Prophylactic/ameliorating agent for adult diseases comprising 5-aminolevulinic acid, derivative of 5-aminolevulinic acid, or salt of 5-aminolevulinic acid or the derivative of 5-aminolevulinic acid as active ingredient

Abstract

A pharmaceutical composition which is different from an existing therapeutic agent of an adult disease, of a biochemical reaction-inhibiting type, and which action mechanism is to improve the basal metabolism, wherein the composition has no side effects, and does not generate drug resistance against adult disease; and a method for preventing/treating an adult disease by using the same. A composition for preventing/ameliorating an adult disease such as metabolic syndrome, diabetes, hyperlipidemia, hypertension, impaired liver function, renal failure, adiposity, erectile dysfunction, menopausal disorder, shoulder discomfort, and low back pain, comprising 5-aminolevulinic acid (ALA), its derivative, or salt thereof, preferably comprising ALA, its derivative, or salt thereof, and an iron compound such as sodium ferrous citrate, iron sodium citrate and iron ammonium citrate; a food or food material for preventing/ameliorating an adult disease comprising the composition; and a method for using the composition for preparing an agent for preventing/ameliorating an adult disease.

Claims

1. A method for treating an adult disease, comprising administering a composition consisting essentially of 5-aminolevulinic acid (ALA), its ester derivative or acyl derivative, or a salt thereof to a subject in need thereof, wherein the adult disease is one or more diseases selected from the group consisting of hyperlipidemia, renal failure, adiposity, erectile dysfunction, menopausal disorder, shoulder discomfort, and low back pain.

2. A method for treating an adult disease, comprising administering a composition consisting essentially of (i) 5-aminolevulinic acid (ALA), its ester derivative or acyl derivative, or a salt thereof, and (ii) an iron compound to a subject in need thereof, wherein the adult disease is one or more diseases selected from the group consisting of hyperlipidemia, renal failure, adiposity, erectile dysfunction, menopausal disorder, shoulder discomfort, and low back pain.

3. The method according to claim 2, wherein the iron compound is one or more compounds selected from the group consisting of ferrous citrate, sodium ferrous citrate, iron sodium citrate, iron ammonium citrate, ferric pyrophosphate, heme iron, iron dextran, iron lactate, ferrous gluconate, DTPA iron, iron sodium diethylenetriaminepentaacetate, iron ammonium diethylenetriaminepentaacetate, iron sodium ethylenediaminetetraacetate, iron ammonium ethylenediaminepentaacetate, iron triethylenetetraamine, iron sodium dicarboxymethylglutamic acid, iron ammonium dicarboxymethylglutamic acid ammonium, lactoferrin iron, transferrin iron, ferric chloride, iron sesquioxide, sodium iron chlorophyllin, ferritin iron, ferrous fumarate, ferrous pyrophosphate, saccharated iron oxide, iron acetate, iron oxalate, ferrous succinate, iron and sodium succinate citrate, iron sulfate, and sulfide glycine iron.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 It is a graph showing the change of blood sugar level by ALA administration using diabetes mouse models.

(2) FIG. 2 It is a graph showing the results of glucose tolerance test by ALA administration using diabetes mouse models.

(3) FIG. 3 It is a graph showing the lipid change by ALA administration using diabetes mouse models.

(4) FIG. 4 It is a graph showing the change of insulin secretion level by ALA administration using diabetes mouse models.

(5) FIG. 5 It is a graph showing the change of fasting blood sugar by ALA administration in a diabetes patient.

(6) FIG. 6 It is a graph showing the change of glycated hemoglobin by ALA administration in a borderline diabetes patient.

(7) FIG. 7 It is a graph showing the change of glycated hemoglobin by ALA administration in a borderline diabetes patient.

(8) FIG. 8 It is a graph showing the change of glycated hemoglobin with and without ALA administration in a diabetes patient.

(9) FIG. 9 It is a graph showing the change of glycated hemoglobin by ALA administration per group in a safety test on healthy person.

(10) FIG. 10 It is a graph showing the change of blood sugar level by ALA administration per group in a safety test on healthy person.

BEST MODE FOR CARRYING OUT THE INVENTION

(11) As for a composition for preventing/ameliorating (agent for preventing/ameliorating) an adult disease of the present invention, it is not particularly limited as long as it is a composition comprising ALAs constituted from ALA, its derivative, or salt thereof as an active ingredient or main ingredient. The above ALA is also referred to as δ-aminolevulinic acid, and is one of amino acids represented by the formula HOOC—(CH.sub.2).sub.2—(CO)—CH.sub.2—NH.sub.2. These ALAs can be produced by any known methods such as chemical synthesis, production from microorganisms, or production from enzymes.

(12) Among ALAs, as a derivative of ALA, for example a derivative comprising an ester group and acyl group of ALA can be exemplified. Preferably, a combination of methylester group and formyl group; methylester group and acetyl group; methylester group and n-propanoyl group; methylester group and n-butanoyl group; ethylester group and formyl group; ethylester group and acetyl group; ethylester group and n-propanoyl group; ethylester group and n-butanoyl group can be exemplified.

(13) Among ALAs, examples of salts of ALA or its derivative include: acid addition salts such as hydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, sulfate, acetate, propionate, toluenesulfonate, succinate, oxylate, lactate, tartate, glycolate, methanesulfonate, butyrate, valerate, citrate, fumarate, maleate, and malate; metal salts such as sodium salt, potassium salt, and calcium salt; ammonium salt, and alkyl ammonium salt. These salts are used as a solution when used, and it is preferred that the action is similar to that of ALA. These salts may form a hydrate or solvate, and it can be used separately, or by combining two or more of them.

(14) In the present invention, an adult disease relates to a lifestyle disease which is strongly associated with lifestyle habits conducted for a long time. Suitable examples include metabolic syndrome, diabetes, hyperlipidemia, hypertension, impaired liver function, renal failure, adiposity, erectile dysfunction, menopausal disorder, shoulder discomfort, and low back pain.

(15) A composition for preventing/ameliorating an adult disease of the present invention is preferred to further comprise an iron compound as an active ingredient. The iron compound in the present invention is not particularly limited as long as it is a compound having iron in its molecule. Examples include: ferrous citrate, sodium ferrous citrate, iron sodium citrate, iron ammonium citrate, ferric pyrophosphate, heme iron, iron dextran, iron lactate, ferrous gluconate, DTPA iron, iron sodium diethylenetriaminepentaacetate, iron ammonium diethylenetriaminepentaacetate, iron sodium ethylenediaminetetraacetate, iron ammonium ethylenediaminepentaacetate, iron triethylenetetraamine, iron sodium dicarboxymethylglutamic acid, iron ammonium dicarboxy-methylglutamic acid ammonium, lactoferrin iron, transferrin iron, ferric chloride, iron sesquioxide, sodium iron chlorophyllin, ferritin iron, ferrous fumarate, ferrous pyrophosphate, saccharated iron oxide, iron acetate, iron oxalate, ferrous succinate, iron and sodium succinate citrate, iron sulfate, and sulfide glycine iron. Among these, ferrous citrate and iron sodium citrate are preferred. These iron compounds can be used separately, or by combining 2 or more of them. The iron compound contained in a composition for preventing/ameliorating an adult disease of the present invention is usually 0 to 100-fold the administration level of ALA in molar ratio, and preferably 0.1 to 8-fold.

(16) A composition for preventing/ameliorating an adult disease of the present invention is useful as an agent for preventing/ameliorating an adult disease, and can be used as an oral administration type, or intravenous injection type. As for a formulation of an agent for preventing/ameliorating an adult disease of an oral administration type, examples include powder, granule, tablet, capsule, syrup, and suspension. As for a formulation of intravenous injection type, injection and intravenous fluid can be exemplified. When preparing a composition for preventing/ameliorating an adult disease of the present invention as an aqueous solution for injection, etc., it is preferred to prepare with attention so that the aqueous solution does not become alkaline in order to prevent degradation of ALAs. In case it becomes alkaline, degradation of active ingredients can be prevented by removing oxygen.

(17) A composition for preventing/ameliorating an adult disease of the present invention can be further supplemented with other optional components such as medicinal components, nutritional supplements, and carriers as necessary. Optional components include, pharmaceutically acceptable normal carrier, binding agent, stabilizer, solvent, dispersant, bulking agent, excipient, diluent, pH buffer, disintegrant, solubilizer, solubilizing agent, and isotonic agent, such as crystalline cellulose, gelatine, lactose, starch, magnesium stearate, talc, vegetable and animal fat, fat and oil, gum, and polyalkylene glycol.

(18) Among ALAs contained in an agent for preventing/ameliorating an adult disease of the present invention, the most preferred are ALA, ALA methylester, ALA ethylester, ALA propylester, ALA butylester, ALA pentylester, and hydrochloride, phosphate and sulfate of these ALA esters.

(19) A preferred method for administering an agent for preventing/ameliorating an adult disease of the present invention, include oral administration comprising sublingual administration; intravenous injection comprising intravenous fluid; and transdermal administration by poultice, or suppository. The amount of ALAs contained in these agents for preventing/ameliorating an adult disease may be 0.1 mg to 1000 mg in terms of ALA hydrochloride per day for adult, preferably 0.3 mg to 300 mg, more preferably 1 mg to 100 mg. The time for administrating the agent for preventing/ameliorating an adult disease of the present invention is not particularly limited, and it may be administered in the morning or in the afternoon. When the administration quantity is large, it is preferred to be administered in several times.

(20) The agent for preventing/ameliorating an adult disease of the present invention may be used by combining with other agents for preventing, ameliorating, or treating an adult disease. As existing medicines of this field are inhibitors of a particular reaction, and have a different action mechanism from that of the agent of the present invention which enhances basal metabolism, an additive effect, and in some cases synergistic effect can be expected by using them in combination.

(21) As for a food or food material for preventing/ameliorating an adult disease of the present invention, it is not particularly limited as long as the above composition for preventing/ameliorating an adult disease of the present invention is added. By adding a composition of the present invention containing ALAs to food or drink, a food or food material for preventing/ameliorating an adult disease can be made. Further, as for a method for using the present invention, it is not particularly limited as long as it is a method for using a composition for preventing/ameliorating an adult disease for preparing an agent for preventing/ameliorating an adult disease. A method for using a composition of the present invention comprising ALAs for preparing an agent for preventing/ameliorating an adult disease, can be exemplified by a method for preparing an agent for preventing/ameliorating an adult disease of an oral administration type or intravenous injection type by compounding the above optional components to ALAs. Further, as a method for preventing/ameliorating an adult disease of the present invention is not particularly limited as long as it is a method comprising administrating a composition for preventing/ameliorating an adult disease of the present invention. The administration method can be exemplified by oral administration, intravenous injection, and transdermal administration, as is stated in the above.

(22) Embodiment of a food or food material for preventing/ameliorating an adult disease of the present invention include: a food or food material added with ALAs, with a label stating that it can be used for preventing/ameliorating an adult disease; a method for using a food or food material added with ALAs, as a food or food material for preventing/ameliorating an adult disease; a method for using ALAs as a compounding agent of a food or food material for preventing/ameliorating an adult disease; a method for manufacturing food or food material for preventing/ameliorating an adult disease, comprising adding ALAs to the food or food material.

(23) As a food or food material for preventing or ameliorating an adult disease of the present invention include: various drinks such as yoghurt, drink yoghurt, juice, milk, soy milk, alcohols, coffee, red tea, boiled tea (sencha), oolong tea, and sport drink; baked confectionery such as pudding, cookie, bread, cake, jelly, and rice cake; Japanese cakes such as faded black; breads and snacks such as cold desserts and chewing gum; noodles such as wheat noodle and buckwheat noodle; fish cakes such as steamed fish paste, ham, fish meat sausage; seasonings such as soybean paste (miso), soybean sauce, dressing, mayonnaise, sweetener; dairy products such as cheese and butter; soy bean cake (tofu), yam paste, various prepared foods such as fish boiled in soy sauce, kop-zi, croquette, and salad; and nutritional foods. “For preventing/ameliorating an adult disease” means that the use of ALAs is intended for preventing/ameliorating an adult disease, such as being indicated on the package or instructions of the food or food material that it is effective for preventing/ameliorating an adult disease.

(24) In the following, the present invention will be further explained, while the present invention is not limited to these Examples.

EXAMPLE 1

(25) A 61 years-old male ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate (5-aminolevulinic acid phosphate) and 2.87 mg of sodium ferrous citrate each morning and afternoon, and improvement of the following biochemical values was observed in 2 weeks.

(26) TABLE-US-00001 TG 314 .fwdarw. 132 GOT 19 .fwdarw. 19 GPT 17 .fwdarw. 15 γ-GTP 60 .fwdarw. 48 HbA1c 6.2 .fwdarw. 5.9

(27) Lipid metabolism, liver function, and sugar metabolism were all improved. Particularly, lipid metabolism was improved to a normal level, and a treatment effect was clearly shown. It was shown from this Example that the administration of ALA is effective for various adult diseases.

EXAMPLE 2

(28) A 60 years-old male ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day, and improvement of the following biochemical values was observed 1 month after.

(29) TABLE-US-00002 TC 264 .fwdarw. 260 LDL 192 .fwdarw. 173 HDL 65 .fwdarw. 58

(30) It was shown from this example that the administration of ALA is effective for improving lipid metabolism and liver function.

EXAMPLE 3

(31) A 73 years-old male ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day, and hypertension was ameliorated. 1 month after, he stopped taking antihypertensives which he had been taking until then, but the blood pressure maintained a normal level. It was shown from this example that the administration of ALA is effective for hypertension.

EXAMPLE 4

(32) A 70 years-old male being a borderline diabetes patient ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day, and improvement of the following biochemical values was observed 1 month, 2 months, and 3 months after initiating ingestion.

(33) TABLE-US-00003 Before After 1 After 2 After 3 initiation month months months HbAlc 7.4 7.2 6.9 6.8

(34) It was shown by this example that administration of aminolevulinic acid is effective for amelioration and prevention of diabetes.

EXAMPLE 5

(35) A 68 years-old male ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day. Improvement of shoulder discomfort from which he was suffering for a long time was observed from 1 week after initiating ingestion. It was shown from this example that administration of aminolevulinic acid is effective for tension such as shoulder discomfort.

EXAMPLE 6

(36) A 42 years-old male ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 23 mg of sodium ferrous citrate per day. From the day after initiating ingestion, amelioration of migraine which he suffered since he was 40 years of age was observed. After 1 week of ingestion, migraine was completely cured. This shows that administration of aminolevulinic acid is effective for male menopause.

EXAMPLE 7

(37) A 47 years-old male ingested 2 capsules each comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day. The next morning, erection which was not observed for a long time was observed. The next day of ingestion, he had sexual intercourse for the first time in a year, and since then, he continuously has sexual intercourse once every 2 weeks on average. This shows that administration of aminolevulinic acid is effective for erectile dysfunction, and also effective for preventing mental depression accompanied with aging.

EXAMPLE 8

(38) A 45 years-old male ingested 2 capsules each comprising 5 mg of aminolevulinic acid phosphate and 23 mg of sodium ferrous citrate per day. From the day following the ingestion, he felt fulfilled physically and mentally. Three days after initiating ingestion, he had sexual intercourse for the first time in half a year, and after that, he continuously has sexual intercourse twice a week on average. This shows that administration of aminolevulinic acid is effective for erectile dysfunction, and also effective for preventing mental depression accompanied with aging.

EXAMPLE 9

(39) A 47 years-old male ingested 1 capsule comprising 50 mg of aminolevulinic acid phosphate and 57.4 mg of sodium ferrous citrate per day. From the day following the ingestion, he felt fulfilled physically and mentally. By measuring his temperature with a female thermometer, an increase of 0.1 to 0.2° C. was observed compared to before ingestion. After 3 months of ingestion, his body weight decreased by 5 kg from 79 kg to 74 kg, and gray hair and crimples were also ameliorated. This shows that administration of aminolevulinic acid is effective for adult diseases such as metabolic syndrome.

EXAMPLE 10

(40) A 46 years-old female suffering from sensitivity to cold temperature, ingested 1 capsule comprising 5 mg of aminolevulinic acid phosphate and 2.87 mg of sodium ferrous citrate per day. From 2 days after initiating ingestion, she felt warmth to her limbs, and the sensitivity to cold temperature was ameliorated, and constipation was not observed. This shows that administration of aminolevulinic acid is effective for sensitivity to cold temperature and constipation.

EXAMPLE 11

(41) A 55 years-old female suffering from menopausal disorder, ingested 2 capsules each comprising 5 mg of aminolevulinic acid phosphate and 23 mg of sodium ferrous citrate per day. From 1 week after initiating ingestion, she felt improvement of physical strength and facial rejuvenation, and that symptoms of menopausal disorder such as hot-flash or frustration were gone. This shows that administration of aminolevulinic acid is effective for menopausal disorder.

EXAMPLE 12

(42) A 47 year-old male suffering from shoulder discomfort, applied 1 wt % each of aminolevulinic acid phosphate and DTPA iron (diethylene triamine penta acetic acid)-Fe) once a day to the sites of low back pain and shoulder discomfort, and shoulder discomfort was gone in a week.

EXAMPLE 13

(43) After obtaining informed consent before the initiation of the test, 30 men and women of age 22 to 63 participated in a double-blind test, and ingested a soft capsule comprising ALA phosphate, and ALA phosphate and ferrous citrate. Groups I, II, and III all ingested 1 capsule per day continuously for 4 weeks. The capsule of Group I comprised 5 mg of ALA phosphate; the capsule of Group II comprised 15 mg of ALA phosphate; and the capsule of Group III comprised 5 mg of ALA phosphate and 2.87 mg of ferrous citrate. Biochemical examination of blood was performed 2 weeks and 4 weeks after initiating ingestion, and 2 weeks after the end of the test. The following items showed a significant change in the biochemical examination of blood. 1) ALP Group II showed a decrease of 18.0±23.2 U/L in 2 weeks (195.2±74.7 vs 177.2±55.2 U/L). 2) Total proteins Group II showed a decrease of 0.29±0.22 g/dL in 4 weeks (7.28±0.48 vs 6.99±0.47 g/dL). 3) Albumin Group III showed a decrease of 0.12±0.11 g/dL in 2 weeks (4.43±0.26 vs 4.31±0.26 g/dL). 4) Creatinine Group II showed a decrease of 0.040±0.037 mg/dL in 4 weeks (0.701±0.134 vs 0.661±0.109 mg/dL) 5) Total cholesterol Group III showed a decrease of 13.2±15.0 mg/dL in 2 weeks (204.1±21.0 vs 190.9±30.3 mg/dL) 6) HDL-cholesterol Group I showed a decrease of 3.7±4.9 mg/dL in 4 weeks (64.6±17.3 vs 60.9±15.8 mg/dL). Group III showed a decrease of 2.6±2.8 mg/dL in 2 weeks (67.8±12.4 vs 65.2±11.7 mg/dL). 2 weeks after the end of the test, the level decreased by 2.8±3.7 mg/dL (67.8±12.4 vs 65.0±11.4 mg/dL). 7) LDL-cholesterol Group III showed a decrease of 10.7±7.8 mg/dL in 2 weeks (122.5±20.6 vs 111.8±25.9 mg/dL). 8) Na Group III showed an increase of 0.7±0.7 mEq/L, 2 weeks after the end of the test (140.4±1.6 vs 141.1±1.5 mEq/L).

(44) Decrease of ALP is a favorable change showing amelioration of liver function, and decrease of total protein, alubumin, and creatinine shows the improvement of protein metabolism. Further, decrease of total cholesterol, HDL-cholesterol, LDL-cholesterol is a favorable change showing that lipid metabolism is heading to amelioration. It can be estimated that increase of sodium is related to sodium discharge from cells, and improvement of kidney function can be expected.

(45) The above tests were conducted to healthy subjects, but metabolisms related to adult diseases showed a good tendency. Thus, the effect of prevention/amelioration of the present invention was shown.

EXAMPLE 14

(46) Naturally occurring-type II diabetes mouse models, KK-Ay mice, were bred according to a common method, and made to have obesity. FIG. 1 shows the blood sugar levels of when 10 mg of 5-aminolevulinic acid (ALA) and 92 mg of sodium ferrous citrate (iron citrate) per 1 kg of body weight; and when 30 mg of ALA and 276 mg of iron citrate per 1 kg of body weight were administered to the mice. FIG. 2 shows the results of glucose tolerance test; FIG. 3 shows the transition of neutral fat during this period; and FIG. 4 shows the development of insulin secretion during this period. Each experiment was conducted with 10 mice.

(47) As it is clear from the figures, by administering ALA and iron, blood sugar levels decreased, sugar tolerance ability increased, lipid metabolism increased and insulin secretion was ameliorated, suggesting that the administration was effective for diabetes and dyslipidemia. General drug for improving diabetes worsen lipid metabolism, while ALA and iron activated mitochondrial electron transfer system, and improved chained rotation of TCA cycle. Therefore, the so-called basal metabolism was improved, and it is assumed that consumption of both sugar and lipid has improved.

EXAMPLE 15

(48) A 53 year-old type II diabetes patient was having insulin treatment, and was administered insulin in an amount of 10 units in the morning, 5 units at noon, and 10 units in the evening. FIG. 5 shows the change of fasting blood sugar when 25 mg of ALA phosphate and iron citrate in an amount of 0.5-fold in molar ratio of ALA per day were administered to this patient.

(49) The fasting blood sugar differs significantly depending on the diet of the previous day, increasing and decreasing, while as it is shown by the auxiliary line, it decreased averagely by about 15 mg/dl in 1 month, showing to be effective for ameliorating diabetes.

EXAMPLE 16

(50) The male patient of Example 4 continued ingestion under the same conditions. Five months after the initiation of administration, HbA1c decreased to 5.9, and further decreased to 5.2 eight months later, and he was completely free of diabetes. The results are shown in FIG. 6.

EXAMPLE 17

(51) A 72 years-old woman suffering from type II diabetes, had been living being careful of her eating habit and taking exercises under the guidance of her doctor, while HbA1c increased gradually. On Nov. 7, 2008, she started to ingest 50 mg of ALA phosphate and iron citrate in an amount of 0.5-fold in molar ratio of ALA per day. A rapid improvement of HbA1c was observed, and her condition improved in 6 months. The development during this time period is shown in FIG. 7. Meanwhile, the fasting blood sugar level on Nov. 7, 2008, at the time of initiation of ingestion was 195 mg/dl, which was ameliorated to 107 mg/dl on May 9, 2009.

EXAMPLE 18

(52) A 69 years-old woman having type II diabetes started to digest 15 mg of ALA phosphate and iron citrate in an amount of 0.5-fold in molar ratio of ALA per day, interrupted the ingestion once, and then restarted the ingestion. FIG. 8 shows the change of HbA1c during this time period. Bold arrow shows the ingested period. HbA1c is ameliorated by ingestion. As HbA1c increased when the ingestion was interrupted, it has been clarified that it is an effect exhibited by ALA.

EXAMPLE 19

(53) As a safety test, healthy subjects started to ingest 25 mg of ALA phosphate and iron citrate in an amount of 0.5-fold in molar ratio of ALA per day, which ingestion was continued for 4 weeks. Blood was tested every two weeks including before ingestion, and after termination of ingestion. No significant change was observed in average levels. Further, the stratified results of healthy subjects which were divided into a group in which HbA1c before ingestion was higher than 4.8, and a group in which HbA1c before ingestion was 4.8 or less are observed in FIG. 9. As it is shown from FIG. 9, some decreasing tendency was shown in the group with HbA1c higher than 4.8, while a rather increasing tendency was observed for the group of 4.8 or less, suggesting that it is an effect with high safety, which does not affect healthy subjects. Similarly, change of blood sugar level when the subjects were divided into a group with fasting blood sugar level of 90 or more, and a group with a level of less than 90 is shown in FIG. 10. As it is clear from FIG. 10, a mild decrease is observed for the group having a relatively high level within the normal range, while almost no change is observed in the lower group, suggesting that it is an effect with high safety, which does not affect healthy subjects.

EXAMPLE 20

(54) The ingested amount of ALA, ingested period, and HbAlc change of 6 male borderline diabetes patients are shown in Table 1. HbA1c was ameliorated in all of 6 patients, showing that the present invention is highly probable.

(55) TABLE-US-00004 TABLE 1 Results of pilot study in diabetes patients by 5-ALA amount period before after age sex mg/day month HbA1c(%) 47 men 50 3 6.1 5.7 45 men 50 2 7.5 6.1 40 men 50 2 7.5 6.1 58 men 10 2 6.7 5.7 70 men 10 8 7.4 5.2 61 men 10 0.5 6.2 5.9

INDUSTRIAL APPLICABILITY

(56) According to the present invention, it is possible to improve or prevent an adult disease by improving basal metabolism which decreases with advancing age. The present invention is different from an existing therapeutic agent of an adult disease, of a biochemical reaction-inhibiting type, and its action mechanism is to increase the basal metabolism, in other words its action mechanism is the rejuvenation of metabolism, and has no side effect, and does not generate drug resistance. Further, as the action mechanism is different from that of an existing drug, it is expected that its effect can be enhanced by using in combination with an existing drug.