What Is Collagen Hydrolysate?

Collagen is a biopolymer, the main component in connective tissue of animals, and the most abundant and widely distributed functional protein in mammals, accounting for 25% to 30% of the total protein. In some organisms, it is even as high as 80% or more. . ^[1-3]

Collagen is a type of protein family, and at least 30 types of collagen chain codes have been found.

The collagen content of aquatic animals is higher than that of terrestrial animals, such as catfish, catfish and grass carp skins, which are 25.9%, 23.6%, and 29.8%, respectively, which are higher than the protein content of their respective fish: 17.8%, 15.3% and 16.6%. The highest collagen content in fish skin can exceed 80% of its total protein, which is much higher than other parts of the fish body. Studies have reported that collagen in the sea bream skin accounts for 80.5% of crude protein, and eel is as high as 87.3%. . Such a high content means that the yield is also high, such as the bream 42.5%; Japanese sea bass 40.7%; sweetfish 53.6%; yellow sea bream 40.1%; horse mackerel 43.5% (both on dry weight basis).

However, there are much fewer types of collagen. The types of collagen that have been isolated and identified from fish include: Type I, which is widely distributed in the dermis, bones, scales, ridges, muscles, etc., Type and Type of cartilage and chordae. And the V shape of the muscles. The type I collagen contained in fish skin and fish bone is its main collagen. In addition, type XVII collagen has also been found, but mammals with relatively abundant type III collagen have not been found in aquatic animals. Among them, only type collagen can be accepted by people; other types of collagen such as , , are only prepared in research, and are not suitable for mass production due to the high price. ^[21-25]

Since collagen is an extracellular interstitial component, it exists in the body as an insoluble macromolecular structure, and is combined with proteoglycans, glycoproteins, etc. Therefore, the preparation of collagen includes the selection of materials, pretreatment, extraction with acid-alkali saline method, different Isolation and purification of type collagen. ^[86]

Collagen Biomedical Materials

Collagen is a natural protein of the body. It has greater affinity for protein molecules on the skin surface, weaker antigenicity, good biocompatibility, and biodegradation safety. It can be degraded and absorbed, and has good adhesion. Surgical suture made of collagen has the same high strength as natural silk, and it is absorbable. It has excellent platelet aggregation performance, good hemostatic effect, and good smoothness and elasticity when used. The knot is not easy to loose, it is not easy to damage the body tissue during operation, and it has good adhesion to the wound. Generally, only a short time of compression is required to achieve a satisfactory hemostatic effect. So collagen can be made into powder, flat and sponge-like hemostatic agents. At the same time, the use of synthetic materials or collagen in the research and application of plasma substitutes, artificial skin, artificial blood vessels, bone repair and artificial bone and immobilized enzyme carriers are very extensive. ^[154-155]

The collagen molecule peptide chain has a variety of reactive groups, such as hydroxyl, carboxyl, and amino groups, which are easy to absorb and bind a variety of enzymes and cells to achieve solidification.

Clinical application of collagen medical products ^[143] Qualitative, it has the characteristics of good affinity and adaptability to enzymes and cells. In addition, collagen is easy to process and shape, so purified collagen can be made into many different forms of materials, such as membranes, tapes, flakes, sponges, beads, etc., but the most reported applications in the form of membranes. Collagen preparation membrane is used in biomedicine. In addition to biodegradability, tissue absorbability, biocompatibility, and weak antigenicity, it mainly includes: strong hydrophilicity, high tensile strength, and dermis-like structure , Good water permeability and gas permeability; bioplasticity determined by high tensile strength and low ductility; there are many functional groups, which can be moderately cross-linked and modified to control the rate of biodegradation; it can adjust dissolution (swelling); and other biological activities The components are used together to have a synergistic effect; they can interact with drugs; cross-linking or enzymatic treatment of ateloceptides can reduce antigenicity, isolate microorganisms, have physiological activities, such as hemagglutination and other advantages. At the same time, it also has the following disadvantages: the separation, purification and processing of collagen are complicated, and the cross-linked density and fiber size of the separated collagen are diverse. The rate of enzymolysis of collagen varies, and the conditions are difficult to control; and the texture of pure collagen after drying is brittle, the film-forming ability is not strong, its membrane is low in ductility, easy to crack, poor in water resistance, easy to swell in water, easy to degrade in the body, and humid The environment is susceptible to bacterial erosion and deterioration, and may also cause some side reactions, such as tissue calcification. Therefore, in practical applications, collagen is often modified by a certain method, the disadvantages of collagen preparation materials are avoided through modification, the tensile strength and resistance to degradation of collagen are improved, the expansion rate is reduced, and the mechanical properties and water resistance of collagen are improved. ^[156-157]

Clinical application forms include aqueous solutions, gels, granules, sponges and films. These same shapes can be used for sustained release of drugs, have been approved for marketing and

Collagen drug sustained release application ^[158] The sustained-release applications of collagen drugs under development mostly focus on anti-infection and glaucoma treatment in ophthalmology, local treatment in trauma and infection control in wound repair, cervical dysplasia in gynecology, and local anesthesia in surgery. ^[159]

Collagen tissue engineering

Since collagen is widely distributed in various tissues of the human body, it is an important component in each tissue and constitutes the tissue extracellular matrix (Extracelluarmatrix, ECM), which is a natural tissue scaffold material in nature. From the perspective of clinical application, people use collagen to make a variety of tissue engineering branches.

Collagen-based tissue-engineered skin ^[160] Frames such as skin, bone tissue, trachea, and vascular stents. However, in terms of collagen itself, there are two categories, namely, scaffolds made of pure collagen and composite scaffolds compounded with other components. Pure collagen tissue engineering scaffolds have the advantages of good biocompatibility, easy processing, plasticity, and can promote cell adhesion and proliferation, but also have poor mechanical properties of collagen, difficult to shape in water, and can not support tissue reconstruction. Secondly, the new tissue at the repair site will produce a variety of enzymes that hydrolyze collagen and cause the scaffold to disintegrate. Crosslinking or compounding can be used to improve and improve. Collagen-based biomaterials have been successfully used in tissue engineering products such as artificial skin, artificial bone, cartilage transplantation, and nerve catheters. Some people use collagen gels embedded in chondrocytes to repair cartilage defects and try to adapt epithelial, endothelial, and corneal cells to collagen sponges to adapt to corneal tissue. There are also people who mix stem cells and collagen gels in autologous mesenchymal cells to make tendons for post-tendon repair. ^[161-163]

The tissue engineering artificial skin drug sustained-release gel composed of collagen as the dermis and epithelial components is a drug delivery system with collagen as the main component. It is widely used to shape collagen aqueous solutions into various forms of drug delivery systems. Such as ophthalmic collagen protectors, collagen sponges for burns or wounds, protein-transporting microparticles, collagen gel forms, regulatory materials for transdermal administration, and nano-particles for gene transmission. In addition, it can also be used as tissue engineering including matrix of cell culture system, scaffold material of artificial blood vessels and valves, etc. ^[164-165]

Collagen burn

Autologous skin transplantation has been the global standard method for treating second- and third-degree burns. However, for patients with severe burns, the lack of suitable transplantable skin has become the most serious problem. Some people have used bioengineering technology to produce babies through infant skin cells. Skin tissue, this kind of collagen tissue can cure different degrees of burns in a period ranging from 3 weeks to 18 months without autotransplantation, and the newly grown skin rarely shows hypertrophy and resistance . There are also people who use artificially synthesized poly-DL-lactic-glycolic acid (PLGA) and natural collagen to cultivate three-dimensional human skin fibroblasts. The results show that the cells grow faster on the synthetic mesh, and the inside and outside grow almost simultaneously. Proliferating cells and secreted extracellular matrix are more homogeneous. When this fiber is implanted into the back of skinless rats, dermal tissue grows after 2 weeks, and epithelial tissue grows after 4 weeks. ^[166-167]

Collagen beauty

Collagen is extracted from animal skin. In addition to collagen, the skin also contains proteoglycans such as hyaluronic acid and chondroitin sulfate. They contain a large number of polar groups, are moisturizing factors, and prevent the conversion of tyrosine in the skin into melanin. Therefore, collagen has the functions of pure natural moisturizing, whitening, anti-wrinkle and freckle removal, and can be widely used in beauty products. The chemical composition and structure of collagen make it the foundation of beauty. Collagen is similar to the structure of human skin collagen. It is a water-insoluble fibrous sugar-containing protein. The molecule is rich in amino acids and hydrophilic groups. It has a certain surface activity and good compatibility. A lot of hydroxyl groups, so it has a pretty good moisturizing effect. At 70% relative humidity, it can still retain 45% of its own weight. The test proves that: 0.01% pure collagen solution can form a good water-retaining layer and supply all the water needed by the skin. ^[168-171]

With the increase of age, the ability of fibroblasts to synthesize declines. If collagen is lacking in the skin, collagen fibers will be co-solidified, reducing the intercellular mucopolysaccharides, the skin will lose its softness, elasticity and gloss, and aging will occur. Fiber breakage, fat atrophy, and reduced secretion of sweat glands and sebaceous glands in the dermis make the skin appear a series of aging phenomena such as pigmentation and wrinkles. When it is used as an active substance in cosmetics, the latter can diffuse deep into the skin. The tyrosine contained in it competes with the tyrosine in the skin and combines with the tyrosinase catalytic center, thereby inhibiting the melanin It can increase the collagen activity in the skin, maintain the moisture of the stratum corneum and the integrity of the fiber structure, promote the metabolism of the skin tissue, and have a good moisturizing, moisturizing and wrinkle-reducing beauty effect on the skin. As early as the early 1970s, the United States was the first to introduce bovine collagen for injection, which is used to remove spots and wrinkles and repair scars. ^[172-173]

However, in cosmetics, purely used as nutritional skin care raw materials usually require molecular weight below 2KD to allow the hydrolyzed collagen to penetrate into the skin. In addition to the requirement for hydrolyzed collagen to have moisturizing properties, hair care cosmetics should also have a certain film-forming property. Therefore, the molecular weight of the hydrolyzed collagen is required to be higher. ^[174-176]

Collagen food

Collagen can also be used in food. As early as the twelfth century, St. Hilde-gard of Bingen described the use of calf cartilage soup as a medicine to treat joint pain. For a long time, some collagen-containing products were used by people. Think it's good for joints. Because it has some properties suitable for food: Food grades usually have a white appearance, a soft taste, a light taste, and easy digestion. It can reduce blood triglyceride and cholesterol, and can increase certain essential trace elements that are lacking in the body to maintain it within a relatively normal range. It is an ideal hypolipidemic food. In addition, studies have shown that collagen can help eliminate aluminum in the body, reduce the accumulation of aluminum in the body, reduce the harm of aluminum to the human body, and promote the growth of nails and hair to a certain extent. Type II collagen is a major protein in articular cartilage and is therefore a potential autoantigen. After oral administration, T cells can induce immune tolerance and thus suppress T cell-mediated autoimmune diseases. Collagen polypeptide is a product with high digestion and absorption, and a molecular weight of about 2,000 to 30,000, which is obtained after degradation treatment of collagen or gelatin by protease or the like. ^[146] ^[177-178]

Some qualities of collagen make it useful as a functional substance and nutrient in many foods. It has advantages that are difficult to compare with other alternative materials: the helical structure of collagen macromolecules and the existence of crystalline regions make it a certain degree of thermal stability; collagen is naturally compact The fiber structure makes the collagen material show strong toughness and strength, which is suitable for the preparation of thin film materials. Because the collagen molecular chain contains a large number of hydrophilic groups, it has a strong ability to bind with water. This property makes collagen in food It can be used as a filler and gel; collagen swells in acidic and alkaline media. This property is also used in the processing of collagen-based materials. ^[179]

Collagen powder can be added directly to meat products to affect the tenderness of the meat and the texture of the muscles after cooking. Studies have shown that collagen is very important for the formation of raw meat and cooking meat texture. The higher the collagen content, the harder the meat texture. Fish tenderization is considered to be related to V-type collagen degradation, and the lysis of peripheral collagen fibers caused by the destruction of peptide bonds is considered to be the main cause of muscle tenderization. By destroying the hydrogen bonds in the collagen molecule, the original tight supercoil structure is destroyed, and gelatin with smaller molecules and relatively loose structure is formed, which can improve the tenderness of the meat and increase its use value, making it good Quality, increase protein content, both taste good and nutritious. Japan has also developed animal collagen as a raw material, which is hydrolyzed by collagen hydrolase and formulated to develop new condiments and sake, which not only have special flavors, but also supplement some amino acids. ^[28] ^[180-182]

With the increasing proportion of various types of sausage products in meat products, natural casing products are seriously lacking. Researchers are working on the development of alternatives. Collagen casings with collagen as the main ingredient are nutrient-rich, high-protein substances. During the heat treatment process, as the water and fat evaporate and dissolve, collagen has almost the same shrinkage rate as meat food. , And other edible packaging materials have not been found to have this quality. In addition, collagen itself has the function of immobilizing enzymes, has antioxidant properties, and can improve the flavor and quality of food. Product stress is directly proportional to the amount of collagen, while strain is inversely proportional. ^[183-185]

Collagen bone

Collagen is an important component of human bones, especially cartilage tissue. Collagen is like a small hole-filled net in the bone, it will firmly retain the calcium that will be lost. Without this net full of small holes, even if it is supplemented with excessive calcium, it will be lost in vain. The characteristic amino acid hydroxyproline of collagen is a tool for transporting calcium to bone cells in plasma. Bone collagen in osteocytes is a binder of hydroxyapatite, which together with hydroxyapatite constitute the main body of the bone. The essence of osteoporosis is that the rate of synthesizing collagen can not keep up with the need. In other words, the rate of new collagen production is lower than the rate of mutation or aging of old collagen. Studies have shown that if collagen is lacking, no amount of calcium supplementation can prevent osteoporosis. Therefore, only by ingesting enough calcium-binding collagen can calcium be digested and absorbed faster in the body, and Quickly reach the bone site and deposit. ^[186-188]

The collagen-PVP polymer (C-PVP) is prepared by dissolving collagen and polyvinylpyrrolidone in citric acid buffer solution. It is not only effective in strengthening injured bones, but also highly safe, even for long-term continuous medication, Neither the experimental nor clinical trials showed lymphadenopathy, DNA damage, did not cause liver and kidney metabolic disorders, and did not induce the body to produce antibodies against C-PVP. ^[27]

Collagen feed

Collagen powder for feed is a protein product obtained by processing by-products such as leather tannage leathers, skin edges and corners by using physical, chemical or biotechnology methods. The solid waste produced after tanning and trimming in the tannery is collectively called tanning waste residue, and the main component of its dry matter is collagen. After treatment, it can be used as an animal-derived protein nutritional additive to replace or partially replace imported fishmeal for the production of mixed and compound feed, which has better feeding effect and economic benefits. It has a high protein content, is rich in more than 18 kinds of amino acids, contains calcium, phosphorus, iron, manganese, selenium and other mineral elements, and has an aromatic taste. Studies have shown that hydrolyzed collagen powder can partially or completely replace fish meal or soybean meal in growing-finishing pig diets, but the addition ratio cannot exceed 6%. When the content reaches 8%, it significantly reduces production performance and diet digestibility, and increases feeding cost. ^[189-190]

Growth tests and digestion tests have also been performed to evaluate the effectiveness of collagen in replacing fish meal in aquafeeds. In the growth test, 2%, 4% collagen, and other weights were used instead of fishmeal in a basic feed (control group, containing 12% fishmeal) to breed heterozygous silver carp with a total weight of 6.5g (315 fish in total) for 35 days. The body weight gain rates were 71.3%, 70.9%, and 71.9%, respectively. There was no significant difference between the groups (P> 0.05). The digestion test was carried out on the heterozygous silver carp with an average body weight of 110 g. The protein digestibility of collagen is 97.3%. The results show that collagen has a high digestion and absorption rate, and can partially replace fish meal without affecting the weight gain of allogynogenetic silver carp. ^[191]

Collagen other

The relationship between dietary copper deficiency and collagen content in the heart of mice has been studied. Analysis by SDS-PAGE and staining with Coomassie Brilliant Blue showed that detection of altered additional metabolic characteristics of collagen can predict copper deficiency; because liver fibrosis can reduce protein content, it can also be determined by measuring collagen content in the liver To predict liver fibrosis. Anoectochilusformosanus water extract (AFE) can reduce liver fibrosis induced by CCl4 and reduce liver collagen content. Collagen is also the main component of the sclera and its effect on the eyes is very important. If the synthesis of collagen in the sclera decreases and its degradation increases, it can lead to myopia. ^[192-195]