KR100735675B1 - The Processing Method to Improve Efficacy of Collagen by Low-Molecularization and Hydrophilicity, and Collagen Thereof - Google Patents

Abstract

The present invention relates to a manufacturing method for improving the low molecular weight and hydrophilicity of collagen to improve the effective utilization, and a hydrophilic collagen prepared by such a manufacturing method, more specifically lysozyme (lysozyme) to 67 ~ 97.99 parts by weight of collagen 0.01 to 3 parts by weight of the process; Pretreatment with 1-5% citric acid to the collagen treated with lysozyme; Adding 1 to 25 parts by weight of ascorbic acid to the collagen pretreated with citric acid; Mixing the mass ratio of the collagen to which distilled water and the ascorbic acid are added is 1000: 100; And preparing a spherical shape by stirring the surface of the distilled water and collagen under a ultrasonic dispersion of 50 KHz for 1 to 30 minutes at a rotational speed of 600 to 3,000 rpm in a nitrogen dispersion gas atmosphere with a fine dispersion mixer. It relates to a manufacturing method for improving the effective utilization to increase the low molecular weight and hydrophilicity of the collagen comprising a.

Collagen, a kind of light protein, not only has a high molecular weight but also has a poor water affinity, so its absorption rate, metastasis rate and utilization rate are low, and it is easy to change according to various conditions of the living body. There is a limit to the deterioration due to external temperature change and self-endotherm to lose its intrinsic properties and activity.

Therefore, the present invention improves the water affinity by lowering collagen and coating the hydrophilic glucan hydrogel with -cl type, thereby increasing the absorption rate of collagen in the body, lowering the dissolution temperature, and reducing the change factor by increasing the temperature range of collagen. It provides a manufacturing method to improve the effective utilization by improving the low molecular weight and hydrophilicity of the collagen, which has a useful effect of preventing the expansion of the product, as well as removing foaming, moisturizing and protective colloidal properties.

Collagen, protein, -cl water-soluble glucan, low molecular weight, hydrophilic

Description

The Processing Method to Improve Efficacy of Collagen by Low-Molecularization and Hydrophilicity, and Collagen Thereof}

1 is a schematic diagram of the surface composition and action of collagen prepared by a manufacturing method for improving low molecular weight and hydrophilicity of collagen according to the present invention.

2a to 2c are photographs taken by transmission electron microscopy (TEM) of spherical and fluidized phases in the fluid phase of collagen surface-treated with -cl hydrophilic glucan hydrogel according to the present invention. .

Figure 3 is a photograph of the porous bead phase and surface state of the collagen surface treated with -cl type hydrophilic glucan hydrogel according to the present invention by TEM.

The present invention relates to a manufacturing method for improving the low molecular weight and hydrophilicity of the low molecular weight collagen to improve the effective utilization. More specifically, collagen is treated with lysozyme to improve the uniformity of low molecular weight and low molecular weight collagen, and pretreatment with citric acid, an activation factor, to improve the activation rate. Hazardous Ascorbic Acid is added and treated with -cl-type hydrophilic glucan hydrogel to have water affinity. It relates to a manufacturing method for improving the utilization.

Protein is a constituent of the body of the organism and a substance that catalyzes various chemical reactions in the cell. It holds the water or nutrient mixtures to stay and also forms antibodies to form immunity. ) Is a very important organic substance, and its kind is composed of about 20 kinds of living organisms. Collagen is also widely used in animals and aquatic organisms such as bones, cartilage, shells, skin, blood vessel walls, kidney glomeruli, fish shells, scales, jellyfish, starfish and sea cucumbers. It is a natural source material contained. This collagen is a complex fibrous structure that is insoluble in water, dilute acid, and dilute alkali, and dissolves when boiled to become gelatin. It is obtained as gelatinoid. Collagen is not made in unicellular animals but is made in multicellular animals, but it is separated from protein in living tissues. After collagen extraction, acid and alkali treatment, trypsin and hyaluronidase are applied to collagen in insoluble state. collagen).

Protein is one of the five major nutrients, accounting for more than 50% of yeast and composed of 16% of the body weight of an animal, that is, it is a macromolecular organic substance that constitutes the body of all living organisms. Collagen is contained in each part of the human body as much as 30 ~ 40% is made of collagen protein. Such collagen plays an important role in activating cell function and cell proliferation, hemostatic action and macrophages and lymphocytes as immune cells. In addition, as a main component of the radiance, elasticity and tissue composition of the ragen skin, Kohl prevents aging such as osteoporosis and wrinkle removal, and has important functions and compositions in the body such as hemostatic action and antibody action.

In vivo degradation of collagen includes internal proteases (endoprotease), external peptide enzymes (exopeptidase), and peptide peptides (peptidase). Internal proteases include trypsin and chymotrypsin, which break down protein backbones that are linked to residues. External peptide degrading enzymes sequentially remove residues from N-terminus or C-terminus of proteins. Do it. The enzyme that removes from the N-terminus side is called aminopeptidase, and the enzyme that removes from the C-terminus side is called carboxypeptidase. Lastly, peptide degrading enzymes break down oligopeptides into amino acids or peptides linked to two amino acids, or tripeptides linked to three. With the exception of these lysosomes, they are also degraded through the pathway in the cytoplasm.

Most proteins in the cell are synthesized in ribosomes and then change in protein, resulting in changes in protein activity, survival, or the location of the protein in the cell. Changes in proteins are divided into chemical modifications and processing processes. Chemical modifications in which a chemical group is linked to an amino or carboxyl group or to a reactor in a branched chain are called chemical modifications. It is called processing. One of the most common forms of chemical modification is acetylation, in which the acetyl group (CH3CO) is attached to the amino group of the N-terminal. 80% of proteins cause this chemical modification. Collagen obtained by the present invention is also judged to undergo a decomposition process in the body.

In humans, 50% of the collagen is replaced each year, so 5g of collagen should be consumed per day. Collagen production decreases in infancy and at around 18 years of age, causing loss of elasticity and shine, resulting in wrinkles, blotch, and blemishes, weakening bones and joints, and affecting blood vessels and hair. . It is necessary to replace old collagen to revitalize metabolism and to restore the flow of blocked body to normal function, so it is always replaced naturally with new one if it is supplied well such as ingesting new high quality collagen. have. Oral collagen food is supplied to the living body to help collagen production hydroxyproline interacts with ascorbic acid, iron, copper and the like to produce collagen, thereby collagen acts in the body.

Ingestion of most biomaterials as food is limited to its absorption. Collagen also absorbs and disperses such substances as a meal, but the absorption rate varies depending on the degradation characteristics, body formation and tissue characteristics, and various constituent conditions of the living body. In addition, the absorption rate is low, there is a limit that does not reach the validity of the body. Moreover, even in the case of transdermal administration of collagen, the composition of skin tissue is 70 nm, whereas the length of collagen is 300 nm, which is difficult to be absorbed through the skin due to the limitation of the molecular size of collagen. In the case of such an insoluble material, there is a problem in that the bioavailability cannot be increased.

In addition, the form of the protein is changed and the activity is denatured (denaturation), which is mainly due to temperature and heat to degenerate the loss of protein-specific properties, such as collagen, light proteins, such as heat and temperature changes Like proteins, they are easily modified to lose or lose their basic properties, such as their intrinsic properties and activity. In addition, proteins such as collagen are denatured by their endotherms at room temperature, thereby lowering the utilization rate of materials and reducing the range of use.

Thus, the present invention was devised to solve the above problems, by treating the collagen with lysozyme (Lysozyme) to improve the uniformity of the low molecular weight and low molecular weight of the collagen, and the activity of the collagen with citric acid (Citric Acid) And ascorbic acid was added to improve the activation rate, and the surface-activated collagen surface-treated with -cl-type hydrophilic glucan hydrogel in the low-molecular state to provide water affinity. Collagen has a useful effect of increasing the absorption rate and lowering the dissolution temperature, increasing the range of collagen temperature change to reduce or eliminate the change factor, as well as improving the foaming, moisturizing, and protective colloidal properties and preventing the product from expanding. It provides a manufacturing method to increase the effective utilization by improving the low molecular weight and hydrophilicity of As it is.

In the production method for improving the effective utilization of collagen (Collagen) by increasing the low molecular weight and hydrophilicity of the collagen according to the present invention for achieving the above object,

1) administering 0.01 to 3 parts by weight of lysozyme (lysozyme) based on 97 to 99.99 parts by weight of collagen; 2) pre-treating 1 to 5 parts by weight of citric acid (Citric Acid) based on 95 to 99 parts by weight of the collagen treated in step 1); 3) adding 1 to 25 parts by weight of ascorbic acid based on 75 to 99 parts by weight of the collagen pretreated in step 2); 4) mixing and diluting the collagen added with ascorbic acid and distilled water in step 3) such that the mass ratio is 10: 1; And 5) surface treatment of collagen while stirring the distilled water and collagen mixture obtained in step 4) under a ultrasonic dispersion of 50 KHz at a rotational speed of 600 to 3,000 rpm for 1 to 30 minutes in a nitrogen (N ₂ ) gas atmosphere with a fine dispersion mixer. Preparing into a spherical form; Characterized in that it comprises a.

Preferably, the surface treatment is characterized in that the surface treatment with 0.01 to 5 parts by weight of -cl-type hydrophilic glucan hydrogel (glucan hydroxy chloric salt, glucosamic hydroxy chloride, glucan chloric ion type etc) with respect to 95 ~ 99.99 parts by weight of collagen do.

In addition, the surface treatment is characterized in that the surface treatment with 0.01 to 5 parts by weight of -cl-type hydrophilic glucan hydrogel and 0.01 to 5 parts by weight of citric acid to 90 ~ 99.98 parts by weight of collagen.

Also preferably, the surface treatment is characterized in that to increase the surface area 20 ~ 200 times.

Also preferably, the surface-treated collagen is characterized in that the spherical shape (bead) of the size 10 ~ 50nm.

In addition, another object of the present invention is to provide a collagen with improved molecular weight and hydrophilicity by such a manufacturing method is improved effective utilization.

In addition, another object of the present invention is to provide a functional food using collagen with low molecular weight and hydrophilicity is improved by such a manufacturing method is improved effective utilization.

In addition, another object of the present invention is to provide a functional cosmetics using collagen with low molecular weight and hydrophilicity is improved by the manufacturing method is improved effective utilization.

In addition, another object of the present invention is to provide a medical composition using collagen with low molecular weight and hydrophilicity is improved by the production method is improved effective utilization.

Hereinafter, the present invention will be described in detail with reference to Examples. However, the scope of the present invention is not limited to the claims of the present invention by the embodiments or the drawings.

Example 1 Preparation of Low Molecular Collagen

Collagen is reduced in molecular weight by administering 0.01 to 3 parts by weight of lysozyme based on 97 to 99.99 parts by weight of collagen extracted from tuna or shark. The uniformity of low molecular weight was optimal when the lysozyme was 0.01 to 3 parts by weight, and the nonuniformity of the low molecular weight of collagen was high when the lysozyme was 3 parts by weight or more.

Acid treatment to add 1 to 25 parts by weight of ascorbic acid to 75 to 99 parts by weight of the collagen pretreated with citric acid after pre-treatment with 95 to 99 parts by weight of collagen treated with lysozyme Perform the steps. At this stage, when the ratio of citric acid was 1-5 parts by weight and 1-25 parts by weight of ascorbic acid, the optimum conditions for lysozyme enzyme activity (PH 5.5-6) could be established. If the ratio of citric acid and ascorbic acid is outside this range, the activity of lysozyme decreases.

After mixing so that the mass ratio of the collagen to which distilled water and the ascorbic acid were added is 10: 1, in the nitrogen (N ₂ ) gas atmosphere with a fine dispersion mixer, the ultrasonic action of 50KHz at a rotational speed of 600 to 3,000 rpm for 1 to 30 minutes. While stirring the distilled water and collagen, the step of preparing a spherical form by surface treatment of collagen (glucan hydroxy chloric salt) with -cl-type hydrophilic glucan hydrogel.

Thus, the collagen and each mixture were suspended in an aqueous solution to prepare a spherical collagen having a diameter of 10 to 50 nm, and as the reaction proceeds, the suspension maintains stability. Was obtained. At this time, if the diameter of the collagen is 50nm or more, it is difficult to penetrate through the percutaneously, and the finer collagen particles of 10nm or less are difficult to handle, such as adhered to the surface. Do.

 In the surface treatment step, 0.01 to 5 parts by weight of -cl hydrophilic glucan hydrogel is sprayed under centrifugation with respect to 95 to 99.99 parts by weight of collagen to increase the surface area of collagen by 20 to 200 times. 0.01 to 5 parts by weight of -cl hydrophilic glucan hydrogel was found to increase the surface area of collagen 20-200 times.

Example 2 Preparation of Collagen Treated with -cl Hydrophilic Glucan Hydrogel and Citric Acid

In the surface treatment step of Example 1, except that the surface treatment is treated with 0.01 to 5 parts by weight of -cl hydrophilic glucan hydrogel and 0.01 to 5 parts by weight of citric acid in 90 ~ 99.98 parts by weight of collagen same.

The -cl hydrophilic glucan hydrogel (glucan hydroxy chloric salt, glucan chloric ion type etc) has excellent bioavailability and transmission protection, has a cellulose composition and an amino structure at the same time, and has a heat deformation temperature of 265 ° C. as a surface treatment and treatment. It has a feature that makes it possible to exhibit a desired feature, and the difference in the feature exhibiting ability is very large depending on the combination and processing method.

<Example 3.> Toxicity experiment in single oral administration.

The collagen prepared in Examples 1 and 2 was orally administered at 0 and 3,000 mg / kg doses of SD rat cancer, several males. No abnormalities were observed, and weight change was observed to increase on 1 day after administration, but showed normal weight gain after 3 days, and no abnormalities were found by autopsy.

<Example 4.> Immune force experiment.

The collagen prepared in Example 1 and Example 2 was orally administered to BALB / c mice at a dose of 0, 10, 40 mg / kg for 2 weeks and sensitized T cells-dependent cotton erythrocytes 4 days before autopsy with antigen. By autopsy, the weight of immune-related organs of the liver, spleen, and thymus was measured, and the number of cells producing antibodies against sheep cells in spleen cells was measured to calculate the effect of collagen prepared by the present invention on immune function. Evaluated. As a result, the amount of collagen produced in spherical form 10, was at 40mg / kg 1x 10 ⁶ increases spleen cell plaque number of each of 2, 18% sugar, can plaques per spleen is delayed by each of 13, a 27% increase that It was confirmed that there is an immune function phenomenon.

Example 5 Cytotoxicity Experiment

The collagen prepared in Examples 1 and 2 was measured by MTS assay using a PC-12 cell line, and as a positive control using sodium azide (NaN ₃ , sodium azide) 37 48 hours incubation at 5% CO ₂ conditions. The test concentration was 0.2 ml of sodium azide to 0.1, 0.05, 0.001, and 0.005% of the collagen prepared in spherical form, and the absorbance was measured at 490 nm.

<Example 6.> Protein denaturation experiment.

Protein change rate according to the temperature of the collagen prepared in Example 1 and Example 2 was measured, the results are shown in the table below. Generally, protein denaturation occurs at 37 ° C. or higher, but the collagen prepared in Examples 1 and 2 did not appear to denature protein even at 60 ° C. or higher.

Table 1. Protein denaturation experiment data by temperature

Thermal denaturation start temperature (℃)  Thermal denaturation peak temperature (℃) Control group (normal collagen)  35 40 Example 1 77 80 Example 2 77 82

<Example 7.> Ultraviolet ray blocking effect and skin tissue test.

After applying -cl-type water-soluble glucan hydrogel surface-treated collagen prepared in Examples 1 and 2 to the skin, the UV emission and skin tissue were analyzed. The cause of wrinkles on the skin can be seen from collagen deficiency and ultraviolet rays. As a result of this experiment, the sunscreen effect reaches 48% ~ 50%, and collagen is supplemented to make skin tissue solid with tissue organization. It was confirmed that the hardening, tissue collapse, and the length of the wrinkles generation on the skin were long.

<Example 8.> Safety experiment.

In order to confirm the safety of the collagen prepared in Examples 1 and 2, an acute toxicity test, an intradermal reaction test, a hemolytic test, a pyrogenic test, and a tissue transplantation test were performed. The acute toxicity test was carried out by injecting 10 ml of 17-23 g male rats with 1% solution (sample solution) of 50 ml / kg body weight of the test body after 5 days to confirm the abnormality. The intradermal reaction test was compared with the control by sample, and intradermal injection was performed only on one side of the spine of a male rabbit weighing 2.5 kg to confirm abnormal reactions such as erythema, edema, bleeding, and necrosis. In the hemolytic test, a solution prepared in a male rabbit weighing 2.5 kg was put into 10 ml of a sample solution, and 0.1 ml of de-fibrotic blood obtained by removing the fiber from the blood by centrifugation was placed at 37 ° C. for 24 hours, and then judged as having hemolysis. The pyrogenicity test was performed using three male rabbits weighing 2.5 kg or more with a blank test solution as a control, preliminary body temperature was measured by rectal thermometer before injection, and the test solution and blank test solution were injected into the ear vein by 1 ml per 1 kg of weight. The change in body temperature was measured three times per hour to determine the suitability for the determination below 0.6 ° C. In the tissue transplantation test, eight pellet-type specimens were prepared using a 10 mm long and 1 mm wide syringe as a net raw material of the prepared plastic and the prepared solution.They were washed well with neutral detergent and water and sterilized. Two male rabbits weighing more than 2.5 kg were used. Insert the sample into the sterilized gauge needle in advance, and transplant it using a needle stylet at a distance of 2.5cm with a distance of about 3.5cm from the spine of the test animal. Muscle tissues were collected, stained with hematoxylin and eosin, and observed with an optical microscope. No abnormality was observed to confirm the suitability.

Table 2. Safety Tests

Acute Toxicity Test Intradermal reaction test Hemolytic test Pyrogenicity test Tissue Transplantation Test Abnormality Erythema, edema, bleeding, necrosis Hemolysis Formation Temperature change for 1 hour Location of abnormal test animals Example 1 radish radish radish 0.5 ℃ 0.5 places Example 2 radish radish radish 0.4 ℃ 0.4 places

<Example 9.> Surface structure and schematic diagram of the spherical low molecular collagen

1 shows a surface structure and a schematic diagram of a low molecular collagen of a spherical bead prepared in Example 1. FIG. The hydrophilic part and the lipophilic part were formed separately by forming a band, forming a micelle, and the hydrophilic part constituted the outside of the micelle and the lipophilic part constituted the inside of the micelle, and the overall water solubility was increased. Absorption into the body in the form of collagen, when the body is working when the micelle was decomposed back to its original form was confirmed.

<Example 10.> Absorption, dispersion use comparison experiment

12 hours in each organ of the rat after injection into the tail vein of a normal rat 200g of a test animal prepared by the surface treatment of the collagen solution prepared in Example 1 and Example 2 with a 1% solution The extent of absorption and dispersion after 24, 48 and 72 hours were compared. Tables 3 to 4 are dispersion and absorption (transition) utilization comparison tables confirmed by cell collection after each time after the injection of FITC (fluorescent target material) to the collagen prepared in Examples 1 and 2 above.

Table 3: Absorption (transition) utilization comparison table of Example 1

liver kidney Pancreas lungs blood Urinary 12 hours 80% 77.1% 67% 76% 95% 94.3% 24 hours 81.1% 78.2% 67.6% 77% 95.2% 94.8% 48 hours 82.0% 79.2% 69% 78.2% 96.0% 94.9% 72 hours 83,3% 80% 71% 79% 96.1% 95.5%

Horizontal term of table: RECOVERY RATIO (%), Vertical term: test material

Recovery Ratio (%) = (mass of discharge FITC / mass of input FITC) × 100

Based on 100 masses of FITC attached to collagen, after 72 hours after circulation of each organ, the collagen was dissolved and absorbed (transferred) by the human body, and the fluorescent substance was separated from collagen and discharged almost all into urine. I could see that.

Table 4: Absorption (transition) utilization comparison table of Example 2

liver kidney Pancreas lungs blood Urinary 12 hours 80% 77.2% 67% 77% 95% 94.4% 24 hours 81.1% 78.2% 67.7% 77.3% 95.4% 94.8% 48 hours 82.4% 79.5% 69.5% 78.2% 96.0% 95.1% 72 hours 83,5% 81% 72% 79.5% 96.4% 95.8%

In the case of Example 2, it can be seen that there is no significant difference from Example 1.

<Example 11.> Dissociation phase distribution and size of collagen surface-treated with -cl hydrophilic glucan hydrogel

Figures 2a to 2c is a translucent electron microscope (TEM, constituent formation phase and flow-utilized phase in the aqueous phase of collagen surface treated with -cl type hydrophilic glucan hydrogel prepared by the method of Example 2 according to the present invention) Photo taken with transmission eletron microscopy.

Since the use of existing proteins is known only as a method of proteolysis and synthesis of hormones in the body, it is difficult to calculate the effective utilization rate of proteins because there are many variables due to factors and deviations that calculate utilization rates of actual utilization of proteins. have. Therefore, by taking a method of judging the distribution and size of the dissociation phase in the water-affinity state of high water content in the body composition, it is possible to more effectively measure the effective utilization rate of the actual protein, and thus the preparation method of Example 2 in this example. The distribution and size of the collagen surface-treated with the -cl hydrophilic glucan hydrogel prepared by the present invention were measured, and the results are shown in FIGS. 2A to 2C.

The size of collagen surface-treated with -cl hydrophilic glucan hydrogel prepared by the preparation method of Example 2 in Figure 2a has a size suitable for absorption and dispersion at 50nm, the shape of the collagen is a spherical shape with a maximum surface area It was confirmed that it was comprised and formed the core inside.

Figure 3 is a photograph taken by TEM of the porous bead phase and the surface state of the collagen surface treated with -cl-type hydrophilic glucan hydrogel according to the present invention is easy to absorb (transition) by increasing the uniformity of low molecular weight and low molecular weight You can see that you can.

Although the preferred embodiments of the present invention have been shown and described above, the present invention is not limited to the above-described embodiments, and the general knowledge in the field of the present invention without departing from the gist of the present invention as claimed in the following claims. Anyone with a variety of modifications are possible, of course, such modifications will be within the scope of the claims.

As described above, the collagen according to the present invention does not cause degeneration even when the treatment reaction temperature is 37 ° C. or higher, and may improve absorption in the human body by increasing the low molecular weight and water solubility of collagen. In addition, it has excellent colorability as foaming, moisturizing and protective colloid. It can bring about the effect of preventing expansion of the product. It also increases or decreases the change factor by increasing the temperature range of collagen. The effective utilization rate can be further increased.

In addition, the collagen produced by the manufacturing method according to the present invention prevents abnormality of specific proteins or bio-organic materials to increase safety and change to water affinity, thereby making it possible to further increase the utilization of functional foods, household goods, and cosmetic materials. Can have great value.

Claims (10)

1) treating by mixing 0.01 to 3 parts by weight of lysozyme with respect to 97 to 99.99 parts by weight of collagen; 2) pretreatment by mixing 1 to 5 parts by weight of citric acid with respect to 95 to 99 parts by weight of the collagen treated in step 1); 3) adding 1 to 25 parts by weight of ascorbic acid based on 75 to 99 parts by weight of the collagen pretreated in step 2); 4) mixing the collagen added ascorbic acid and distilled water in the step 3) at a mass ratio of 1:10; And 5) Collagen is -cl-type hydrophilic under a nitrogen dispersion (N ₂ ) gas atmosphere, while stirring the mixture of distilled water and collagen obtained in step 4) under an ultrasonic action of 50 KHz at a rotational speed of 600 to 3,000 rpm for 1 to 30 minutes. Surface-treating with glucan hydrogel to prepare spherical forms; Production method for improving the effective utilization to increase the low molecular weight and water affinity of the collagen comprising a. The method of claim 1, wherein the surface-treated collagen has a spherical shape having a size of 10 to 50 nm, thereby increasing the low molecular weight and water affinity of the collagen. According to claim 1, The surface treatment is to increase the low molecular weight and water affinity of the collagen, characterized in that the surface treatment by administering 0.01 to 5 parts by weight of the -cl-type hydrophilic glucan hydrogel with respect to 95 to 99.99 parts by weight of the collagen Manufacturing method for improving the effective utilization rate. According to claim 1, wherein the surface treatment is a low molecular weight collagen, characterized in that the surface treatment by administering 0.01 to 5 parts by weight of the -cl-type hydrophilic glucan hydrogel and 0.01 to 5 parts by weight of citric acid to 90 ~ 99.98 parts by weight of the collagen Manufacturing method for improving effective utilization by increasing the affinity and water affinity. The method of claim 1, wherein the -cl-type hydrophilic glucan hydrogel is made of any one of the glucan hydroxy chloric salt, glucosamine hydroxy chlorine and glucan chloric salt, glucan chloric ion type The manufacturing method for improving the effective utilization to increase the low molecular weight and water affinity of collagen. The method of claim 5, wherein the surface treatment is 20 to 200 times the surface area of the collagen, characterized in that to increase the low molecular weight and water affinity, the manufacturing method for improving the effective utilization. The collagen which improved the effective utilization by lowering molecular weight and water affinity by the manufacturing method of any one of Claims 1-6. delete delete delete

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