Reading guide:Marubeni brings out the ingredients that are far away from the consumer, and turns the ingredients that seem to have nothing to do with the consumer into a product that "flies to the homes of ordinary people".
Recombinant collagen*1, an ingredient that has attracted much attention, is expected to become the "next phenomenal ingredient". At present, the recombinant collagen industry has become a place of capital competition and is booming.
According to the review, there are more than 40,000 keywords of recombinant collagen in Xiaohongshu-related notes, and more than 50,000 related products, with a dazzling array of essences, repair liquids, dressings and other categories. However, the discussion on the consumer side about "is recombinant collagen an IQ tax?", "can it be absorbed through the skin", and "whether it has scientific and technological value" is also becoming more and more intense.
In order to solve these mysteries that have plagued consumers for many years, "Raw Material Gate" came to Marubeni Co., Ltd. (hereinafter referred to as Marubeni), and specially invited Dr. Guo and Dr. Wang from Marubeni R&D Center, two technical experts who have been deeply engaged in the field of skin science for many years, to interpret the "mystery" of recombinant collagen and decode the mystery behind Marubeni's continuous leadership in the development of recombinant collagen industry.
In fact, with the development of science and technology and investment in scientific research, the absorption and efficacy of recombinant collagen are relatively certain in the industry. At present, type III recombinant collagen with skin care activity is the main product on the market, but most type III recombinant collagen has very poor structural stability and is easily decomposed into small molecule polypeptides.
Therefore, the problem of how to maintain stability and effective activity has always been the biggest problem and pain point in the application of recombinant collagen.
Dr. Wang told Raw Material Gate, "Natural collagen*2 has a triple helix structure, and this unique protein structure determines the characteristics of stability and high activity. A protein without structure, even if it has a good sequence, may not be active and stable, let alone exert efficacy. ”
In other words, the fundamental basis of collagen's anti-aging activity*3 is that it has a unique spatial structure, the triple helix, which determines its function in the cellular and extracellular microenvironment, as well as its efficacy.
Following the direction that the triple helix structure determines stability and activity, Marubeni Co., Ltd. subversively developed the "recombinant double collagen" ingredient in 2020, refreshing the ceiling of industry standards. Based on AlphaFold AI-based protein structure prediction*4, recombinant double collagen and natural collagen exhibit a highly similar triple helix structure, which is 100% consistent with the amino acid sequence of natural collagen in the human body, and has superior biological activity and stability.
Is recombinant double collagen anti-fighting?
"Recombinant double collagen is formed by the chimeric chimeric active fragments of the functional domains of type I collagen and type III collagen to form a triple helix structure consistent with native collagen. Type I collagen with strong support capacity and elastic type III collagen are intertwined with each other and work together to work together, which is an important way to prevent aging and wrinkles. ”
According to Dr. Guo, among the 28 types of collagen family, the main ones that are widely used in the skin field and entrusted with important tasks are: type I collagen and type III collagen. Skin aging is caused by the constant loss and imbalance of these two types of collagen.
Based on this principle, the recombinant double collagen is controlled by a 1:1 ratio of chimeric type I and type III collagen in the similar ratio of type I and type III collagen in the "baby muscle"*5, which can not only supplement the two types of collagen at the same time, but also achieve a more stable, safer, and more active effect. Taking the strength of a hundred schools, melting the thoughts of a hundred schools, and promoting the name of a hundred schools, it is very appropriate to describe recombinant double collagen.
Not only that, Marubeni has broken through the boundaries of the stability of the triple helix structure and solved the problem that many manufacturers are currently troubled by - maintaining the stability and activity of the ingredients for a long time.
In order to better maintain the stability of recombinant double collagen, Marubeni added a small cysteine-rich sequence "C-Pro clasp" sequence from type III collagen to the tail of double collagen, so as to lock in double collagen, like a rubber band tied at the end of a braid, so that the collagen triple helix chain is not easy to loosen, so as to form a more stable structure and more active.
Marubeni uses its proprietary "translation pause" technology*6 to rationally control the protein synthesis rate, optimize the translation speed and folding efficiency of recombinant double collagen, and more precisely control the process of cell production of recombinant collagen, so that it is closer to natural collagen in its higher order structure, and ensures that each molecule can have structural and functional activity when expressed.
Generally speaking, although the preparation of proteins by E. coli has the advantages of fast production speed and high yield, it is very easy to achieve protein adhesion polymerization and even denaturation due to the lack of post-translational modification of proteins, so it is difficult to achieve high-quality mass production in the true sense. Using translation pause technology, Marubeni optimizes the collagen gene sequence according to the characteristics of the E. coli expression system, which is like setting up a retardation belt on the collagen assembly line, and when the production speed is too fast and the process is chaotic, the "pause button" is pressed in time to control the speed, so as to ensure that all "products" can be packaged, inspected and transported in an orderly manner, without backlog or even defective products due to excessive production. It is through this orderly and correct production that we can ensure that each collagen is a uniform, stable and active high-quality product.
Based on the translation pause technology, C-Pro buckle technology, and triple helix structure, Marubeni has built three breakthrough unique technical advantages:
High homology: The amino acid sequence is 100% consistent with human collagen, and the skin can actively transdermal absorption.
High stability: The triple helix structure is similar to the structure of human collagen, and the exclusive patented C-Pro buckle technology is more stable.
High biological activity: Translation pause technology controls the synthesis rate to keep collagen highly active.
There is no doubt that compared with recombinant collagen with a single type and no guarantee of stability on the market, Marubeni's recombinant double collagen is once again at the forefront of the recombinant collagen market, leading the recombinant collagen market into an era of high-quality development.
Trial and error
Marubeni breaks the misconceptions of recombinant collagen
The popularity of recombinant collagen has not decreased, the entrants are endless, and there are more and more voices of feedback in the market, and whether it can be effectively absorbed through the skin has become a more concerned issue for consumers.
Marubeni has been confronting this problem head-on, trying to break this limited perception of recombinant collagen.
"The skin is the largest organ in the human body and is constantly in constant flux, and it should not be simply regarded as an inanimate membrane, but we have found that although Marubeni's recombinant double collagen is 27.3 kDa*7, it can be absorbed through the skin follicles or sebaceous glands on the one hand, and penetrate into the dermis through the arrangement of epidermal cells on the other, and is not too large to be absorbed through the skin due to its large molecular weight, as is claimed in the market. Dr. Wang introduced to "Raw Material Gate".
It is worth mentioning that in 2022, scientists from the Experimental Research Institute of the China Academy of Chinese Medical Sciences and other scientists used second harmonic and two-photon excitation fluorescence microscopy to observe the transdermal absorption of collagen in vivo, and proved that it can be effectively transdermally absorbed with a molecular weight of 55kDa*8. Compared to most recombinant collagen, Marubeni's recombinant collagen has a reduced molecular weight of 27.3 kDa, which ensures effective transdermal absorption and preserves the properties of collagen rather than collagen peptides.
In order to verify this "breakthrough common sense" conclusion, Marubeni and a third-party testing institute conducted a multi-dimensional transdermal absorption test on recombinant collagen, and confirmed that Marubeni's recombinant collagen has good transdermal absorption capacity through the Franz diffusion cell test*9 of isolated skin*9, the 3D skin model test*10, the two-photon microscopic imaging test of human skin*11, and the more accurate two-photon synergistic second harmonic imaging test of animal in vivo*12.
Among them, two-photon microscopy of human skin is directly applied on the skin and can track the depth, level and aggregation positioning of recombinant double collagen entering the skin in real time, which is the most intuitive and realistic demonstration of the transdermal absorption process of Marubeni's recombinant double collagen.
▲Schematic diagram of the two-photon imaging results of the top-down transdermal absorption process of Marubeni's recombinant double collagen.
In cooperation with the Chinese Academy of Traditional Chinese Medicine, the animal in vivo two-photon synergistic second harmonic imaging experiment further clarified the mechanism of rapid transdermal absorption of recombinant double collagen through the "dual channel" of epidermal cell space and skin hair follicles, and was pleasantly surprised to find that the exogenous infiltrated Marubeni recombinant double collagen was integrated with the skin endogenous collagen network, which effectively strengthened the skin collagen network.
▲Two-photon synergistic second harmonic imaging of transdermal absorption process of recombinant double collagen in vivo. Figure A: Recombinant bicollagen (red fluorescence) quickly penetrates into the skin in just 0.5 hours, and recombinant bicollagen can be detected in the dermis in only 2 hours and accumulates over time (Figure B), and some of the recombinant bicollagen is gradually concentrated near the hair follicle. As recombinant bicollagen penetrates into the skin, endogenous collagen fibers (green fluorescent signal) in the dermis also intensify, peaking at 1h (Figure C), suggesting that the entry of recombinant bicollagen promotes the increase of collagen fibers in the dermis of the skin.
▲Schematic diagram of Marubeni's recombinant dual collagen "dual channel" transdermal absorption pathway. White arrows: epidermal cells, green arrows: hair follicles, yellow arrows: hair, red fluorescence: recombinant double collagen.
Obviously, this test has effectively dispelled the myth that collagen cannot be absorbed through the skin.
In addition, Marubeni's recombinant double collagen has also passed inspection tests in China, the United States, Japan and the United Kingdom, and has also been tested for sensitive skin, which is safe and effective, bringing a visible and perceptible mild anti-aging effect to the skin.
Take scientific research as the background
Marubeni broke a new path of industrialization
In fact, recombinant collagen is not a "new species".
It has been nearly 30 years since recombinant collagen was successfully developed in 1995 to 2000, when Chinese scientists took the lead in developing recombinant collagen and began industrial research.
However, recombinant collagen has only happened in recent years when it is widely known and applied in the market and has entered explosive growth. All this is inseparable from the rapid landing of many high-quality recombinant collagen products.
In March 2021, Marubeni held the first Recombinant Collagen Anti-Aging Forum, the 2021 Marubeni Biotech Anti-Aging Innovation Forum, and took the lead in launching a series of recombinant dual collagen products*13. This forum proved to be the first shot of Marubeni's slogan of "recombinant collagen" at the domestic cosmetics consumption end.
In fact, from the successful research and development of recombinant double collagen in 2020 to the realization of industrial application and new product launch in 2021, Marubeni only took 1 year. The speed of landing of this product, Marubeni far exceeds the industry average.
"From the very beginning, Marubeni held the idea that 'recombinant collagen is not a concept, let alone an IQ tax', and started from the perspective of market application, and worked backwards to the very beginning of ingredient design to provide consumers with truly effective products. Dr. Wang said.
It is important to know that from basic research, raw material development, evaluation and testing to the production of landing products, it takes a lot of time to repeatedly deploy and verify, which requires a lot of manpower, material and financial resources. Without comprehensive scientific research strength and the construction of a complete and leading production chain, new ingredients can easily disappear in the torrent of the market.
So, what has Marubeni, as a reference model for industrialization, done to promote the industrialization process of recombinant collagen?
In Marubeni's grand blueprint, technology is the first meaning. It is understood that Marubeni has built an integrated full-link advanced scientific research system, that is, 7 full-link functional modules of R&D, including basic research, raw material development, raw material production, formula research, production intelligent manufacturing, inspection and testing, and efficacy evaluation, focusing on R&D, manufacturing, branding, marketing, evaluation, etc., to create a core barrier of comprehensive strength, and is one of the few beauty technology companies in the industry with full-link scientific research strength.
"From research to implementation, Marubeni has already achieved a perfect closed loop through the 'seven-in-one'*14 system, and quickly realized the industrialization of scientific research results. Dr. Guo said that thanks to the "seven-in-one", Marubeni quickly industrialized, commercialized and commercialized its scientific research results, and quickly applied its products to the market, so as to meet the anti-aging needs of consumers with high-quality recombinant collagen products.
In addition, Marubeni, as a master of anti-aging, has established an exclusive "Symptomatic Anti-Aging Pyramid"*15 to develop anti-aging products according to the different degrees of aging and skin performance, and customize solutions to different skin aging problems.
Dr. Guo said, "The anti-aging products developed by Marubeni are very precise, with different strategies and ingredients selected according to the causes and manifestations of different degrees of skin aging, and equipped with different patented anti-aging formulas. For example, the Marubeni Chocolate Rejuvenating Silky Series, which solves the problems of "phenotypic aging" such as dryness, roughness and fine lines, exerts antioxidant, anti-sugar, anti-light, and anti-stress effects through the combination of different ingredients, and inhibits the immediate problems of early aging caused by the internal and external environment. Our recombinant dual collagen series products can accurately replenish the lost collagen, improve the skin barrier and sensitivity problems from the inside out, and even sensitive skin can be relieved to fight aging, and the response in the market is very good. ”
It can be said that Marubeni took the lead in bringing the ingredient "recombinant collagen" from the rear laboratory to the front end of the beauty market, so that the industry and more consumers can know and understand recombinant collagen, highlighting the industrial value, product value and commercial value of recombinant collagen.
In "Out of Control: The New Biology of Machines, Society, and Economy," Kevin Kelly, the "Godfather of the Internet," says, "The most profound technologies are those that weave themselves into the minutiae of everyday life until they become a part of it." Marubeni is undoubtedly doing just that, taking ingredients out of the lab that are far away from consumers, turning ingredients that seem to have nothing to do with consumers into products that "fly to ordinary people's homes".
At present, Marubeni's collagen series has been updated to 10+ SKUs, including recombinant collagen cream, recombinant collagen milk, recombinant collagen serum, recombinant collagen essence cream, recombinant collagen day and night eye cream, recombinant collagen luxury cream, recombinant collagen essence mask, recombinant collagen freeze-dried mask and other products, which are well received by consumers and have received enthusiastic responses.
Take the lead in setting standards and playing home advantage
In general, the preparation technology, production capacity and quality of recombinant collagen in mainland China are at the international leading level, and the "home field" of recombinant collagen has been located in China. We have reason to believe that the recombinant collagen market, which is expanding rapidly, is expected to become the next phenomenal ingredient like "hyaluronic acid".
However, it is also undeniable that the industry is still in the early stage of development, and the uneven market environment affects the healthy development of the industry. More importantly, different from the standardized application of recombinant collagen in the field of medical devices, there is no unified standard for recombinant collagen raw materials in the cosmetics field, due to the inherent "particularity" of cosmetic raw material management, the purity, content and activity of recombinant collagen raw materials of various companies in the cosmetics market are different, the information is not transparent, the quality is uneven, and there are many bad coins driving out good money, which greatly affects the legitimate rights and interests of consumers and the orderly and high-quality development of the recombinant collagen industry.
Reflected at the enterprise level, a group of companies led by Marubeni have long realized the importance of industry standardization and have taken up the responsibility of leading the high-quality development of the recombinant collagen industry.
"If there is no industry standard to guide and standardize behavior, it will limit the development of the industry, the health and safety of consumers will be threatened, and the interests of enterprises that really strive for the development of the industry will also be damaged. Dr. Wang said.
Driven by a sense of responsibility, Marubeni has initiated and successively led the revision, revision and release of a total of 6 recombinant collagen-related technical standards*16 at the 2nd Recombinant Collagen Scientists Forum in 2022. On September 23, 2023, at the 3rd Marubeni Recombinant Collagen Scientists Forum, Marubeni, together with academicians and experts from China, France, Canada, Singapore and other countries, jointly released the "Expert Consensus of International Academicians on Recombinant Collagen", agreeing that the design and preparation of recombinant collagen should restore the structure and functional properties of human collagen as much as possible. The preparation of high-quality recombinant collagen should meet the three standards and principles of consistent sequence, consistent structure and consistent activity.
In addition, the light industry standard "Recombinant Soluble Collagen"*17, which was led by Marubeni, has also been successfully approved by the Ministry of Industry and Information Technology in November 2023, and will formulate standardized standards for the quality control, technical requirements, and testing rules of recombinant soluble collagen used in the cosmetics industry, bringing more standardized and standardized guidance to the industry.
There is no doubt that seeking direction for the healthy development of the industry is Marubeni's responsibility and responsibility as a leading beauty company in China.
epilogue
"At present, the recombinant collagen industry still has a lot of room for imagination and upgrading. "Therefore, we have formulated a 10-year plan to continuously find the direction of our own upgrading and expansion from Class II to Class III mechanical products, hoping to bring greater surprises to the market in serious medical fields such as dermatology, ophthalmology, and orthopedic 3D printing materials." In 2023, Marubeni successfully launched its first recombinant collagen Class II medical device product*18, completing the first small goal of the 10-year plan. ”
Currently, Marubeni has applied for a total of 26 patents related to recombinant collagen*19. Marubeni has never stopped scientific research and continues to break through the technical ceiling. Dr. Guo revealed, "At present, Marubeni's recombinant collagen products are mainly for firming and anti-wrinkle effects, and with the development of technology, Marubeni's recombinant collagen 2.0 will strengthen the research in the direction of anti-wrinkle + repair, which is not only available for sensitive skin, but also has a certain repair effect, which is more suitable for the function of collagen itself." ”
According to reports, Marubeni's recombinant collagen version 2.0 series products will be unveiled at Marubeni's 4th Recombinant Collagen Summit Forum, so stay tuned.
Al Rees, the founder of Positioning Theory, mentioned this point of view in "Positioning": "The best differentiation of a brand is to be the first and be a category leader or pioneer." ”
Spanning the 1.0 era of animal collagen extraction and the 2.0 era of single type of recombinant collagen, Marubeni has taken the lead in entering the recombinant collagen 3.0 era with type I and type III chimeric recombinant double collagen, becoming a leader in recombinant collagen.
From the research process of recombinant collagen, we can see that Marubeni has developed comprehensively in scientific research, production, branding, marketing and other links, laying a deep scientific research foundation for the expansion of corporate value, empowering products in an all-round way, and building an indestructible core barrier. It is believed that Marubeni, which is constantly deeply rooted in the soil of scientific research, will be invincible, create the next subversive achievement, and continue to set up monuments.
Exegesis:
*1: Collagen obtained using recombinant technology.
*2: The most abundant protein in the human body and is the main component of the extracellular matrix.
*3: The terms "anti-aging" and "anti-aging" in this article refer to anti-wrinkle and firming effects.
*4: Refers to an artificial intelligence (AI) tool developed by DeepMind, a cutting-edge artificial intelligence company owned by Google, whose predicted structure covers almost the entire human proteome.
*5: Refers to the condition of delicate and smooth skin like a baby, which is plump and elastic.
*6: A method for improving the soluble expression of proteins through rational redesign of translation pause sequences, and was officially patented on February 11, 2015.
*7: The molecular weight of the tested protein sample is between 25~35kD and can penetrate into the dermis layer of the skin by two-photon confocal microscopy.
*8：In vivo Visualization of Collagen Transdermal Absorption by Second-Harmonic Generation and Two-Photon Excited Fluorescence Microscopy[J].化学前沿.2022.
*9: The collagen content was measured using the modified Franz diffusion cell and the experimental mouse skin of SPF-grade male Kunming mice, and the cumulative transmittance was 35.63% in 160 minutes. Tested by Guangzhou Qidian Biotechnology Co., Ltd. and completed in February 2021.
*10: Based on the epidermal skin model EpiKutis, the experimental results show that the accumulation of fluorescent substances at any time point of the collagen sample at 0.5 h, 2 h, 12 h and 24 h is significantly higher than that of the previous time point. Completed in June 2022.
*11: Two-photon transdermal absorption test on recombinant collagen samples using two-photon microscopy for 3 subjects. The results showed that the recombinant collagen in the recombinant double collagen serum and the recombinant double collagen raw materials showed a certain transdermal ability, and the transdermal diffusion increased with time within 24 hours. Tested by Beijing Yiweishi Testing Technology Co., Ltd. and completed in September 2023.
*12: iFlourTM 594 was used to fluorescently label the protein of the test sample, and the labeled sample was evenly applied to the dorsal skin of mice by SDS-PAGE detection, and the samples were detected in vivo by two-photon confocal microscopy and second harmonic imaging at 0.5, 1, 1.5, 2, 2.5, and 3 h time points, respectively. It was tested by the Medical Experimental Center of the China Academy of Chinese Medical Sciences and completed in September 2023.
*13: Refers to the Marubeni Small Gold Tube Double Collagen series.
*14: Refers to the seven full-link functional modules of R&D: basic research, raw material development, raw material production, formula research, production intelligent manufacturing, inspection and testing, and efficacy evaluation.
*15: Marubeni's exclusive anti-aging pyramid is divided into dry and rough, dull and fine lines, loose fine lines, lack of elasticity, contour deformation, sagging wrinkles, sensitivity and fragility, loose wrinkles, concave face faults, sagging displacement, etc.
*16: General Requirements for Collagen Skin Care Products, Product Quality Requirements for Medical Collagen (Safety/Efficacy Evaluation of Collagen (Medical)), Methods for Evaluating the Efficacy of Recombinant Collagen Raw Materials, Recombinant Soluble Collagen, Recombinant Soluble Collagen for Cosmetic Raw Materials, Evaluation of Oral Collagen Bioavailability (Safety/Efficacy Evaluation of Collagen (Oral) Oral Collagen)
*17: Approved on November 14, 2023, jointly drafted by China Biological Fermentation Industry Association, Guangdong Marubeni Biotechnology Co., Ltd., and Jiangnan University.
*18: Marubeni's medical recombinant collagen dressings and medical recombinant collagen patch dressings are used for the care of non-chronic wounds and surrounding skin such as small wounds, abrasions, and cuts. It was officially approved on April 27, 2023.
*19 利号:【ZL201310579542.4】【ZL201710732936.7】【ZL202111459582.6】【ZL202210633927.3】【ZL202211185401. X】【ZL202310102248.8】【ZL202310123476.3】【ZL202310373961.6】【ZL202311092341.1】【ZL202311155657.0】【ZL202311193533.1】【ZL202311193661.6】【ZL202311208006.3】【ZL202311326664.2】【ZL202311347880.5】ZL202311622947【ZL202311625054.2】【ZL202311623336 ZL202311625054.9】【ZL202311662932.8】【ZL202311688837.5】【ZL202311744656. X】【ZL202311818263.9】【ZL202311874222.1】【ZL202311874253.7】【ZL202311873633.9】【CN202330314691.2】