Text / Xinna
In the past two years, it has been a hot year for medical beauty, and even a branch of collagen has also become popular.
Companies focusing on collagen products will hit the market one after another in 2022. Shanxi Jinbo Bio-Pharmaceutical Co., Ltd. (hereinafter referred to as “Jinbo Bio”), which submitted the form in early June, mainly focuses on recombinant humanized collagen, and has recently received the second round of review inquiry letter from the Beijing Stock Exchange; in May, Giant Bio submitted a listing prospectus to the Hong Kong Stock Exchange; in January, Chuan Bio applied to be listed on the Beijing Stock Exchange.
In addition to being sought after by the capital market, the medical and beauty industry, which is anxious about “involution” and “market consolidation”, also regards it as a growth point. The hyaluronic acid giant Huaxi Bio has laid out the collagen track through acquisitions. In April, it acquired a 51% stake in Yierkang Bio for 230 million yuan, which specializes in collagen-based medical terminal products.
In the field of medical and aesthetic injections, more than 40 products of hyaluronic acid have been approved, and collagen injections have similar properties to hyaluronic acid. A medical analyst analyzed the Caijing reporter that the medical beauty track needs enough effective products with technological innovation. If these products have a certain accumulation of consumer groups, it is easy to produce the next hot product.
Collagen injections are hoped for. However, compared with hyaluronic acid, collagen injections have to face technical difficulties such as high production costs and product stability after mass production, which invisibly raises the threshold for entry. Will this become a filter in the field of medical aesthetics?
| Collagen mass production problems to be solved
Collagen is not a new concept. According to the traditional Chinese concept of supplementing what you eat, Chinese people have always regarded collagen as the “fountain of youth”. food to improve skin texture and delay aging.
Collagen is an important structural protein found in animals. Essentially, it holds the body together, giving the bones, skin, muscles, tendons, ligaments and cartilage strength, structure, elasticity and cohesion. Therefore, it can be seen as a kind of “glue” that integrates the body.
“Nowadays, the public’s demand for medical aesthetics is not only for beauty in form, but also for some biological functions. It is hoped that a product can be used that can reach the same level as its own tissue after use. The level of seamless integration. At this time, everyone thought of collagen.” Meber’s Xiao E’s analysis of the media.
Collagen accounts for 75% of the skin’s dry weight, which plumps the skin and maintains even lines. Unfortunately, collagen breaks down faster than it is replenished, and the body can lose 1% of collagen per year starting at age 20, and 30% in five years of menopause.
As you age, your body produces less collagen, leading to visible signs of aging such as wrinkles and fine lines. This is because there is less and less collagen that provides elasticity and structural support to the skin.
If the body is not producing enough on its own, then artificially supplementing collagen appears to be feasible. However, when injectable collagen fillers first emerged in the 1980s to plump lips and soften fine lines, they weren’t as effective because they didn’t last as long as other fillers, didn’t absorb easily and were prone to allergic reactions.
In order to improve the defects, different technical paths have emerged.
Collagens obtained from humans are mainly divided into animal-derived collagens and genetically engineered human-like collagens. As the name suggests, the former is extracted from animal tissues, such as tendon tissue, skin tissue or small intestine tissue of cattle and pigs. The latter is collagen obtained through genetic recombination and bioengineering technology, and is very similar to the human body’s own collagen in terms of structure and properties.
The animal-derived collagen extraction method has been in development for a long time, the technology is mature, and the technical barriers have begun to decrease. The key now is to solve the supply of raw materials.
The preparation of natural collagen requires the purchase of animal raw materials such as bovine Achilles tendon in the early stage, however, it has a high sensitization rate. Surveys show that about 3% of the population is sensitive to bovine collagen. Now, the extraction technology of natural collagen is more and more mature, and the probability of immunogenic reaction has been greatly reduced.
The problem is that according to the existing domestic regulations, the extracted animal raw materials need to be traced back to three generations of animals to ensure that there is no medical history.
A person in the medical and beauty industry analyzed the Caijing reporter, The requirements for the entire raw material supply chain are very high. For domestic manufacturers, technology is not a problem, but cost is the main consideration factor.
China Taiwan Shuangmei Biotechnology Co., Ltd. (hereinafter referred to as “Shuangmei”), a head natural collagen enterprise, is facing the problem of animal-derived immunogens. Shuangmei had no choice but to raise pigs and extract collagen from pigs to ensure safety. However, the above-mentioned medical and aesthetic industry people pointed out that in this way, enterprises will be limited by the scale of the raw material industry, and it will be difficult to expand production capacity.
Comparatively, the raw materials required for the recombinant collagen extraction technology are very simple, only need to purchase raw materials such as yeast extract powder and strains. Currently, the preferred vector is E. coli or yeast, and plant cells such as rice can also be used. Currently, the technologies of mainstream Chinese companies are expressed in E. coli system. However, the “double-edged sword” of this matter is that it is difficult and expensive to extract.
Due to the limited level of biosynthesis technology, only two types of products, recombinant humanized collagen and recombinant collagen-like protein, are currently approved.
June 29, 2021, JinBo Bio was approved as “Recombinant Type III Humanized Collagen Freeze-dried Fiber”, which is the first and only recombinant humanized collagen in China. At present, such products are still in the preliminary stage of entering the market, and the terminal sales price is about 6,800 yuan/piece.
From small-scale production in the laboratory to mass production, the stability of the product is a test for the entire production system, and the technical threshold is not low.
| Collagen vs Hyaluronic Acid
Collagen medical beauty products were approved more than 20 years earlier than hyaluronic acid products. But the commercialization process lags behind hyaluronic acid.
Up to now, there are only seven collagen “injection implantation” products that have been approved for marketing in China. Except for two imported products, the other three are Shuangmei, Changchun Bo Taihe Jinbo creatures each have one.
Collagen products can replicate the development path of hyaluronic acid if they want to achieve good results with hyaluronic acid, provided that the price is reduced.
Collagen is similar to hyaluronic acid in some functions, and both can be used as fillers and have a certain alternative. The unit price of hyaluronic acid sales has been declining. Bloomage Bio’s previous prospectus disclosed that from 2017 to 2019, the average annual sales unit price of injection-grade hyaluronic acid raw material products decreased by about 5%, and now it is 111.69 yuan / gram.
The current market price of collagen is about 1 million yuan/kg, which is equivalent to 1,000 yuan/gram, which is nine times more expensive than hyaluronic acid.
At present, it is difficult for collagen companies to achieve mass production and achieve large-scale benefits, thereby greatly reducing costs, especially to the same cost as hyaluronic acid.
From the perspective of terminal prices, the terminal price range of mainstream hyaluronic acid fillers is about 3,000 yuan to 5,000 yuan, and the average price of mainstream collagen injections is more than 5,000 yuan, and the most expensive is an imported product , the price is between 13,000 yuan to 16,000 yuan.
“Someone now gets a shot of hyaluronic acid every few months, which (all down) is about the same price as some cosmetics, but it’s much more effective.”One The person in charge of the Beijing Medical Beauty Chain Agency said.
“Caijing” reporters communicated with the heads of several leading medical and beauty chain institutions in different provinces in China and found that compared with hyaluronic acid injections, the number of people who choose collagen injections is still a minority. On the one hand, people’s awareness of this is not as common as hyaluronic acid; on the other hand, the high price is still the main constraint.
The popularity of medical cosmetology is becoming more and more “involution”, which makes it more urgent to develop new products. Collagen at least does not need to spend too much in the Chinese market for user education and popularization. This will save collagen businesses a fortune.
According to Tianyancha data, from 2021, there will be 79 new collagen-related companies in China. As of August 2022, more than 10 collagen-related companies have been added.
This is also related to the rapid development of genetic and bioengineering technology in recent years, and more and more companies have the ability to develop recombinant collagen. A relevant person in charge of a collagen production company in China learned that at present, dozens of recombinant collagen injection products are queuing up outside the gate of the drug regulatory department to apply for listing.
In those years, Bloomage Bio’s path to liberate the production capacity of hyaluronic acid was to find a biological fermentation method to replace the animal extraction method, so as to enlarge the production capacity of raw materials and increase the production capacity on a large scale, thereby greatly increasing the production capacity. Lower the price of hyaluronic acid. The relevant person in charge of the above-mentioned head collagen production enterprise found that the current development of the collagen market is similar to that of the hyaluronic acid market.
According to the research report of Guohai Securities, compared with hyaluronic acid, collagen will not be displaced and deformed during the filling process, and there will be no swelling, which is more natural in comparison. This property makes collagen more suitable for filling areas with little soft tissue and large active sites, such as the tear trough around the eye. Of course, hyaluronic acid filling has a wider scope of application, but filling it in places such as the eye area puts forward more precise requirements on the molecular weight and degree of cross-linking of the product.
In addition, collagen will form a scaffold, and surrounding tissue cells will grow on the scaffold. This regeneration function is not possessed by hyaluronic acid. However, in terms of shaping time, collagen is not as good as hyaluronic acid.
From the perspective of future development trends, compared with animal-derived collagen products, recombinant collagen injections have the advantage of scale. From the perspective of the domestic market, the producers of animal-derived collagen are Taiwan Shuangmei, Changchun Botai, and Chuanger Bio. Recombinant collagen manufacturers include Jinbo Bio and Juzi Bio.
The above-mentioned people in the industry believe that the cost of the former is limited by upstream raw materials and the stability of extraction technology, and it is difficult to significantly reduce the cost. The cost of recombinant collagen in the research and development process will be much higher than that of hyaluronic acid. It is difficult to reduce the cost of hyaluronic acid in the short term, but once it breaks through the test of mass production, the price may drop in the long run, and it will have more advantages in the market. .