MG Pharma Inc.

Ōsaka, Japan

MG Pharma Inc.

Ōsaka, Japan
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Abe M.,Tokyo Medical University | Abe M.,MG Pharma Inc. | Yuki Y.,Tokyo Medical University | Yuki Y.,Tokyo International University | And 8 more authors.
Journal of Biotechnology | Year: 2014

Tumor necrosis factor alpha (TNF) plays a pivotal role in chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. Although anti-TNF antibody therapy is now commonly used to treat patients suffering from these inflammatory conditions, the cost of treatment continues to be a concern. Here, we developed a rice transgenic system for the production of a llama variable domain of a heavy-chain antibody fragment (VHH) specific for mouse TNF in rice seeds (MucoRice-mTNF-VHH). MucoRice-mTNF-VHH was produced at high levels in the rice seeds when we used our most recent transgene-overexpression system with RNA interference technology that suppresses the production of major rice endogenous storage proteins while enhancing the expression of the transgene-derived protein. Production levels of mTNF-VHH in rice seeds reached an average of 1.45% (w/w). Further, approximately 91% of mTNF-VHH was released easily when the powder form of MucoRice-mTNF-VHH was mixed with PBS. mTNF-VHH purified by means of single-step gel filtration from rice PBS extract showed high neutralizing activity in an in vitro mTNF cytotoxicity assay using WEHI164 cells. In addition, purified mTNF-VHH suppressed progression of collagen-induced arthritis in mice. These results show that this rice-expression system is useful for the production of neutralizing VHH antibody specific for mTNF. © 2014 Elsevier B.V.


Sasakawa Y.,MG Pharma Inc. | Nakao M.,MG Pharma Inc. | Yamamoto K.,MG Pharma Inc. | Fukuhama C.,MG Pharma Inc.
Japanese Pharmacology and Therapeutics | Year: 2015

Magnesium is a food with nutrient function claims (FNFC) in Japan, but the effect of magnesium (Mg) hydroxide containing Mg of the amount of the FNFC limit on the blood pressure was unknown. In the present study, the effect of the combination of magnesium (Mg) hydroxide with globin digest (GD), an oligopeptide mixture derived from edible globin proteins, on the blood pressure and life span in stroke-prone spontaneously hypertensive rats (SHRSP/Izm: SHRSP) was examined. Male SHRSP at 6 weeks of age were fed a diet containing the combination of Mg hydroxide (1.22 wt%, as Mg 0.51 wt%) with GD (1.67 wt%) for 27 weeks. The elevation of the systolic blood pressure in SHRSP was suppressed after ingestion of the combination of Mg hydroxide with GD compared with the control group. The combination of Mg hydroxide with GD extended the life span in SHRSP compared with the control group. These findings indicate that the combination of Mg hydroxide with GD has the antihypertensive effect and protective effect against stroke in SHRSP.


Fukuhama C.,MG Pharma Inc. | Tsuruta R.,MG Pharma Inc. | Fukuhara I.,Fukuhara Clinic
Japanese Pharmacology and Therapeutics | Year: 2016

Globin digest (GD), an oligopeptide mixture derived from edible globin proteins, used as Food for Specified Health Use (FOSHU) in Japan, Health Food in China and Functional Food in Korea. We have reported that the combination of magnesium hydroxide and GD has the antihypertensive effect in spontaneously hypertensive rats and protective effect against stroke in stroke-prone spontaneously hypertensive rats. The present clinical study attempted to evaluate the hypotensive effect and the safety of magnesium hydroxide and GD in a double blind, placebo-controlled, parallel group study. The study was conducted on 42 subjects with mild hypertension (male/female =16/26). These subjects were randomly divided into two groups. The test group ingested the supplements containing magnesium hydroxide 700 mg/day (as Mg 292 mg/day) and GD 1000 mg/day. Control group ingested this active placebo. Each group was given 6 tablets by orally twice a day for 8 weeks. After 8 weeks ingestion, the systolic blood pressure and the diastolic blood pressure of the test group were significantly suppressed 7.6 mmHg (P<0.01) and 3.1 mmHg (P<0.05) compared to 0 week values. Any abnormal changes in clinical findings such as blood test, urinalysis and physical examination were not observed. These results demonstrated that the supplements containing of magnesium hydroxide and globin digest are safety and useful for suppressing blood pressure in the subjects with mild hypertension. (Jpn Pharmacol Ther 2016 ; 44 : 101-11).


Nakaoka F.,MG Pharma Inc | Sasakawa Y.,MG Pharma Inc | Yamamoto K.,MG Pharma Inc | Nakao M.,MG Pharma Inc | And 4 more authors.
Life Sciences | Year: 2010

Aims: Leu-Ser-Glu-Leu (LSEL) is the main active ingredient of globin digest (GD) that has an anti-diabetic effect. Here, we investigated the anti-diabetic effect of LSEL for the first time. Main methods: The anti-diabetic effects of GD and LSEL in ICR mice, streptozotocin (STZ)-induced diabetic mice and KK-Ay mice were examined. Key findings: GD and LSEL suppressed the elevation of blood glucose in an oral glucose tolerance test (OGTT) in ICR mice, STZ-induced diabetic mice and KK-Ay mice as well as in an oral sucrose tolerance test in ICR mice and in an insulin tolerance test (ITT) in KK-Ay mice. GD and LSEL decreased the blood glucose levels in the basal state in STZ-induced diabetic mice and KK-Ay mice. Furthermore, GD and LSEL elevated the serum insulin levels in an OGTT in ICR mice and KK-Ay mice and promoted the use of insulin in an ITT in KK-Ay mice. GD and LSEL increased the translocation or expression of the glucose transporter 4 in the muscle of ICR mice, STZ-induced diabetic mice and KK-Ay mice and increased the expression of the uncoupling protein 2 (UCP2) in the muscle of ICR mice. Significance: These results indicate that GD and LSEL control blood glucose through the promotion of glucose uptake in the muscle of the mice. The acceleration of glucose uptake by GD and LSEL may be controlled by the promotion of insulin secretion and the up-regulation of UCP2 expression. GD and LSEL seem to be useful for lowering the incidence of hyperglycemia. © 2010 Elsevier Inc.


Sasakawa Y.,MG Pharma Inc. | Nakao M.,MG Pharma Inc. | Yamamoto K.,MG Pharma Inc. | Fukuhama C.,MG Pharma Inc.
Japanese Pharmacology and Therapeutics | Year: 2015

Globin digest (GD), an oligopeptide mixture derived from edible globin proteins, improved hyperlipidemia and hyperglycemia in human and other mammals, and is used as Food for Specified Health Use (FOSHU) in Japan and Health Food in China, but the effect of GD on the blood pressure was unknown. In the present study, the effect of GD on the blood pressure in spontaneously hypertensive rats (SHR/Izm: SHR) was examined. At first, GD was administered orally once to SHR (15-18 weeks old). GD (500 mg and 1000 mg/kg body weight) suppressed the systolic blood pressure in SHR after a single administration. Next, SHR (7 weeks old) were fed a diet containing GD (0.5 wt%), magnesium (Mg) hydroxide (1.95 wt%, as Mg 0.81 wt%) or the combination of Mg hydroxide with GD for 12 weeks. The elevation of the systolic blood pressure in SHR was suppressed by GD or Mg hydroxide and most suppressed by the combination of Mg hydroxide with GD. GD inhibited the activity of angiotensin-converting enzyme in vitro. These findings indicate that GD has the antihypertensive effect and more effective by use with Mg in SHR.


Yamamoto K.,MG Pharma Inc. | Sasakawa Y.,MG Pharma Inc. | Nakaoka F.,MG Pharma Inc. | Nakao M.,MG Pharma Inc. | And 5 more authors.
Life Sciences | Year: 2011

Aims: We investigated the effect of globin digest (GD) on the liver injury and hepatic gene expression profile in galactosamine (GalN)-induced liver injury. Main methods: The effect of GD on the liver injury was examined by measuring the activities of serum transferases and hepatic antioxidant enzymes, histopathological analysis, gene expression profile, and proteins of the peroxisome proliferator-activated receptor alpha (PPARα) and met proto-oncogene (c-Met) in SD rats at 24 h after GalN administration. The effect of GD on the expression of PPARα and its target gene in AML-12 mouse hepatocytes was also examined. Key findings: GD suppressed the elevated activities of serum transferases in GalN-induced liver injury in SD rats. The thiobarbituric acid reactive substance content in GalN-injured liver was a decreasing tendency by GD. GD suppressed the increased oxidized glutathione content, and increased the decreased protein, reduced glutathione contents, and catalase activity in GalN-injured liver. GD may improve the antioxidant defense system and protein synthesis in GalN-injured liver. GD suppressed the elevated expression of the genes related to the inflammation, and decreased the histopathological grade value of inflammatory cell infiltration in GalN-injured liver. GD increased the expression of PPARα protein in GalN-injured liver, and also increased the expression of PPARα and its target gene in AML-12 hepatocytes. The total and phosphorylated c-Met proteins in GalN-injured liver were the increasing tendencies by GD. Significance: These findings indicate that GD has the hepatoprotective effect on GalN-induced liver injury in SD rats. © 2011 Elsevier Inc.


Patent
Mg Pharma Inc. | Date: 2011-07-06

The present invention provides a composition (a blood glucose increase inhibitor) that has an effect of lowering blood glucose level in a hyperglycemic patient and that is therefore used to reduce blood glucose level in the patient. The present invention further provides a composition that is used to prevent or treat diseases caused by hyperglycemia, in particular, diabetes and diabetic complications (a composition for preventing or treating diseases caused by hyperglycemia, an antidiabetic), based on the above-mentioned effect. A feature of the present invention is using a peptide consisting of the amino acid sequence of Leu-Ser-Glu-Leu as an active ingredient.


Patent
Mg Pharma Inc. | Date: 2010-04-28

The present invention provides an anti-hypertensive agent. The anti-hypertensive agent of the present invention contains, as an active ingredient, at least one peptide selected from the group consisting of peptides originally derived from globin proteolysate, each of which consists of one of the following amino acid sequences (1) to (6), or a globin proteolysate containing at least one of the peptides: (1) Val-Val-Tyr-Pro (SEQ ID: NO. 1); (2) Trp-Gly-Lys-Val-Asn (SEQ ID: NO. 2); (3) Trp-Gly-Lys-Val (SEQ ID: NO. 3); (4) Trp-Gly-Lys (SEQ ID: NO. 4); (5) Ala-Ala-Trp-Gly-Lys (SEQ ID: NO. 5); and (6) Phe-Glu-Ser (SEQ ID: NO. 6).


PubMed | MG Pharma Inc.
Type: Journal Article | Journal: Life sciences | Year: 2011

We investigated the effect of globin digest (GD) on the liver injury and hepatic gene expression profile in galactosamine (GalN)-induced liver injury.The effect of GD on the liver injury was examined by measuring the activities of serum transferases and hepatic antioxidant enzymes, histopathological analysis, gene expression profile, and proteins of the peroxisome proliferator-activated receptor alpha (PPAR) and met proto-oncogene (c-Met) in SD rats at 24 h after GalN administration. The effect of GD on the expression of PPAR and its target gene in AML-12 mouse hepatocytes was also examined.GD suppressed the elevated activities of serum transferases in GalN-induced liver injury in SD rats. The thiobarbituric acid reactive substance content in GalN-injured liver was a decreasing tendency by GD. GD suppressed the increased oxidized glutathione content, and increased the decreased protein, reduced glutathione contents, and catalase activity in GalN-injured liver. GD may improve the antioxidant defense system and protein synthesis in GalN-injured liver. GD suppressed the elevated expression of the genes related to the inflammation, and decreased the histopathological grade value of inflammatory cell infiltration in GalN-injured liver. GD increased the expression of PPAR protein in GalN-injured liver, and also increased the expression of PPAR and its target gene in AML-12 hepatocytes. The total and phosphorylated c-Met proteins in GalN-injured liver were the increasing tendencies by GD.These findings indicate that GD has the hepatoprotective effect on GalN-induced liver injury in SD rats.


PubMed | Tokyo International University, MG Pharma Inc., Japan National Agriculture and Food Research Organization, Tokyo Medical University and Heinrich Heine University Düsseldorf
Type: | Journal: Journal of biotechnology | Year: 2014

Tumor necrosis factor alpha (TNF) plays a pivotal role in chronic inflammatory diseases such as rheumatoid arthritis and Crohns disease. Although anti-TNF antibody therapy is now commonly used to treat patients suffering from these inflammatory conditions, the cost of treatment continues to be a concern. Here, we developed a rice transgenic system for the production of a llama variable domain of a heavy-chain antibody fragment (VHH) specific for mouse TNF in rice seeds (MucoRice-mTNF-VHH). MucoRice-mTNF-VHH was produced at high levels in the rice seeds when we used our most recent transgene-overexpression system with RNA interference technology that suppresses the production of major rice endogenous storage proteins while enhancing the expression of the transgene-derived protein. Production levels of mTNF-VHH in rice seeds reached an average of 1.45% (w/w). Further, approximately 91% of mTNF-VHH was released easily when the powder form of MucoRice-mTNF-VHH was mixed with PBS. mTNF-VHH purified by means of single-step gel filtration from rice PBS extract showed high neutralizing activity in an in vitro mTNF cytotoxicity assay using WEHI164 cells. In addition, purified mTNF-VHH suppressed progression of collagen-induced arthritis in mice. These results show that this rice-expression system is useful for the production of neutralizing VHH antibody specific for mTNF.

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