SBI ALApromo Co.

Tokyo, Japan

SBI ALApromo Co.

Tokyo, Japan

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Yamamoto J.,University of Occupational and Environmental Health Japan | Ogura S.-I.,Tokyo Institute of Technology | Tanaka T.,SBI ALApromo Co. | Kitagawa T.,University of Occupational and Environmental Health Japan | And 5 more authors.
Oncology Reports | Year: 2012

5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy and fluorescence-guided resection of malignant gliomas due to its high cellular uptake in tumours. Porphyrin compounds act not only as photosensitizers but also as radiosensitizers. In the present study, the possible use of 5-ALA as a radiosensitizer for malignant gliomas was examined in vitro. Rat glioma cell lines (9L, C6) were pre-treated with 5-ALA and exposed to ionizing irradiation. The radio-sensitizing effect of 5-ALA was evaluated by colony-forming assay. Intracellular reactive oxygen species (ROS) produced by 5-ALA and irradiation were evaluated by confocal laser scanning microscopy. Pre-treatment with 5-ALA enhanced the radiosensitivity of 9L cells to single-dose ionizing irradiation compared with controls (D 0 value, 4.35±0.20 and 4.84±0.23 Gy, respectively, P≤0.05). Exposure to multi-dose ionizing irradiation revealed high radiosensitivity in both 9L and C6 cells pre-treated with 5-ALA compared to controls. Production of intracellular ROS increased in 9L cells pre-treated with 5-ALA after ionizing irradiation compared to control cells. Thus, 5-ALA functions as a specific radiosensitizer for malignant gliomas. Intracellular 5-ALA-induced PpIX plays an important role in the production of ROS and the radiosensitizing effect under ionizing irradiation conditions.


Mizutani K.,Aichi Medical University | Akita Y.,Aichi Medical University | Yanagishita T.,Aichi Medical University | Kimura M.,Toin University of Yokohama | And 6 more authors.
Photodermatology Photoimmunology and Photomedicine | Year: 2012

Background/Purpose: Topical 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective treatment for Bowen's disease (BD). In order to compare the efficacy of two different light sources, using either an excimer-dye laser (EDL) (630nm) or a metal-halide lamp (MHL) (600 to 740nm) a protocol for topical ALA-PDT for treatment of BD of the extremities was established, and responses during 12 months follow-up were assessed. Methods: From 25 patients a total of 26 lesions that had been histopathologically diagnosed as BD from 2005 to 2010 in the Department of Dermatology at the Aichi Medical University Hospital were randomly selected. The light source used for the topical ALA-PDT was EDL in 17 lesions and MHL in 9 lesions. The photosensitizing protoporphyrin IX that is produced within BD lesions 4h after application of 20% ALA cream was mostly consumed after exposure to 100 J/cm 2 irradiation using 630nm EDL. Each lesion was irradiated once a week for 3 weeks, for a total dosage of 300J/cm 2 (100 mW/cm 2). Patients were followed up clinically every 3 months for 12 months, and at 1 month after the final treatment lesions were evaluated histopathologically. Results: Histologically, the complete response (CR) rate at 1-month follow-up was 82% (14/17 lesions) in the EDL treatment group and 100% (9/9 lesions) in the MHL treatment group (P>0.05). The recurrence rate at 12 months after PDT was 46% (6/13 lesions, one patient lost to follow-up) in the EDL group and 0% in the MHL group (P<0.05) (χ 2 test with Fisher's exact test). The average period before recurrence after EDL treatment was 6.5 months. Conclusion: A novel protocol for topical ALA-PDT in Japanese in Asian patients with BD was developed and implemented. The protocol improved the CR rate compared with previous studies. Moreover, the present results indicate that the efficacy of topical ALA-PDT using MHL was superior to that using EDL for BD patients. © 2012 John Wiley & Sons A/S.


Ishizuka M.,SBI ALApromo Co. | Hagiya Y.,Tokyo Institute of Technology | Mizokami Y.,Tokyo Institute of Technology | Honda K.,Tokyo Institute of Technology | And 8 more authors.
Photodiagnosis and Photodynamic Therapy | Year: 2011

Background: Tumor markers are commonly used for cancer screening and as indicators of therapeutic effects. Certain types of tumor have been known to produce a variety of porphyrins after 5-aminolevulinic acid (ALA) administration. In this study, porphyrins in tumor-bearing mouse urine were analyzed after oral administration of ALA in order to identify new tumor markers excreted in the urine. Methods: Porphyrin concentrations in the urine of tumor-bearing mice were measured after administration of 1.0mg of ALA (approximately 50mgkg -1). Results: Porphyrin concentrations in the urine of tumor-bearing mice increased after administration of ALA. HPLC analysis of the urine revealed the existence of uroporphyrin (UP) and coproporphyrin (CP) in the urine of ALA-treated tumor-bearing mice. Furthermore, at 3. h after ALA administration, UP concentrations in the urine of tumor-bearing mice significantly increased compared to those in the urine of normal mice. Conclusion: These results suggest that UP as a precursor of heme detected in the urine of tumor-bearing mice after ALA administration is a potential marker of tumor development. © 2011 Elsevier B.V.


Ogura S.-I.,Tokyo Institute of Technology | Maruyama K.,Shizuoka Cancer Center Research Institute | Hagiya Y.,Tokyo Institute of Technology | Sugiyama Y.,Tokyo Institute of Technology | And 7 more authors.
BMC Research Notes | Year: 2011

Background: 5-Aminolevulinic acid (ALA) is a precursor of heme that is fundamentally important in aerobic energy metabolism. Among the enzymes involved in aerobic energy metabolism, cytochrome c oxidase (COX) is crucial. In this study, the effect of ALA on cytochrome c oxidase activity was measured. Findings. c57BL/6N species of mice were administered ALA orally for 15 weeks. After ALA administration, mice were sacrificed and livers were obtained. COX activity in mitochondria from ALA-administered mouse livers was 1.5-fold higher than that in mitochondria from PBS-administered mouse livers (P < 0.05). Furthermore, ATP levels in ALA-administered mouse livers were much higher than those in PBS-administered mouse livers. These data suggest that oral administration of ALA promotes aerobic energy metabolism, especially COX activity. Conclusions: This is the first report of a drug that functions in aerobic energy metabolism directly. Since COX activity is decreased in various diseases and aging, the pharmacological effects of ALA will be expanding. © 2011 Ogura et al; licensee BioMed Central Ltd.


Hagiya Y.,Tokyo Institute of Technology | Endo Y.,Kanazawa University | Yonemura Y.,NPO Organization to Support Peritoneal Dissemination Treatment | Takahashi K.,SBI ALApromo Co. | And 7 more authors.
Photodiagnosis and Photodynamic Therapy | Year: 2012

Background: Recently, 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is being widely used in cancer therapy owing to the tumor-specific accumulation of photosensitizing protoporphyrin IX (PpIX) after the administration of ALA. In the present study, by focusing on genes involved in the porphyrin biosynthesis pathway, we aimed to explore biomarkers that are predictive for the efficacy of ALA-PDT. Methods: We used five lines of human gastric cancer cells to measure the ALA-based photocytotoxicity. ALA-induced production of PpIX in cancer cells was quantified by fluorescence spectrophotometry. To examine the potential involvement of PEPT1 and ABCG2 in the ALA-PDT sensitivity, stable cell lines overexpressing PEPT1 were established and ABCG2-specific siRNA used. Results: We observed that three cell lines were photosensitive, whereas the other two cell lines were resistant to ALA-based photocytotoxicity. The ALA-based photocytotoxicity was found to be well correlated with intracellular PpIX levels, which suggests that certain enzymes and/or transporters involved in ALA-induced PpIX production are critical determinants. We found that high expression of the peptide transporter PEPT1 (ALA influx transporter) and low expression of the ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) determined ALA-induced PpIX production and cellular photosensitivity in vitro. Conclusion: PEPT1 and ABCG2 are key players in regulating intracellular PpIX levels and determining the efficacy of ALA-based photocytotoxicity against gastric cancer cells in vitro. Evaluation of the expression levels of PEPT1 and ABCG2 genes could be useful to predict the efficacy of ALA-PDT. Primers specific to those target genes are practical and useful biomarkers for predicting the photo-sensitivity to ALA-PDT. © 2011 Elsevier B.V.


It is to provide 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. It is to provide 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.


Patent
SBI ALApromo Co. | Date: 2010-11-12

The present invention provides an external preparation for skin which contains 5-aminolevulinic acids as active components and which is excellent in skin-beautifying effects such as prevention/amelioration of skin roughness, dry skin, wrinkles, sagging and flecks of skin, and improvement of turnover of corneum; and in an ameliorating effect on skin diseases such as atopic dermatitis. An external preparation for skin which contains one or more compounds selected from the group consisting of 5-aminolevulinic acid, its salt and a derivative of them; and an iron compound; as active components, is used.


Patent
SBI ALApromo Co. | Date: 2011-04-06

The present invention is intended to provide an agent for treating male infertility which is highly effective to male infertility, and having few side effects. To achieve the object, an agent for treating male infertility comprising -amino levulinic acid shown by general formula (1), its derivative or salt thereof:R^(2)R^(1)NCH_(2)COCH_(2)CH_(2)COR^(3)(1)[wherein R^(1) and R^(2) independently represent a hydrogen atom, alkyl group, acyl group, alkoxycarbonyl group, aryl group, or aralkyl group; R^(3) represents a hydroxy group, alkoxy group, acyloxy group, alkoxycarbonyloxy group, aryloxy group, aralkyloxy group or amino group] can be used.


Trademark
SBI Pharmaceuticals Co. and SBI ALApromo Co. | Date: 2012-07-03

Cosmetics; skin soap; dentifrices; laundry bleach; fabric softeners for laundry use; shoe cream; shoe black; polishing preparations; perfumery. Pharmaceutical preparations containing aminolevulinic acid for use in dermatology; nutritional additives for medical purposes in the form of tablets, pills, capsules, powder, liquid, jelly and blocks, whose main ingredients is aminolevulinic acid, all for use in foods and dietary supplements for human consumption; capsules sold empty for pharmaceuticals; gauze for dressings; eyepatches for medical purposes; surgical ear bandages; absorbent cotton for medical purposes; adhesive medical plasters; bandages for dressings; pharmaceutical preparations for wounds, namely, collodion containing aminolevulinic acid; powdered flour milk containing lactose and aminolevulinic acid for babies. Edible oils and edible fats; proteins being foodstuffs for human consumption; milk products excluding ice cream, ice milk and frozen yogurt; charcuterie; processed seafood; processed vegetables and fruits; soya milk; tofu; fermented natto soybeans.


Patent
SBI ALApromo CO. and Kochi University | Date: 2011-01-12

Provided is a sensitizing detection agent of an oral or intravenous administration type which enables the detection of bladder cancer with a higher sensitivity without causing pain to the patient. A sensitizing detection agent for bladder cancer comprising 5-aminolevulinic acid (ALA), a derivative thereof, or a salt of these is orally or intravenously administered, and a video camera system is inserted via the urethra and a blue light at 380-440 nm is irradiated to observe the red fluorescent part. Further, VLD-M1 is inserted and a blue light at 405 nm is irradiated to observe fluorescence intensity (relative intensity) of the red light part. For oral administration, 20 mg/kg (maximum of 1 g) of ALA is dissolved in 50 mL of a 5% glucose solution prior to the administration.

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