcers with the expectation of promoting wound treatment. There is a report that the effect is not clear and invalid (Non-Patent Documents 1 to 3). In addition, there are various ultrasonic conditions used in reports that ultrasonic irradiation was effective for pressure ulcers, including ultrasonic waves with a frequency of 3.0 MHz, a repetition period of 1 kHz, a burst width of 200 μs, and an output of 200 mW / cm ^2. Some use the thermal effect (Non-Patent Document 4). A report that therapeutic ultrasound is effective for wound treatment describes that ultrasound reaches soft tissue and promotes tissue repair at the wound site (Non-Patent Document 5). In addition, it has been reported that cell growth and cytokine production are promoted by applying low-power ultrasonic stimulation to a cell culture system related to a wound site (Non-patent Document 6). In any case, the meta-analysis of the results of a plurality of randomized comparative clinical trials does not provide clear results showing the effectiveness of therapeutic ultrasound for pressure ulcer treatment (Non-patent Document 7).

Here, it is known that fracture repair is promoted by a low-intensity pulsed ultrasound (hereinafter LIPUS). LIPUS, which has such effects, has been studied for fracture treatment by Duarte et al. (Patent Document 1: US Pat. No. 4,530,360), and subsequently developed by US Exogen Corp. Ultrasound Fracture Machine Safes ^TM (SAFHS ^TM ) Has been. Ultrasound Fracture Machine Safes ^TM (SAFHS ^TM ) is effective in clinical trials for promoting healing of tibial shaft fractures (Non-patent Document 8), distal radius fractures (Non-patent Document 9) and animal models. (Non-Patent Document 10) has been proved. As a mechanism that brings about such effects, it is considered that LIPUS increases cyclooxygenase 2 (COX-2) transcriptional activity in osteoblasts, resulting in increased prostaglandin (PGE2) production (non-patent literature). 11).

  PGE2 is thought to play an important role in angiogenesis (Non-patent Document 12), and angiogenic factors such as vascular endothelial growth factor (Non-patent Document 13) and fibroblast growth factor (bFGF) (non-patent document 12). (Patent Document 14), or the construction of a neovascular system induced by angiogenic factors (Non-Patent Document 15).

U.S. Pat.No. 4,530,360 Phys Ther: 76,1996 Clin Exp Dermatol: 17,1992 Ostomy Wound Manage: 48,2002 Phys Ther: 74,1994 Reumatology 40: 1331-1336, 2001 J Oral Maxillofac Surg 57: 409-419, 1999 Cochorane Database Syst. Rev .: CD001275, 2000 J Bone and Jiont Surg, 76A: 25-34, 1994 J Bone and Joint Surg, 79A: 961-973, 1997 J Bone Miner Res. 16: 671-680, 2001 Biochem. Biophys. Res. Commun. 256: 284-287, 1999 Proc.Soc.Exp.Biol.Med. 172: 214-218, 1983 Lung Cancer 31: 203-212, 2001 Kobe J Med Sci 47: 35-45, 2001 Blood 102: 1966-1977, 2003

  For the treatment of wounds, conservative treatments such as wound surface protection are mainly used. However, the conservative treatments are often ineffective, and treatment by surgery is also performed. The present invention makes it possible to shorten the period of conservative therapy, treat cases that do not respond to conservative therapy, and avoid surgery by promoting repair of the wound site. In addition, this treatment method is thought to bring the gospel to wounded patients and to reduce bedridden patients by resuming functional training through wound treatment and improving care.

  As a result of intensive studies on such problems, the present inventors have promoted the proliferation of fibroblasts and PGE2 production, which have an important role in wound healing, by giving mechanical and mechanical stimulation to fibroblasts. It has been found that the present invention has been found to play a major role in wound healing by promoting angiogenesis by giving similar stimulation to endothelial cells.

That is, the present invention provides a wound treatment apparatus comprising an ultrasonic treatment head module incorporating an ultrasonic transducer and a control means for controlling the irradiation of ultrasonic waves, and irradiating an ultrasonic pulse to a wound site. It is to provide. Further, according to the present invention, the control means outputs an ultrasonic pulse in a range of an ultrasonic frequency of 20 kHz to 10 MHz, a burst width of 10 μsec to 1 msec, a repetition period of 5 Hz to 10 kHz, and an ultrasonic output of 5 to 75 mW / cm ^2. In particular, the ultrasonic output is in the range of 5 to 30 mW / cm ² , and among these, the control means has an ultrasonic frequency of 1.5 MHz, a burst width of 200 μsec, and a repetition period of 1 It is a means for controlling the output of ultrasonic waves in the range of 0.0 kHz and ultrasonic output of 7.5 mW / cm ² .

  Furthermore, the present invention provides a wound treatment device characterized in that the device is a device applied to a pressure ulcer or an ulcer site.

   In the present invention, ultrasonic stimulation promotes 1) proliferation of fibroblasts and 2) lumen formation (angiogenesis) by vascular endothelial cells. Furthermore, it was suggested that these effects were due to the production promotion of cell growth factors PGE2 and bFGF. Therefore, this apparatus can shorten the period required for wound treatment than before, and can treat a wound that could not be treated by the conventional method.

  By using this apparatus when culturing cells and tissues such as skin, connective tissue, blood vessels and the like outside the body, for example, the time required for preparation of the tissue for transplantation can be shortened.

  The present invention is directed to a wound treatment apparatus characterized in that by applying ultrasonic waves to a wound site, mechanical and mechanical stimulation (mechanical stress) having a certain pattern is applied to the affected area to promote repair of the wound site. It is.

  The following are examples of embodiments of the wound treatment procedure of the present invention. The wound treatment apparatus of the present invention includes an ultrasonic treatment head module that incorporates an ultrasonic transducer and irradiates ultrasonic waves to a wound site, control means for controlling the ultrasonic wave, and the wound site of a wound patient. A function for fixing the ultrasonic treatment head module is provided.

  Such an ultrasonic transducer is made of piezoelectric ceramic. Using the property that minute distortion occurs when voltage is applied, an electrical signal generated by an ultrasonic waveform synthesizer is applied to the piezoelectric ceramic of the transducer, and the transducer surface This produces longitudinal vibration (ultrasonic waves).

The ultrasonic wave used is a low-power ultrasonic pulse having an ultrasonic frequency of 20 kHz to 10 MHz, a burst width of 10 μsec to 1 msec, a repetition period of 5 Hz to 10 kHz, and an ultrasonic output of 5 to 75 mW / cm ^2. It can be expected as a therapeutic effect, and in particular, the ultrasonic frequency is 1.5 MHz, the burst width is 200 μsec, the repetition period is 1.0 kHz, the ultrasonic output is 5 to 30 mW / cm ² , especially 7.5 mW / cm. ^Two are preferred.

  The control means includes an ultrasonic waveform synthesis function for synthesizing ultrasonic waves emitted from the ultrasonic transducer, output control, storage calculation means, and power ON / OFF control function. Each function may be integrated in the ultrasonic treatment head module or may be divided into the ultrasonic treatment head module and the main body.

[Example 1]
Below, the example which divided | segmented the treatment apparatus of this invention into the main-body part and the ultrasonic treatment head module is demonstrated using drawing. The wound treatment apparatus of the present invention includes a main body portion and an ultrasonic treatment head module.

[Main unit]
As shown in FIG. 1, the main body includes a power source, a storage arithmetic device, and an input / output device.
(1) Power supply: The power is turned on by operating the front panel, and the power is automatically turned off when the treatment is completed. The treatment head is also powered from the same power source.
(2) Storage arithmetic unit: A CPU (central control unit) is mounted on the printed circuit board, which not only manages the treatment time but also monitors the operation and wearing state of the treatment head and performs self-diagnosis. Also, the patient's treatment record is stored in the backup memory, and it is designed so that it can be taken out as needed.
(3) Input / output device: In addition to the operation switch, liquid crystal display panel, and buzzer, the treatment head module is controlled and supplied with power through a connection cable. As a control signal for the treatment head module, a signal having an ultrasonic pulse burst width of 200 Hz and a repetition period of 1 KHz is sent. In addition, a trouble signal is sent back from the treatment head.

[Ultrasonic therapy head module]
As shown in FIG. 2, the ultrasonic treatment head module includes an oscillation device, an ultrasonic waveform synthesis device, an ultrasonic generation device, and a detection device. The connection cable to the main unit is an integrated type.
(1) Oscillator: Generates a 1.5 MHz ultrasonic signal.
(2) Ultrasound waveform synthesizer: Synthesizes control signal from the main unit and 1.5MHz ultrasound signal, therapeutic ultrasound, ie ultrasound frequency: 1.5MHz, ultrasound output: 7.5mW / cm ² , burst width : Generates an electric signal with a waveform having a signal characteristic of 200 μsec and a repetition frequency of 1 kHz.
(3) Ultrasonic generator: Piezoelectric ceramics have the property of producing minute distortions when a voltage is applied. Using this, an electrical signal generated by an ultrasonic waveform synthesizer is applied to the piezoelectric ceramic inside the transducer, and longitudinal vibration (ultrasound) is generated on the transducer surface to apply it to therapy. An ultrasonic absorber is attached to the back surface of the piezoelectric ceramic to prevent ultrasonic leakage.
(4) Abnormality detection device: The treatment head detects fixation to the fixture and lack of ultrasonic conduction jelly, transmits it to the main body, and warns the patient with a liquid crystal display and an alarm. In order to detect improper fixation between the treatment head and the fixture for fixing the treatment head to the wound site, the physical contact of the fixed portion is determined by the presence or absence of conductivity. Detection of lack of jelly for ultrasonic transmission used to irradiate the wound surface with ultrasonic waves is performed by detecting that the drive current increases more than usual by detecting changes in the resonance state of the ultrasonic transducer due to lack of jelly. .

[Method of treatment]
An ultrasonic treatment head module is applied to the wound site and irradiated with ultrasonic waves. In the treatment, usually, an ultrasonic treatment head module is attached to a wound site using a fixture to perform the treatment.
If an air layer enters between the ultrasonic treatment head module and the wound surface, most of the irradiated ultrasonic waves will be reflected, so the ulcer surface is covered with a gel-like dressing, and ultrasonic transmission is performed from there. The gel is placed, the ultrasonic treatment head module is applied, and ultrasonic waves are irradiated.

[Example 2]
[Cell culture]
Fibroblasts from human pressure ulcer dermis were seeded in Dulbecco's Modified Eagle's Medium (DMEM) containing 2% fetal calf serum (FCS) to 5 × 10 ⁵ cells / φ34 mm well. , Left overnight. After confirming cell adhesion, the medium was replaced with 4 mL / well of 2% FCS-DMEM immediately before the test.

[Ultrasonic irradiation conditions]
The ultrasonic head module was placed in 37 ° C. water, and the culture dish was placed at a position 20 mm away from the surface of the module. Furthermore, an ultrasonic absorber was placed so as to be in direct contact with the medium in the culture dish to prevent ultrasonic scattering (FIG. 3). The ultrasonic wave used was irradiated with a signal having an ultrasonic frequency of 1.5 MHz, a burst width of 200 μsec, and a repetition frequency of 1 kHz.

[result]
After irradiating an ultrasonic pulse with an output of 7.5 mW / cm ² for 20 minutes, the culture was continued until 24 hours, and the PGE2 concentration in the medium was measured. As a result, the amount of PGE2 in the irradiated group 1 hour after the ultrasonic irradiation increased significantly to 1.28 times that in the case of non-irradiation, and this difference was maintained until 24 hours later (FIG. 4).

Next, ultrasonic power was irradiated at 0 to 60 mW / cm ² for 20 minutes, and PGE 2 concentration was measured 1 hour or 3 hours later. As a result, the amount of PGE2 was significantly increased by ultrasonic irradiation, and the maximum was obtained when the output was 7.5 mW / cm ² (1.25 times after 1 hour and 1.26 times after 3 hours compared with non-irradiation). (Fig. 5).

The ultrasonic power is irradiated at 0 to 120 mW / cm ² 20 min and the measurement results of the bFGF concentration after 24 hours or 48 hours, compared to non-ultrasonic irradiation group, the ultrasonic wave irradiation output 7.5 mW / cm ² In some cases, bFGF production was increased (not shown). It is thought that the increase in bFGF production was subsequently caused by the increase in production of PGE2 in fibroblasts by ultrasonic irradiation (7.5 mW / cm ² ). The result of further proliferation of fibroblasts was evaluated by absorbance OD 490 ^nm, significantly growth promotion was observed in 7.5mW / cm 2, 30mW / cm 2 ( FIG. 6).

[Example 3]
[Cell culture]
Human umbilical cord-derived vascular endothelial cells were seeded at 5 × 10 ⁵ cells / φ34 mm well in Dulbecco's Modified Eagle's Medium (DMEM) containing 2% fetal calf serum (FCS) and allowed to stand overnight. I put it. After confirming cell adhesion, the medium was replaced with 4 mL / well of 2% FCS-DMEM immediately before the test.

[result]
In the presence or absence of endothelial growth factor (GF), culturing is performed for up to 24 hours after irradiation with ultrasonic waves of 7.5 mW / cm ² for 20 minutes. Measured using ^TM Angiogenesis system. As a result, the ability of endothelial cells to form a lumen increased regardless of the presence or absence of GF when irradiated with ultrasound (FIG. 7). These suggest that the ability to form blood vessels is enhanced by ultrasonic irradiation.

The block diagram which shows the structure of the main-body part of the wound apparatus of this invention. The block diagram which shows the structure of the ultrasonic treatment head module of the wound treatment apparatus of this invention. 1 is a schematic view of an apparatus for irradiating cultured cells used in this experimental system with ultrasonic waves. Fibroblast PGE2 production up to 24 hours after ultrasonic irradiation. Ultrasonic output and PGE2 production by fibroblasts. Ultrasonic power and fibroblast proliferation. Ultrasound irradiation and vascular endothelial cell lumen formation.

Claims (5)

  An ultrasonic treatment head module incorporating an ultrasonic transducer, a control means for controlling irradiation of the ultrasonic wave, and irradiating an ultrasonic pulse to a wound site. The control means is means for controlling the output of ultrasonic pulses in the range of ultrasonic frequency of 20 kHz to 10 MHz, burst width of 10 μsec to 1 msec, repetition period of 5 Hz to 10 kHz, and ultrasonic output of 5 to 75 mW / cm ^2. The wound treatment apparatus according to claim 1. The wound treatment apparatus according to claim ² , wherein the ultrasonic output is a means for controlling the output of an ultrasonic pulse in a range of 5 to 30 mW / cm2. The control means is means for controlling the output of ultrasonic waves in a range where the ultrasonic frequency is 1.5 MHz, the burst width is 200 μsec, the repetition period is 1.0 kHz, and the ultrasonic output is 7.5 mW / cm ^2. The wound treatment apparatus according to claim 3.   The wound treatment device according to any one of claims 1 to 4, wherein the device is a device applied to a pressure ulcer or an ulcer site.

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