日本日油NOF 藥用的修飾性PEG

日本日油NOF 藥用的修飾性PEG

NOF produces the world’s best quality Activated PEGs from our high-quality methoxypoly(ethylene glycol) (mPEG). NOF also supplies our proprietary high-purity branched, multi-arm and hetero-functional Activated PEGs tailored to meet our customers’ PEG Drugs. NOF can supply Activated PEGs produced under GMP standards in our state-of-the-art GMP facility. NOF can help you to modify your drugs by using our PEGylation technology and our high-quality Activated PEGs.

Nof從我們的高質量甲氧基聚乙二醇(MPEG)中生產出世界上優質的活化支架.NOF還提供我們的專利高純度分支,多臂和異功能活化釘定制,以滿足我們的客戶的PEG藥物。在我們先進的gmp設施中,Nof可以提供按GMP標準生產的活化釘.Nof可以通過使用我們的PEG化技術和我們的高質量的激活釘來幫助您修改您的藥物。

Activated PEGs
Overview
PEGylation
Functional Group
Quality
GMP Supply
Custom Mfg
Overview
NOF has been producing a high-quality activated PEGs, SUNBRIGHT series, which possess the most suitable quality for preparation of physiologically active drug and biologics. SUNBRIGHT series are characterized as extremely high-purity PEGs with a variety of functional groups, whereby the products of this series are recognized as optimal PEGylation drugs. As illustrated in this figure, application of the activated PEGs with various functional groups enable introduction of the PEG chains into drugs, enzymes, phospholipids and other biologics. Covalent conjugation of hydrophobic macromolecules with activated PEGs leads to the formation of macromolecular micelles (Polymer Micelles), which allow homogeneous dispersion of hydrophobic drugs in aqueous media. Furthermore, when the PEGylated phospholipids are used as liposomes, the aqueous layer can be added to its surface, with homogeneous dispersal of the liposome preparations encapsulating drugs within them.

As stated above, PEGylation plays an important role in the stabilization of drugs, reduction of their antigenicity and decrease in the drug doses, besides augmenting the targeting ability via binding biologics onto their surfaces. We can do supply our activated PEGs from small scale reagent grade to huge amount GMP grade with high purity.

 

PEGylation
PEGylation technology is applied for biologics modifications such as cytokines, antibody fragment, interleukins, hormones, oligonucleotides and some of proteins and peptides.

PEGylation can be effected to

Improving Bioavailability
Prolonging Blood Circulation
Maximizing Pharmacokinetics
Low-profiling Immunogenicity
NOF provides high-performance activated PEGs for PEGylated drugs from early development stage to commercial use with our 20 years of experience of manufacturing high-quality methoxy polyethylene glycol, which is a starting material of activated PEG for pharmaceutical area. Our activated PEGs have a narrow polydisperity and low diol content with wide range of molecular weight, from 2kDa to 80kDa.

PEG -conjugation
Analysis of PEG-ALD-Insulin by SDS-PAGE with Coomassie brilliant blue. Insulin was reacted with NOF PEG-ALD at 4°C. The PEGylated insulin was purified on Q Sepharose Fast Flowcolumn.

 

lane M molecular weight markers
lane 1 Insulin
lane 2 PEG(ME-050AL)-insulin eluate
lane 3 PEG(ME-100AL)-insulin eluate
lane 4 PEG(ME-200AL)-insulin eluate
lane 5 PEG(ME-300AL)-insulin eluate
Coupling of PEG derivatives to Proteins: examples of conditions

Coupling of PEG-NHS derivatives to protein amines (PEG-NHS + Protein-NH 2) Conditions 1: 50 mM phosphate buffer (pH 7.2), 4℃, 6 hrs *1)
Conditions 2: Borate-phosphate buffer (pH 8.0), 25℃, 2 hrs *2)
Coupling of PEG-Aldehyde derivatives to the NH 2 group of proteins (PEG-Ald + Protein-NH 2)
Conditions : sodium cyanoborohydride (10 eq . .), 4 deg C, 20 hrs *3)
Coupling of PEG-Maleimide derivatives to the SH group of proteins (PEG-Maleimide + Protein-SH)
Conditions: 100 mM phosphate buffer (pH 6.5), 4 deg C, 4 hrs
Coupling of PEG-NH 2 derivatives to the COOH group of proteins (PEG-NH 2 + Protein-COOH)
Conditions: 50mM phosphate buffer (pH 7.2), WSC (2 eq.), 4 deg C, 10 hrs
Coupling of PEG-p-Nitrophenyloxycarbonyl derivatives to the NH 2 group of proteins (PEG-NP + Protein-NH 2)
Conditions: borate-phosphate buffer (pH 8.0-8.3), r.t, overnight *2)
References:
*1) Abuchowski, A., et al. (1984) Cancer Biochem. Biophys. 7, 175.
*2) Sartore, L., et al. (1991) Appl. Biochem. Biotechnol. 27, 45
*3) US 5,824,784
Functional Group
We supply different series of PEG derivatives with various versatile functional groups.

Quality

Purity of NOF’s activated products
We use our advanced technologies to measure the quality of our activated PEGs. The following are the typical analysis data for each type of activated PEGs which are measured by NMR or HPLC methods. Please note that those numbers are not specification of the product.

NHS type

CS type mPEG-succinimidyl succinate (Mw 2k and 5k) : activity over 95% (NMR)

GS type mPEG-succinimidyl glutarate (Mw 5k, 10k, 20k, 30k and 40k) : activity around 95% (NMR)

AS type mPEG-succinimidyl methyl ester (Mw 2k and 5k) : activity around 95% (NMR)

HS type mPEG-succinimidyl pentyl ester(Mw 5k, 10k, 20k, 30k and 40k): activity around 95% (NMR)

TS type mPEG-succinimidyl carbonate(Mw 5k, 10k, 12k, 20k, 30k and 40k): activity over 95% (HPLC)

pNP type (NP series)

mPEG-p-nitrophenyl (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity over 95% (HPLC)

Aldehyde type(AL series)

mPEG-propylaldehyde (Mw 5k, 10k, 20k, 30k and 40k): activity over 85% (HPLC). The activity for Mw20k, it is over 92% as actual data by HPLC.

Amine type

PA type mPEG-propylamine (Mw 2k, 5k, 10k, 12k, 20k, 30k and 40k): activity over 95% (HPLC)

EA type mPEG-ethylamine (Mw 5k, 10k, 20k, 30k and 40k): activity over 95% (HPLC)

thiol type(SH series)

mPEG-thiol (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Maleimide type(MA series)

mPEG-maleimide (Mw 2k, 5k, 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Oxyamine type(CA series)

mPEG-oxyamine (Mw 10k, 20k, 30k and 40k): activity around 95% (HPLC)

Iodoacetoamide type(IA series)

mPEG-irdoacetoamide (Mw 20k, 30k and 40k): activity around 90% (HPLC)

Analytical Technology

NOF has more than 20 years history for manufacturing of high-quality mPEGs and Activated PEGs. These experiences enable NOF to have thorough knowledge of PEGs and considerable achievement in analysis of Activated PEGs. We also have invented innovative analytical methods for assaying purity of activated PEGs and for determining impurity levels. (*Patent No.: JP4543917) Previously, the activity for activated PEGs is measured by NMR. However, this method is not very good detection due to polymer, especially for high molecular weight. We developed the analysis method by using HPLC. As the result of the analysis, the activity sometime seems lower than the result of NMR because main peak can completely separate from non-active peak and activated impurity peaks (like dimer).

HPLC analysis for M-PEG-COOH

GPC Analysis of M-PEG5K and M-PEG-30K

MALDI-TOF-MS Analysis of M-PEG5K and M-PEG-30K

GMP Supply

cGMP Manufacturing Facilities
NOF Activated PEGs, SUNBRIGHT? series are produced in facilities with state-of-the-art technology, operated under cGMP. The cGMP facilities are capable of producing small to large batch sizes, using proprietary know-how on scale-up procedure, depending on customers’ needs. These cGMP facilities have been audited by pharmaceutical companies throughout the world. NOF receives high reputation from our customers.

Research & Development
Our R&D facility was opened in December 2005. This allows us to continue our development of novel activated PEGs and technologies for PEGylation.
Custom Mfg
Research & DevelopmentOur R&D facility was opened in December 2005. This allows us to continue our development of novel activated PEGs and technologies for PEGylation.

Custom Manufacturing

NOF has over 20 years of experience in supplying high-quality methoxy polyethylene glycol (mPEG) for pharmaceutical market. The mPEG is starting material of PEG derivatives, which are patented through our proprietary technology. Based on extensive range of technological know-how and capabilities, NOF offers custom manufacturing of Activated PEGs from early stage development to commercial scale. Sizewise, we can offer gram size synthesis to kg size for non GMP product. We also offer cGMP custom synsthesis.

Please feel free to contact us :?Contact form
1. Mono-functional Linear PEGs
2. Bi-Functional PEGs
3. Multi-Arm PEGs
4. Branched PEGs
5. Forked PEGs
6. Heterofunctional PEGs
7. Single Molecule PEGs PUREBRIGHT? Series
8. Poly-Hydroxyl Activated PEGS
10. Biodegradable Polymers for gene / nucleic acid Delivery SUNBRIGHT? ME-DT & DT series
11. Biodegradable block polymer for drug delivery
12.PEGylation Service

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PUREBRIGHT? 2TS-B12-AZ

Molecular weight: 1555.66

PUREBRIGHT? 2TS-B12-BO

Molecular weight: 1530.65

PUREBRIGHT? 2TS-B12-DB

Molecular weight: 1717.85

PUREBRIGHT? 2TS-B12-MA

Molecular weight: 1581.65

PUREBRIGHT? A-L08-PC

X = 8 Molecular weight: 441.51

PUREBRIGHT? A-L12-PC

X=12 Molecular weight: 617.72

PUREBRIGHT? BO-L08-PC

X=8 Molecular weight: 541.63

PUREBRIGHT? BO-L12-PC

X=8 Molecular weight: 717.84

PUREBRIGHT? MA-L08-PC

X=8 Molecular weight: 592.63

PUREBRIGHT? MA-L08-PS

X=8 Molecular weight: 689.71

PUREBRIGHT? MA-L12-PC

X=12 Molecular weight: 768.84

PUREBRIGHT? MA-L12-PS

X=12 Molecular weight: 865.92

日本油脂株式會社(日油)(NOF CORPORATION)代理

日本油脂株式會社(日油)(NOF CORPORATION)代理

日本日油代理

日本日油NOF代理

Business Overview

Oleo & Speciality Chemicals/Functional Products Combining Advanced Oleochemistry With Petrochemicals

自1910年成立以來,作為日本油化學領域的先驅,油化企業一直是該行業的領頭羊。

油化業務是NOF集團的核心業務,該集團作為石油化學的先驅,在日本一直處于該領域的領先地位。

目前,除油酸及其衍生物、表面活性劑等油化產品外,還有多種以環氧乙烷衍生物、(甲基)丙烯酸酯等為基礎的功能性產品。在石油化學領域,資源、環境和能源領域、電子和信息技術領域、醫療保健領域等技術創新已成為新興領域的發展方向。

今后,油化企業不僅將在油脂、新材料等領域尋求更大的發展潛力,而且將在長期積累的原有技術基礎上,在油化學、石化等多個領域開發高功能、高附加值的產品,以高技術拓展這些增長領域的業務。

Functional Chemicals & Polymers/Using Inventive Approaches to Open Up New Chemical Fields

Functional Chemicals & Polymers Division has being expanding organic peroxides business since the start of production in 1957, and we are now developing various businesses based on organic peroxides, functional polymers and petrochemicals.

NOF CORPORATION has become a world leading manufacturer of organic peroxides by continuous R&D for new products and applications in this field.

In the business of functional polymers, we develop high performance polymers such as unique graft and block copolymers applied to the improvement of plastics and other synthetic resins.

In the business of petrochemicals, we produce polybutene, isoparafin-baced odorless solvents and other products, which make a substantial contribution to the various industrial field.

We will continue to focus on the cutting edge materials for the next-generation technology and develop the frontier of chemistry by innovation.

自1957年開始生產以來,功能化學品和聚合物部門一直在擴大有機過氧化物業務,目前我們正在開發各種基于有機過氧化物、功能聚合物和石油化學品的業務。

Nof公司已成為世界領先的有機過氧化物制造商,通過不斷研發新產品和在這一領域的應用。

在功能聚合物行業中,我們開發了高性能的聚合物,如獨特的接枝共聚物和嵌段共聚物,用于改善塑料和其他合成樹脂。

在石化行業,我們生產聚丁烯、異氰酸酯無味溶劑等產品,為各種工業領域做出了巨大貢獻。

我們將繼續專注于下一代技術的尖端材料,以創新開拓化學前沿。

Functional Foods/Creating Wider Choice of Tasty and Healthy Food Products

Business Overview

Business Overview

The Functional Foods Division has always been a pioneer in the innovations in edible oils and fats re-fining and processing techniques since it was established in 1917. At present, it is expanding its business areas such as processing oils and fats for food and the health related business.

The processing of oils and fats for food contributes widely to the food industry by striving for the development of products in pursuit of deliciousness based on the technologies cultivated as a pioneer of processing oils and fats such as margarine, shortening, refined fat for confectionery use, depanning oil, filling and topping materials, powder oils and fats, and materials for cooking and frozen foods.

The health related business has developed one new product after another such as functional lipids, emulsifying and nano-emulsion products, oils and fats coating products, and external nutritional products while striving for steady researches to provide the society with health.

The Functional Foods Division will supply products which can contribute to the society by enriching people’s “food culture” step by step, tasty and healthy.

自1917年成立以來,功能食品部一直是食用油和油脂精制和加工技術創新的先驅。目前,該公司正在擴大其業務領域,如食品加工油脂和與健康有關的業務。

食品油脂的加工為食品工業作出了廣泛的貢獻,致力于開發追求美味的產品,這些技術是作為加工油脂的先驅而培育的,如人造黃油、酥油、糖果用精制脂肪、脫皮油、填充和澆頭材料、粉末油和脂肪以及烹飪和冷凍食品材料。

健康相關企業在不斷開發功能油脂、乳化納米乳液產品、油脂包衣產品、外營養產品等一系列新產品的同時,努力尋求穩定的研究,為社會提供健康。

功能食品部將提供能為社會做出貢獻的產品,逐步豐富人們的“食品文化”,美味可口,健康。

DDS Development/Playing Our Part in the DDS Revolution With High-purity Materials and New Technologies

?1. PEGylation for PEG-Drug
NOF produces the world’s best quality Activated PEGs from our high-quality methoxypoly(ethylene glycol) (mPEG). NOF also supplies our proprietary high-purity branched, multi-arm and hetero-functional Activated PEGs tailored to meet our customers’ PEG Drugs. NOF can supply Activated PEGs produced under GMP standards in our state-of-the-art GMP facility. NOF can help you to modify your drugs by using our PEGylation technology and our high-quality Activated PEGs.

 

?2. Phospholipid and Liposome
NOF supplies the high-purity phospholipids which have been produced under GMP operation since the 1990’s with good reputation from worldwide customers.
NOF supplies purified egg PC, egg PG, soy PC, hydrogenated soy PC and sphingomyelin for natural phospholipids.
NOF supplies following synthetic phospholipids,

  • PC series: DDPC, DLPC, DMPC, DPPC, DSPC, DOPC, POPC, DEPC
  • PG series: DMPG, DPPG, DSPG, POPG
  • PA series: DMPA, DPPA, DSPA
  • PE series: DMPE, DPPE, DSPE, DOPE
  • PS series: DOPS

PEG or polyglycerin attached phospholipids (PEG phospholipid) are available for long circulating liposome formulations.
Activated functional group attached phospholipids either PEG end or non PEG end are also available for immunoliposome or targeting use liposome.
NOF also offers custom-made synthesis of phospholipid and provide unique liposome research kit (Empty liposome) for drug delivery systems (DDS).

 

?3. Ultra-Purity Polysorbate 80
Polysorbate 80(HX)™ of NOF is ultra-purity Polysorbate 80 for injectable grade which has outstanding features as follows;

  • Low Allergic Reaction (Low degranulation characteristics)
  • Low Cell Toxicity and Low Hemolysis
  • Low Peroxide, Colorless and Odorless
  • Vegetable Source (No animal sources)
  • Multi-Compendial (NF (USP), EP and JP)

Our Polysorbate 80(HX)™ has an outstanding safer characteristic and will be a world wide standard product in pharmaceutical especially for injectable purpose.