CA1314942C - Apparatus for treatment of cancer with photodiode - Google Patents
Apparatus for treatment of cancer with photodiodeInfo
- Publication number
- CA1314942C CA1314942C CA000545718A CA545718A CA1314942C CA 1314942 C CA1314942 C CA 1314942C CA 000545718 A CA000545718 A CA 000545718A CA 545718 A CA545718 A CA 545718A CA 1314942 C CA1314942 C CA 1314942C
- Authority
- CA
- Canada
- Prior art keywords
- photodiodes
- light
- light source
- photosensitive substance
- support member
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/24—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/067—Radiation therapy using light using laser light
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B2018/208—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser with multiple treatment beams not sharing a common path, e.g. non-axial or parallel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
- A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
- A61N2005/0645—Applicators worn by the patient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/065—Light sources therefor
- A61N2005/0651—Diodes
- A61N2005/0652—Arrays of diodes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
Abstract
ABSTRACT OF THE DISCLOSURE
Apparatus for the treatment of a cancerous lesion part by irradiating a light energy from a light source to the cancerous lesion part having absorbed and accumulated in advance therein a photosensitive substance with an affinity for tumors, in which said light source comprises a first photodiode adapted to excite the photosensitive substance from the ground state thereof to a singlet state of higher energy level and a second photodiode adapted to exite an energy level of the photosensitive substance which has transited from the singlet state to a triplet state to a still higher energy level.
Apparatus for the treatment of a cancerous lesion part by irradiating a light energy from a light source to the cancerous lesion part having absorbed and accumulated in advance therein a photosensitive substance with an affinity for tumors, in which said light source comprises a first photodiode adapted to excite the photosensitive substance from the ground state thereof to a singlet state of higher energy level and a second photodiode adapted to exite an energy level of the photosensitive substance which has transited from the singlet state to a triplet state to a still higher energy level.
Description
31~9~2 APPARATUS FOR TREATMENT OF' CANCER WITH PHOTODIODE
This inverltion relates to an apparatus for the treatment of a cancer by irradiating a light generated from a photodiode such as light-emitting dlode or laser diode to a cancerous lesion part in which is absorbed and accumulated in advance a photosensitive substance such as a hematoporphyrin derivative or a compound of phthalocyanine series having an affinity for tumors.
In recent years ! studies on the application of the laser to the medical field have been gaining in impetus.
Particularly in the field concerning diagnosis and treatment of cancers, growing attention has been focused on the method for the treatment of a cancex, which comprises preparatorily administering a photosensitive substance such as a hemato- .
porphyrin derivative to a cancer-carrying patient thereby causing the photosensitive substance to be selectively absorbed and accumulated in the tumorous area of the~patient's:body, irradiating the tumorous area with a laser beam thereby exciting the photosensitive substance into liberating a superoxide anion radical (~2 )! hydrogen peroxide (H202)~ a hydroxy radical ( OH)~ or a singlet oxy~en (102), and utilizing the ~:
oxidizing power of the liberated radical ox equivalent in destroying cancerous cells. Heretofore, as a laser beam for use in this method of treatment, a continuous wave laser beam 131~9~2 such as the argon-excited dye laser has been widely known.
Since the energy of a laser beam injected into living tissues is axponentially attenuated relative to the depth of living tissues, however, the low-output continuous beam such as the aforementioned argon-excited dye laser has a small degree of energy penetration to the affected part and, consequently, possesses as a problem the insu~ficient effect of treatment on a cancerous lesion part of a large size. In this field, therefore, emphasis is placed on the utilization or development of a laser beam source possessing a high output and a high degree of energy concentration. For example, Japanese Patent Application Laying-Open No. 59(1984)-40!869 discloses apparatus for the therapy and diagnosis of a cancer by the use of a pulsating iaser beam ln the place of a continuous wave laser beam. This method and apparatus for the treatment is expected to attain its full growth in the future in the cense of improving the degree of penetration of the energy of a laser beam to the interior of the lesion part. -Incidentally, any apparatus for the treatment of a cancer by the use of a laser beam source entails many problems concerning its practical utility because the device for emission of a laser beam is voluminous, expensive~
troublesome in terms of maintenance and management, and devoid of versatility and because the laser beam source unexceptionally required to possess high energy has the possibility of destroying ëven normal cells besides the cell~ in trouble.
_ 3 _ 13~ 2 The inventors continuëd a diligent study in search of a breakthrough to the true state of affairs mentioned above.
They have consequently found that by using a photodiode as a light source for irradiation of a lesion part having absorbed and accumulated in advance therein a photosensitive substance with affinity for tumors and devislng a method for excitation of the aforementioned photosensitive substance, treatment of a cancer can be efficiently carried out even when the continuous wave beam emitted from the photodiode possesses an extremely feeble energy which is one-some tenths to one-some tens-t:housandths of the energy of the laser beam. The present -invention has been perfected as the result.
Specifically, the present invention which is based on the finding mentioned above provides apparatus for the treatment of a cancerous lesion part with a light energy which is irradiated from a ligh~ sou:rce to the cancerous lesion part having absorbed and accumu~ated in advance therein a photosensltive substance with an affinity for tumors, wherein said light source comprises a:first photodiode adapted to excite said photosensitive substance from the ground state . .
thereof to a singlet state of a high~energy level and a second photodiode adapted to excite an energy level of the photosensi-tive substance which has transited from said singlet state to a triplet state to a still higher energy level.`
13~L~942 Owing to the construction described above, the apparatus of this invention for the treatment of a cancer is inexpensive and, as a whole, is small and light as compared with the thera-peutic apparatus using a laser beam source. Whereas the conven-tional therapeutic apparatus using the laser beam source inevi-tably requires a patient to approach himself to the apparatus by walking, the apparatus of the present invention can be approxi-mated to the patient (affected part) and enjoys many advantages from the standpoint of clinical therapy.
Moreover, the apparatus of the present invention utilizes a feeble energy radiation source as a llght source and, therefore, excels the conventional countertype in terms of the safety from misoperation (erroneous irradiation).
Further, as regards the effect of treatment! since the apparatus of this invention effects destruction and exfoliation of tumorous cells rom the surface part thereof, it has the advantage that even when a tumor under treatment happens to be large, this apparatus is capab~e of bringing about complete cure of the tumor in a deep portion ~ithout adversely affecting the normal tissue adjacent to the tumor.
Now, the present Lnvention will be described further in detail below with reference to the accompanying drawings.
- Fig. 1 is a basic circuit diagram of apparatus of this invention for the treatment of a cancer. Fig. 2 is a diagram showing a concept of the treatment of a cancerous lesion part by the use of the apparatus of the present ;.nvention.
.
~31~4~
Fig. 3a and Fig. 3b are diagrams illustrating typical embodiment of a light emission part of the apparatus of this invention. Fig. 4 is a diagram illustrating another typical em~odiment of the light emission part in the apparatus of this invention. Fig. 5 is a dia~ram illustrating the relation between the time of irradiation with the beam from a photodiode and the proportion of surviving cells.
In Fig. 1 is shown the basic circuit diagram of the apparatus of this invention for the treatment of a cancer.
As a power source 1, for example an AC-DC converter or, where the apparatus is intended as a portable version, a battery is used. A light emission part 3 comprises photodiodes 3a, 3b. One of these two photodiodes is used for exciting a photosensitive substance in the ground state (SO) to a singlet state (Sn) and the other photodiode :is used for exciting the energy lèvel which has transited from the aforementioned singlet state to a triplet state ~) to a further higher level. The number of these photodiodes 3a, 3b and the manner of their disposition can be freely selected, depending on the position of the area for treatment on a patlent's body, the size of a lesion part, the shape of the lesion part, etc.
A circuit part 2 is intended to protect or control an over-current to the light emission part 3. It is formed of a .
protective resistance, for example~
i~l49~2 The basic circuit shown in Fig. 1, when necessary, may be provided with such an auxiliary device as a fan 4 adapted to deprive the light emission part 3 of the heat generated therein.
Fig. 2 is a diagram showing a concept of the treatment of a cancerous lesion part by the use of the apparatus of the present invention. In Fig. 2, 1 denotes a power source part and an overcurrent protection part or control circuit part and 3 a light emission part respectively~ In the li~ht émission part 3, a plurality of photodiodes 3a, 3b are disposed.
Then, A stands for a cancerous lesion part, B for a peripheral part thereof, and C for a normal part respectively.
Preparatory to the actual treatment, a photosensitive substance such as a hematoporphyrin~derivative is diluted with a pharmaceutically acceptahle diluent and prepared otherwise and administered to a patient by intravenous injec-tion, local injection, or abdominal injection, for example.
On elapse of several days after the administration, the photosensitiYe substance is speci~ically absorbed and accumu~
lated in the cancerous tissue and ceases to exist substantially in the normal tissuè.
At this time, the apparatus of the present invention is operated so as to irradiate the cancerous lesion part . . . ~ . : .
with the beam issuing from the photodiodes for necessary - treatment. The photodiodes 3a, 3~ are suitably selected from 13149~2 light-emi-tting diodes or laser diodes, depending on the light absorption characteristic of the photosensitive substance being used. Where the photosensitive substance happens to be a hematoporphyrin derivative ~HpD: product of Queen Elizabeth Hospital), for example; the combination of light-emitting diodes of GaAsP having a wavelength of 630 nm and light-emitting diodes of ~aP having a wavelenath of 690 nm proves to be a preferred choice. By irradiating the lesion part simultaneously with the beams from these two kinds of light-emittin~ diodes, the photochemical reaction of the hematoporphyrin derivative is conspicuously enhanced and the effect of treatment consequently improved.
Compounds of phthalocyanine series may be cited as other concrete examples of the photosensitive substance under discussion. This invention, however, does not restrict the photosensitive substance only to those mentioned above.
Fig. 3a and Fig. 3b illustrate typical embodiment of the light emission part 3 in the apparatus of this inven-tion for th~ treatment of a cancer. Fig. 3a is a plan view of the light emission part 3 and Fig. 3b a cross section of the light emission part 3.
In ~ig. 3a and Fig. 3b ! 3a and 3b stand for photodiodes having different wavelengths. The conventional photodiodes .. . .
can be utilized in their u~modified form. For the purpose of . . .
eliminating the directivity of emission, however, the leading ' 131~L9~2 end of each of the photodiodes may be cut out as indicated by the symbol D in Fig. 3b.
The structure of light emission part illustrated in Fig. 3a and Fig. 3b is intended for the treatment of such cancers as various epithelial cancers and mammary cancers.
By suitably varying the shape and dimensions of the structure of light emission part, this structure may be adapted to permit treatment of such coeliac cancers as tumors in digestive organs like the ~ullet, the colon, and the stomach and cancers of the larynx.
Fig. 4 illustrates a typical applicator for the use of the apparatus for endotract or intracavitary treatment. In Fig. 4/ 3a and 3b denote photodiodes different in kind from each other and 5 denotes a balloon made of a free~y expansible and contractive matqrial such as, for example, silicone rubbër and adapted to enclose the photodiodes. This balloon 5 is provided with flow paths E and F for introducing and discharglng a coolant such as distllled ~ater ! physiological saline water, or olive oil which has a small capacity ~or ~ight ahsorption. The balloon 5 advantageously functions in increàsiny the output of the photodiodes, preventing the normal tissue in the neighborhood .
of the affected part ~rom damage by burning, and ensuring fixation of the applicator to the affected part. Optionally, the flow path for the coolant may be formed inside the sturcture of photodiodes.
~ 1314942 g Now, the effect to be brought about by the use of the apparatus of this invention in the treatment of a cancer will be described below.
The test for the confirmation of this effect was performed as follows.
[Preparation of test specimen~
In a plastic dish 35 mm in diameter, 0.1 ml of a cancer cell (HeLa-S3) solution having a cell concentration of 2 x 105 per ml was placed and 2 ml of a culture medium was added and the resultant mixture was left standing at 37C
for 48 hours under an atmosphere containin~ 5% of carbon dioxide gas for culture of the cells. The culture medium was prepared by adding blood serum albumin in a concentration of 10~ and Kanamycin ~product of Meiji Seika Kaisha, ~td.) in a concentration of 100 yg~ml to an MEM Eagle culture solution ~product of GIBCO Corp.~. After completion of the culture, the supernatant formed in the dish was removed and then 2 ml of a culture solution containing a hematoporpyrin derivative (HpD: product of Queen Elizabeth Xospital~ in a concentration of 2 yg/ml was introduced to continue the culture f,or two hours under thè same conditions as mèntioned above. Then, the supernatant formed in the dish at the end of the culture was discarded and the remaining culture broth was washed with 2 ml of an MEM-Eagle cùlture solution to remove the hemato-porphyrin derivative which had not been absorbed and accumulated in the cells. By further adding 2 ml of culture medium to the cleaned remaining culture broth, there was obtained a test specimen.
- lo- ~31~9~2 [Irradiation test]
In a structure of light emission part illustrated in Fig. 3a and Fig. 3b, five photodiodes (TLS-154i product of Toshiba Limited) having a wavelength of 635 nm were used as 3a and four photodiodes ~TLR-145; product of Toshiba Limited) having a wavelength of 690 nm were used as 3b respectively were incorporated to form the apparatus of this invention for the treatment of a cancer. The aforementioned test specimen was set at such a position that the photodiodes are separated by a distance of 8` mm from the upper side of the test specimen.
It was irradiated with the beams of light emitted from the photodiodes at an output of 18 mA of a supplied current, to find the relation between the time of irradiation and the ratio of surviving cells. The test specimens subjected to this test were taken as forming one group.
For comparison, an apparatus was formed by incorpo-rating nine photodiodes of a wavelength of 635 nm as 3a and 3b in a similar structure of light emission part. With this apparatus, a comparative test was carried out in the same manner as the test method mentioned above. The test specimens subjected to this comparative test were taken as forming another group.
In the tests described above, a forced air cooling duct was disposed bètween the plane of light emission and the test specimen for the purpose of preventing the temperature ~3i~2 of the test specimen from rising, and the difference of temperature between the outlet and inlet thereof was kept below 0.4C.
Table 1 shows the relation between the time of irradiation and the ratio of surviving cells in given two groups of test specimens relative to the control group (devoid of irradiation) as determined by the test with the apparatus of this invention and the comparative test.
` Table 1 -: .. .. ..
, . . _ . . _ ~ 3 6 18 24 48 .. . . .. . . __ ~ _ : _ . __ Comparative 1.0 1.0 0.88 0.91 0.81 - . . _ _ This inventlon 1. O O . ga O . 84 0 75 O . 41 .
By pLotting ~he results o~ Tahle 1, there are obtained the two curves shown in Fig. 5.
The curve A represents the results of test obtained by the use of the apparatus of this invention and the curve B those obtained by the use of the apparatus for comparative test.
In Fig. 5, the vertical axis is the scaIe of the ratio of surviving célls (~) in the respective groups realtive to the control group (devoid of irradiation) ànd the horizontal axis the scale of time (hr) of irradiation.
The data of Fig. 5 evince the effectiveness of the apparatus of this invention.
This inverltion relates to an apparatus for the treatment of a cancer by irradiating a light generated from a photodiode such as light-emitting dlode or laser diode to a cancerous lesion part in which is absorbed and accumulated in advance a photosensitive substance such as a hematoporphyrin derivative or a compound of phthalocyanine series having an affinity for tumors.
In recent years ! studies on the application of the laser to the medical field have been gaining in impetus.
Particularly in the field concerning diagnosis and treatment of cancers, growing attention has been focused on the method for the treatment of a cancex, which comprises preparatorily administering a photosensitive substance such as a hemato- .
porphyrin derivative to a cancer-carrying patient thereby causing the photosensitive substance to be selectively absorbed and accumulated in the tumorous area of the~patient's:body, irradiating the tumorous area with a laser beam thereby exciting the photosensitive substance into liberating a superoxide anion radical (~2 )! hydrogen peroxide (H202)~ a hydroxy radical ( OH)~ or a singlet oxy~en (102), and utilizing the ~:
oxidizing power of the liberated radical ox equivalent in destroying cancerous cells. Heretofore, as a laser beam for use in this method of treatment, a continuous wave laser beam 131~9~2 such as the argon-excited dye laser has been widely known.
Since the energy of a laser beam injected into living tissues is axponentially attenuated relative to the depth of living tissues, however, the low-output continuous beam such as the aforementioned argon-excited dye laser has a small degree of energy penetration to the affected part and, consequently, possesses as a problem the insu~ficient effect of treatment on a cancerous lesion part of a large size. In this field, therefore, emphasis is placed on the utilization or development of a laser beam source possessing a high output and a high degree of energy concentration. For example, Japanese Patent Application Laying-Open No. 59(1984)-40!869 discloses apparatus for the therapy and diagnosis of a cancer by the use of a pulsating iaser beam ln the place of a continuous wave laser beam. This method and apparatus for the treatment is expected to attain its full growth in the future in the cense of improving the degree of penetration of the energy of a laser beam to the interior of the lesion part. -Incidentally, any apparatus for the treatment of a cancer by the use of a laser beam source entails many problems concerning its practical utility because the device for emission of a laser beam is voluminous, expensive~
troublesome in terms of maintenance and management, and devoid of versatility and because the laser beam source unexceptionally required to possess high energy has the possibility of destroying ëven normal cells besides the cell~ in trouble.
_ 3 _ 13~ 2 The inventors continuëd a diligent study in search of a breakthrough to the true state of affairs mentioned above.
They have consequently found that by using a photodiode as a light source for irradiation of a lesion part having absorbed and accumulated in advance therein a photosensitive substance with affinity for tumors and devislng a method for excitation of the aforementioned photosensitive substance, treatment of a cancer can be efficiently carried out even when the continuous wave beam emitted from the photodiode possesses an extremely feeble energy which is one-some tenths to one-some tens-t:housandths of the energy of the laser beam. The present -invention has been perfected as the result.
Specifically, the present invention which is based on the finding mentioned above provides apparatus for the treatment of a cancerous lesion part with a light energy which is irradiated from a ligh~ sou:rce to the cancerous lesion part having absorbed and accumu~ated in advance therein a photosensltive substance with an affinity for tumors, wherein said light source comprises a:first photodiode adapted to excite said photosensitive substance from the ground state . .
thereof to a singlet state of a high~energy level and a second photodiode adapted to excite an energy level of the photosensi-tive substance which has transited from said singlet state to a triplet state to a still higher energy level.`
13~L~942 Owing to the construction described above, the apparatus of this invention for the treatment of a cancer is inexpensive and, as a whole, is small and light as compared with the thera-peutic apparatus using a laser beam source. Whereas the conven-tional therapeutic apparatus using the laser beam source inevi-tably requires a patient to approach himself to the apparatus by walking, the apparatus of the present invention can be approxi-mated to the patient (affected part) and enjoys many advantages from the standpoint of clinical therapy.
Moreover, the apparatus of the present invention utilizes a feeble energy radiation source as a llght source and, therefore, excels the conventional countertype in terms of the safety from misoperation (erroneous irradiation).
Further, as regards the effect of treatment! since the apparatus of this invention effects destruction and exfoliation of tumorous cells rom the surface part thereof, it has the advantage that even when a tumor under treatment happens to be large, this apparatus is capab~e of bringing about complete cure of the tumor in a deep portion ~ithout adversely affecting the normal tissue adjacent to the tumor.
Now, the present Lnvention will be described further in detail below with reference to the accompanying drawings.
- Fig. 1 is a basic circuit diagram of apparatus of this invention for the treatment of a cancer. Fig. 2 is a diagram showing a concept of the treatment of a cancerous lesion part by the use of the apparatus of the present ;.nvention.
.
~31~4~
Fig. 3a and Fig. 3b are diagrams illustrating typical embodiment of a light emission part of the apparatus of this invention. Fig. 4 is a diagram illustrating another typical em~odiment of the light emission part in the apparatus of this invention. Fig. 5 is a dia~ram illustrating the relation between the time of irradiation with the beam from a photodiode and the proportion of surviving cells.
In Fig. 1 is shown the basic circuit diagram of the apparatus of this invention for the treatment of a cancer.
As a power source 1, for example an AC-DC converter or, where the apparatus is intended as a portable version, a battery is used. A light emission part 3 comprises photodiodes 3a, 3b. One of these two photodiodes is used for exciting a photosensitive substance in the ground state (SO) to a singlet state (Sn) and the other photodiode :is used for exciting the energy lèvel which has transited from the aforementioned singlet state to a triplet state ~) to a further higher level. The number of these photodiodes 3a, 3b and the manner of their disposition can be freely selected, depending on the position of the area for treatment on a patlent's body, the size of a lesion part, the shape of the lesion part, etc.
A circuit part 2 is intended to protect or control an over-current to the light emission part 3. It is formed of a .
protective resistance, for example~
i~l49~2 The basic circuit shown in Fig. 1, when necessary, may be provided with such an auxiliary device as a fan 4 adapted to deprive the light emission part 3 of the heat generated therein.
Fig. 2 is a diagram showing a concept of the treatment of a cancerous lesion part by the use of the apparatus of the present invention. In Fig. 2, 1 denotes a power source part and an overcurrent protection part or control circuit part and 3 a light emission part respectively~ In the li~ht émission part 3, a plurality of photodiodes 3a, 3b are disposed.
Then, A stands for a cancerous lesion part, B for a peripheral part thereof, and C for a normal part respectively.
Preparatory to the actual treatment, a photosensitive substance such as a hematoporphyrin~derivative is diluted with a pharmaceutically acceptahle diluent and prepared otherwise and administered to a patient by intravenous injec-tion, local injection, or abdominal injection, for example.
On elapse of several days after the administration, the photosensitiYe substance is speci~ically absorbed and accumu~
lated in the cancerous tissue and ceases to exist substantially in the normal tissuè.
At this time, the apparatus of the present invention is operated so as to irradiate the cancerous lesion part . . . ~ . : .
with the beam issuing from the photodiodes for necessary - treatment. The photodiodes 3a, 3~ are suitably selected from 13149~2 light-emi-tting diodes or laser diodes, depending on the light absorption characteristic of the photosensitive substance being used. Where the photosensitive substance happens to be a hematoporphyrin derivative ~HpD: product of Queen Elizabeth Hospital), for example; the combination of light-emitting diodes of GaAsP having a wavelength of 630 nm and light-emitting diodes of ~aP having a wavelenath of 690 nm proves to be a preferred choice. By irradiating the lesion part simultaneously with the beams from these two kinds of light-emittin~ diodes, the photochemical reaction of the hematoporphyrin derivative is conspicuously enhanced and the effect of treatment consequently improved.
Compounds of phthalocyanine series may be cited as other concrete examples of the photosensitive substance under discussion. This invention, however, does not restrict the photosensitive substance only to those mentioned above.
Fig. 3a and Fig. 3b illustrate typical embodiment of the light emission part 3 in the apparatus of this inven-tion for th~ treatment of a cancer. Fig. 3a is a plan view of the light emission part 3 and Fig. 3b a cross section of the light emission part 3.
In ~ig. 3a and Fig. 3b ! 3a and 3b stand for photodiodes having different wavelengths. The conventional photodiodes .. . .
can be utilized in their u~modified form. For the purpose of . . .
eliminating the directivity of emission, however, the leading ' 131~L9~2 end of each of the photodiodes may be cut out as indicated by the symbol D in Fig. 3b.
The structure of light emission part illustrated in Fig. 3a and Fig. 3b is intended for the treatment of such cancers as various epithelial cancers and mammary cancers.
By suitably varying the shape and dimensions of the structure of light emission part, this structure may be adapted to permit treatment of such coeliac cancers as tumors in digestive organs like the ~ullet, the colon, and the stomach and cancers of the larynx.
Fig. 4 illustrates a typical applicator for the use of the apparatus for endotract or intracavitary treatment. In Fig. 4/ 3a and 3b denote photodiodes different in kind from each other and 5 denotes a balloon made of a free~y expansible and contractive matqrial such as, for example, silicone rubbër and adapted to enclose the photodiodes. This balloon 5 is provided with flow paths E and F for introducing and discharglng a coolant such as distllled ~ater ! physiological saline water, or olive oil which has a small capacity ~or ~ight ahsorption. The balloon 5 advantageously functions in increàsiny the output of the photodiodes, preventing the normal tissue in the neighborhood .
of the affected part ~rom damage by burning, and ensuring fixation of the applicator to the affected part. Optionally, the flow path for the coolant may be formed inside the sturcture of photodiodes.
~ 1314942 g Now, the effect to be brought about by the use of the apparatus of this invention in the treatment of a cancer will be described below.
The test for the confirmation of this effect was performed as follows.
[Preparation of test specimen~
In a plastic dish 35 mm in diameter, 0.1 ml of a cancer cell (HeLa-S3) solution having a cell concentration of 2 x 105 per ml was placed and 2 ml of a culture medium was added and the resultant mixture was left standing at 37C
for 48 hours under an atmosphere containin~ 5% of carbon dioxide gas for culture of the cells. The culture medium was prepared by adding blood serum albumin in a concentration of 10~ and Kanamycin ~product of Meiji Seika Kaisha, ~td.) in a concentration of 100 yg~ml to an MEM Eagle culture solution ~product of GIBCO Corp.~. After completion of the culture, the supernatant formed in the dish was removed and then 2 ml of a culture solution containing a hematoporpyrin derivative (HpD: product of Queen Elizabeth Xospital~ in a concentration of 2 yg/ml was introduced to continue the culture f,or two hours under thè same conditions as mèntioned above. Then, the supernatant formed in the dish at the end of the culture was discarded and the remaining culture broth was washed with 2 ml of an MEM-Eagle cùlture solution to remove the hemato-porphyrin derivative which had not been absorbed and accumulated in the cells. By further adding 2 ml of culture medium to the cleaned remaining culture broth, there was obtained a test specimen.
- lo- ~31~9~2 [Irradiation test]
In a structure of light emission part illustrated in Fig. 3a and Fig. 3b, five photodiodes (TLS-154i product of Toshiba Limited) having a wavelength of 635 nm were used as 3a and four photodiodes ~TLR-145; product of Toshiba Limited) having a wavelength of 690 nm were used as 3b respectively were incorporated to form the apparatus of this invention for the treatment of a cancer. The aforementioned test specimen was set at such a position that the photodiodes are separated by a distance of 8` mm from the upper side of the test specimen.
It was irradiated with the beams of light emitted from the photodiodes at an output of 18 mA of a supplied current, to find the relation between the time of irradiation and the ratio of surviving cells. The test specimens subjected to this test were taken as forming one group.
For comparison, an apparatus was formed by incorpo-rating nine photodiodes of a wavelength of 635 nm as 3a and 3b in a similar structure of light emission part. With this apparatus, a comparative test was carried out in the same manner as the test method mentioned above. The test specimens subjected to this comparative test were taken as forming another group.
In the tests described above, a forced air cooling duct was disposed bètween the plane of light emission and the test specimen for the purpose of preventing the temperature ~3i~2 of the test specimen from rising, and the difference of temperature between the outlet and inlet thereof was kept below 0.4C.
Table 1 shows the relation between the time of irradiation and the ratio of surviving cells in given two groups of test specimens relative to the control group (devoid of irradiation) as determined by the test with the apparatus of this invention and the comparative test.
` Table 1 -: .. .. ..
, . . _ . . _ ~ 3 6 18 24 48 .. . . .. . . __ ~ _ : _ . __ Comparative 1.0 1.0 0.88 0.91 0.81 - . . _ _ This inventlon 1. O O . ga O . 84 0 75 O . 41 .
By pLotting ~he results o~ Tahle 1, there are obtained the two curves shown in Fig. 5.
The curve A represents the results of test obtained by the use of the apparatus of this invention and the curve B those obtained by the use of the apparatus for comparative test.
In Fig. 5, the vertical axis is the scaIe of the ratio of surviving célls (~) in the respective groups realtive to the control group (devoid of irradiation) ànd the horizontal axis the scale of time (hr) of irradiation.
The data of Fig. 5 evince the effectiveness of the apparatus of this invention.
Claims (12)
1. An apparatus for treating a cancerous lesion part having absorbed and accumulated in advance a photosensitive substance with an affinity for tumours, the apparatus being adapted to irradiate said cancerous lesion part with light energy from a light source, wherein said light source comprises at least one first photodiodes adapted to emit light to excite molecules of said photosensitive substance from its ground state to a singlet state at a higher energy level than said ground state, molecules of said photosensitive substance decaying from the singlet state to a triplet state, and one or more second photodiodes adapted to emit light to excite those molecules of said photosensitive substance which have decayed from said singlet state to said triplet state to a still higher energy level, said first photodiode and said second photodiode emitting respectively beams different in wavelength from each other.
2. An apparatus according to claim 1, wherein a plurality of pairs of first and second photodiodes are disposed on a curved surface of a part spherically shaped support member, any two randomly selected adjacent photodiodes comprising one of the first photodiodes and one of the second photodiodes.
3. An apparatus according to claim 1, wherein a plurality of pairs of such first and second photodiodes are disposed on a side surface of one end of a flexible support member, in rows extending longitudinally of the flexible support member and transversely to said longitudinal direction, ones of the first and second photodiodes being positioned adjacent to one another and first and second photodiodes being surrounded with a freely expansible and contractable balloon fastened at the opposite ends thereof to said support member, said balloon being adapted to be provided with a flow path for introduction and discharge of a coolant.
4. The apparatus according to claim 3, wherein said flow path for introduction and discharge of a coolant is disposed inside said flexible support member.
5. The apparatus according to any one of claims 1 to 4, wherein said first and second photodiodes are respectively laser diodes.
6. The apparatus according to any one of claims 1 to 4, wherein said first and second photodiodes are respectively light-emitting diodes.
7. The apparatus according to claim S, wherein said first photodiodes are light-emitting diodes of GaAsP type adapted to emit light at a wavelength of 630 nm.
8. The apparatus according to claim 6, wherein said second photodiodes are light emitting diodes of GaP adapted to emit light at a wavelength of 690 nm.
9. The apparatus according to any one of claims 1 to 4, 7 and 8 wherein said light source is connected to a power source via a circuit adapted to limit any overcurrent flowing to said light source.
10. The apparatus according to claim 9, wherein said circuit part comprises a protective resistance.
11. The apparatus according to claim 1, wherein said light source comprises a plurality of first and second photodiodes, which are alternately connected in series.
12. The apparatus according to any one of claims 1 to 4, 7, 8, 10 and 11, which is provided with cooling means adapted to remove heat generated in said light source.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61257345A JPS63111886A (en) | 1986-10-29 | 1986-10-29 | Cancer remedy apparatus using optical diode |
| JP257345/86 | 1986-10-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1314942C true CA1314942C (en) | 1993-03-23 |
Family
ID=17305081
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000545718A Expired - Fee Related CA1314942C (en) | 1986-10-29 | 1987-08-31 | Apparatus for treatment of cancer with photodiode |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4822335A (en) |
| EP (1) | EP0266038B1 (en) |
| JP (1) | JPS63111886A (en) |
| CA (1) | CA1314942C (en) |
| DE (1) | DE3774071D1 (en) |
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-
1986
- 1986-10-29 JP JP61257345A patent/JPS63111886A/en active Granted
-
1987
- 1987-08-28 EP EP87307666A patent/EP0266038B1/en not_active Expired
- 1987-08-28 DE DE8787307666T patent/DE3774071D1/en not_active Expired - Fee Related
- 1987-08-31 CA CA000545718A patent/CA1314942C/en not_active Expired - Fee Related
- 1987-09-08 US US07/094,111 patent/US4822335A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0266038A2 (en) | 1988-05-04 |
| EP0266038A3 (en) | 1989-01-25 |
| DE3774071D1 (en) | 1991-11-28 |
| US4822335A (en) | 1989-04-18 |
| JPS63111886A (en) | 1988-05-17 |
| JPH0341194B2 (en) | 1991-06-21 |
| EP0266038B1 (en) | 1991-10-23 |
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