KR102584027B1 - Method for extracting polydeoxyribonucleotides and polynucleotides derived from algae with the effect of neovascularization and cell regeneration - Google Patents

Abstract

The present invention is a method of extracting polydeoxyribonucleotides (PDRN) from seaweed and producing low-molecular-weight PDRN through a low-molecular process to a size of 50 kDa or less with excellent skin and tissue penetration. More specifically, it is a method of producing low-molecular-weight PDRN. It provides an economical and safe method of extracting low-molecular-weight PDRN by minimizing the use of organic solvents and processing steps by using eco-friendly and safe materials without using substances such as phenol.

Description

Polydeoxyribonucleotides and polynucleotides derived from seaweed having neovascularization and cell regeneration effects {Method for extracting polydeoxyribonucleotides and polynucleotides derived from algae with the effect of neovascularization and cell regeneration}

The present invention extracts polydeoxyribonucleotides (PDRN) from marine ecologically disturbing species and seaweeds that can be produced all year round, are economical, and are eco-friendly, and undergoes a small molecule process to produce a small molecule with excellent skin and tissue penetration of less than 50 kDa. This is a method of manufacturing PDRN. More specifically, it relates to low-molecular-weight PDRN derived from seaweed that is eco-friendly and economical and safe by minimizing the use of organic solvents and processing processes by using plant-based eco-friendly and safe materials without using substances such as phenol, which are harmful to the human body.

Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) have viscoelasticity, a characteristic of polymers, and at the same time exhibit tissue repair effects when injected intradermally. In other words, it becomes the main ingredient of a new concept of tissue restoration medical device that can induce the regeneration of skin tissue rather than a simple skin filler by proliferating and activating the fibroblasts that make up skin tissue and promoting the secretion of extracellular matrix such as collagen.

This is a cell growth activator. As a tissue regeneration material, it has a special effect on regenerating tissues in our body such as ligaments, tendons, and skin and relieving inflammation. This is a substance that is contained in very small amounts in the human placenta, but there are ethical issues and difficulties with pharmaceutical productivity, so PDRN in fish was developed as an alternative.

PDRN and PN contain phosphoric acid and the four bases adenine, guanine, thymine, and cytosine, and the structure in which the four bases, deoxyribose, and phosphoric acid are combined forms a repeating unit to form a high molecular weight double-stranded polymer. Additionally, four types of bases, adenine (A), guanine (G), cytosine (C), and uracil (U), sugar, and phosphate become repeating units to form a single-stranded polymer (hereinafter abbreviated as gene). )am.

These genetic materials such as DNA or RNA can be hydrolyzed and are distributed in all living things either bound to proteins or in a free state. Single-stranded RNA in a free state forms a hairpin structure by forming hydrogen bonds between complementary parts, thereby partially forming a double strand.

Compared to other tissues, the sperm or egg of an animal or the growth point of a plant has relatively high PDRN and PN content, and these genetic materials are divided into efficiency and effectiveness depending on low molecule, high molecule, and extraction method, and the final product is It is known that PDRN and PN are made of small molecules with guaranteed safety, form a complex with the adenosine A2 Receptor, promote VEGF secretion, induce angiogenesis, and activate fibroblasts, osteoblasts, and cartilage cells.

Domestic Published Patent No. 10-2019-0139633 and Domestic Registered Patent No. 10-2031152 disclose a method for extracting PDRN, but the preceding literature does not cover a method for extracting PDRN from animals. This is different from the original invention.

Currently, in the case of animal-derived PDRN, there is a possibility of contamination with viruses derived from animal tissue and it is difficult to continuously secure raw materials. Accordingly, we aim to produce functional small molecule PDRN that can secure both safety and stability by solving the above problems by using marine ecologically disturbing species and seaweed that can be produced all year round and are economical and eco-friendly.

The present invention relates to a low-molecular-weight process method for extracting PDRN from seaweed (comprehensively seaweed), and specifically, to extract PDRN from seaweed (generally seaweed) or marine ecologically disturbing species (seaweed, etc.). We aim to provide an economically cost-saving method of extracting PDRN by extracting PDRN in a minimal process without using toxic substances.

In addition, it provides an eco-friendly method and a method of extracting and purifying genetic materials such as PDRN (polydeoxyribonucleotide) or PN (polynucleotide), which have cell-activating effects, from eco-friendly raw materials such as seaweed. In particular, the present invention isolates genetic material such as PDRN and PN from all tissues other than specific tissues of seaweed (comprehensively seaweed), and produces a mixture of low-molecular-weight PDRN and PN that activates adenosine A2 receptor from the obtained seaweed-derived gene mixture. Provides a manufacturing method.

Domestic Patent Publication No. 10-2019-0139633 discloses a method of extracting PDRN from the semen and testes of salmonid fish with high efficiency in a process and cost-effective manner without using organic solvents such as phenol. . Domestic registered patent number 10-2031152 contains a salmon-derived polydeoxyribonucleotide (PDRN, polydeoxyribonucleotide)-polymer complex, a PDRN core-shell nanocapsule containing salmon cartilage enzyme decomposition product and salmon oil by treating salmon cartilage extract with a hydrolytic enzyme. It relates to a method of manufacturing a skin-improving functional cosmetic composition and a cosmetic composition prepared thereby. Accordingly, skin containing core-shell nanocapsules with polydeoxyribonucleotides that protect the skin-improving ingredients of salmon to prevent degeneration and can easily penetrate into the dermis of the skin to improve whitening, wrinkles, and pore improvement effects. Disclosed is an improved functional cosmetic composition and a method for manufacturing the same. Domestic Patent Publication No. 10-2018-0060693 relates to a cosmetic composition with improved skin wrinkle removal and elasticity improvement effects, and includes a culture medium cultured with human-derived perivascular stem cells and polydeoxyribonucleotides; Disclosed is a cosmetic composition with improved skin wrinkle removal and elasticity improvement effects, which has the advantage of suppressing the formation of wrinkles on the user's skin, removing wrinkles, and improving skin elasticity.

Jong-Guk Yoon and 4 others, Effect of low-molecular-weight polydeoxynucleotide (PDRN) on surgical wound healing in rats, J. Soc. Cosmet. Sci. Korea, Vol. 41, No. 4, December 2015, 401-41

In order to solve the risk of virus contamination in existing salmon, trout, etc. (animal raw materials) and limitations in the supply of raw materials, it is possible to smoothly supply raw materials such as seaweed, kelp, seaweed, etc., and soybean, Coix, green tea extract, soybean fatty acid, tocopherol cocamidopropyl betain, and olive oil carboxylate are added to provide genetic material with a molecular weight between 50kDa and 20000kDa.

As mentioned above, it does not use harmful substances such as phenol and sodium hydroxide, which are previously used to isolate genetic material derived from tissues containing the growth point of natural seaweed that is not of animal origin and is safe from the risk of viral infection, while also using the manufacturing process and low-molecular-weight We aim to provide PDRN and PN with price competitiveness by simplifying the process.

The present invention provides polydeoxyribonucleotides and polynucleotides purified and extracted from seaweed. The seaweed may be one or more selected from maesaengi, mojaban, kelp, seaweed, and seaweed.

The seaweed of the present invention contains 10% by weight of soybeans, 10% by weight of coix seed, 20% by weight of green tea extract, 20% by weight of soybean fatty acid, 20% by weight of tocopherol and cocamidopropyl betaine, It can be obtained by preparing and adding a protein dissolution mixed solution consisting of 20% by weight of olive oil carboxylate to dissolve the protein, then adding ribonuclease to separate and react the polynucleotide and polydeoxyribonucleotide mixture. In addition, the polydeoxyribonucleotide and polynucleotide extracted in the present invention are characterized by a molecular weight of 5kDa-20000kDa.

The present invention uses eco-friendly seaweed or seaweed, which has a smooth supply of raw materials, and uses eco-friendly raw materials rather than hazardous substances in the process, thereby ensuring safety. In addition, it uses physical methods in the extraction and small molecule process, so it can be used by conventional methods. A more economical and effective PDRN can be used.

Figure 1 shows a schematic diagram of a method for extracting low-molecular-weight polydeoxyribonucleotides and polynucleotides using seaweed.
Figure 2 shows the electrophoresis results according to Experimental Example 1 of the present invention.
Figure 3 shows the results of an in vitro neovascularization experiment for low-molecular-weight processed PDRN derived from seaweeds (maesaengi, mojaban, kelp, seaweed, seaweed, etc.), existing salmon-derived high-molecular PDRN, and the control group.
Figure 4 shows the results of in vitro cell regeneration experiments on low-molecular-weight processed PDRN derived from seaweed (maesaengi, mojaban, kelp, seaweed, seaweed, etc.), existing salmon-derived polymer PDRN, and control.

The terms polydeoxyribonucleotide (PDRN) and polynucleotide (PN; polynucleotide) referred to in the present invention include phosphoric acid and the four bases adenine, guanine, thymine, and cytosine, and include the four bases, deoxyribose, and phosphoric acid. The combined structure constitutes a repeating unit to form a high molecular weight double-stranded polymer or a low molecular weight double-stranded polymer, and in addition, four types of adenine (A), guanine (G), cytosine (C), and uracil (U) It refers to genetic material (hereinafter abbreviated as gene) in which bases, sugars, and phosphoric acids become repeating units to form a single-stranded polymer.

In addition, the molecular weight of the low-molecular-weight polydeoxyribonucleotide and polynucleotide produced in the present invention may be 5kDa-20000kDa, and more specifically, the low-molecular-weight polydeoxyribonucleotide may be 5kDa or less.

The present invention minimizes the use of biphenols and organic solvents by using seaweed, including seaweed, mosaengi, kelp, seaweed, seaweed, etc., to improve the problem of supply of raw materials other than animal raw materials and the risk of mixing viruses, and by using the existing centrifugation method. By using the vacuum extraction method, the process and cost were minimized. Additionally, the low-molecular-weight process was carried out using non-toxic substances and physical processes without using toxic substances such as sodium hydroxide and hydrochloric acid.

Hereinafter, the method of extracting seaweed-derived polydeoxyribonucleotides with neovascularization and cell regeneration effects according to the present invention using the biphenol method will be described in detail with accompanying drawings.

Figure 1 shows a schematic diagram of polydeoxyribonucleotide and polynucleotide extraction method. The method of extracting polydeoxyribonucleotides derived from seaweed of the present invention, which is comprehensively derived from seaweed, such as seaweed, mosaengi, kelp, and seaweed, includes the step (a) of securing raw materials of drying and pulverizing seaweed; Prepare a mixed solution consisting of 10% by weight of soybean extract, 10% by weight of coix extract, 20% by weight of green tea extract, 20% by weight of soybean fatty acid, 20% by weight of tocopherol cocamidopropyl betaine, and 20% by weight of olive oil carboxylate. and adding it to the dried and pulverized seaweed raw material through step (a) to dissolve the protein, and then adding ribonuclease to separate and react the polynucleotide and polydeoxyribonucleotide mixture. Protein removal. and decomposition step (B); Impurity removal and purity separation step (c) of centrifuging the mixture that has gone through step (b) to remove impurities, filtering, and drying to pure isolate polydeoxyribonucleotides and polynucleotides; A washing and drying step (d) of washing and drying the polydeoxyribonucleotides and polynucleotides purified through step (c); The result dried in step (d) above is diluted by adding 1 ml of 1% sodium purified water, then treated with fermented acetic acid for 10 minutes, followed by sonication for 10 minutes, and then centrifuged to produce low-molecular-weight polydeoxyribonucleotides and polynucleotides. Small molecule process step (e) to secure; It can be comprised of a quality inspection step (b) in which the DNA absorbance of the resultant from step (e) is measured to confirm low-molecular-weight polydeoxyribonucleotides and polynucleotides of 99% purity with a value of 1.7 to 2.0 and powdered.

(A) Raw material procurement stage

The raw material securing step (a) of the present invention includes drying seaweed and removing and decomposing proteins. The seaweed referred to in the present invention may be one or more selected from seaweed, mosaengi, kelp, seaweed, and seaweed. The prepared seaweed is dried and ground.

(B) Protein removal and degradation step

The protein removal and decomposition step (B) of the present invention includes 10% by weight of soybean extract, 10% by weight of coix extract, 20% by weight of green tea extract, 20% by weight of soybean fatty acid, 20% by weight of tocopherol and cocamidopropyl betaine, Prepare a mixed solution consisting of 20% by weight of olive oil carboxylate. The prepared mixed solution is added to the dried and pulverized seaweed raw material through step (a) to dissolve the protein, and after protein dissolution, ribonuclease is added to separate and react the polynucleotide and polydeoxyribonucleotide mixture. May include steps.

The soybean extract, coix extract, and green tea extract that make up the mixed solution are obtained by adding each material and distilled water in a 1:5 ratio, heating at 100 degrees for 2 to 3 hours, and freeze-drying the hot water-extracted solution to obtain each powder. Each powder is mixed in the respective mixing ratios constituting the mixed solution and mixed with distilled water of the same weight as the mixed powder to prepare a solution. Here, soybean fatty acid, tocopherol cocamidopropyl betaine, and olive oil carboxylate are mixed in respective proportions to complete the mixed solution. The above sloybean) fatty acid, tocopherol cocamidopropyl betaine, and olive oil carboxylate were commercially available products.

The mixed solution prepared to remove the polysaccharide, dissolve cells, and decompose proteins can be dissolved by adding 40 ml of the seaweed raw material weight per 1 g in step (a).

After the protein dissolution step, 0.1 ml of ribonuclease can be added per 1 g weight of the seaweed raw material in step (a) to separate the PN (Polynucleotide) / PDRN (Polydeoxyribonucleotide) mixture. The substance added to remove and decompose the protein in step (b) according to the present invention is an eco-friendly decomposition enzyme, which can ensure stability compared to existing methods.

(c) Impurity removal and pure water separation step

The impurity removal and pure water separation step (c) includes the step of centrifuging the mixture that has undergone step (b) above to remove impurities, filtering, and drying to pure isolate polydeoxyribonucleotides and polynucleotides.

The mixture that passed step (b) above was centrifuged at 2000 rpm for 1 hour to obtain a supernatant. Afterwards, the obtained supernatant was diluted with purified water 1:1 by volume and centrifuged at 5000 rpm for 30 minutes to further separate the supernatant and remove residue.

Afterwards, purified water is added twice the volume of the separated supernatant, and filtering is performed for 30 minutes using a 500 mbar vacuum pressure pump using a micro filter. The filter paper that has completed filtering is dried at room temperature for 1 hour.

The separation step is generally performed by centrifugation to recover the supernatant, but in the present invention, it was possible to separate high-purity polydeoxyribonucleotides and polynucleotides by using vacuum pump pressure and a micro filter in parallel.

(D) Washing and drying steps

The washing and drying step (d) of the present invention includes washing and drying the polydeoxyribonucleotide and polynucleotide purely separated through step (c). Add 10 ml of purified water to the dried filter paper and dry the filtered product through step (c) for 1 hour at 30-60 degrees Celsius.

(E) Small molecule processing steps

In the small molecule process step (e) of the present invention, the result dried in step (d) is diluted by adding 1 ml of 1% sodium purified water, treated with fermented acetic acid for 10 minutes, followed by sonication for 10 minutes and centrifuged. It includes the step of securing low-molecular-weight polydeoxyribonucleotides and polynucleotides.

The result dried in step (d) above is diluted by adding 10 ml of 1% sodium purified water, and 10 ml of fermented acetic acid mixed with apple and rice in a 1:1 ratio based on volume ratio is added and treated at 30-60°C for 30 minutes. .

Afterwards, sonication treatment was performed for 10 minutes, then transferred to a micro-filter column and centrifuged at 8000 rpm for 10 minutes. Afterwards, 5 ml of purified water was added and centrifugation was performed at 12,000 rpm for 2 minutes to obtain the final low-molecular-weight polydeoxyribonucleotide and polynucleotide.

(f) Quality inspection stage

The quality inspection step (b) of the present invention involves measuring the DNA absorbance of the resultant from step (e) above, confirming low-molecular-weight polydeoxyribonucleotides and polynucleotides of 99% purity with a value of 1.7 to 2.0, and powdering them. Includes. DNA absorbance according to the present invention is measured using Thermo's nanodrop-1000 equipment, and when the 260 (DNA)/280 nm (protein) value is between 1.7 and 2.0, purity is determined to be 99%.

The concentration of the DNA stock solution is measured by measuring the absorbance (A) at 260 nm using a spectrophotometer. To check the purity of the extracted PDRN, the absorbance is measured at 260/280 nm and the ratio is 1.7 to 2.0. It is judged to have a purity of 99% or higher. In the case of general PDRN purity measurement, the content is measured using DNA absorbance, and if the value is 1.7 to 2.0, it can be considered to have a high purity of more than 99% on average.

The method according to the present invention uses seaweed as a raw material to generate external mucilage and polysaccharide, which requires a process to remove them. It is more environmentally friendly and stable because it decomposes without using harmful substances such as biphenol, sodium hydroxide, and hydrochloric acid. It is effective and uses sea plants rather than animals as raw materials, which reduces the possibility of virus introduction and is effective in reducing economic costs.

In addition, the present invention is intended to solve the risk of virus contamination and limitations in raw material supply in existing salmon, trout, etc. (animal raw materials), and enables smooth supply of raw materials and economical and eco-friendly seaweed such as maesaengi, mojaban, kelp, seaweed, and seaweed. And it is possible to extract genetic material with a molecular weight of 5kDa-20000kDa or less than 5kDa by reducing eco-friendly materials and processing processes from the tissues of marine ecologically disturbing species.

As described above, the manufacturing process is simplified to extract and extract genetic material derived from tissues containing the growth point of natural seaweed that is not of animal origin and is safe from the risk of viral infection. It is possible to reduce small molecule processing time and manufacture PDRN and PN with price competitiveness. Hereinafter, the present invention will be described in detail with an experimental example as follows.

Experimental Example 1. Small molecule electrophoresis experiment

According to Experimental Example 1 of the present invention, electrophoresis experiments were conducted on polymer PDRN, which is currently used for medical purposes, and low-molecular PDRN, derived from seaweed, prepared by the method according to the present invention.

Figure 2 shows the electrophoresis results according to Experimental Example 1 of the present invention. In general, a low-molecularization process is necessary for effective skin absorption, tissue penetration, and absorption rate. Therefore, as can be seen from the results of this experiment, it is believed that genetic material produced through a small molecule process of 5 kDa or less can increase the penetration and absorption rate in tissues, skin, etc. in the future.

Experimental Example 2. In vitro neovascularization experiment

Experimental Example 2 of the present invention is a photograph of the results of an in vitro neovascularization experiment on small molecule processed PDRN derived from seaweed (maesaengi, mosaengi, kelp, seaweed, seaweed, etc.), the existing salmon-derived polymer PDRN, and the control group, showing the formation of new blood vessels. was analyzed under a microscope through a tube formation experiment using human umbilical vein endothelial cells, which is an essential process for the supply of nutrients and oxygen in the wound healing process.

After adding 20% FBS, Growth factor, and 1% penicillin/streptomycin to EGM2 medium, culture the cells, coat the plate with 50 ㎕ of 1X Matrigel, distribute HUVEC (3x10 ⁵ cell/ml), and dispense reagents (control group, experimental group, VEH (experimental group) 4 hours later, tube formation was confirmed (control group treated with only the solvent used in , other company's product).

Figure 3 shows the results of an in vitro neovascularization experiment for low-molecular-weight processed PDRN derived from seaweeds (maesaengi, mojaban, kelp, seaweed, seaweed, etc.), existing salmon-derived high-molecular PDRN, and the control group. As a result, the formation of new blood vessels is an essential process for the supply of nutrients and oxygen in the wound healing process. As a result of microscopic analysis through a tube formation experiment using human umbilical vein endothelial cells, the seaweed of the present invention (Maesaengi, It was confirmed that the tube formation effect of low-molecular-weight PDRN substances (such as caps, kelp, seaweed, seaweed, etc.) increased by more than 30% compared to other companies' products and by about 100% compared to the control.

In the case of tube formation, it is a new blood vessel formation experiment, which is essential for the supply of nutrients and oxygen and the removal of waste products during the wound healing process. The experiment is a tube formation experiment using human umbilical vein endothelial cells (HUVEC), and a migration assay is performed. By verifying whether HUVEC cells migrate by PDRN, the effect of PDRN in inducing tube formation of human umbilical vein endothelial cells on Matrigel was confirmed.

Experimental Example 3. In vitro cell regeneration experiment

In Experimental Example 3 of the present invention, an in vitro cell regeneration experiment was conducted on small molecule processed PDRN derived from seaweed (maesaengi, mosaengi, kelp, seaweed, seaweed, etc.), existing salmon-derived polymer PDRN, and a control group.

In the case of wound healing, the continuity of wound tissue refers to the state of its original continuity due to external action, and tissue mainly refers to the skin. The skin is the largest organ in our body and is protected from external stimulation and risk of infection. It plays a primary defensive role. The skin is made up of the epidermis and dermis, and the epidermis is layered in the order of the basal layer, spinous layer, granular layer, and stratum corneum from the inside. The keratinocytes that make up the epidermis are basal cells produced through cell division and are called polar cells. After differentiating into granular cells and keratinocytes in that order, the metabolism (turnover) of exfoliation from the surface as flakes is repeated, and the process is as follows.

In the wound healing stage, when a person's skin tissue is damaged for any reason, a reaction to heal the wound begins immediately. This is a process that occurs in all wounds regardless of the type of wound healing. Let's look at each reaction step by step. As follows.

1) Inflammatory stage: When a wound occurs, cells (hematophages, white blood cells, macrophages, etc.) in the damaged blood vessels around the wound are activated to remove bacteria, foreign substances, necrotic tissue, etc., and various active substances are secreted from these cells. Step to stimulate skin cells around the wound

2) Epithelialization stage: A stage in which skin cells (epithelial cells) on the wound surface undergo cell division to differentiate and move, and the entire wound is filled with dividing epithelial cells.

3) Proliferation stage: This is the stage in which the cytoplasm and cell matrix proliferate and mainly involves collagen synthesis.

4) Maturation stage: A stage in which the balance between collagen production and decomposition is achieved within the scar tissue formed through the epithelialization and proliferation stages.

The above reactions overlap without a clear distinction and go through a series of stages. A wound is a destruction of the normal tissue continuum due to a physical or chemical wound or bacterial infection, causing various cellular and molecular aftereffects. Wound healing is carried out in a special way. It is a systematic biochemical and cellular process that induces the growth and regeneration of injured tissue, and is a complex process that involves interactions between blood cells, cytokines, and growth factors to restore damaged skin or tissue to a normal state.

In addition, it is important to allow wounds to heal as early as possible. If the wound remains open for a long time, secondary complications such as infection may occur, and pain and discomfort in daily life may occur during the treatment period, so the wound must be closed early. do.

However, due to the indiscriminate use of synthetic drugs in some areas, the emergence of pathogenic microorganisms with immunity to antibiotics has increased, and the high price and side effects of synthetic drugs have emerged as a major problem in disease treatment, with better bioactivity potential and side effects. Continued development of these small drugs is required.

Accordingly, in Experimental Example 4 of the present invention, after adding 10% FBS and 1% penicillin/streptomycin to DMEM medium, culturing the cells, dispensing HaCaT on a plate ( ^2x105 cell/ml), incubating for 4 hours, and starvating HaCaT in serum-free medium. After 16 hours of incubation, scratches were made on the plate, and 24 hours after dispensing reagents (control group, experimental group, VEH (control group treated with only the solvent used in the experimental group), third-party product), wound healing was confirmed, and human epithelial cell line (HaCaT)-wound healing model: As a result of analyzing with a microscope the extent to which cells move by scratching a confluent cell, the narrower the range of the scratch, the more effective the regeneration is. The graph quantifies the scratch area, and the lower the value, the more effective it is. can see.

Figure 4 shows the results of in vitro cell regeneration experiments on low-molecular-weight processed PDRN derived from seaweed (maesaengi, mojaban, kelp, seaweed, seaweed, etc.), existing salmon-derived polymer PDRN, and control. As a result of analyzing the extent of cell migration by scratching a human epithelial cell line (HaCaT) using the wound healing model, it was found that the low-molecular-weight PDRN material of the seaweed of the present invention (maesaengi, mosaengi, kelp, seaweed, seaweed, etc.) was found to be a product of other companies. It was confirmed that the wound healing effect increased by more than 5% and by more than 25% compared to the control group.

The present invention provides a method of isolating genetic material such as PDRN and PN from all tissues, not just specific tissues of seaweed, and producing a low-molecular PDRN and PN mixture that activates adenosine A2 receptor from the obtained seaweed-derived gene mixture, thereby providing a new method. It has angiogenesis and cell regeneration effects, so it has the potential for industrial use as it satisfies the needs of related consumers and helps increase profits in related industries.

Claims (3)

A composition that is isolated and extracted from seaweed and has a skin regenerative effect containing polydeoxyribonucleotides and polynucleotides with a molecular weight of 5kDa to 40kDa. delete delete