JP5611548B2 - Cancer preventive / ameliorating agent containing 5-aminolevulinic acid or a derivative thereof, or a salt thereof as an active ingredient - Google Patents

Description

  The present invention relates to cancer containing 5-aminolevulinic acid (hereinafter also referred to as “ALA”) or a derivative thereof, or a salt thereof, and, if necessary, an iron compound (hereinafter also referred to as “ALA and iron compound”). Regarding prevention / amelioration agents, in detail, cancer prevention / improvement compositions administered orally, intravenously, sublingually, intraperitoneally, enteral transfusions, transdermal agents, suppositories, etc., and prevention / improvement of cancer For methods.

  Cancer is currently the most terrible disease for mankind who has overcome infections and is the top cause of death in developed countries. In advanced countries, which are facing aging, the number of patients is increasing rapidly, and soaring medical costs are becoming a social problem. Unlike infectious diseases, cancer is a disease caused by genetic abnormalities in its own cells, so there are few differences from normal cells, and unlike infectious diseases, there are no specific drugs such as antibiotics. There are three current cancer therapies: surgical excision, radiation, and anticancer drugs, all of which are painful and lower QOL as well as ineffective. It is.

  Especially for anti-cancer drugs, many anti-cancer drugs are inhibitors that focus on the fast growth of cancer cells and focus on DNA replication and the cell cycle, so they also damage fast-growing normal cells. Give the patient unbearable pain. In successful cases, cancer may shrink, but cancer stem cells that are not normally proliferating cannot be killed, so there is a high possibility that they will eventually recur. In recent years, molecular targeted drugs have been developed, but their effects are limited. In addition, immunotherapy and hyperthermia have been studied as complementary therapies, but the effects are unknown.

  On the other hand, ALA is known as an intermediate of a pigment biosynthesis pathway widely present in animals, plants and fungi, and is usually biosynthesized from succinyl CoA and glycine by 5-aminolevulinate synthetase. Although ALA itself is not light sensitive, it is metabolically activated into protoporphyrin IX (hereinafter also referred to as “PpIX”) by a series of enzymes in the heme biosynthetic pathway in the cell, and directly to tumor tissues and new blood vessels. When laser light is irradiated after accumulation, singlet oxygen generated by excitation of light can denature / necrotize cells. In addition, photodynamic therapy or photodynamic therapy (hereinafter also referred to as “ALA-PDT”) using ALA has been developed, and has attracted attention as a treatment method that is low in invasiveness and maintains QOL. Tumor diagnosis / treatment agents used have been reported (see, for example, Patent Documents 1 to 3). However, since light irradiation is essential, it cannot be applied to all cancers.

  In addition, various health foods and treatments have been proposed for cancer prevention, but as many fraud cases have been detected, the needs are great, but effective preventive drugs and methods are known. Not. In addition, active oxygen was considered to be the cause of cancer, and antioxidants were expected to help prevent cancer. However, large-scale studies have shown that beta-carotene increases the incidence of cancer in smokers. Being shocked is new to memory. In general, it has been advertised that a vegetable-centered meal is good or that more than 30 kinds of ingredients should be taken, but these are not based on statistical evidence.

Japanese Patent No. 2731032 JP 2006-124372 A Special table 2002-512205 gazette

  An object of the present invention is to provide a preventive / ameliorating agent that is truly effective and has low side effects, rather than a simple treatment for cancer.

  Life is said to have been born on the primitive earth of 3.6 billion years ago, and primitive organisms that use chemical energy such as the difference in ion concentration across the membrane and light energy are early organisms. It is said to be. It is said that the birth of life with the current precise mechanism was the birth of eukaryotes, which was triggered by the infestation of the ancestors of photosynthetic bacteria with archaea 1.6 billion years ago. The archaea that became the host metabolized organic matter anaerobically and lived under anaerobic conditions, but the ancestors of photosynthetic bacteria were able to acquire energy efficiently using oxygen. In addition to being able to live underneath, it has become possible to efficiently produce energy using oxygen and eventually evolved into a complex multicellular organism. During the evolution process, most of the genes of the parasitic species have been transferred to the host nuclear genes, and are thought to have changed to mitochondria, which are responsible for eukaryotic energy production.

  Traces of parasite-host conflict remain in our current cells. Most of the original mitochondrial genetic information has been transferred to the nucleus, but important genes related to energy production remain in the mitochondria and are transmitted through maternal inheritance independently of nuclear information. In addition, mitochondria are deeply involved in a system that detects nuclear gene abnormalities and eliminates cells. For example, if the membrane potential required for mitochondrial energy production falls, it is eliminated by apoptosis, and for some reason the mitochondrial membrane is damaged, and cytochrome C, which plays a role in carrying electrons in the mitochondrial electron transport system, leaks into the cytoplasm The case is also eliminated by apoptosis. It is also known that the p53 gene, which is famous as a tumor suppressor gene, has a function of promoting aerobic sugar metabolism in mitochondria. The monitoring mechanism of mitochondria during aerobic metabolism is known as the Bax and Bak systems, and is considered to be a system that detects mitochondrial abnormalities under aerobic conditions.

  There is no doubt that canceration is caused by genetic abnormalities in the nucleus of the cell, but cancer research has known a wide variety of genetic abnormalities, which makes cancer treatment difficult. Yes. A common feature of diverse cancer cells is that cancer cells give priority to anaerobic metabolism and glycolysis even under conditions with sufficient oxygen, and aerobic metabolism using mitochondria is said to be low. . This phenomenon was found by Warburg in the 1950s and is called the Warburg effect as the basic law of cancer metabolic abnormalities. PET diagnosis, which is said to be the most accurate cancer diagnostic method at present, is a diagnostic method based on consuming a large amount of glucose because cancer gives priority to glycolysis.

  Why is cancer abandoned efficient aerobic respiration taken by eukaryotes and chose anaerobic metabolism, but genes related to growth abnormalities occur randomly, but mitochondria aerobic As long as metabolism is used, abnormal cells are eliminated by monitoring systems such as the Bax and Bak systems. However, if a mutation that prioritizes glycolysis occurs simultaneously, these monitoring systems based on aerobic metabolism do not work. Many mutations of proliferative abnormalities occur, but it is easy to understand if cancers that have passed through the exclusion system will grow only if mutations that prioritize anaerobic metabolism occur simultaneously.

  It is known that when a relatively large amount of aminolevulinic acid is administered to a cancer patient, PpIX, which is a metabolite and is a precursor of heme and cytochrome, is accumulated in the cancer. Since this PpIX is a photosensitizer, it can diagnose and treat cancer in combination with ALA administration and light irradiation, and is called photodynamic diagnosis (PDD) or photodynamic therapy (PDT), respectively. It has already been put to practical use in some cancers such as skin cancer and brain tumor.

  There are various theories as to why PpIX accumulates only in cancer when ALA is administered, but there is no established theory. Aminolevulinic acid is biosynthesized in human cells by condensation of glycine and succinyl CoA by aminolevulinate synthase in mitochondria. The biosynthesized aminolevulinic acid is once transported to the cytoplasm, and two molecules are condensed by aminolevulinate dehydrogenase (porphobilinogen synthase) in the cytoplasm to form a pyrrole ring to form porphobilinogen. The four porphobilinogen molecules form a porphyrin ring to form a tetrapyrrole structure, which is sequentially converted by an enzyme in the cytoplasm to become coproporphyrinogen III. Coproporphyrinogen III is taken up into mitochondria by ABC transporter and is sequentially oxidized to PpIX, and divalent iron is coordinated by ferrochelatase to become heme and cytochrome. At this time, iron in the body is trivalent, but is reduced to divalent by ferrochelatase. Ferrochelatase generates heme by reducing trivalent iron to divalent using the reducing power of NADH and coordinating with PpIX. The generated heme acts as a heme, and as a heme enzyme and cytochrome, but it is an important component of the electron transport system in the mitochondria. The aforementioned cytochrome C can also be synthesized from ALA if traced back.

  We have already mentioned that mitochondrial aerobic metabolism is a common property of cancer cells. A weak mitochondrial aerobic metabolism is accompanied by a decrease in the TCA cycle and a shortage of NADH in the mitochondria. If NADH is insufficient, ferrochelatase cannot reduce iron, so heme cannot be generated, PpIX accumulates, and the electron transport system further deteriorates due to lack of heme. As mitochondrial metabolism falls, the production of ALA itself is also reduced, and the negative linkage reduces mitochondrial aerobic metabolism, bypasses the monitoring of the Bax and Bak systems, and allows cancer growth.

  Cancer with its own ability to synthesize ALA absorbs ALA from the surrounding area and excretes it as porphyrin. As the cancer progresses, the whole body becomes ALA deficient, and hemoglobin decreases, causing anemia and liver toxic degradation. As the enzyme P450 is decreased, liver function is decreased. Naturally, cytochrome is also deficient, resulting in exhaustion of physical strength.

  In order to stop this vicious cycle of canceration, it is effective to exogenously administer ALA, and the simultaneous administration of iron is more effective. Mitochondrial aerobic metabolism has decreased, ALA production ability has decreased, and the risk of canceration has increased. Exogenously, ALA and iron are given to cells, and the electron transport system is activated by the action of heme and cytochrome. Is strengthened, and aerobic metabolism can be restored and canceration can be prevented. Also, the recovery of aerobic metabolism can treat cancer by leading cells that have already had genetic abnormalities to apoptosis. Mitochondrial activation is difficult when canceration is progressing, but ALA administration accumulates various porphyrins in the cytoplasm of cancer cells, causing cancer cells due to porphyrin toxicity and energy consumption for porphyrin excretion. Can be weakened. Although PDT which irradiates light is a well-known technique, even if it does not accompany light irradiation, it can damage a cancer cell by the above-mentioned mechanism. ALA is also a raw material for cytochrome, which is a signal for inducing apoptosis, and thus assists in inducing apoptosis of cells themselves. These are effective not only for normal proliferating cancer cells but also for resting cancer stem cells.

  ALA administration is useful for improving systemic symptoms such as improving anemia, improving liver function, and improving physical strength by supplying ALA to other organs in which ALA has been exploited in cancer cells. Although it has already been mentioned that canceration is caused by genetic abnormalities, radiation and chemical substances are also known as factors that cause genetic abnormalities, but the biggest cause is reactive oxygen generated in the mitochondrial electron transport system It is said. Electron leakage from the electron transfer system generates active oxygen and damages DNA. Heme and cytochrome derived from aminolevulinic acid in mitochondria are reaction centers of II, III, and IV of the complex of electron transport system, and cytochrome C directly carries electrons from complex III to IV. If heme or cytochrome, which is the reaction center, is insufficient, electrons do not flow smoothly and electrons leak, and active oxygen is generated. However, the administration of ALA and iron moves the electron transport system smoothly and prevents electron leakage. Prevent outbreaks.

  The present inventors have found that cancers that are less than the size of a tennis ball are the cause of decreased physical fitness, anemia, decreased liver function, etc., eventually leading to death. The reason why there are so many different types of cancer and the nature of the cancer, what the cancer is in the first place. If a cancer caused by a genetic abnormality goes through immunity and proliferates abnormally, mitochondrial activity must be reduced, more specifically, the mitochondrial electron transport system must be weakened. Since the decrease in mitochondrial activity suppresses the production of heme and cytochrome that control the reaction of the electron transport system, there is a vicious circle in which mitochondrial activity further decreases, When ALA is administered to cancer cells, the decrease in chondria's TCA cycle is the cause of selective accumulation of porphyrins, and cancer cells waste ALA that should originally become heme and cytochrome. I have come to know that this is the cause of cancer pathology, weakness, anemia, and decreased liver function.

  The present inventors have intensively studied the administration method of ALA and the compounds used in combination, but in order to break the vicious circle to canceration, it is essential to enhance the activity of mitochondria. The administration of iron is effective, that is, the administration of ALA and iron enhances heme and cytochromes in the mitochondria of cancer cells or cells that have become abnormal in the nucleus that is becoming cancer cells, and the electron transport system Under the expectation that if the mitochondrial activity such as TCA cycle is improved, and there is an irrecoverable nuclear abnormality, it will eliminate cancer cells by invoking the Bax and Bak system and causing caspase type IX apoptosis, Surprisingly, when ALA or a composition containing ALA and an iron compound as an active ingredient is administered to a cancer patient, light of a specific wavelength is irradiated. Without, it has been found to bring the epiphytic inhibition of the reduction effect and cancer of cancer. Furthermore, the present inventors have continued to study the type and amount of iron combined with ALA, established a cancer preventive / ameliorating agent characterized by containing 5-aminolevulinic acid, and completed the present invention. .

That is, the present invention comprises (1) 5-aminolevulinic acid (ALA) or a derivative thereof, or a salt thereof, and an iron compound as active ingredients, and 10 mg to 1000 mg per day per adult in terms of ALA hydrochloride, Cancer prevention / improvement composition (excluding food and food material aspects) characterized by reducing cancer by administering 0.1 to 8 times the molar ratio of iron to the dose (2) The iron compound is ferrous citrate, ferrous sodium citrate, sodium iron citrate, ammonium iron citrate, ferric pyrophosphate, heme iron, dextran iron, iron lactate, ferrous gluconate Iron, DTPA iron, sodium diethylenetriaminepentaacetate, ammonium diethylenetriaminepentaacetate, sodium iron ethylenediaminetetraacetate, iron ammonium amethylenediaminepentaacetate , Triethylenetetraamine iron, sodium dicarboxymethyl glutamate, ammonium ammonium dicarboxymethyl glutamate, lactoferrin iron, transfer iron, ferric chloride, iron sesquioxide, iron chlorophyllin sodium, ferritin iron, ferrous fumarate , One or more selected from ferrous pyrophosphate, iron oxide containing sugar, iron acetate, iron oxalate, ferrous succinate, sodium iron citrate succinate, iron sulfate, and iron glycine sulfide The cancer preventive / improving composition as described in (1) above.

  By administering the cancer preventing / ameliorating composition of the present invention, cancer can be improved or prevented by improving basal metabolism. The present invention has a completely different mechanism from PDT using an existing anticancer drug or ALA, and is focused on the metabolism of cancer cells. It is very effective for. In addition, since the mechanism of action is different from that of existing drugs, it is also expected to increase the effect by using it together with existing drugs.

In a pancreatic cancer patient (45-year-old male), the amount of porphyrin excreted in the urine from the start of ingestion of a capsule containing 50 mg of ALA phosphate and 1: 0.5 sodium ferrous citrate in a molar ratio Show. BALB-c-nu / nu nude mice (male: 10 weeks old) are transplanted with human prostate cancer-derived cultured cells ((PC-3) 10 ⁶ cells / mouse) subcutaneously in the thigh, and the cancer is sufficient Growing mice from 4 weeks after transplantation were not administered ALA phosphate, 15 mg / kg.bw. , 50 mg / kg. bw. And a change in body weight after forcibly orally administering an aqueous solution in which sodium ferrous citrate corresponding to a molar ratio of 1: 0.5 is dissolved once a day. BALB-c-nu / nu nude mice (male: 10 weeks old) are transplanted with human prostate cancer-derived cultured cells ((PC-3) 10 ⁶ cells / mouse) subcutaneously in the thigh, and the cancer is sufficient Growing mice from 4 weeks after transplantation were not administered ALA phosphate, 15 mg / kg.bw. , 50 mg / kg. bw. The change of the tumor size per body weight after the oral administration of the aqueous solution which melt | dissolved the ferrous sodium citrate equivalent to 1: 0.5 by molar ratio once a day is shown.

The cancer prevention / amelioration composition (prevention / amelioration agent) of the present invention is not particularly limited as long as it is a composition containing ALAs composed of ALA, its derivatives and salts thereof. A composition containing an iron compound as an active ingredient or main component can be particularly preferably exemplified. The ALA is also called δ-aminolevulinic acid and is a kind of amino acid represented by the formula HOOC— (CH ₂ ) ₂ — (CO) —CH ₂ —NH ₂ . These ALAs can be produced by any known method such as chemical synthesis, production by microorganisms, production by enzymes, and the like.

  Among ALAs, examples of ALA derivatives include those having an ester group and an acyl group of ALA, preferably a methyl ester group and a formyl group, a methyl ester group and an acetyl group, and a methyl ester group and n. -Illustrate combinations of propanoyl group, methyl ester group and n-butanoyl group, ethyl ester group and formyl group, ethyl ester group and acetyl group, ethyl ester group and n-propanoyl group, ethyl ester group and n-butanoyl group Can do.

  Among the ALAs, as salts of ALA or its derivatives, for example, hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, acetate, propionate, toluenesulfonate Acid addition of succinate, oxalate, lactate, tartrate, glycolate, methanesulfonate, butyrate, valerate, citrate, fumarate, maleate, malate, etc. Examples thereof include metal salts such as sodium salts, potassium salts, and calcium salts, ammonium salts, and alkylammonium salts. These salts are used as a solution at the time of use, and the action thereof is preferably the same as that of ALA. These salts may form a hydrate or a solvate, and can be used alone or in combination of two or more.

  The iron compound used in combination with ALAs as the cancer prevention / amelioration composition of the present invention is a compound having iron in the molecule and is not particularly limited as long as it does not adversely affect the effects of the present invention. , Ferrous citrate, sodium ferrous citrate, sodium iron citrate, ammonium iron citrate, ferric pyrophosphate, heme iron, dextran iron, iron lactate, ferrous gluconate, DTPA iron, diethylenetriamine Sodium iron acetate, ammonium diethylenetriaminepentaacetate, sodium ethylenediaminetetraacetate, ammonium ammonium ethylenediaminepentaacetate, triethylenetetraamineiron, sodium iron dicarboxymethylglutamate, ammonium ammonium dicarboxymethylglutamate, iron lactoferrin, iron transferrin, chloride Ferric iron Iron sesquioxide, iron chlorophyllin sodium, ferritin iron, ferrous fumarate, ferrous pyrophosphate, sugar-containing iron oxide, iron acetate, iron oxalate, ferrous succinate, iron citrate sodium citrate, iron sulfate Examples thereof include iron glycine sulfide and the like, among which ferrous citrate and sodium iron citrate are preferable. These iron compounds may be used alone or in combination of two or more, and the iron compound contained in the cancer prevention / amelioration composition of the present invention is administered simultaneously or separately with ALAs. be able to. The dosage form and administration method may be the same as those of ALA, and may be used separately.

  In the present invention, cancer is malignant melanoma, skin cancer, lung cancer, trachea and bronchial cancer, oral epithelial cancer, esophageal cancer, stomach cancer, colon cancer, rectal cancer, colon cancer, Liver and intrahepatic bile duct cancer, kidney cancer, pancreatic cancer, prostate cancer, breast cancer, uterine cancer, ovarian cancer, cancer / tumor in which epithelial cells such as brain tumor have become malignant, myoma, bone Cancers and tumors in which muscles and bones that form the supporting tissues such as sarcoma and Ewing sarcoma have become malignant, and cancers and tumors derived from hematopoietic cells such as leukemia, malignant lymphoma, myeloma, Burkitt lymphoma, etc. Can be mentioned.

  The cancer preventing / ameliorating composition of the present invention is useful as a cancer preventing / ameliorating agent, and can be used as an oral administration type intravenous injection type or a transdermal dosage form. Examples of the dosage form of the preventive / improving agent for oral administration include powders, granules, tablets, capsules, syrups, suspensions, etc. May include injections, infusions and the like. When preparing the cancer preventing / ameliorating composition of the present invention as an aqueous solution of an injection or the like, it is preferable to prepare it so that the aqueous solution does not become alkaline in order to prevent decomposition of ALAs. When it becomes alkaline, decomposition of the active ingredient can be prevented by removing oxygen.

  Other optional ingredients such as other medicinal ingredients, nutrients, and carriers can be added to the preventive / improving composition of the present invention as necessary. As an optional component, for example, crystalline cellulose, gelatin, lactose, starch, magnesium stearate, talc, vegetable and animal fats, fats and oils, gums, polyalkylene glycols and the like, pharmaceutically acceptable ordinary carriers and binders Various formulation ingredients such as stabilizers, solvents, dispersion media, extenders, excipients, diluents, pH buffers, disintegrants, solubilizers, solubilizers, isotonic agents, etc. it can.

  Among the ALAs contained in the cancer prevention / amelioration agent of the present invention, the most desirable ones are ALA, ALA methyl ester, ALA ethyl ester, ALA propyl ester, ALA butyl ester, ALA pentyl ester, these ALA esters, etc. Hydrochloride, phosphate, sulfate and the like.

  Desirable administration methods of the cancer preventive / ameliorating agent of the present invention include oral administration including sublingual administration and intravenous administration including infusion, transdermal administration such as a suppository, suppository, and the like. The amount of ALA contained in the preparation may be 1 mg to 10000 mg per day per adult in terms of ALA hydrochloride, preferably 3 mg to 3000 mg, more preferably 10 mg to 1000 mg. Moreover, the dosage of iron should just be 0-100 times in molar ratio with respect to the dosage of ALA, 0.01 times-10 times are desirable, and 0.1 times-8 times are more desirable. The administration time of the cancer preventive / ameliorating agent of the present invention is not particularly limited and may be morning or evening, but when the dose is large, it is better to administer it in multiple doses.

  The cancer preventive / ameliorating composition of the present invention can also be used in combination with other cancer preventive, ameliorating and therapeutic agents. The administration preventive / improving composition of the present invention is an additive, sometimes synergistic, because existing pharmaceuticals in the field are inhibitors of specific reactions and differ from the mechanism of action of this drug that enhances basal metabolism. Anticancer effect can be expected.

  The food or food material for preventing or improving cancer according to the present invention is not particularly limited as long as the composition for preventing or improving cancer according to the present invention is added, and the composition according to the present invention containing ALAs. Alternatively, a food or food material for preventing or improving cancer can be obtained by adding a composition of the present invention containing ALAs and an iron compound to a food or drink. In addition, the method of use of the present invention is not particularly limited as long as it is a method of using the cancer prevention / amelioration composition of the present invention for the preparation of a cancer prevention / amelioration agent. Examples of the method of using the composition of the present invention include a method for preparing an oral administration type or intravenous injection type preventive / improving agent by blending an ALA compound with an iron compound or the above-mentioned optional component. . Furthermore, the method for preventing / ameliorating cancer according to the present invention is not particularly limited as long as it is a method for administering the composition for preventing / ameliorating cancer according to the present invention. Administration, intravenous injection, and transdermal administration can be mentioned.

  As an embodiment of the food for preventing or ameliorating cancer according to the present invention or a food material, it is characterized by adding ALA alone or ALA and an iron compound, and used for preventing or improving cancer. Food or food material with a certain indication; ALA alone or a food or food material containing ALA and an iron compound added as a food or food material for preventing or improving cancer; ALA A method of using ALA alone or an ALA compound and an iron compound as a food or food ingredient combination for cancer prevention / amelioration; ALA alone or ALA and iron compound added to food or food ingredient And a method for producing a food or food material for preventing or improving cancer.

  Examples of the food or food material for preventing or improving cancer according to the present invention include various beverages such as yogurt, drink yogurt, juice, milk, soy milk, liquor, coffee, tea, sencha, oolong tea, sports drink, and pudding. Baked confectionery such as cookies, bread, cakes, jelly, rice crackers, Japanese confectionery such as sheep crab, bread and confectionery such as frozen confectionery, chewing gum, noodles such as udon and soba, fish paste products such as kamaboko, ham and fish sausage , Miso, soy sauce, dressing, mayonnaise, sweeteners, dairy products such as cheese, butter, tofu, konjac, other boiled fish, dumplings, croquettes, salads it can. In addition, the use of the composition of the present invention is used for the prevention / improvement of cancer, such as when the food or food material packaging container or instructions indicate that it is effective for the prevention / improvement of cancer. Means being directed at preventing or improving cancer.

  Hereinafter, the present invention will be supplemented by examples, but the present invention is not limited to these examples.

  The patient with uterine fibroids (a 47-year-old woman) was not suitable for surgery due to severe anemia (RBC 2.5 million) and lack of physical strength. However, when aminolevulinic acid hydrochloride was dissolved in sugar water in the morning and evening, it was gradually recovered. After 3 months, the anemia also improved (RBC 3 million). The excised uterine fibroids were clearly lighter than the expected pathology at the time of inadequate operation. This example shows that ALA administration is effective in restoring physical strength and treating cancer.

  A patient with pancreatic cancer (a 45-year-old male) underwent excision surgery but found cancer remaining on the head of the pancreas. Combined with post-surgical treatment with an anticancer drug (Gemzar (registered trademark) Eli Lilly) and ingested capsules containing 50 mg of ALA phosphate and 1: 0.5 sodium ferrous citrate in a molar ratio . The amount of porphyrin excreted in urine from the start of ingestion is shown in FIG. It is known that when cancer cells are present, porphyrin produced in the cancer cells by ALA administration is excreted in urine, and the amount thereof is proportional to the size of the cancer.

  As can be seen from FIG. 1, urinary porphyrin decreases linearly with the ingestion of ALA, and the cancer is reduced. The patient has been operating for 1 year, but has returned to society with no signs of recurrence. In cases where cancer cells remain after surgery, treatment with only an anticancer drug does not show such a great effect, and is considered to be an effect of ALA. In addition, there were few side effects at the time of anticancer drug treatment.

  A capsule containing 50 mg of ALA phosphate and 1: 0.5 sodium ferrous citrate at a molar ratio of morning and evening for patients with colorectal cancer (70-year-old female) who was diagnosed with stage 2 or stage 3 Each one was ingested. Two weeks later, a resection was performed, but the resected cancer was equivalent to stage 1. It was shown that the cancer was reduced by the effect of ALA.

BALB-c-nu / nu nude mice (male: 10 weeks old) were transplanted with human prostate cancer-derived cultured cells ((PC-3) 10 ⁶ cells / mouse) subcutaneously in the thigh. Mice 4 weeks after transplantation in which cancer was sufficiently grown were not administered with ALA phosphate, 15 mg / kg.bw. , 50 mg / kg. bw. An aqueous solution in which sodium ferrous citrate corresponding to a molar ratio of 1: 0.5 was dissolved was forcibly orally administered once a day. The change in body weight after administration and the change in tumor size per body weight are shown in FIGS. 2 and 3, respectively. In the non-administration group (control), the body weight decreased from the 18th day after administration, and all the heads died by the 26th day. On the other hand, the ALA administration group maintained steady growth, no body weight phenomenon was observed, and no death occurred by the 29th day when the observation was performed. The tumor size per body weight was 18% in the 15 mg group and 9% in the 50 mg group compared to 26 days before the control died. From these facts, it can be seen that ALA administration reduces cancer and suppresses injury and death due to cancer.

C57BL / 6 mice (male: 10 weeks old) were not administered ALA phosphate, 15 mg / kg. bw. , 50 mg / kg. bw. An amount of sodium ferrous citrate in a molar ratio of 1: 0.5 was forcibly orally administered as an aqueous solution once a day. Two weeks after administration, Lewis lung cancer 2 (LL / 2) having a cell number of 4 × 10 ⁵ was injected into the peritoneal cavity, followed by oral administration of ALA for 4 weeks, and then sacrificed to establish cancer in the abdominal cavity. When the presence or absence was investigated, the result of the following Table 1 was obtained. The results showed that the administration of ALA and iron prevented the growth of cancer, and it can be seen that the administration of ALA is useful for the prevention of cancer.

  A 70-year-old woman developed early cancer in the right lung and was removed by thoracoscopic surgery. A shadow was also observed in the left lung, but when 3 capsules containing 5 mg of aminolevulinic acid phosphate and 23 mg of iron citrate were ingested 3 times a day, improvement in physical strength was felt. After half a year, the left lung shadow disappeared. This indicates that aminolevulinic acid administration is effective in improving physical strength reduction associated with cancer and preventing or improving cancer.

Claims (2)

5-aminolevulinic acid (ALA) or a derivative thereof, or a salt thereof, and an iron compound as active ingredients,
10 mg to 1000 mg per day for adults in terms of ALA hydrochloride, and 0.1 to 8 times the molar ratio of iron to the dose of ALA administered to reduce cancer. Preventive / improving composition (excluding food and food ingredients) . Iron compounds are ferrous citrate, ferrous sodium citrate, sodium iron citrate, ammonium iron citrate, ferric pyrophosphate, heme iron, dextran iron, lactate iron, ferrous gluconate, DTPA iron , Sodium diethylenetriaminepentaacetate, ammonium diethylenetriaminepentaacetate, sodium ethylenediaminetetraacetate, ammonium ammonium diaminepentaacetate, triethylenetetraamineiron, sodium iron dicarboxymethylglutamate, iron ammonium dicarboxymethylglutamate, iron lactoferrin, transferrin Iron, ferric chloride, ferric sesquioxide, iron chlorophyllin sodium, ferritin iron, ferrous fumarate, ferrous pyrophosphate, sugar-containing iron oxide, iron acetate, iron oxalate, ferrous succinate, succinic acid Quen Iron sodium, claim 1 prophylaxis or improvement composition cancer, wherein the at least one selected from iron sulfate, and sulfide glycine iron.