NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity(up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
NMN was only considered as a source of cellular energy and an intermediate in NAD+ biosynthesis, currently, the attention of the scientific community has been paid on anti-aging activity and a variety of health benefits and pharmacological activities of NMN which are related to the restoring of NAD+. Thus, NMN has therapeutic effects towards a range of diseases, including age-induced type 2 diabetes, obesity, cerebral and cardiac ischemia, heart failure and cardiomyopathies, Alzheimer’s disease and other neurodegenerative disorders, corneal injury, macular degeneration and retinal degeneration, acute kidney injury and alcoholic liver disease.
1、“Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability of production of NMN powder
3、Industrial leading technology: 15 domestic and international NMN patents
4、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMN powder
5、Multiple in vivo studies show that Bontac NMN powder is safe and effective
6、Provide one-stop product solution customization service
7、NMN raw material supplier of famous David Sinclair team of Harvard University.
NMN powder in general is typically produced via chemical or enzymatic synthesis, or fermentation biosynthesis. There are pros and cons to all three methods.
Chemical synthesis is expensive and labor intensive, and all raw ingredients used are categorized as “unnatural,” i.e., not from biological systems. There are, however, some advantages from the manufacturer’s perspective. The yield is well suited to mass NMN powder production, and all of those unnatural raw ingredients can be carefully controlled. But there are a number of drawbacks as well. Some of the solvents used in the manufacturing process are seriously bad from an environmental standpoint, and impurities and by-products can be challenging to remove from the finished product – that’s seriously bad for the consumer.
Enzymatic production of NMN powder, on the other hand, is considered a “green preparation method.” Like the chemical route, it’s pricey, but it offers a higher yield and impressively high purity. The finished NMN ticks all the boxes – stable, easily absorbed, lightweight, low density, and a low molecular structure.
Fermentation has also been explored as a method of producing NMN, but yield, though high quality, is pretty abysmal, so many supplement companies quite sensibly look to other, more efficacious processes.
Aging, as a natural process is identified by downregulation of energy production in mitochondria of various organs such as brain, adipose tissue, skin, liver, skeletal muscle and pancreas due to the depletion of NAD+ . NAD+ levels in the body decrease as a consequence of increasing NAD+ consuming enzymes when aging There are three different biosynthesis pathways to produce NAD+ in mammalian cells including de novo synthesis from tryptophan, salt and Preiss-Handler pathways. Among these three pathways, NMN is an interproduct by is involved in NAD+ biosynthesis through salt and Preiss-Handler pathways. The salvage pathway is the most efficient and the main route for the NAD+ biosynthesis, in which nicotinamide and 5-phosphoribosyl-1-pyrophosphate are converted to NMN with the enzyme of NAMPT followed by conjugation to ATP and conversion to NAD by NMNAT. Furthermore, NAD+ consuming enzymes are responsible for degradation of NAD+ and consequence nt formation of nicotinamide as a by-product.
The safety of NMN powder cannot be assessed since required clinical and toxicological studies have not been completed yet to establish the recommended safe levels for long term administration. Nevertheless, their safety and efficacy are uncertain and unreliable since most of them have not been back by Rigorous scientific preclinical and clinical testing. This issue has been arisen as manufacturers are hesitant to pay for research and clinical trials due to potential lower profit margin, and there is no authorizing agency to regulate NMN products because it is often product sold as functional food than heavily regulated therapeutic drug. Therefore, more strict approval process has been demanded by consumer advocacy groups requesting regulatory agencies to set standard and restrictions for marketing anti-aging health products, considering safety, health and wellbeing of N red besumers. a panacea for the elderly, because boosting NAD levels when not required may yield some detrimental effects. Therefore, the dose and frequency of NMN supplementation should be carefully prescribed depending on the type of age-related deficiency and all other confronting health conditions of the people. Other NAD precursors over have been studied to diverse age-related deficiencies and they are used for particular deficiencies, only after they are proven for effectiveness and safe to use. Therefore, the same principle should be applied to NMN as well
First, inspect the factory. After some screening, NMN companied that directly face consumers pay more attention to brand building. Therefore, for a good brand, quality is the most important thing, and the first thing to control the quality of raw materials is to inspect the factory. Bontac company actually manufacturing NMN powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NMN powder. If high purity NMN cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMN powder produced by Bontac reach the purity of 99.9%. Finally, a professional test spectrum is needed to prove it. Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound ca n be preliminarily determined.
1. Introduction On January 9, 2024, the expert team of selection organizing committee from Deloitte visited BONTAC, and presented the trophy of “China Life Sciences & Healthcare Rising Star” to BONTAC on site. By virtue of its unique and innovative technology in the field of coenzymes, professional R&D team with rich experience, and excellent performance in the industry of biosynthesis, BONTAC has stood out from the crowd and won the award of "Deloitte China Life Sciences & Healthcare Rising Star". 2. 2023 Deloitte China Life Sciences & Healthcare Rising Star Since the launch of “Deloitte China Life Sciences & Healthcare Rising Star” campaign by the end of June 2023, extensive attention has been attracted by the Chinese medicine and health industry. Following verification by site visit of the enterprises, 50 enterprises with prominent comprehensive strength are finally determined to be eligible, which are subjected to rigorous review of multiple dimensions such as financial asset valuation, founding team, technical innovation, market prospect, industrial rank, etc. The awarded enterprises in this selection campaign encompass the advanced enterprise in the niche areas of life sciences and healthcare, who comprehensively display their multiple innovation achievements in the field of life sciences and healthcare. The “Deloitte China Life Sciences & Healthcare Rising Star” selection campaign is a key subproject of Deloitt on the selection project of high-tech and fast-growing enterprises, aiming to recognize and award the outstanding enterprises who take the lead in their niche areas of life sciences and healthcare and have great growth potential. 3. The candidate enterprises must meet the the following criteria: * Business headquartered within China Mainland, Hong Kong or Macao. * Own leading technology and viable business models. * Have extensive growth potential with a leading position in their niche segments. 4. Current situation on Chinese medicine and health industry The technical innovation and product quality in Chinese medicine and health industry have continuously improved, which is driven by healthcare reform policies, emerging technologies and capital markets. In China, independent innovation has penetrated into all tracks of the major health industry, which greatly promotes the research and development of domestically produced innovative medicines and medical technologies. Substantial promising innovative enterprises has emerged and gradually gained recognition in the global market, ranking among the first echelon of global technological innovation. 5. About BONTAC BONTAC is the pioneer of NMN industry and the first manufacturer to launch NMN mass production, with the first whole-enzyme catalysis technology around the world. At present, BONTAC has become the leading enterprise in niche areas of coenzyme products. Notably, BONTAC is the NMN raw material supplier of famous David Sinclair team at the Harvard University, who uses the raw materials of BONTAC in a paper titled “Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging”. Our services and products have been highly recognized by global partners. Furthermore, BONTAC has the first national and the only provincial independent coenzyme engineering technology research center in Guangdong, China. The coenzyme products of BONTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture. BONTAC adheres to independent innovation, with more than 160 invention patents. In the future, BONTAC will adhere to the innovation-driven concept, continue to increase investment in research and development, dig into the field of synthetic biology, and commit to developing more high-quality raw material products. At the same time, BONTAC will actively expand the international market, and work with global partners to promote the prosperous development of synthetic biology industry. In this era full of challenges and opportunities, BONTAC is confident to make greater contributions to the cause of human health.
1. Introduction The NAD precursor nicotinamide mononucleotide (NMN) shows a beneficial effect on ageing, yet excessive NMN accumulation may lead to axon degeneration. How to make the anti-ageing effect of NMN compatible with axonal degeneration caused by NMN accumulation is still a challenge. A preliminary discussion on this issue is conducted in this study. 2. The definition and pathological changes of axonal degeneration Axonal degeneration refers to degenerative changes in the axon as a result of direct damage to the primary or as a result of diseases such as neuronal metabolic disorders, which is a common pathological change of the nervous system. The pathological changes after axonal injury include axonal swelling, fracture, retraction and atrophy. 3. The relationship between NMN and sterile alpha and TIR motif–containing 1 (SARM1) SARM1 is a multi-functional enzyme with base exchange activity, which can cleave nicotinamide adenine dinucleotide (NAD) into adenosine diphosphate ribose (ADPR), cyclic adenosine diphosphate ribose (cADPR) and nicotinamide (NAM). A substantial body of evidence mirrors that the degenerative enzyme SARM1 will be bound to and be activated by NMN. Hence, failed conversion of sufficient NMN into NAD may give rise to toxic NMN accumulation and axon degeneration. 4. The specific pathway of axon degeneration NMN only induces axon degeneration in the presence of SARM1, placing the toxic accumulation on a common pathway of axon death. Notably, nicotinamide mononucleotideadenylyltransferases (NMNATs) has a broader, compartment-specific regulatory role in SARM1 activity. For instance, NMNAT2 depletion is associated with SARM1 activation in axons. In a nutshell, NMNAT2 depletion can give rise to NMN accumulation. Next, NMN binds to and activates the pro-degenerative protein SARM1, leading to rapid NAD consumption and axon degeneration. 5. The impacts of NAD precursors upon axonal health NAD precursors are likely to be safe for most people, but there is a risk for people with compromised NMNAT activity, as these supplements could cause SARM1 activation and neurodegeneration. In healthy individuals, rapid conversion from NMN into NAD can be accomplished by NMNAT2, which is conductive to the prevention of NMN toxic accumulation and maintenance of healthy neurons and axons. Yet, downregulation of NMNAT2 level or activity may result in the upregulation of NMN, thereby leading to SARM1 activation, increased axonal vulnerability and/or axon degeneration. 6. The factors for SARM1 activity SARM1 activity is regulated by a ratio between NMN and NAD. When NMN rises, partial inhibition of SARM1 is only seen at high concentrations of NAD. Inefficient conversion of NMN into NAD because of compromised NMNAT activity is the most likely scenario in which NMN can become toxic. The change in NMN level close to the physiological concentration has a much more significant impact on SARM1 activity than NAD level. A twofold increase in NAD level is not sufficient to delay axon degeneration after injury, and even higher NAD level only temporarily delays axon degeneration. 7. The interaction between SARM1 activation and ageing effect of NMN Sub-lethal/chronic SARM1 activation could increase axonal vulnerability or have a significant impact upon NAD homeostasis and important intracellular signalling pathways in neurons.It is pivotal for life to preserve NAD homeostasis. Maintaining NAD homeostasis could be a viable anti-ageing strategy. Similarly, NMNAT2 depletion increases axon vulnerability and the level of the NMNAT2 is declined with ageing. These findings signify that SARM1 and NMNAT2 may be the key factor to reconcile the axonal degeneration caused by the accumulation of the NAD precursor NMN and ageing effect of NMN. 8. Conclusion Efficient conversion of NMN into NAD is key to preventing SARM1 activation and neurotoxicity. SARM1 and NMNAT2 may be the intersection factors between axon degeneration and anti-ageing therapy. Reference Loreto, Andrea et al. “NMN: The NAD precursor at the intersection between axon degeneration and anti-ageing therapies.” Neuroscience research vol. 197 (2023): 18-24. doi:10.1016/j.neures.2023.01.004 BONTAC NMN product features and advantages * Industrial leading technology: 15 domestic and international NMN patents * Self-owned factories and a number of international certifications to ensure high quality and stable supply of products * NMN raw material supplier of famous David Sinclair team of Harvard University Disclaimer BONTAC shall hold no responsibility for any claims arising directly or indirectly from your reliance on the information and material on this website.
Introduction The crucial parts of nicotinamide adenine dinucleotide (NAD+) and its metabolites in aging and neurodegeneration have been widely recognized. To spur progress toward biochemical research and interventions targeting aging and neurodegenerative diseases, it is of great significance to accurately quantify NAD+ and its metabolite levels in the NAD+ salvage pathway. Here, a robust and accurate LC-MS/MS method is applied to quantify NAD+ and its metabolites levels in normal and injured mouse sciatic nerve. Limitations of existing methods for quantifying NAD+ and its metabolites Traditional methods for quantifying NAD+ and its metabolites, such as HPLC-UV, NMR, capillary zone electrophoresis, or colorimetric enzymatic assays, face various challenges in sensitivity, selectivity, and indirect measurement. As for existing LC-MS/MS assays for cellular or tissue NAD+ and its metabolites measurements, there are still many difficulties to overcome, such as extended run times, poor chromatographic retention behavior, and unsatisfactory peak shapes. Moreover, only one to three substances in the NAD+ salvage pathway can be covered by these methods. The modifications of LC-MS/MS method On the basis of existing LC-MS/MS assays, the modifications regarding the chromatographic conditions, surrogate matrix and MS/MS conditions are conducted. Specifically, 5 μM of methylene phosphonic acid is employed as the mobile phase additive, which explicitly promotes the signal intensity and peak shape. Given the relatively clean and simple nature of never samples and their small size, ultrapure water is tested as a substitute matrix. Instead of hydrophilic interaction liquid chromatography column and hypercarb column, the Waters Atlantis Premier BEH C18 AX column is utilized, whose unique MaxPeak HPS high-performance surface technology (passivating the column inner wall, eliminating metal surface) enables the high reproducibility, peak symmetry, and baseline separation of all analytes. Besides, MS conditions are optimized to minimize the NAD+ interference signal in the cyclic adenosine diphosphate ribose (cADPR) channel while maintaining the response of cADPR and nicotinamide mononucleotide (NMN), with 4000V for ion spray voltage, 450℃ for turbo heater temperature, 50 psi for Gas 1, 50 psi for Gas 2, 30 psi for curtain gas, and 12 psi for collision gas. Representative chromatogram of nerve samples (normal vs injured) All five analytes achieve baseline separation, where cADPR is a sensitive biomarker in the neurodegeneration model. Herein, sciatic nerve axotomy induces axonal degeneration, leading to reduced NAD+ level and elevated NMN level in the injured nerves, resulting in about a 2-fold increase in the NMN/NAD+ ratio. Simultaneously, the levels of nicotinamide (NAM) and adenosine diphosphate ribose (ADPR), are decreased by about 2-fold, while cADPR level is increased by more than 8-fold. These results are consistent with those of previously reported research, verifying the accuracy of this modified LS-MS/MS method in quantifying NAD+ and its metabolites. Conclusion This modified LC-MS/MS method enables effective baseline separation of NAD+, NMN, NAM, ADPR, and cADPR within a brief runtime of 5 min, which is contributive to early diagnoses of various neurological disorders and drug development for aging and neurodegenerative diseases. Reference Ma Y, Deng L, Du Z. Development and validation of an LC-MS/MS method for quantifying NAD+ and related metabolites in mice sciatic nerves and its application to a nerve injury animal model. J Chromatogr A. doi:10.1016/j.chroma.2024.464821 BONTAC NAD BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR). There are various types of NAD to be selected, encompassing NAD ER Grade (endoxin removal), NAD Grade I (IVD/dietary supplement/cosmetics raw powder), NAD Grade II (API/intermediates) and NAD Grade IV (if any higher requirement on the solubility), which can be provided in the form of lyophilized powder or crystalline powder. The purity of BONTAC NAD can reach above 98%. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses or costs resulting or arising directly or indirectly from your reliance on the information and material on this website.