JPH0672873A - Therapeutic agent for ulcer and photochemical diagnostic for ulcer - Google Patents

Abstract

PURPOSE:To obtain a new therapeutic agent for photochemical treatment of cancer having good light absorbing property to long-wavelength light having very good selective accumulation to a cancer tissue and good permeability into the tissue and being wide in the range capable of treating by including a specific phthalocyanine. CONSTITUTION:The objective therapeutic agent contains a phthalocyanine compound of formula I [X is H, F, etc.; Y is OR5Zj-m, OR6Zn-q (R5 and R6 are phenyl or benzyl; Z is sulfone; (b) to (q) are 0-7 and sum of (b) to (q) is >=1); M is H, Zn, etc.; (a) is 0-3]. This compound of formula I is obtained by reacting, e.g. a compound of formula II with a compound of the formula R5OH in the presence of KF which is a condensing agent in nitriles and subjecting the resultant compound of formula III to phthalocyanylation. Furthermore, when photochemical treatment is carried out using the ulcer agent, laser beam having 720-830nm wavelength is preferably used as an irradiation source.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a therapeutic agent for tumor and tumor containing a specific phthalocyanine compound as an active ingredient, which is particularly useful for treatment and diagnosis of tumor or cancer tissue of human or animal by therapeutic and photochemical diagnosis. Regarding photochemical diagnostics.

[0002]

2. Description of the Related Art Conventionally, a porphyrin derivative or the like having a selective accumulation property with respect to a cancer tissue has been administered into the body, and then the cancer cells are irradiated with a strong light beam such as a laser beam, thereby absorbing these light-affected affinity. A so-called photochemotherapy method in which a sexual substance chemically reacts to destroy cancer cells is known.

Examples of such photochemotherapy agents are described in J.
Moan et al. (Photobiol. Photochem, Volume 43 681)
P. 1986) describes an example using a hematoporphyrin derivative. However, these have the drawbacks that they have insufficient selective accumulation properties for cancerous tissue and poor light absorption for long-wavelength light having good tissue permeability, thus limiting the therapeutic range.

A method of using a water-soluble phthalocyanine compound has been disclosed to improve these. For example,
N. Brasseur et al. (Photochem. And Photobio
l. 45, 581 1987) and N. Bra
sseur et al. (Photochem. and Photobiol. 47
Pp. 705, 1988) describes examples using zinc phthalocyanine, chloroaluminum phthalocyanine, chlorogallium phthalocyanine, etc., in which the phthalocyanine skeleton is directly sulfonated.

These have been improved in light absorptivity with respect to light having a long wavelength, which has a good selective accumulation property for cancer tissue and good tissue permeability as compared with the above porphyrins and the like.
Since it can be effective for various tissues in the body, further light-absorbing property for long-wavelength light with good selective accumulation property and tissue permeability to cancer tissue is required, In that respect it is still insufficient.

[0006]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances of the prior art. That is,
The object of the present invention is to obtain a long-wavelength light of 620 nm or more, which has extremely good selective accumulation and accumulation properties in cancer tissue and good tissue permeability.
In particular, it is intended to provide a substance which has a good light absorption property for light having a wavelength of 680 nm or more, has a wide therapeutic range and is effective as a tumor therapeutic agent, and also provides a substance which can be effectively used as a tumor photochemical diagnostic agent.

[0007]

The inventors of the present invention have at least an ether aryl group or a thioether aryl group in the phthalocyanine skeleton, and optionally have a fluorine atom, an ether aryl group, a thioether aryl group at the residue, Those containing a phthalocyanine compound in which an aryl substituent in a phthalocyanine having either an ether alkyl group or a thioether alkyl group is sulfonated,
The present invention has been completed by finding that it can be used as a therapeutic agent for tumors and a photochemical diagnostic agent for tumors that satisfy the above-mentioned object.

That is, according to the present invention, the following general formula (I):

[Chemical 3]

[In the formula, X is independently of each other a hydrogen atom, a fluorine atom, OR ₁ Zb to e, SR ₂ Zf to i, OR ₃ ,
SR ₄ (provided that R ₁ and R ₂ are each independently a phenyl group or a benzyl group, and the phenyl group or the benzyl group is an alkyl group, an alkoxyl group, a carboxyl group, an alkoxycarbonyl group or a halogen atom having 1 to 4 carbon atoms. may be substituted with atoms, R _3, R ₄ is an alkyl group of C1~C20 independently of one another, a cycloalkyl group of C4-C6, Z represents a represents a sulfone group), Y mutually _{independently, OR 5 Zj~m, SR 6 Zn~q} (R 5,
R _{6 s} are each independently a phenyl group or a benzyl group, which may be substituted with an alkyl group having 1 to 4 carbon atoms, an alkoxyl group, a carboxyl group, an alkoxycarbonyl group or halogen. , Z represents a sulfone group), a is an integer of 0 to 3, b to q is an integer of 0 to 7 and the sum of b to q is 1 or more, and M is zinc or aluminum chloride. Or a compound containing a novel fluorine-containing phthalocyanine compound represented by gallium chloride] is provided as a tumor photochemotherapeutic agent and a tumor photochemical diagnostic agent.

Examples of such a phthalocyanine include a hydrogen atom; a fluorine atom; a methoxy group; an ethoxy group; a butoxy group; an octyloxy group; a cyclohexyloxy group; a partially sulfonated or non-phenoxy phenoxy group. Group, carboxylphenoxy group, methoxycarbonylphenoxy group, ethoxycarbonylphenoxy group, benzyloxy group, tolyloxy group, or
Xylyloxy group; Phenoxy group substituted with fluorine or chlorine atom; Methylthio group; Ethylthio group; Butylthio group; Octylthio group; Cyclohexylthio group;
Partially sulfonated or unsulfonated, phenylthio, carboxylphenylthio, methoxycarbonylphenylthio, ethoxycarbonylphenylthio, benzylthio, tolylthio or xylylthio;

A phenylthio group substituted with a fluorine or chlorine atom; and Y partially sulfonated, a phenoxy group, a carboxylphenoxy group, a methoxycarbonylphenoxy group, an ethoxycarbonylphenoxy group, a benzyloxy group, A tolyloxy group or a xylyloxy group; a phenoxy group substituted with a fluorine or chlorine atom; a partially sulfonated phenylthio group, a carboxylphenylthio group,
Methoxycarbonylphenylthio group, ethoxycarbonylphenylthio group, tolylthio or xylylthio;
Or a phenylthio group substituted with a fluorine or chlorine atom; and M is Zn, aluminum chloride or gallium chloride, and 1 to 16 sulfonic acid groups are introduced to 1 mol of the phthalocyanine molecule. Is mentioned.

The phthalocyanine represented by the general formula (I) used in the present invention is specifically a phthalocyanine compound in which an aryl group of the following is sulfonated, and the central metal is preferably zinc, It is preferable to use chloroaluminum or chlorogallium. The sulfonic acid group is introduced in an amount of 1 to 16 per 1 mol of the phthalocyanine molecule, and preferably 1 to 10 is introduced.

A-type skeleton 4,5-octakis (phenylthio) -3,6-octafluorophthalocyanine Abbreviation: PcF8 (PhS) 8 4,5-octakis (o-methylphenylthio) -3,
6-octafluorophthalocyanine abbreviation; PcF8 (o-MePhS) 84,5-octakis (p-methylphenylthio) -3,
6-octafluorophthalocyanine abbreviation; PcF8 (p-MePhS) 84,5-octakis (p-fluorophenylthio)-
3,6-octafluorophthalocyanine abbreviation; PcF8 (p-FPhS) 84,5-octakis (o-methoxyphenylthio)-
3,6-Octafluorophthalocyanine Abbreviation: PcF8 (o-MeOPhS) 8

4,5-Octakis (p-methoxyphenylthio) -3,6-octafluorophthalocyanine Abbreviation: PcF8 (p-MeOPhS) 8 4,5-octakis (o-carboxylphenylthio)
-3,6-Octafluorophthalocyanine Abbreviation: PcF8 (o-cPhS) 84,5-octakis (p-carboxylphenylthio)
-3,6-Octafluorophthalocyanine Abbreviation; PcF8 (p-cPhS) 84,5-Octakis (phenoxy) -3,6-octafluorophthalocyanine Abbreviation; PcF8 (PhO) 84,5-Octakis (o-methylphenoxy) ) -3,6
-Octafluorophthalocyanine abbreviation; PcF8 (o-MePhO) 8

4,5-Octakis (p-methylphenoxy) -3,6-octafluorophthalocyanine Abbreviation: PcF8 (p-MePhO) 8 4,5-octakis (o-methoxyphenoxy) -3,
6-octafluorophthalocyanine abbreviation; PcF8 (o-MeOPhO) 84,5-octakis (p-methoxyphenoxy) -3,
6-octafluorophthalocyanine abbreviation; PcF8 (p-MeOPhO) 84,5-octakis (o-fluorophenoxy) -3,
6-octafluorophthalocyanine abbreviation; PcF8 (o-FPhO) 8 4,5-octakis (o-carboxylphenoxy)-
3,6-octafluorophthalocyanine abbreviation; PcF8 (o-cPhO) 8 4,5-octakis (p-carboxylphenoxy)-
3,6-octafluorophthalocyanine abbreviation; PcF8 (p-cPhO) 8

B-type skeleton 4-tetrakis (phenoxy) -5-tetrakis (phenylthio) -3,6-octafluorophthalocyanine Abbreviation: PcF8 (PhO) 4 (PhS) 4 4-tetrakis (phenoxy) -5-tetrakis ( o-
Methylphenylthio) -3,6-octafluorophthalocyanine Abbreviation; PcF8 (PhO) 4 (o-MePhS) 4 4-tetrakis (phenoxy) -5-tetrakis (p-
Fluorophenylthio) -3,6-octafluorophthalocyanine Abbreviation; PcF8 (PhO) 4 (p-FPhS) 4 4-Tetrakis (o-methoxyphenoxy) -5-tetrakis (phenylthio) -3,6-octafluorophthalocyanine Abbreviation PcF8 (o-MeOPhO) 4 (o-MeOP
hS) 44-Tetrakis (o-carboxylphenoxy) -5-
Tetrakis (phenylthio) -3,6-octafluorophthalocyanine Abbreviation; PcF8 (o-cPhO) 4 (PhS) 4

4-tetrakis (tetrafluorophenoxy) -5-tetrakis (phenylthio) -3,6-octafluorophthalocyanine Abbreviation: PcF8 (F4PhO) 4 (PhS) 4 4-tetrakis (methoxy) -5-tetrakis (phenylthio) -3,6-Octafluorophthalocyanine Abbreviation; PcF8 (MeO) 4 (PhS) 4 4-Tetrakis (phenoxy) -5-tetrakis (tetrafluorophenoxy) -3,6-octafluorophthalocyanine Abbreviation; PcF8 (PhO) 4 ( F4PhO) 4 4-tetrakis (phenoxy) -5-tetrakis (methoxy) -3,6-octafluorophthalocyanine abbreviation; PcF8 (PhO) 4 (MeO) 4 4-tetrakis (phenoxy) -5-tetrakis (benzyloxy)- 3,6-oct Fluoro phthalocyanine Abbreviation; PcF8 (PhO) 4 (BzO) 4

C-type skeleton 4-tetrakis (phenoxy) -3,5,6-dodecafluorophthalocyanine Abbreviation: PcF12 (PhO) 4 4-tetrakis (o-methylphenoxy) -3,5,6
-Dodecafluorophthalocyanine abbreviation; PcF12 (o-MePhO) 44-tetrakis (p-methylphenoxy) -3,5,6
-Dodecafluorophthalocyanine abbreviation; PcF12 (p-MePhO) 44-tetrakis (o-fluorophenoxy) -3,5
6-Dodecafluorophthalocyanine Abbreviation: PcF12 (o-FPhO) 4

4-Tetrakis (o-methoxyphenoxy) -3,5,6-dodecafluorophthalocyanine Abbreviation: PcF12 (o-MeOPhO) 4 4-Tetrakis (p-methoxyphenoxy) -3,5
6-dodecafluorophthalocyanine abbreviation; PcF12 (p-MeOPhO) 44-tetrakis (o-carboxylphenoxy) -3,
5,6-Dodecafluorophthalocyanine Abbreviation; PcF12 (o-cPhO) 44-tetrakis (p-carboxylphenoxy) -3,
5,6-Dodecafluorophthalocyanine Abbreviation; PcF12 (p-cPhO) 4

D-type skeleton 4-tetrakis (phenoxy) phthalocyanine Abbreviation; Pc (PhO) 4 4-tetrakis (o-methylphenoxy) phthalocyanine Abbreviation; Pc (o-MePhO) 4 4-Tetrakis (p-methylphenoxy) phthalocyanine Abbreviation; Pc (p-MePhO) 4 4-tetrakis (o-fluorophenoxy) phthalocyanine Abbreviation; Pc (o-FPhO) 4 4-Tetrakis (o-methoxyphenoxy) phthalocyanine Abbreviation; Pc (o-MeOPhO) 4

4-Tetrakis (p-methoxyphenoxy) phthalocyanine Abbreviation; Pc (p-MeOPhO) 4 4-Tetrakis (o-carboxyphenoxy) phthalocyanine Abbreviation; Pc (o-cPhO) 4 4-Tetrakis (p-carboxylphenoxy) Phthalocyanine abbreviation; Pc (p-cPhO) 4 4-tetrakis (phenylthio) phthalocyanine abbreviation; Pc (PhS) 4 4-tetrakis (o-methylphenylthio) phthalocyanine abbreviation; Pc (o-MePhS) 4 4-tetrakis (p- Methylphenylthio) phthalocyanine Abbreviation; Pc (p-MePhS) 4

4-Tetrakis (o-fluorophenylthio) phthalocyanine Abbreviation; Pc (o-FPhS) 4 4-Tetrakis (o-methoxyphenylthio) phthalocyanine Abbreviation; Pc (o-MeOPhS) 4 4-Tetrakis (p-methoxy) Phenylthio) phthalocyanine Abbreviation; Pc (p-MeOPhS) 4 4-Tetrakis (o-carboxylphenylthio) phthalocyanine Abbreviation; Pc (o-cPhS) 4 4-Tetrakis (p-carboxylphenylthio) phthalocyanine Abbreviation; Pc (p- cPhS) 4 and the like.

The phthalocyanine (general formula I) used in the present invention has already been synthesized by the present inventors in Japanese Patent Application Nos. 63-65806 and 1).
It is disclosed in Japanese Patent Application No. 103554, Japanese Patent Application No. 1-103555, Japanese Patent Application No. 1-209599 and Japanese Patent Application No. 4-42586. The schemes of these synthetic methods are shown below. With regard to type D), the synthesis method will be shown below as a reference example.

[0024]

[Chemical 4]

[0025]

[Chemical 5]

[0026]

[Chemical 6]

[0027]

[Chemical 7]

The structure at each step of each synthesis method
R in the formula₁, R₂, R₃, R_Four, R _FiveAnd R₆Is general
R in formula (I)₁, R₂, R₃, R_Four, R_FiveAnd R
₆Is the same as In addition, the first step of the A type synthesis method
The first and second steps of the B type synthesis method, the C type
In the first step of the synthesis method,
Nitrogen such as cetonitrile can be used as a condensation agent.
Potassium iodide or the like can be used. C type synthesis method
The reaction conditions in the first step of are ROH and KF
Other than the difference in the charge ratio of tetrafluorophthalonitrile
Is the same as the first step in A-type synthesis method (1).
It is like.

In the B type synthetic method, the reaction condition of the first step was relaxed to prevent the 4-position from being completely replaced with OR.
It is also possible to use a material in which a fluorine atom remains in part of the positions as the raw material for the second step. Also, in the second step, the reaction conditions may be relaxed so that a compound in which the 5-position is not completely replaced with OR or SR and a fluorine atom remains in a part of the 5-position can be used as the raw material in the third step.

In the A-type synthesis method and the C-type synthesis method, the reaction conditions of the first step are relaxed so that the 4-position or 5-position is not completely replaced with OR or SR, and some fluorine atoms remain. Can also be used as the raw material for the second step. In these cases, phthalocyanine, which is the final product, may contain an unsubstituted fluorine atom at the 4th and 5th positions in addition to the fluorine atom at the 3rd and 6th positions, but this may affect the physical properties such as solubility. You may contain this thing in the range which is not given.

The phthalocyanine compound of the present invention is useful for photochemical diagnosis and photochemical diagnosis of tumors of malignant tissues such as cancer. When a human or animal with a tumor is administered a therapeutic agent containing the compound of the present invention and irradiated with a suitable light ray or electromagnetic wave, the compound is excited and then fluoresces from an excited triplet state. This allows the presence, location and size of the tumor to be measured. That is, this is photochemical diagnosis. Oxygen species activated by the excited state or energy transition of the compound exerts a cell killing action on the tumor. This is photochemical treatment. Thus, in order to be effective as a photochemotherapeutic agent, it is preferable that the excited triplet lifetime be as long as possible.

The compounds of the present invention can be used in the diagnosis and treatment of a wide range of tumors. Examples of tumors include gastric cancer, intestinal cancer, lung cancer, breast cancer, uterine cancer, esophageal cancer, ovarian cancer, pancreatic cancer, bladder cancer, maxillary cancer, tongue cancer, cerebral tumor, skin cancer, malignant goiter, leukemia and malignant lymph. There are cell tumors. For therapeutic purposes, light energy must penetrate tissue and penetrate tumors well. Therefore, the use of long wavelength light is desirable to facilitate penetration into tumor tissue.

The compound of the present invention has a light absorption property even in a long wavelength region and has a light ray of 620 nm or more, preferably 6 rays.
80 nm to 900 nm, particularly preferably 720 nm to 830 nm
Can be used. Moreover, since fluorescence is emitted in those wavelength ranges, photochemical diagnosis is possible. The irradiation source of the light beam is not limited, but a laser beam is preferable. This is because a strong light ray can be selectively applied within a desired wavelength range. For laser irradiation, it is usually good to guide the laser with an optical fiber for irradiation. The irradiation intensity is 20 to 500 mW / cm ²
It is preferable to use in the range of.

The optimum dose of the compound of the present invention is determined according to the symptoms, type of phthalocyanine, irradiation dose and type of tumor, based on the judgment of a doctor. Generally, a small amount of 1 mg / kg is effective for diagnosis, and about 20 mg / kg is effective.
Dosages up to kg are used. The same applies to therapeutic doses. The dosage form of the compound of the present invention is not particularly limited and is prepared according to the means commonly used in this field. The compounds of the present invention are especially water soluble and may therefore be administered orally, intravenously,
Either intramuscular or subcutaneous administration is possible. In that case, it can also be administered together with another inert diluent. It may also be administered in the form of gelatin capsules or tablets.

A cationic surfactant such as cetyltrimethylammonium bromide or a neutral surfactant such as Triton can be added to the compound of the present invention. Fluorescence can also be effectively emitted by using these. Hereinafter, the effects of the compound of the present invention as a photochemotherapeutic agent and a photochemical diagnostic agent will be shown by specific examples.

Example 1 A compound of the above-mentioned A- skeleton: ZnPc (PhS) 8 [the number of sulfonation for 11 molecules of Pc: 11 molecules] (λmax: 730 nm / water) dissolved in water was added to the medium in the HeLa cell culture in the dish. It was added to ^give a concentration of 4.0 × 10 ⁻⁶ M. Then 1
After culturing for a period of time, phthalocyanine was taken up by the cells.
After that, after washing the inside of the petri dish three times with the medium, a laser device with variable oscillation wavelength (titanium sapphire laser 680 nm)
~ 850nm variable type (wavelength 730nm, output 100mW
/ Cm ² , total irradiation amount of light 15 J / cm ² ) and laser irradiation was performed for 2.5 minutes. After 4 hours from the light irradiation, trypan blue staining was performed.

The cell killing effect was judged from the staining rate of cells by light microscope observation. As a result, the dyeing rate is 100
%Met. Therefore, it was revealed that the above compound has a cytocidal effect on tumor cells.

Example 2-10 . Instead of the phthalocyanine compound and the concentration of the phthalocyanine in Example 1, the kind of the phthalocyanine compound shown in Table 1 was used, the concentration shown in Table 1 was used, and the same laser device as in Example 1 was used to generate the oscillation light of the wavelength of Table 1. Was carried out, and the cell killing effect of each phthalocyanine compound was determined as in Table 1 except that the irradiation was carried out with the light irradiation amount shown in Table 1.

[0039]

[Table 1]

Example 11 Murine hepatoma-derived cells (MH134) were transplanted into C3H / He mice, and the resulting solid tumors had the above-mentioned phthalocyanine compound C-PcF12.
(PhO) 4 [Sulfonation number: 5] Triton X-10
A solution containing 0% of 0 was injected intravenously. After 24 hours, the tumor part and the normal tissue part were cut out and extracted with methanol, and the fluorescence spectrum was measured using a fluorescence spectrophotometer. As a result, the tumor area is 720 nm
A peak derived from fluorescence having λmax was confirmed, whereas no fluorescence spectrum was confirmed in the normal tissue portion.

Example 12 Instead of the phthalocyanine compound of Example 11, A-compound PcF8 (PhS) 8
The fluorescence spectra of the tumor part and the normal tissue part were confirmed in the same manner as in Example 11 except that the light of 730 nm was selected using [Sulfonation number: 5]. As a result, in the tumor part, a peak derived from fluorescence having λmax at 760 nm was confirmed, while in the normal tissue part, no fluorescence spectrum was confirmed.

Reference Example 1. Type Synthesis Example (D-9) -Synthesis of 4-phenylthiophthalonitrile In a 100 ml separable flask, 26.0 g (0.15 mol) of 4-nitrophthalonitrile and 1 of thiophenol were added.
6.2 g (0.15 mol) and 20 ml of N, N-dimethylformamide are added. A mixture of 10 ml of N, N-dimethylformamide and 22.84 g (0.15 mol) of 1,8-diazabicyclo [5.4.0] undec-7-ene was added dropwise thereto at room temperature over 1 hour. After completion of dropping, 10
The temperature was raised to 0 ° C. and the reaction was continued for 3 hours. After the completion of the reaction, the reaction mixture was put into 500 ml of a 1% hydrochloric acid aqueous solution, and the precipitated solid was washed with water and dried under vacuum to obtain 30.6 g of a target yellow cake. (Yield 86.4%)

Synthesis of 4-tetrakisphenylthiozinc phthalocyanine 3.54 g (15 mmol) of 4-phenylthiophthalonitrile in a 100 ml separable flask and 1.4 of zinc iodide.
Charge 4 g (18 mmol) benzonitrile 30 ml,
The reaction was carried out at 5 ° C for 4 hours. After completion of the reaction, benzonitrile was distilled off, and the obtained solid was washed twice with 200 ml of methanol to obtain 3.34 g of a target green cake. (Yield 88.2%)

Synthesis of sulfonated 4-tetrakisphenylthiozinc phthalocyanine In a 100 ml separable flask, 2.02 g (2 mmol) of 4-tetrakisphenylthiozinc phthalocyanine, 1,
Charge 50 ml of 1,2,2-tetrachloroethane at 80 ℃
It was stirred at. A mixture of 25 ml of 1,1,2,2-tetrachloroethane and 2.08 g (8 mmol) of chlorosulfonic acid was added dropwise thereto over 30 minutes. After completion of the dropping, the reaction temperature was raised to 140 ° C. and the reaction was further continued for 2 hours. After the reaction was completed, the precipitated solid was washed twice with 200 ml of dichloromethane to obtain 2.42 g of the desired green cake. As a result of analysis, it was found that this compound had four sulfonic acid groups in one molecule.

D-9 for other D type
Can be synthesized in the same manner as.

Claims (2)

[Claims] 1. The following general formula (I): [In the formula, X is independently of each other a hydrogen atom, a fluorine atom, O
R ₁ Zb to e, SR ₂ Zf to i, OR ₃ , SR ₄ (wherein R ₁ and R ₂ are each independently a phenyl group or a benzyl group, and the phenyl group or the benzyl group has a carbon number of 1).
~ 4 alkyl group, alkoxyl group, carboxyl group,
It may be substituted with an alkoxycarbonyl group or a halogen atom, and R ₃ and R ₄ are each independently C1 to C2.
0 alkyl group, a cycloalkyl group of C4-C6, Z represents a represents a sulfone group), Y is independently of one _{another, OR 5 Zj~m, SR 6 Zn~q} (R 5, R 6 are Each independently a phenyl group or a benzyl group, which may be substituted with an alkyl group having 1 to 4 carbon atoms, an alkoxyl group, a carboxyl group, an alkoxycarbonyl group or halogen;
Represents a sulfone group), a is an integer of 0 to 3, b to q is an integer of 0 to 7, and the sum of b to q is 1.
Above, M represents hydrogen, zinc, aluminum chloride or gallium chloride] A tumor therapeutic agent comprising a phthalocyanine compound represented by the above formula. 2. The following general formula (I): [In the formula, X is independently of each other a hydrogen atom, a fluorine atom, O
R ₁ Zb to e, SR ₂ Zf to i, OR ₃ , SR ₄ (wherein R ₁ and R ₂ are each independently a phenyl group or a benzyl group, and the phenyl group or the benzyl group has a carbon number of 1).
~ 4 alkyl group, alkoxyl group, carboxyl group,
It may be substituted with an alkoxycarbonyl group or a halogen atom, and R ₃ and R ₄ are each independently C1 to C2.
0 alkyl group, a cycloalkyl group of C4-C6, Z represents a represents a sulfone group), Y is independently of one _{another, OR 5 Zj~m, SR 6 Zn~q} (R 5, R 6 are Each independently a phenyl group or a benzyl group, which may be substituted with an alkyl group having 1 to 4 carbon atoms, an alkoxyl group, a carboxyl group, an alkoxycarbonyl group or halogen;
Represents a sulfone group), a is an integer of 0 to 3, b to q is an integer of 0 to 7, and the sum of b to q is 1.
And above, M represents hydrogen, zinc, aluminum chloride or gallium chloride].