TWI228991B - Pharmaceuticals, foods, beverages, feeds or cosmetics inducing growth factor production - Google Patents

Abstract

Remedies or preventives for diseases with a need for a growth factor production-inducing effect, characterized by containing member(s) selected from the group consisting of acidic polysaccharides and degradation products thereof, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols and salts thereof each having an effect of inducing the production of growth factor; foods, drinks or feeds for inducing the production of growth factor; cosmetics for inducing the production of growth factor; and growth factor production regulators.

Description

1228991 A7 B7 V. Description of the Invention (!) Technical Field The present invention relates to the use of a physiologically active acid sugar compound in medicine, food, beverages, feed or cosmetics. BACKGROUND ART Acidic polysaccharides obtained from seaweeds are known as green alga-derived rhamnosulfuric acid, red algae-derived sulfated galactan, and brown algae-derived sulfated fucose containing sulfated polysaccharides such as polysaccharides. For example, fucoi dan is a sulfated horsetail sugar contained in brown algae, echinoderms and the like, which contains a polysaccharide, which uses sulfated horsetail as the unit sugar. In addition, shark cartilage and the like also contain sulfated polysaccharides. The physiological effects of sulfated polysaccharides, such as fucoidan, are known to include cancer proliferation inhibitory activity, cancer metastasis inhibitory activity, anticoagulant activity, and antiviral activity, etc., and their development as a pharmaceutical product is expected. Heparin, aceto heparin sulfate, and low-molecular-weight heparin with an average molecular weight of 4400 to 5600 (Japanese Patent Application Laid-Open No. 6-312941) and the like have substances that induce hepatocyte proliferation factor production. There is no report on the induction of polysaccharides, such as algal, synthetic sulfated polysaccharides, and other growth factors. The opening of the invention reveals that the present invention discovers new physiological effects of various acidic sugar compounds, such as acid polysaccharides such as algal polysaccharides, and the object of the present invention is to provide a medicine, food, beverage, feed or cosmetics, which uses various acidic Sugar compounds, such as acidic polysaccharides such as algin, produce growth factors, especially hepatocyte proliferation factor production, insulin-like growth factor production, or nerve growth factor production. I _ I Paper Standards Applicable Country Standards (CNS) A4 Specification (21GX297 mm) 1228991 A7 B7 V. Description of the Invention In summary, the first invention of the present invention relates to a need for growth factors to generate slander. It is a therapeutic or preventive agent for the disease, which is characterized in that it contains an acidic polysaccharide that has a defensive effect on growth factors, its degradation products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, and salts thereof. The selected one (except for heparin and acetoin sulfate) as active ingredients. The second invention of the present invention relates to a food, beverage (hereinafter, may also include food and beverage) or feed for inducing growth factor production, It contains acidic polysaccharides selected from the induction of growth factor production, their degradation products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, and salts thereof. The third invention of the present invention relates to a chemical grain for inducing growth factor production, which contains an acid saccharide selected from an inducing effect of inducing growth factor production, a degradation product thereof, an acidic oligosaccharide, an acidic monosaccharide, and an acidic sugar. Alcohols and their salts. The fourth invention of the present invention relates to a growth factor production regulator, which contains an acidic polysaccharide, a degradation product thereof, an acidic oligosaccharide, an acidic monosaccharide, an acidic sugar alcohol, and a salt thereof. In the present invention, the acidic polysaccharide having a defamatory effect of growth factors, such as a sulfated polysaccharide, the sulfated polysaccharide has a desert-derived sulfur-, a sugar-derived polysaccharide derived from a bamboo animal (eg, echinoderm derived Sulfated polysaccharides, sea cucumber-derived sulfated polysaccharides), fish-derived sulfated polysaccharides (for example, shark cartilage-derived sulfated polysaccharides), microbial-derived sulfated polysaccharides, plant-derived sulfated polysaccharides (for example Sulfated polysaccharides) and synthetic sulfated polysaccharides are suitable. -5- 1228991 A7 B7 V. Description of the invention ") Also, algae-derived sulfated polysaccharides with growth factor-inducing effects are suitable for users with rhamnose sulfate, sulfated galactan, or sulfated horsetail. Sugar contains polysaccharides. Synthetic sulfated polysaccharides include, for example, dextran sodium sulfate, starch sulfate, sulfated galactan, sulfated pectin, and the like. Further, highly sulfated sulfated polysaccharides obtained by sulfated sulfated polysaccharides are more suitable for use. Acid oligosaccharides are ideally sulfated oligosaccharides, such as sulfated maltose, sulfated lactose, sulfated sucrose, sulfated trehalose, sulfated lactulose, sulfated melibiose, sulfated cellobiose, and sulfated isomeric Maltose, sulfated sucrose, sulfated parathionose, sulfated maltotriose, sulfated maltohexose, sulfated maltoheptose, sulfated lauryl maltohexose, etc. can be represented by the following formula ( A compound represented by I) or a compound represented by the following formula (II).

R Η -6-This paper size applies to China National Standard (CNS) Α4 size (210 X 297 mm) 1228991 A7 B7

(Where R is OH or 0S03H)

(In the formula, R is OH or OS03H) In addition, the acidic monosaccharide is preferably a sulfated monosaccharide, such as sulfated glucose sulfated galactose, sulfated xylose, sulfated 2 · deoxy-glucose, and tarotose. And sulfated mannose. Examples of the acidic sugar alcohol include sulfates such as sugar $, such as sulfated sorbitol. These sulfated oligosaccharides, sulfurized monosaccharides, and sulfated sugar alcohols can be synthesized by ordinary synthetic methods. The positions of the sulfate groups and the number of sulfate groups in these sugar compounds can be as long as the sulfated oligosaccharides, Sulfated monosaccharides and sulfated sugar alcohols are not particularly limited as long as they have an induction effect on growth factor production. In the present invention, a decomposition product of an acidic polysaccharide having an effect of inducing growth factor production can also be used. This decomposed product also includes heparin decomposed products having a destructive effect on growth factors and a molecular weight of 4,000 or less, and acetamidine sulfate decomposed products. The aforementioned acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, and acidic paper standards are in accordance with the Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 ι, the description of the invention, "substances" You can use them individually, or use more than two kinds of salt, or their salts are also suitable. ^ Middle-class growth factors include, for example, hepatocyte proliferation factor, insulin-type proliferation factor, and nerve growth factor. The therapeutic or preventive agent of the first invention of the present month, the food, drink or feed of the second invention, and the granulated material of the third invention can be multiplied by adding acidic polysaccharides, Decomposed substances, acidic oligosaccharides, acidic early sugars, acidic sugar alcohols, or salts thereof which induce growth factors, such as cytokines, prostaglandins, cyclohexyl compounds, and chlorhexidine (Idil), and carpium chloride (Carp_ium chloride) 〇 Also, the food, beverage or feed of the second invention of the present invention, suitable for hepatocyte proliferation factor production defamation, insulin form proliferation factor production : Food, drink or word for inducing or nerve growth factor production In addition, the cosmetics of the third invention of the present invention are suitable for inducing liver cell proliferation factor production, insulin form proliferation factor production induction or nerve Growth factors produce defamatory cosmetics. The cosmetic materials of the third invention of the present invention include, for example, lotions, lotions, creams, masks, bath preparations, face cleansers, bath sticks or bath lotions. The "acidic polysaccharides, their decomposed products, acid sugars, acidic monosaccharides, acidic sugar alcohols' and their salts" mentioned in the present invention are also expressed as "active ingredients" in the present invention. -8- 孓 The paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 public directors) ^ 28991 A7, Description of the invention Q Brief description of the drawings Figure j shows the DEAE- Diagram of dissolution form of Cellulan A 800 column. Figure 2 shows the calibration curve of the sulfuric acid content using a sodium sulfate solution as a standard sample. The best form of implementing the invention, there is no particular limitation on the so-called acidic acid that has a defamatory effect on the growth factor in the present invention. Acidic polysaccharides such as alginic acid, pectin, pectinic acid, hyaluronic acid, etc., sulfated polyanimal-derived sulfated polysaccharides such as chondroitin sulfate, gelatin sulfate, chondroitin sulfate B, etc. ^), Fish-derived sulfated polysaccharides (such as shark cartilage-derived sulfated polysaccharides), plant-derived acidic polysaccharides (such as mountain wormwood-derived polysulfates, sugar, bitter melon-derived sulfated polysaccharides, and aloe-derived sulfuric acid Polysaccharides, sulfated polysaccharides from Hesheng chrysanthemum leaf), sulfated polysaccharides derived from microorganisms (such as sulfated polysaccharides derived from Chlorella vulgaris, sulfated polysaccharides derived from spirulina, sulfated polysaccharides derived from algae), etc. Deep-derived polyacids such as algae-derived rhamnose sulfate, red algae-derived sulfated galactan (eg, cauliflower, lettuce, giant konbu Utwick sugar, carrageena η) , Agarose, agarose, soya pectin, laver sugar), brown algae-derived sulfated fucose (e.g., fucoid, sulfated seaweed galactan, sulfated seaweed glucuronic acid mannan) , Glucuronic acid xylanofucan, fucosyl, glucuronic acid mannogalactan, xylanyl alga glucuronide, asco sugar, glucose-9-this paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1228991

V. Description of the invention Galacturonic acid, galactosan, sulfated glucuronic acid alginan). In particular, gamma alginan, sulfated seaweed galactan, lambda red algal gum, chondroitin & acid B, chondroitin sulfate D, alginic acid, and agar pectin are particularly suitable for the present invention. In addition, blue strips are derived from "acidic polysaccharides (such as spiral polyacid-derived acidic polysaccharides), green algae-derived acid polysaccharides (e.g., chlorella-derived acid polysaccharides). In particular, the sulphate-derived sulphated polysaccharide derived from helix desert induces an effect through its hepatocyte proliferative factor, which is useful for improving liver function, such as improving the symptoms of hepatitis C. X. The acidic polysaccharide of the present invention also includes phosphorylated polysaccharides such as nucleic acids. Ideally, the sulfated sargassum used in the present invention is, for example, the aforementioned: Algae-derived algal polysaccharides, as long as the polysaccharide is composed of sulfated horsetail thin sugar as a constituent component, and has a growth factor production-inducing effect, that is, Yes, there is no particular limitation, such as derived from echinoderm (such as sea cucumber, sea urchin, starfish). These can be used alone or in combination of two or more. In addition, the decomposition products and salts of the acidic polysaccharide in this example can be used as long as they have a growth factor-producing effect, and are not particularly limited. " Each of these acidic polysaccharides can be prepared by a known method, and the purified product or the acidic polysaccharide-containing material can also be used in the present invention ', τ 1. Acidic sugar content is suitable for users to divide into sulfated polysaccharides. For the purposes of classification, you can use sulfated polysaccharides derived from algae, derived from /, 1 = 4, fish broad, and chondrite stone cloud acidified polysaccharides. In addition, sulfated polysaccharides contain substances such as chrysanthemum, sea cucumber, shark cartilage, and the like. For example, 茏 目 Kunbu, ^ 牝 牝, Hailing,, 糸, lime algae, seaweed, Ryukyu seaweed, sugar ribbon dishes, holy… meat dishes, "Yala -10-

1228991 A7 B7 V. Description of the invention ^) Beauty ", black vegetables," Lessonia nigrescence "," Ascophyllum nodosum ", Kumbu, perennial algae, lime algae, etc. The seaweed is very suitable as a raw material because it is particularly rich in fucan suitable for use in the present invention. The synthetic sulfated polysaccharide used in the present invention can be used as long as it has a defamatory effect on the growth factor, and there is no particular limitation. So far, the sulfated polysaccharide used as a pharmaceutical is most suitable. Examples of the synthetic sulfurized polysaccharide include dextran sodium sulfate. This compound is made of Leuconostoc mesenteroides van Tieghem to ferment glucosamine to produce a partially decomposed product of dextran, which is further sulfated to obtain the sodium salt of sulphuric acid &gt; 1-yl ester. In the present invention, synthetic sulfated polysaccharides such as sulfated starch, sulfated curdlan, and sulfated pectin can be used, and highly sulfated sulfated polysaccharides obtained by sulfated sulfated polysaccharides are particularly useful. Suitable for use. The position of the sulfate group of the sulfated polysaccharide used in the present invention is not limited as long as it can show the induction effect of growth factors. Suitable for users are lycan, λ-red glutin, and chondroitin sulfate D, and its decomposition products. The sulfuric acid content (or number of sulfuric acid groups) of the sulfated polysaccharide is not particularly limited as long as it can express a defamatory effect of growth factors. In addition, the degradation products of acidic polysaccharides also include oligosaccharides and monosaccharides. In the present invention, oligosaccharides and monosaccharides having two sulfate groups (for example, fucose-2-sulfuric acid and glucose-2-sulfuric acid) may be used. These sulfated monosaccharides, sulfated oligosaccharides, and sulfated polysaccharides can be synthesized by their general synthetic methods, and the preparations, pure -11- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) ) 1228991 V. Description of the invention (g A7 B7 compounds can also be used in the present invention. In addition, the monosaccharides referred to in the present invention refer to the sugars defined by 2 to 10 monosaccharides and are 11 More than one monosaccharide is combined. &Quot; <Compounds' and polysaccharides, for example, can be prepared from algae from Cageles kumbu to produce algae containing gluconic acid (called υ-thin, from which Isolates of uronic acid (referred to as F-fucoidan), and those which do not contain glucose ^ ^ ^ ^ m, 'are used as the active ingredient of the present invention. Also, it can also be used as a polysaccharide. Sugar. Τ The production of sulfated «galacin from Lombok kumbu. Further, agar pectin can be prepared from agar. U-« sugar and F _ '«sugar can be prepared from kumbu kumbu, then anion exchange resin, interface Separation of active agents, etc. U-fucoidan and F_drug polysaccharide derived from Cages At a ratio of about 1: 2, u_ fucose contains fucose, mannose, galactose, and glucuronic acid, and the sulfuric acid content is about 20%, and F_ drug glycan contains fucoidan and galactose sulfuric acid content. It is about 50% and has a molecular weight of about 200,000 in two substances and is distributed in the center (the main collection of the 18th sugar workshop, page 159, 1996). After being injected into the DEAE-Selovalfan A-800 column, the algal solution was dissolved in a buffer solution containing sodium chloride by concentration distribution method, and the algal and algalan could be added. Separation. An example of this is shown in Figure 1. That is, Figure 1 shows the separation of U-fucoidan and F-fucoidan. It is F-fucoidan. For example, sulfated polysaccharide derived from stone cauliflower, sulfated polysaccharide derived from turnip, sulfated polysaccharide derived from proteose, and other -12- Applicable to China National Standard (CNS) A4 specification (210X 297 mm) Binding 1228991 x \ 7 ----— B7___ V. Description of the invention (1Q)- Sulfated sulfated polysaccharides from the side class, fucans derived from lime algae, arachis derived from sea turtles, fucans derived from present seaweed, fucoids derived from wakame, derived from Leuzoniil. " The algae from Lessonia nigrescence can be produced from Ascophyllum nodosum, the fucoidan from Ascophyllum nodosum, and the fucoidan from algae, which can be prepared by conventional methods and used in the present invention. The sea cucumber containing deep polysaccharides is described in, for example, Japanese Unexamined Patent Publication No. 4-91〇27 &lt; Sea cucumber, and fucan can be prepared from sea cucumber by the method described in the publication. In addition, the solution of acidic polysaccharides (for example, &amp; acidified polysaccharides and algal decomposed products) that have a defensive effect of the growth factors of the present invention can be used in enzyme methods, chemical methods, and physical methods. It is prepared by a known method, and a decomposition product having an inducing effect of the target growth factor is selected and used. The decomposed product is known from an acidic polysaccharide to be decomposed, and preferably has a molecular weight of about 100,000 to 200, and more preferably 30,000 to ㈧. An appropriate method for preparing the decomposed product of the acidic polysaccharide used in the present invention is an acid decomposition method. By subjecting the acidic polysaccharide to acid decomposition, a decomposed product having an effect of inducing growth factor production can be prepared. The acid decomposition conditions of the acidic polysaccharide used in the present invention are not particularly limited as long as it is a condition capable of generating a decomposed product (hereinafter, referred to as a decomposed product of the present invention) having an induction effect on growth factor production. For example, the decomposed product of the present invention can be produced by dissolving or suspending an acidic polysaccharide in an acidic aqueous solution and reacting it. Also, with -13-

1228991 A7 __ B7, description of the invention (η Γ &quot; '---- heating during the reaction can shorten the time required for the decomposition of the present invention. ~ The type of acid that dissolves or suspends the acidic polysaccharide, which does not have In particular, inorganic salts such as hydrochloric acid, sulfuric acid, and nitric acid; organic acids such as citric acid, formic acid, acetic acid, lactic acid, and ascorbic acid; or solid acids such as cation exchange resins, 1% ion exchange fibers, and cation exchange membranes can be used. The concentration of the acid is not particularly limited, and is preferably 0 0001 to 5, more preferably about 0.01 to 1. Also, the reaction temperature is not particularly limited, and is preferably 0 to 200 ° C, and more preferably 20 to 130. The temperature is set by ° C. The reaction time is not particularly limited, but is preferably set in a few seconds to several days. The type and concentration of the acid, the reaction temperature, and the reaction time can all be generated according to the amount of decomposition products used in the present invention. The degree of polymerization of the decomposition product is appropriately selected. For example, in the production of the decomposition product of fucoidan, by using organic acids such as citric acid, lactic acid, and malic acid, the acid concentration is several. mM ~ several M 'heating temperature is 50 ~ ii0 ° c, ideally 70 ~ 95 ° C, heating time is in the range of 4 li ~ 24 hours, and the decomposition of the present invention can be prepared by appropriate selection For example, the acid-decomposed product of fucoidan is, for example, an acid-decomposed product of fucoidan derived from the genus Kumbu, and this decomposed product can be used as a strong new physiology to induce growth factor production, especially hepatocyte proliferation factor production. Function, use of dietary fiber. The decomposed product of the present invention can be classified using the growth factor to produce a derogatory effect as an index. For example, the acid decomposed product can be subjected to gel filtration method, molecular weight division film division method, etc. Molecular weight division. Examples of gel filtration methods include the use of Cellulan GCL-300, for example, 1-4.

The size of this paper is suitable for financial purposes _ transfer standard _) A4 specification (inflated 297 public love) 1228991 A7 B7 V. Description of the invention (| 2) Available molecular weight of 25,000 or more, molecular weight of 25,000 to 10,000, molecular weight of 10,000 to 5000, or molecular weight of 5000 or less Molecular weight division; using Cellulan GCL-25, for example, the molecular weight division below 5000 is prepared into any molecular weight division of molecular weight 5000 ~ 3000, molecular weight 3000 ~ 2000, molecular weight 2000 ~ 1000, molecular weight 1000 ~ 500, molecular weight 500, etc. . In addition, the out-of-limit filtration method can be used for industrial molecular weight division. For example, FE10-FUSO382 manufactured by Daicel Corporation can be used to divide molecular weight below 30,000, and then FE-FUS-T653 can be used to divide molecular weight below 6000. . Furthermore, a nanofiltration membrane can be used to obtain a molecular weight of 500 or less. In addition, these filtration methods and molecular weight division methods may be combined to prepare arbitrary molecular weight divisions. Decomposed products of acidic polysaccharides that have a defensive effect on growth factors that can be used in the present invention include, for example, degraded products of fucoidan (such as compounds represented by formula (I), compounds represented by (II)), these Compounds can be prepared according to the methods described in International Publication No. 97/26896 pamphlet and International Publication No. 99/41288 pamphlet. In addition, sulfated polysaccharides and oligosaccharides having a repeating structure of the compound represented by formula (I) can also be used as acidic polysaccharides having a growth factor-causing effect in the present invention. A compound represented by formula (I), which can convert the aforementioned F-alanin to an endosulfonated polysaccharide degrading enzyme (F-algae) produced by alteromonas sp. SN-1009 (CCRC 910070) Glycan specifically decomposes the enzyme), and then the decomposed product is purified to obtain it. The content, site, and the like of the sulfate group in the compound can be obtained by purifying any of the decomposed products. In addition, the decomposition product also contains a polymer of a compound represented by the formula (I), and its -15- paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention ( 3) It can be separated and purified according to the purpose. A compound represented by formula (II), which can convert the aforementioned U-alanin to an endogenous sulfated polysaccharide degrading enzyme (U-algal polymer) produced by flavobacterium sp. SA-0082 (CCRC 910069) Sugar-specific degradation enzymes) are processed and purified from the degradation products. The content, site, and the like of the sulfate group in the compound can be obtained by purifying any of the decomposed products. In addition, the decomposed product also contains a polymer having a compound represented by formula (II) as a basic skeleton, which can be separated and purified according to the purpose. Examples of the compound represented by the formula (I) include compounds represented by the formula (VI) described later. Examples of the compound represented by the formula (II) include a compound represented by the formula (VII) described later. In addition, the alginans derived from Kumbu can be placed in the presence of an organic acid, and a glucuronic acid and a mannose polymer can be obtained by heat treatment. These polymers can also be used to induce growth factors of the present invention. Acidic polysaccharides. In addition, a polymer having an arbitrary degree of polymerization can be prepared according to the adjustment of the heat treatment conditions, the heating time, and the like. The acidic polysaccharides with induction of growth factor production in the present invention also include synthetic sulfated polysaccharides, which can be used by users such as cellulose, starch, mannan, xylan, brown acid, pectin, pectate, rich Lankotan, arabinan, chitin, pullulan, xylan dextran, dextran, starch and other sulfates. Further, for example, synthetic sulfated polysaccharides such as ribose furan, xylan furan, citronose sulfuric acid, curdlan sulfuric acid, mannan p-sulfuric acid, and synthetic sulfuric acid such as palmitic acid-containing ribose furan sulfuric acid can also be used. Alkyl polysaccharide. Further, by sulfating the sulfated polysaccharide and its decomposition-16- This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 | ___ B7 V. Description of the invention) can be prepared Highly sulfated sulfated polysaccharides and highly sulfated decomposition products. These sulfated polysaccharides, highly sulfated sulfated polysaccharides, and highly sulfated decomposition products can be prepared by various conventional methods, and the decomposed products can also be prepared by conventional methods and used in the present invention. In addition, commercially available dextran sulfur red and thiodegraded cellulose can be used, and salts of synthetic sulfated polysaccharide and the like can also be used. Therefore, ideal saccharides include sulfated oligosaccharides and the like, and acidic monosaccharides include, for example, sulfated monosaccharides, and specific examples thereof include the same as those described above. These sulfated oligosaccharides or sulfated monosaccharides can be prepared by sulfating the corresponding saccharides and monosaccharides as raw materials, and sulfating them by conventional methods. These salts are also suitable for use. Even sulfated polysaccharides, sulfated oligosaccharides, and fatty acid derivatives of sulfated monosaccharides are also included in the sulfated polysaccharides, sulfated oligosaccharides, and sulfated monosaccharides of the present invention. These can be used individually or in mixture of 2 or more types. The inducing growth factor desired in the present invention is not particularly limited as long as it has an activity that can promote the growth of cells. Examples include hepatocyte proliferation factor (HGF), nerve growth factor (NGF), and nerves. Nutritional factor, epithelial growth factor, milk-derived growth factor, fibrospore growth factor, brain-derived fibroblast growth factor, acidic fibroblast growth factor, platelet-derived growth factor, platelet basic protein, connective tissue activation Peptide, insulin-like proliferation factor (IGF), colony-shaped 2 stimulating factor, erythropoietin, slomposin, τ cell growth factor ^: Leukocyte interstitials (eg Leukocyte interstitial 2, 3, 4, 5, 7, 9, , Chaxia 15), B cell growth factor, cartilage-derived factor, cartilage-derived growth factor-17-

1228991 A7 r___B7 V. Description of the invention k) ~ '------ Seeds, bone growth factor, osteogenic growth factor, endothelial cell-derived growth factor, eye-derived growth factor, seminal vesicle-derived growth factor, Saitoli cells , Mammary gland stimulating factor, spinal cord-derived growth factor, macrophage-derived growth factor, circulating mesenchymal growth factor, transforming proliferation factor ^, transforming proliferation factor, heparin-binding EGF form proliferation factor, afragren, SDGF, stone -Wood fiber, upper reglin, neoreglin 丨, 2, 3, vascular endothelial growth factor, neurotropin, BDNF, NT_3, nt_4, NT-5, NT-6, NT-7, Crelia Cell line-derived neurotrophic factors, stem cell factors, intermediate hormones, pleiotropine, etholin, angiopoietin, activin, tumor necrosis factor, interferon, etc. Among them, from the viewpoint of prevention and treatment of liver diseases, prevention and treatment of neurological diseases, and prevention and treatment of diabetes, at least one type is selected from the group consisting of HgF, NGF, and IGF. It is desirable to invent effective ingredients to induce. HGF has a hepatocyte proliferation effect, a protein synthesis promotion effect, an improvement effect on bile obstruction, and even a preventive effect on renal disorders caused by pharmaceuticals. The mRNA of HGF is synthesized by the brain, kidney, lung, etc., and it also has proliferative activity in hepatocytes, renal tubule cells, epidermal cells, and the like, and is a mesodermal cell growth factor. Therefore, by inducing the production of hepatocyte proliferation factors, treatment or prevention of hepatitis, severe hepatitis, violent hepatitis, cirrhosis, and intrahepatic bile obstruction, chronic nephritis, pneumonia, and trauma can be performed. IGF has abundant physiological effects in various cells. By inducing the production of igf, type II diabetes (insulin non-independence) and growth can be performed. -18- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 reputation) 1228991 A7

Treatment or prevention of disorders (dwarfism). The survival and function of the eight nerve cells are extended according to the concentration: ^ NG 广 ΓΓ, and is an intrinsic growth factor, which can be performed by Alzheimer's disease such as Alzheimer's disease and Peripheral nerve disorders, cerebrovascular disorders, brain tumors, brain apex, degenerative diseases of head trauma, anesthesia poisoning, etc., which require the repair and regeneration of nerve functions, the treatment or prevention of diseases. 〖The therapeutic or preventive agent of the present invention has nerves Induced effect of nutritional factors 丨 The therapeutic or preventive agent of the present invention induces the production of NGF · neurotrophic factor] 1 It can be used for muscular atrophic lateral sclerosis, medicinal dysfunction peripheral nerve disorder, diabetic peripheral nerve disorder , Alzheimer's disease, Parkinson's disease, sensory redness, pigmented omentum, macular degeneration, etc. are useful for treatment or prevention. Acidic polysaccharides used in the present invention, their degradation products, acid oligosaccharides, acidity Monosaccharides, acidic sugar alcohols, or their salts have the effect of inducing growth factor production, and these compounds can be manufactured as active ingredients A therapeutic agent or preventive agent for a disease caused by growth factor production. A therapeutic agent or preventive agent for a disease induced by growth factor production of the present invention may be an acidic polysaccharide used in the present invention, a degradation product thereof, an acidic oligosaccharide, and an acidic agent. Monosaccharides, acidic sugar alcohols, and salts thereof are selected as active ingredients. They can also be prepared by combining them with a conventional pharmaceutical carrier. The preparation of the preparation can generally be made from the acidic polysaccharides used in the present invention, The decomposition products, acid oligosaccharides, acidic monosaccharides, acidic sugar alcohols, and salts thereof are selected with pharmaceutically acceptable liquid or solid carriers, and can be used at the same time. Standard (CNS) A4 size (2 × 297 mm) 1228991 A7

If there is a need for stabilizers, pastilles, granules, and medicines before use, the vitamins and jade can be further formulated with an accelerator, in addition to solvents, dispersants, emulsifiers, excipients, Binders, disintegrating agents, lubricants, etc. can still be: granules, powders, powders, capsules, etc., solid agents, 俨 suspending agents, emulsions, etc ... It can also be made into a dry agent and add an appropriate carrier to Liquid. ^ The carrier can be selected according to the above dosage forms. If it is an oral preparation, starch, lactose, sugar, mannitol, carboxymethyl cellulose starch, inorganic salts, etc. are used. In the preparation of an oral preparation, a binding agent, a disintegrating agent, a surfactant, a flavoring agent, a coloring agent, a fragrance, and the like may be combined. If it is a non-oral preparation, it can be prepared according to conventional methods, and the active ingredients of the present invention can be made from acidic polysaccharides, their decomposed products, acidic storm sugars, acidic monosaccharides, and acid sugar alcohols. And the salt chooser, the county floats and is insoluble in diluent for injection steaming water, physiological saline, glucose water-soluble solution, vegetable oil for injection, sesame oil, groundnut oil, soybean oil, corn oil, propylene glycol, Towels such as polyethylene glycol can also be added with insecticides, stabilizers, isotonic agents, analgesics, etc. if necessary. The therapeutic or preventive agent of the present invention can be administered by an appropriate route depending on the dosage form. There are no particular restrictions on the method of administration, and it can be used internally, externally, and as the main shot. Injections include, for example, those administered intravenously, intramuscularly, subcutaneously, and intradermally, and external preparations also include a pedestal. The dosage of the therapeutic or preventive agent of the present invention can be appropriately set according to the dosage form, the purpose of administration, and the age, weight, and claws of the patient to which it is applied. It is not specific, but it is generally included in the system of -20-x ^ 97 mm.) Applicability of the degree 122891 A7 B7 V. Description of the invention Q) The acidic polysaccharide used in the present invention, its decomposition product, acid oligosaccharide, acid mono The amount of sugar, acid sugar alcohol, and salt thereof is preferably 0.01 to 2000 mg / kg per adult. Of course, as mentioned above, the amount will vary due to various conditions. It may be enough that the amount is less than the above amount, or it may be necessary to exceed the range. In the case of an oral preparation, the desired dosage range of the therapeutic or preventive agent of the present invention can be directly administered orally, and can also be added to any food or drink for daily intake. The acidic polysaccharides used in the present invention, their degradation products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, and salts thereof can also be selected as raw materials for food and beverage products for inducing growth factor production. A partially resected liver will quickly regenerate and return to its original size. The entity of its liver regeneration factor has been unknown for many years, and finally HGF was found in the plasma of patients with severe hepatitis, and was isolated and purified from the patient's plasma (J. Clin. Invest ·, 88 414-419 , 1988). Further, human HGF cDNA was also cloned, and the structure of HGF once became clear. (Biochem. Biophys. Res. Commun., 163 967-973, 1989). It is also clear that the scatter factor (SF) and the tumor cytotoxic factor (TCF) which make the cell motility particularly superior are the same substances as HGF (Proc. Natl. Acad. Sci. USA, 88 7001 -7005, 1991: Biochem. Biophys. Res. Commun. 5 1 80 1 1 5 1- 1 1 58, 1991) 〇HGF not only hepatocytes, but also promote bile duct epithelial cells, renal urinary capillary epithelial cells, gastric mucosal cells, etc. Proliferation of most epithelial cells. In addition, it is a tube that promotes the mobility of epithelial cells, angiogenesis, and the tube of epithelial cells. 21- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 5. Description of the invention ( 19 Cavity formation and other types of visible multifunctional actives; and when it has extremely rich physiological barriers to living the organ, it is used in various organs, which is involved in repairing ^^^ ding epithelial cells. The promotion of proliferation, the improvement of motility, and the induction of blood formation and other types of formation. HGF has the role of liver cell proliferation to promote your protein # synthesis, bile resistance A. ^ ^ Prevention of renal disorders. Based on 14 facts, 7 t Θ can be treated as a cure for severe hepatitis, liver cirrhosis, and intrahepatic bile obstruction. However, the use of HGF entities as a therapeutic agent has not yet been put into practical use. .Into a cow, + grid *, ,,, and progress 斫 try to introduce HGF genes into the gene therapy <method ', but because it will cause side effects in unnecessary periods and places, its distance is still practical Shang Yao In this way, it is also considered that if HGF is not externally administered and can be induced arbitrarily, it is extremely useful in the treatment and prevention of diseases that require enhanced performance such as hepatitis, cirrhosis, and intrahepatic bile obstruction. Effective. So far, it has been confirmed that IL_1, prostaglandin dagger, dagger, heparin, etc. have induction effect. IL-1, prostaglandin, E2, heparin can induce the production of HGF by inducing the transcription of HGF gene. On the one hand, heparin is known to induce HGF production, but it will not blame HGF gene transcription, but rather promote the subsequent steps of mRNA translation and blame HGF production. That is, ^ [ie the gene's transcription if When there is no defamation, there is no defamation effect of HGF. Conversely, if the transcription of the HGF gene is defamation, a significant induction of production can be seen. Also, it is presumed that the active ingredient of the present invention may not necessarily be directly To induce the transcription of growth factors such as HgF, and when this transcription is defamated, intentionally -22-1228991 V. Description of the Invention)) Promote the transcription and further promote the subsequent steps of transcription such as translation, The results of the growth factors produced having a conductivity of abusive enhancement effect. That is, the so-called "growth factor production-inducing effect" in the present invention refers to an enhanced effect of the growth factor. Such an effect, for example, can be an effective ingredient that is administered to human growth factors before and after administration. Enhance to judge. Here, the so-called "when transcription is induced", Teng Teng's transcription is carried out at its necessary stage, and with the former:; there = points, the transcription of HGF's transcription will be promoted even more at the beginning, After that, HGF will not be over-produced, so that HGF production will be enhanced when necessary in the body, thereby making it possible to produce extremely safe HGF.

guide. V The therapeutic agent or preventive agent of the present invention may further contain growth factors that induce the acidic polysaccharides used in the present invention, their degradation products, acid oligosaccharides, acid monosaccharides, acid sugar alcohols, or their growth factors, Multiplicatively increased matter. The so-called “multiplying substance” in the present invention means that if the active ingredient of the present invention is used together with the substance, transcription and translation can be actively performed because of the substance, and as a result, the present invention is effective. The component-induced growth factor production is multiplied. The acidic polysaccharides used in the present invention, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof can be multiplied to increase the growth factor-inducing effect. As long as these acidic polysaccharides, There is no particular limitation as long as the growth factors of the degradation products, acid oligosaccharides, acid monosaccharides, acid sugar alcohols, or their salts produce a multiplicative increase in defamatory effects. Example -23- ® ® Family Standards (CNS) A4 Specification (X-Nongong Dong) 1228991 A7 B7 V. Description of the invention) For example, cytokines, prostaglandins, compounds with cyclopentane, minoxidil, and chlorine Carpronium chloride The substance of choice. In addition, gingerol, gingerol, etc. contained in ginger, and curcumin, etc. contained in turmeric are also substances that can increase the defamatory effect of HGF, and can also be used as a multiplicative addition to the present invention. Use of acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or growth factors of salts thereof has a defamatory effect. Examples of cytokines include the aforementioned IL-1, and examples of prostaglandins include the aforementioned prostaglandins Ei, E2, and the like. Examples of the compound having a cyclopentane ring include a compound represented by the following formula (III) and its conductor. These can be used individually or in mixture of 2 or more types. For example, a compound having a cyclopentane ring represented by each of the following formulae (III) to (V) can induce the transcription of the HGF gene in the same manner as the prostaglandins Ei and E2. Acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or their salts produce a multiplicative effect, which significantly increases the production of HGF. That is, a substance selected from cytokines, prostaglandins, cyclopentane-containing compounds, ginger-derived compounds, and turmeric-derived compounds having a transcription-inducing effect of HGF, and those used by the present invention Acidic polysaccharides, degradation products thereof, acid oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof are used as a mixture, and the acidic polysaccharides and degradation products thereof used in the present invention can be multiplied. , Acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or their growth factors produce defamatory effects, resulting in very high levels of HGF production -24- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 Mm) 1228991 A7 B7 V. Description of Invention) Defamatory effect. In addition, the mixture can also be used as a raw material for food and beverages or feed for growth factor production. Ο

(III)

.H2 N—C H—CH2—C H, —C—NH—C H—C—NH—C H2—C Ο Ο H

: OOH

A

s (IV)

-C—C, H «(V) O—C—C 2 H &lt; II &quot; o For example, the method for producing a compound represented by formula (III) is described in International Publication No. 98/13328, (IV) The compounds indicated are in China -25- This paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of Invention b) International Publication No. 98/39291, The compound represented by the formula (V) is described in the pamphlet of International Publication No. 98/40346, and can be produced by the methods described in these. Various methods can be used for the production method of the compound represented by the formula (III). For example, a chemical synthesis method can be used [Carbohydrate Res ·, Vol. 2478, pp. 217-222 (1993), Helvetica Chimica Acta, No. Vol. 55, pp. 2838 ~ 2844 (1972)]; Alternatively, it can be composed of sugar compounds containing uronic acid, uronic acid derivative, uronic acid and / or uronic acid derivative, and uronic acid At least one substance is selected from the sugar compound content of the uronic acid derivative and / or cyclopentanone and its purified product produced in the heat-treated product. The compound represented by formula (IV) can be obtained, for example, by reacting a compound represented by formula (III) with glutathione. The compound represented by the formula (V) can be obtained, for example, by reacting a compound represented by the formula (III) with anhydrous propionic acid. In the therapeutic or preventive agent of the present invention, the acidic polysaccharide of the present invention, its degradation product, acidic oligosaccharide, acidic monosaccharide, acidic sugar alcohol, or a salt thereof can be multiplied to induce the growth factor to multiply. The content of the substance is not limited as long as it can multiply increase the induction effect. Generally speaking, an adult's daily ideal amount is about 0.001 to 2000 mg / kg. A substance that multiplies the defamatory effect may also be a compound formulated by the acid polysaccharide of the present invention, a degradation product thereof, an acid oligosaccharide, an acid monosaccharide, an acid sugar alcohol, or a salt thereof, Alternatively, it may be formulated separately. For the preparation method, as long as it is administered according to the method described in the description of the present invention, you can get -26- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7

V. Description of the Invention) The desired growth factor produces a synergistic multiplier effect. The acidic polysaccharide, its decomposed product, acidic oligosaccharide, acidic monosaccharide, acidic sugar alcohol, or a salt thereof of the present invention also has acetamidine inhibitory activity, cancer metastasis inhibitory activity, and angiogenesis inhibitory activity. Therefore, these selected ones can be produced and provided as an active ingredient as a cancer metastasis inhibitor and an angiogenesis inhibitor. In particular, the compound represented by the formula ⑴ derived from fucoidan has a strong inhibitory activity of heparanase and cancer metastasis, and a pharmaceutical composition containing the compound as an active ingredient as a cancer metastasis inhibitor Is extremely useful. In addition, foods and drinks containing the compound are extremely valuable as foods and drinks for suppressing cancer metastasis and angiogenesis. "" The acidic polysaccharide of the present invention, which has a defamatory effect on growth factors, its degradation products, acid oligosaccharides, acid monosaccharides, acid sugar alcohols, or salts thereof, contains foods for induction of growth factor production selected by them, Beverages or feeds can have a defamatory effect through the growth factor, and need to be sensitive to the acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof used in the present invention. Symptoms of diseases that induce growth factor production #, prevent or improve the body length of the organisms described below1, are extremely useful.… In addition, in the food, beverage or feed of the present invention, or the cosmetics described below, if mentioned The term "contained" refers to the meaning of containing, adding, or diluting. The so-called "containing" refers to a state in which food, beverage or feed contains the active ingredient used in the present invention; the so-called "adding" refers to food, beverage or The state in which the active ingredient used in the present invention is added to the feed; the so-called dilution is -27- 1228991 A7

The appearance of the raw materials on the active ingredients used in the present invention. Addition of food, beverages or feeds, and the aforementioned substances which can multiply increase the induction of growth factors, for example, if it further contains a compound selected from cytokines, prostaglandins and cyclopentane, From the point of improvement of the symptoms, prevention or improvement of body length of the aforementioned diseases, it is ideal. In addition, even in the food and drink of the present invention, the above-mentioned active ingredient, growth factor, or growth factor is desirably referred to as m, and the ideal form of the substance is multiplied, which is the same as the aforementioned therapeutic agent or preventive agent. . In particular, the food or drink or feed of the present invention is used for liver cell proliferation factor production, insulin form proliferation factor production, and liver function improvement, from the viewpoint of improvement of liver disease, neurological disease change, and improvement of diabetes mellitus, Or the nerve growth factor produces ideal foods or feeds, which is ideal. The method for producing a food or beverage of the present invention is not particularly limited as long as it is a food or beverage having an effect of inducing growth factors. For example, blending, conditioning, processing, etc. can be performed according to general foods, that is, according to the manufacturing method of these foods or beverages, it can be produced, and then produced in the foods or beverages produced by the growth factors The acidic polysaccharide, its degradation product, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof used in the present invention for inducing action can be selected as an active ingredient by adding them. The food or beverage of the present invention is not particularly limited, such as processed shell products (wheat flour processed products, starch processed products, pre-mixed vitamin rice processed products, noodles, macaroni, bread, stuffed bread) Type, buckwheat noodles, bran-28- This paper size applies to Chinese National Standard (CNS) A4 size (210 X 297 mm) 1228991 V. Description of the invention m powder, packaged cakes, etc.), processed oils (plasticized oil, = Oil, salad oil, mayonnaises, sauces), processed soybeans (Danfu, miso, natto, etc.), containing ^^. Bu] processed meat products (ham, smoked pork, smoked ixiangzhi, Sausages, etc.), aquatic product rounds, abundance slices: Touma bang fish meat, fish plate, bamboo braid-"s fish balls, sushi, fish ham, sausages, t products, canned aquatic products, fine cooking, etc.), dairy products (Raw materials: ,, = leaching, yogurt, cream, milk road, condensed milk, milk powder, ice flooding, tobacco processing, fruit processing w (pastes, sauces, mashes, fruit drinks, sparse rice beverages, Mixed drinks), light varieties) cakes (chocolate, biscuits, cakes: bread, cakes, cakes Point, rice, etc.), alcohol (Japanese wine, two country wine = grape wine, whiskey, shochu, vodka, brandy, juniper: tincture, rum, beer, cool alcoholic beverage, fruit wine, sweet wine Jiuji Temple), hobby drinks (green tea, black tea, oolong tea, coffee, refreshing drinks, shaped drinks, etc.), seasonings (soy sauce, spicy soy sauce, vinegar, liqueur, etc.), canned food, canned food, and canned food (cow Baked rice, small pot grab rice, red bean rice,: mile =, various other prepared foods), semi-dried or concentrated food (liver paste, other spread foods, naphthalene noodles, udon noodle sauce, concentrated soups ), Dry food (instant noodles, instant curry rice, instant coffee, powdered fruit juice, powder soups, instant soups, prepared foods, prepared soups, etc.), cold bunch foods (sukiyaki, Steamed tea bowls, grilled eel skewers, hamburger patties, yakiniku, dumplings, various steaks, cocktails, etc.), solid foods, liquid foods (soups, etc.), agricultural products such as forest products, processed animal products, and processed fish products Etc. of the invention Food or beverage, as long as it contains products with growth factors _ -29- This paper size applies Chinese National Standard (CNS) A4 specifications (210X297 public attack) 1228991 A7 _____ Β7 V. Description of the invention &amp; The polysaccharide, its decomposed product, acid oligosaccharide, acid monosaccharide, acid sugar alcohol, or a salt thereof may be selected as long as it is a necessary amount capable of exhibiting its physiological effect, and its shape is not particularly limited, including a tablet shape , Granules, capsules, etc. can be ingested orally. In addition, the algae-derived sulfated polysaccharides and their decomposed substances (such as bath polysaccharides and their decomposed substances), which have a growth factor production effect, are compatible with the physiology. Health food materials that function and dietary fiber functions), and are extremely useful food or beverage manufacturing materials. In the foot food or beverage of the present invention, the acidic polysaccharide, its degradation product, acidic oligosaccharide, acidic monosaccharide, acidic sugar alcohol, or a salt thereof is selected (as an active ingredient) from an acidic polysaccharide having an induction effect on the growth factor, its food or There is a certain amount of drink in the beverage and it is specially limited. It can be appropriately selected from the point of its function and physiological activity. The content of the active ingredient, for example, the food can be 10-9 weight per 100 weight parts of the food. The number of parts is preferably 10-7 to 2 parts by weight, and the beverage may be, for example, 10.9 parts by weight or more per 100 parts of food, and the number of parts is preferably 10 7 to 2 parts. In addition, an adult can ingest the active ingredient in an amount of 0.001 to 2000 mg / kg, and induce growth factor production orally to obtain the desired effect of the present invention. In addition, according to the present invention, there can be provided a biological feed containing an acidic polysaccharide having an inducing action by a growth factor, a decomposed product thereof, an acidic oligosaccharide, an acidic monosaccharide, an acidic sugar alcohol, or a salt selected therefrom. Furthermore, a method for breeding an organism is also provided, characterized in that the feed is administered to the organism. 30- This paper size applies to China National Standard (CNS) Α4 size (210 X 297 mm) 1228991

[Description of the Invention] According to the present invention, a biological breeding agent can be provided, which contains an acidic polysaccharide that induces sexual effects, a degradation product thereof, an acid, an acidic monosaccharide, an acidic sugar alcohol, or a salt thereof. The choice. Etc. &amp; T &apos; The so-called organisms include, for example, farm animals, pet animals, and amphibians, such as domestic animals, experimental animals, poultry, fish, shellfish, and shellfish. 5 J For example, there is a mud-improving feed for the body based on the defamatory effects of growth factors. Examples of animal feed θ include immersion agents, feed additives, and beverage additives. ^ Ε | Ί 〆 ^ Dry 'is induced by growth factor-producing acidic polyphenols /, knives, substances, allogenic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof, and the selectors have the ability to raise organisms. Efficiency (such as survival rate, fattening rate, spawning rate, litter rate, weaning rate, etc.). Acid polysaccharides, their decomposed products, and acids: oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof, which are induced by growth factors. Generally, $, ideally based on the weight of the target organism, kg. 0.001 mg is administered daily, which can be added and mixed in the raw materials of artificial compound feed, or mixed with the powder raw materials of artificial compound feed, and then further added and mixed in other raw materials. Also 'Although it is selected from acidic polysaccharides having a growth factor-inducing effect, its decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof, in the finally obtained target biological feed, There is no particular limitation on the content, but it can be used according to the purpose, and it is 0.001 to 15% by weight -31-

This paper size applies the Chinese National Standard (CNS) A4 specification (210X297) 1228991 5. The ratio of invention description is appropriate. For example, for the purpose of improving liver function, a ratio of 0.01 to 10% by weight is suitable. Artificial compound feeds include, for example, animal raw materials such as fish meal, casein, cuttlefish meal, vegetable raw materials such as large meal, wheat flour, starch, microbial raw materials such as yeast, cod liver oil, cuttlefish oil % Physical oils, vegetable oils such as soybean oil, vegetable oils, vitamins, substances, antioxidants, etc. as artificial compound feed. It is also possible to use fish feed such as fish. The production method of the multi-salt feed according to the present invention is not particularly limited, and the combination of its contents may be based on general feeds, as long as the produced feed contains an effective amount of an inducer having a growth factor Acidic sugar, its degradation product, acidic oligosaccharide, acidic monosaccharide, acidic sugar alcohol, or

The selected one can be selected from the group consisting of an acidic polysaccharide having a growth factor-inducing effect, a decomposed product thereof, an acidic oligosaccharide, an acidic monosaccharide, an acidic sugar alcohol, or a salt thereof. The method of administration can also be determined by Add directly to the pond, sink, water in the feeding area, seawater, etc., and immerse the target organism to 2 j. This immersion method is particularly useful when the feed intake of the target organism is reduced. The acidic polysaccharide that induces the growth factor, its octahydrolysate, acid oligosaccharide, acid monosaccharide, acid sugar alcohol, or salt thereof. The concentration in water or seawater is not particularly limited, and it is used for its purpose That is, the ratio is desirably 0.00001 to 1% by weight. In addition, acidic polysaccharides that induce growth factor production, and their decomposition -32- This paper is suitable for use _ Tuzhuang (CNS) A4_21GX297 public shame 1228991 、 Instructions of the invention ^, acid oligosaccharide, acid monosaccharide, acid sugar The person selected by alcohol or its salt can be included in the beverage, and made into a breeding beverage to make the subject bio-recovery. A. An acidic polysaccharide, its decomposed product, acidic oligosaccharide, which has a destructive effect by growth factors, The concentration of the acidic monosaccharide, acidic sugar alcohol, or salt thereof in the beverage is not particularly limited, and the user should ideally use a ratio of 0.0001 to 1% by weight for the purpose. Biofeeding agents containing, as an active ingredient, acid polysaccharides having a growth factor-inducing effect, decomposed products such as acidic sugar, acidic monosaccharides, acidic sugar alcohols, or salts thereof, such as immersion agents, The feed additives and beverage additives can be prepared according to their conventional contents and manufacturing methods. The organisms applicable to the present invention are not particularly limited, and farm animals such as horses, cattle, It, sheep, goats, road knees, road horses and other domestic animals, rats, rats, marmots, rabbits and other experimental animals, hard, duck, Starlings such as turkeys and sharp birds, real sea bream, stone sea bream, flounder, catfish, lion fish, rice fish, Yue fish, fish, striped horse mackerel, diamond fish, drum fish • squid fish, tiger river vein, humming fish , Mud-grade, catfish and other fish, black tigers, crustaceans such as prawns, crabs and other shellfish, abalone, butterfly snails, sea fans, snails and other shellfish, dogs and other pets, so it is widely used in Land animals in water. By ingesting a feed containing an acidic polysaccharide having an inducing effect by a growth factor, a degradation product thereof, an acid oligosaccharide, an acid monosaccharide, an acid sugar alcohol, or a salt thereof, or by impregnating a target organism Contains acidic polysaccharides, their decomposed products, and acidic oligo-33 with the induction of growth factors. This paper is sized to Chinese National Standard (CNS) A4 (2 (^^ 1Τ 1228991 A7

: Diacid monosaccharides, acid sugar alcohols, or salts thereof in the selected liquid, laboratory animals, poultry, fish, crustaceans, shellfish, treatment: improvement, as a result, bacterial infections can be prevented or private And viral infections, which significantly improves the symptoms of infection. In addition, if the health of the target organism is achieved, its survival rate, growth rate, birth rate, farrowing rate, weaning rate, page growth rate, etc. can be significantly improved. Also, some breeding animals may have maggots that frequently cause diseases due to bacterial infections, and because they are farmed in a limited space, as long as infectious diseases occur quickly, all infections die; maggots are prone to parasitic diseases and nutrition. Diseases, environmental diseases, tumors, etc. (3) In a narrow breeding area, the pressure of breeding 2 is very high, and the breeding facilities will scratch its surface, and it is easy to attach bacteria and parasites everywhere; (4) and The pressure makes the situation of eating feed worse, the growth is slow, etc .; by the improvement of the physical condition of the feed of the present invention, it can greatly reduce the pressure of animals that are bred in a narrow area, so that its body surface will not Abrasion to feeding facilities can increase appetite, and growth rate, spawning rate, litter rate, weaning rate, fertility rate, disease prevention rate, etc. can be significantly improved. The acidic polysaccharide used in the present invention having a growth factor-inducing effect, a decomposed product thereof, an acid oligosaccharide, an acidic monosaccharide, an acidic sugar alcohol, or a salt thereof can be successfully used as an active ingredient of a cosmetic. The growth factor of the acidic polysaccharide, its decomposed product, acidic oligosaccharide, acidic monosaccharide, acidic sugar alcohol, or its salt as an active ingredient, which has a defamatory effect, can provide, for example, HGF, etc. Guide for makeup-34- This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ^) — material. Also, the aforementioned substance multiplying the growth factor's defamatory effect, for example, a compound containing a cytokine, a prostaglandin, and a cyclopentane ring, which is ideal from the viewpoint of assisting a desired effect . In addition, even in the cosmetic of the present invention, a substance that multiplies the induction effect of the aforementioned active ingredient, growth factor, or growth factor, its ideal form is the same as that of the aforementioned therapeutic agent or preventive agent. In particular, from the viewpoint of activation of epithelial cells, the cosmetic of the present invention is preferably a cosmetic for inducing hepatocyte proliferation factor production, insulin form proliferation factor production induction, or nerve growth factor production induction. . The active ingredient of the granulated material is particularly preferably algal and its decomposed product. For example, F-algal and / or its decomposed product, or a compound represented by formula ⑴ is used as an active ingredient to induce growth factor production. Biochemical cosmetics with effects (such as HGF production-inducing effects). The content of acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or their salts in the growth factor-inducing cosmetic is generally preferably from 0.0000 to 2% by weight 'More preferably, it is 0.001 to 5% by weight. The growth factor-generating cosmetics of the present invention (for example, HGF-generating cosmetics) can be manufactured in accordance with the conventional contents of combination. Cosmetics for inducing growth factor production according to the present invention include, for example, lotions, lotions, facial masks, facial masks, bath preparations, face cleansers, bath soaps or bath lotions. θ The cosmetic material of the present invention can be matched with the required I according to its use type. For example, if it is a lotion, it is suitable for the entire face of a person. Standard ⑴⑽) A4 specification (210x297 reputation) --- 1228991 A7 ---- __B7 V. Invention theory)-The ideal one per person is 〇01 ~ 5 grams, the more ideal is 〇1 ~ 2 The effect of beautifying the skin expected by the present invention that activates epithelial cells can be obtained in about grams. The present invention provides a growth factor production inducer containing an active ingredient selected from an acidic polysaccharide, a decomposed product thereof, an acidic oligosaccharide, an acidic monosaccharide, an acidic sugar alcohol, or a salt thereof as an active ingredient. It is also very useful in the research on the function of growth factors and the screening of medicines for diseases related to growth factors. Progress' The present invention also provides a growth factor production regulator containing an active ingredient selected from acidic polysaccharides, degradation products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof. The growth factor production-inducing agent and growth factor production-adjusting agent of the present invention can be formulated by using the above-mentioned effective ingredients according to a conventional formulation method. An example is a growth factor-producing agent such as the aforementioned therapeutic agent. In addition, the so-called growth factor production regulating agent of the present invention refers to a preparation that can promote the transcription of growth factors in vivo in the initial stage of transcription of the growth factors. By using the growth factor production regulator of the present invention, the growth factor can be generated, which can be enhanced only in a necessary state, so that there is no overproduction of growth factor. The fucoidan and / or the decomposed product thereof used in the present invention is particularly effective as an effective ingredient in the preparation of the present invention because it has a strong growth factor induction effect and a growth factor production adjustment effect. Heparin, which has been known to induce HGF production in the past, does not promote the transcription of HGF mRNA. However, algal and its degradation products are in -36-

1228991 A7 B7 V. Description of the invention) In the early stage of the transcription of HGF mRNA was promoted, the transcription of its mRNA was further promoted. HGF mRNA is not transcribed frequently in vivo, but is transcribed only when necessary. Fucoidan and its degradation products (such as 7-12SFd-F described below) will only transcribe HGF in the early stage when the transcription of HGF is promoted in the body, so that HGF will not be excessive From the point of view that the production status of HGF can only be promoted when necessary in the body, in fact, it is an extremely safe HGF production regulating substance. Therefore, in another form of the present invention, the aforementioned therapeutic agent or preventive agent, food or drink, etc. can be used directly for the purpose of adjusting the induction of growth factor production. The dosage of the growth factor production regulator is not limited as long as it is a producer who can adjust the growth factor. The dosage of the effective ingredient of the present invention, for example, the dosage of the effective ingredient to humans, The amount is preferably 0.01 to 2000 mg / kg (body weight). In addition, the acidic polysaccharides having a defamatory effect on growth factors used in the present invention, such as algal and / or its decomposed matter, are administered orally at a rate of 1 g / kg even in a single oral administration to rats. No deaths occurred through oral administration. Also, dextran sodium sulfate is a safe compound. In addition, other acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, acidic sugar alcohols, or salts thereof used in the present invention have not been confirmed to be toxic even if they are administered orally to rats in a physiologically effective amount. Situation. In addition, in other aspects, the present invention may also include the extract of mountain wormwood, bitter gourd extract, aloe vera extract, inulin extract, chlorophyll extract, and spiral Algae Extract -37- This paper size applies to China National Standard (CNS) A4 (210X 297mm) # Order

Line 1228991 A7 B7 V Description of the Invention ^ The selected extract is used as an active ingredient to provide a therapeutic and preventive agent for diseases that require growth factors to produce and guide. In addition, it contains extracts selected from the wormwood extract, bitter gourd extract, aloe vera extract, chrysanthemum extract, chlorella extract, and spirulina extract which have a defensive effect on growth factors. In addition, a food or feed for inducing growth factor production can also be provided. It further contains extracts selected from the wormwood extract, bitter gourd extract, aloe vera extract, inulin extract, chlorophyll extract, and spirulina extract that have a defensive effect on growth factors. Shi 'can also provide a makeup amount for inducing growth factor production. The aforementioned extracts obtained from these plants and microorganisms can be extracted and purified according to the following conventional methods. The fruits, seeds, leaves, stems, rhizomes, etc. of the plant as raw materials, or microorganisms are taken at an appropriate time, and directly or after being subjected to a drying step such as ordinary air drying &lt; raw material. When the raw material is a plant juice or sap ', it can be used directly as an extraction raw material. Containing the aforementioned active ingredients obtained from the above-mentioned dried plants and microorganisms, the scoop extract can be extracted according to a conventional method as follows. The raw materials are pulverized or ground, and then cut, and then the batch is used as a continuous extraction method. Examples of the extraction solvent include water, chloroform, ethanol, propanol, etc., ketones such as propane, methyl ethyl ketone, etc., hydrophilic or lipophilic solvents such as methyl acetic acid & ethyl acetate, and they can be used alone or as a mixture液 使用。 Liquid use. The extraction temperature is generally 0 ~ 150 ° c, ideally 5 ~ 12 (rc. If the extraction is performed in batches, the extraction time is aging clock ~ fine left-3 8-this paper is suitable for scale S g (CNS) A # specifications (21 () &gt; &lt; 297 public reply) ^ ---- 1228991 A7 &quot; &quot; &quot; &quot; &quot; &quot; &quot; ------ ___ —__ B7 V. Invention Explanation Q) &quot; 一 &quot; &quot; -----: Lalisu is 1 ~ 30 times the weight of dry raw materials, ideally 2 ~ 20 times the weight. The extraction step can be stirred or immersed, or used in combination. The extraction step can be repeated 2 to 3 times if necessary. For continuous extraction, desulfurization can be performed using a Soxhlet extraction method combining a reflux cooler and a siphon. The solvent amount and extraction time are the same as those of the aforementioned batch extraction method. The extracts used in the present invention also include those obtained by filtering the crude extract obtained by the aforementioned operation steps, and removing the insoluble residue by centrifugation. In addition, insoluble residues are also used as active ingredients. The purification of the active ingredient from the crude extract is only required to be a conventional method for purifying the active ingredient of the plant, such as two-phase solvent separation method, column chromatography, etc. can. Using the obtained extract as an active ingredient, pharmaceuticals, foods, feeds, and cosmetics can be prepared according to the purpose. These productions may be performed according to the methods of the first to third inventions. The content of the extract in the product for each purpose can be determined according to the defamatory effect of the growth factor, but in general, the product is preferably 0.001 to 100% by weight, and more preferably 0. 01 to 30% by weight, and most preferably 0.1 to 20% by weight. Moreover, even if the extracts of the present invention were orally administered to rats in an effective amount, no toxicity was confirmed. Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to the scope of these descriptions. In addition, about the components in the examples -39- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention The percentage refers to the weight of 0 / 〇. Reference Example 1 (1) After the kambu kumbu was sufficiently dried, 20 kg of the dried matter was ground with a free grinder (Nara Machinery Co., Ltd.). 73 kg of calcium chloride dihydrate (manufactured by Soda Co., Ltd.) was dissolved in tap water = 0 liter, and then mixed with 20 kg of ground kumbu grind. Use water strip gas to perfuse it to make the temperature within 40 minutes, from liquid temperature12. 〇L to a liquid temperature of 90 ° C, and then kept at 妁 ~ "with stirring, and then cooled to obtain 1100 liters of cooling. Then, a solid-liquid separation device (CNA type manufactured by Westphalia) was used. ), To perform solid-liquid separation of the cooling material, to prepare about 900 liters of solid-liquid separation supernatant. Use FE10_FC_FUS0382 (divided molecular weight of 30,000) manufactured by Daicel Corporation to separate the solid-liquid supernatant. 36 liters of concentrated liquid was concentrated to 2 0 liter. Then add 20 liters of tap water to re-concentrate to 2 () liters step, check back and forth, go to desalination treatment, and prepare 25 liters of Kumbu-derived extract solution. 1 liter of this extract is cold; East After drying, 13 g of dried kumbu derivatives were obtained. The sugar was prepared from ground kumbu dried powdered ground powder according to the above-mentioned method. Also, similarly, "Raisoni "Dryoma" (Lessoma nigrescence) dry powder (commercial name: seagrass powder Disy ^ Yi company sales) Preparation ^) t Bi Tiansuo Nier grass-derived dried algal polysaccharides 0% (2) Reference examples 7 g of dried fucoidan as described in 1_ (1), dissolved in paper ruler Suitable materials Choi ® s home -40- 1228991 A7 B7 V. invention described ς) 20 mM imidazole buffer containing 50 mM of sodium chloride and 10% ethanol (pH 8.0) 700 ml, insoluble matter was removed by centrifugation. Place the DEAE-Seloflav A-800 column (0 11.4 cm x 48 cm) in the same buffer to equilibrate. After injecting the centrifuged supernatant, add 50 mM sodium chloride to 1.95 Partition the concentration of M and perform dissociation (1 division: 250 ml). According to the phenol sulfuric acid method and the carbazole sulfuric acid method, the total content and the amount of uronic acid are calculated. According to the order of dissolution, it is divided into 43 to 49, divided into 50 to 55, and divided into 56 to 67. Then, these divisions were subjected to electronic dialysis and freeze-dried after desalting, and each was prepared from divisions 43 to 49 into I division (340 mg), divisions from 50 to 55 into II division (870 mg), and divisions 56 to 67. Prepared into III divisions (2.64 g). FIG. 1 is a diagram showing the dissolution form of DEAE-Seleflovin A-800 column of fucoid derived from Cage. In Figure 1, the vertical axis represents the absorbance at 530 nm (black circle in the figure) obtained by the carbazole sulfuric acid method, the absorbance at 480 nm (white circle in the figure) obtained by the phenol sulfuric acid method, and the conductivity (mS / cm · • white square in the figure), the horizontal axis represents the division number. Reference Example 2 (1) Alteromonas sp. SN-1009 (CCRC 910070) was dispensed in artificial seawater containing 0.25% glucose, 1.0% protein gland, and 0.05% yeast extract (Jamalin Lab. 600 ml of the culture solution composed of the company) and having a pH value of 8.2, inoculated into a sterilized 2 liter triangular conical flask, and cultured at 25 ° C for 26 hours as a seed culture solution. Artificial seawater containing 1.0% of protein glands, 0.02% of yeast extract, 0.2% of the sulfated polysaccharide described in Reference Example 2- (2) below, and 0.01% of an antifoaming agent (KM70, manufactured by Shin-Etsu Chemical Industry Co., Ltd.) and pH 20 liters of culture solution with a value of 8.0, added -41- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ") Small fermentation tank with a capacity of 30 liters The medium was sterilized at 120 ° C for 20 minutes. After cooling, 600 ml of the above-mentioned culture solution was inoculated, and cultured at 24 ° C for 24 hours, aeration volume of 10 liters per minute, and stirring speed of 250 rpm. After the completion of the culture, the culture solution was centrifuged to obtain the bacterial cells and the culture supernatant. The obtained culture supernatant was concentrated by an external limiter filter having a molecular weight of 10,000 hollow fibers, and then concentrated with 85% saturated ammonium sulfate Salting out, collecting the resulting precipitate by centrifugation, and then fully dialyzing a 20 mM Tris-hydrochloric acid buffer (pH 8.2) containing artificial seawater at a concentration of 1/10, to prepare a selective action In 600 ml of sulfated poly'sugar Enzyme solution for the decomposition of internal sulfated polysaccharides. (2) 2 kg of dried caged kumbu was ground with a cutting mill (manufactured by Zengxing Industry Co., Ltd.) equipped with a 1 mm sieve, and the obtained kumbu fragments were suspended. Stir in 20 liters of 80% ethanol at 25 ° C for 3 hours, filter through filter paper, and wash the residue thoroughly. 20 mM of 40 liters of 50 mM sodium chloride warmed at 95 ° C The sodium phosphate buffer solution (pH 6.5) was suspended in the obtained residue, and occasionally stirred at 95 t for 2 hours, and then the sulfated polysaccharide was extracted. The suspension of the extract was filtered, and after the filtrate was prepared, it was filtered. The residue was washed with 3.5 liters of 100 mM sodium chloride to obtain a filtrate. After combining the two filtrates, the temperature was lowered to 30 ° C, and 3000 U of alginate dissociation enzyme (manufactured by Nagase Biochemical Industry Co., Ltd.) was added, and 4 liters were added. The ethanol was stirred at 25 ° C for 24 hours. Then, the supernatant was obtained by centrifugation, and concentrated to 4 liters using an external filter with a molecular weight of 100,000 hollow fibers. 100 mM sodium chloride in ethanol, out of limit -42- paper size With China National Standard (CNS) A4 size (210 X 297 mm) Order #

Line 1228991 A7 B7 V. Description of the invention ^ Filter until the coloring matter is filtered out. The precipitate generated in the non-filtered solution is removed by centrifugation, the temperature of the supernatant is reduced to 5 ° C, and the pH value is adjusted to 20 with 0.5N hydrochloric acid, and the produced proteins are precipitated by centrifugation After removing it, the obtained supernatant was quickly adjusted to pH 8.0 with 1N sodium hydride. Then, use an out-of-limit filter that removes hollow fiber with a molecular weight of 100,000 to perform out-of-limit filtration. After completely replacing the solvent with 20 mM sodium chloride (pH 80), the mixture is centrifuged at pH 8.0 and frozen. It was dried to prepare about 95 g of sulfated polysaccharide. (3) Grind 2 kg of dried cage kumbu with a cutting mill equipped with a diameter Ø mm sieve. The obtained kumbu fragments are suspended in 20 liters of 80/100 ethanol at 25 ° C. After stirring for 3 hours, it was filtered with filter paper, and the residue was thoroughly washed. It was suspended in a solution containing 30 liters of the endosulfated polysaccharide degrading enzyme solution prepared in the above Reference Example 2- (1), 100/0 ethanol, 10 () mM steel chloride, 50 mM Chlorinated # 5 and 50 mM Mijun in 20 liters of buffer (pH 8.2) were stirred at 25 ° C for 48 hours. This suspension was filtered through a stainless steel metal mesh with a mesh diameter of 32 # m, and the residue was washed with 10% ethanol containing 50 mM calcium chloride. Further, the residue was suspended in 10 liters of 10% ethanol containing 50 mM calcium chloride, and after stirring for 3 hours, it was filtered through a stainless steel mesh and washed. After the residue was suspended under the same conditions, it was stirred for 16 hours and filtered through a stainless steel metal mesh with a diameter of 32 # m. The thus-obtained filtrate and washing liquid were collected, and the out-of-limit filtration was performed using an out-of-limit filter having an apparatus for removing hollow fiber with a molecular weight of 3000, and then the out-of-limit and out-of-filtration were separated. [__ -43- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention L) After concentrating this filter liquid to about 3 liters with an evaporator, centrifugation Supernatant. The resulting supernatant was desalted by an electronic dialyzer equipped with a membrane having a molecular weight of 300, and calcium acetate was added so that the concentration of the solution became 0.1 M, and the resulting sink was removed by centrifugation. The supernatant was injected into a DEAE-Seloflav A-800 column (resin amount: 4 liters) which had been equilibrated with 50 mM calcium acetate, and washed thoroughly with 50 mM calcium acetate and 50 mM sodium chloride. . Then dissolve in a gradient of 50 mM to 800 mM sodium chloride. At this time, the volume is 500ml per tube. The classification was analyzed by cellulose acetate membrane electrophoresis [Analytical Biochemistry, Vol. 37, pp. 197 ~ 202 (1970)], and it was dissolved when the sodium chloride concentration was about 0.4M. The sulfated sugar (divided near 63) is homogeneous. Then, the solution of Division 63 was first concentrated to 150 ml, and sodium chloride was added to make the concentration 4M, and then injected into a phenyl-Seloflav column (200 ml of resin) equilibrated with 4M sodium chloride beforehand. ), Wash thoroughly with 4M sodium chloride. The non-adsorbed sulfated sugar was collected and desalted with an electronic dialyzer equipped with a membrane with a molecular weight of 300 to remove, to obtain 505 ml of desalted solution. From the obtained desalting solution, 40 ml was taken for injection into a Celoflav GCL-90 column (4.1 cm x 87 cm) equilibrated with 0.2M sodium chloride containing 10% ethanol, and then subjected to gel filtration. Divide each into 9.2 ml. For the analysis of the total sugar content of the full division, the phenol sulfuric acid method [Analytical Chemistry, Vol. 28, p. 350 (1956)] was performed. As a result, because the sulfated sugar forms a peak, the central part of the peak is divided into 63 ~ 70, and a film with a molecular weight of 300 is excluded. -44- This paper standard applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 5. Description of the invention The electronic dialyzer of ί 2 is desalted and freeze-dried to obtain 112 mg of a dried product of the compound represented by formula (VI) below. Hereinafter, this compound is referred to as 7-12SFd-F.

(4) In 80 ml of a 2.5% aqueous solution of Class III (F-alanin) prepared in Reference Example 1- (2), 16 ml of 1 M Tris-hydrochloric acid buffer (pH 7.6) and 16 ml of 1M calcium dichloride aqueous solution, 24 ml of 4M sodium chloride aqueous solution, 8 ml of the endosulfated polysaccharide degrading enzyme solution obtained in Reference Example 2- (1), and 176 ml of distilled water, and heated at 30 ° C 3 hours. The enzyme-treated F-alanin solution was concentrated on a rotary evaporator to a final concentration of 2% of the F-alanin solution, followed by dialysis operation in distilled water to prepare a 2% enzyme-treated F-alanin. Aqueous solution. This sample was analyzed by HPLC (column: SB802.5, column temperature: 35 ° C, mobile phase: 50 mM sodium chloride, flow rate: 0.5 ml / min, detection: RI ATT = 8). As a result, it was confirmed that about 40% of the samples were 7-12SFd-F. Reference Example 3 -45- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of the invention L) (1) 2 kg of dried cage mesh konbu with a 1 mm screen A cutting mill (manufactured by Maso Kogyo Co., Ltd.) was ground, and it was stirred in 25 liters of 80 ° / 〇 ethanol at 25 ° C for 3 hours, and then filtered and washed with filter paper. The obtained residue was suspended in alteromonas sp. SN containing 50 mM calcium chloride, 100 mM sodium chloride, 10% ethanol, and 1U prepared in Reference Example 2- (1) above. -1009 (CCRC 910070) Endosulfated polysaccharide degrading enzyme solution in 20 liters of 30 mM imidazole buffer (pH 8.2), stirred at 25 ° C for 2 days, and then filtered through a stainless steel metal mesh with a pore size of 32 // m And washed. The obtained residue was dissolved in 40 liters of sodium phosphate buffer (pH 6.6) containing 100 mM calcium chloride, 10% ethanol, and 4 g of alginate dissociation enzyme (manufactured by Nagase Biochemical Industry Co., Ltd.) at 25 °. After stirring at C for 4 days, the supernatant was obtained by centrifugation. The low molecular weight alginic acid compound contained in the supernatant was concentrated to 2 liters using an external limiter filter equipped with a molecular weight of 100,000 hollow fibers, and then 100 mM sodium chloride containing 10% ethanol was used. Perform solution exchange. To this solution, an equal amount of 400 mM acetic acid was added. After stirring, the mixture was centrifuged, and the resulting supernatant was adjusted to pH 2 with 1N hydrochloric acid in an ice bath. The resulting precipitate was removed by centrifugation, and the resulting supernatant was adjusted to pH 8.0 with 1N sodium hydride. The solution was concentrated to 1 liter by filtration outside the limit, and the solution was exchanged with 100 mM steel chloride. The precipitate produced at this time was removed by centrifugation. In order to remove the water-repellent substance in the obtained supernatant, sodium chloride was added to make the supernatant 1M, and it was injected into a 3 liter phenyl siroflavin column equilibrated with 1M sodium chloride in advance. (Made by biochemical industry), directly collect its division. After the division was concentrated by an external filter, the solution was exchanged with 20 mM steel chloride and cold-rolled to dry. Cold rolled dry matter -46- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) 1228991 A7 B7 V. Description of the invention Q) The weight is 29.3 grams. (2) To 15 g of the above-mentioned freeze-dried product, 400 mM sodium chloride was added and cultured in Flavobacterium sp. SA-0082 (CCRC 910069) described in the International Publication No. 97/26896 booklet. The 9U endosulfated polysaccharide degrading enzyme obtained from the culture was dissolved in 1.5 liters of 50 mM Tiris-hydrochloric acid buffer solution, and after reacting at 25 ° C for 6 days, it was concentrated to about 300 ml by an evaporator. Add the concentrated solution to a dialysis tube with a molecular weight of 3500 to thoroughly perform dialysis, and then fill the remaining liquid in the dialysis tube to 4 liters of DEAE-Saluro, which has been equilibrated with 50 mM sodium chloride beforehand. After the A-800 column is thoroughly washed with 50 mM sodium chloride, it is dispensed at a concentration of 50 mM to 050 mM sodium chloride for dissolution. Further, the same column was fully dissolved with 050 mM sodium chloride. Collect the dissociation of 650 mM sodium chloride in the dissolution division, and divide it as sulfated seaweed galactan. After concentrating with a filter that excludes the molecular weight of 100,000, exchange it with a 10 mM steel chloride solution. Tumble dry to obtain 0.85 g of lyophilized sulfated seaweed galactan. The obtained sulfated seaweed galactan contains galactose and fucose, and has a molar ratio of about 2: 1. Reference Example 4 120 g of the sulfated polysaccharide prepared in Reference Example 2- (2) was suspended in 20 mM calcium chloride, 300 mM sodium chloride, 10% ethanol, and 10U of the above-mentioned Reference Example 2- (1 ) In the prepared internal sulfated polysaccharide degrading enzyme solution in 8 liters of 20 mM imidazole buffer (pH 7.5), stir at 25 ° C for 3 days, and then use the device to filter outside the limit of 100,000 hollow fibers Machine, while adding the above buffer solution, perform external filtration. -47- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of the invention ^ In the outer limit filtration solution 34U, add the internal sulfuric acid prepared in Reference Example 3- (2) The polysaccharide-degrading enzyme was stirred at 25 ° C for 2 days, and then an external-limiting filter equipped with an external-limiting filter excluding hollow fiber with a molecular weight of 100,000 was used for external-limiting filtering. Water was added for external-limiting filtering. The filtrate was collected 'concentrated to 1.5 liters in an evaporator and completely desalted in a desalination apparatus' and refilled to 3 liters previously equilibrated with a 5 mM imidazole hydrochloride buffer (pH 6.5) containing 30 mM sodium chloride After washing with 6 liters of the same buffer solution in a 〇ΑΕ-cellulofan A-800 column, 30 mM to 500 mM sodium chloride was used to dissolve it. The amount of liquid required for dissolution was 48 liters. The eluate was collected in 180 ml portions, and its sugar content was measured by the phenol sulfuric acid method. The absorbance at 232 nm was also measured. Since 130 mM ~ 170 mM sodium chloride dissolves and divides to form only one octyl portion, these divisions are taken here, and then desalted by a desalination device, and then freeze-dried to obtain 5.85 g of oligosaccharide. The molecular weight of the oligosaccharide was confirmed by mass analysis to be 1,128, and the compound represented by the following formula (vii) was confirmed by NMR analysis. Hereinafter, this compound is referred to as 6_2S. 〇 η 0

〇 = S =: 0 {OH 〇 = s = 0 I OK -48- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of invention) Reference example 6 will be sold on the market 1 kg of dried wakame was ground with a cutting mill equipped with a 1 mm sieve and suspended in 10 liters of 80% ethanol. After stirring for 3 hours, it was filtered with filter paper to obtain a funeral. The residue was suspended in 20 liters of 50 mM sodium chloride in 40 mM phosphate buffer (pH 6.5) and left at 95 ° C for 2 hours. After the treatment solution was cooled to 37 ° C, ethanol was added to 10%, and then 12,000 U of commercially-available alginic acid dissociating enzyme K (manufactured by Nagase Biochemical Industry Co., Ltd.) was added, followed by stirring at room temperature for 24 hours. The obtained treatment solution was centrifuged, and the supernatant was concentrated to 2 liters using an external-limiting filter equipped with a hollow fiber having a molecular weight of 100,000, and the resulting precipitate was separated and removed by centrifugation. The temperature of the supernatant was cooled to 5 ° C, and 0.5N hydrochloric acid was added to adjust the pH to 2.0, followed by stirring for 30 minutes. The supernatant was adjusted to pH 8.0 with 0.5 N sodium hydroxide, and the solution was replaced with 20 mM sodium chloride by filtration outside the limit. After adjusting the solution to pH 8.0, centrifugation was performed, and the resulting supernatant was freeze-dried to obtain 90.5 g of wakame-derived fucoidan. Reference Example 7 One kilogram of the ground dried Fucus vesiculosus was suspended in 10 liters of 80% ethanol, and after stirring for 3 hours, it was filtered with filter paper to obtain a stalemate. The residue was suspended in 30 liters of 100 mM sodium chloride in 30 mM phosphate buffer (pH 6.0) and left at 95 ° C for 2 hours. After the treatment solution was cooled to 37 ° C, 100 g of activated carbon was added and stirred for 30 minutes. After further adding 3000U of a commercially available 10% alginate dissociating enzyme K, ethanol was added to 10%, and the mixture was stirred at room temperature for 24 hours. The obtained treatment solution is centrifuged. -49- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention G) The supernatant solution is removed by the device. The hollow fiber with a molecular weight of 100,000 was condensed to 2 liters, and the resulting precipitate was removed by centrifugation. One side of the extract was added to the supernatant and filtered out to limit the pigment. After the obtained non-filtered liquid was cooled down, 0.5 N hydrochloric acid was added to adjust the pH to 2.0, and the resulting precipitate was stirred and removed by centrifugation for 30 minutes. The supernatant was adjusted to pH 8.0 with 0.5 N sodium hydride, and the solution was replaced with 20 mM sodium chloride by filtration outside the limit. After adjusting the solution to pH 8 · 0, centrifugation was performed, and the resulting supernatant was freeze-dried to obtain 71 g of polysaccharides derived from limy algae. According to the above method ', a dry powder of Ascophyliuin nodosum (trade name: Alkin Gold, sold by Andes Trading Company) was used to prepare an alkano-derived algin. Reference Example 8 Dissolve 2 g of Cageme-derived Algae Derived from the method described in Reference Example 1- (1) in 00 ml of water, adjust the pH to pH 3 with citric acid, and adjust the pH to 100. After treatment at ° C for 3 hours, the acid-lysate of the fucoidan was obtained. This hydrolysate was gel-filtered with Sailuofan GCL_300 or Sailuofan GCL-25 to divide its molecular weight, which was divided into molecular weights of 25,000 or more (A division), 25,000 to 10,000 or more (B Division), 10,000 to 5,000 or more (c division), 5000 to 2000 or more (0 division), 2000 to 500 or more (E division), or 500 or less (F division). These divisions and freeze-drying after desalting the acidolysate are performed to prepare the acidolysate and the divided products of the acidolysate. Reference Example 9 5 kg of commercially available salt-contained seaweed was mixed with 20 liters of ethanol, and scissors were used.

1228991

Cut it carefully. Let it stand for 1 night and use the filter paper to filter it. The resulting residue floats in 12.5 liters of water and is placed in 95t—Heart, Top, &gt;, 1 and 4 books. After processing the defects with filter paper, add 2600 liters of each right Ayre λ hairy owl has 350 mM sodium gaseous sodium chloride 2.5% chlorinated exo I in the mouth; deposit the liquid and place it for 3 夭. Separate the part of the sink, and discard it for 3 days to discard the supernatant. After centrifugation, add 2.5 liters of 350 mM sodium chloride to the resulting precipitate. The homogenizer centrifuged it uniformly. Repeat this washing step 3 times. After 400 ml of 400 mM sodium chloride was added to the obtained precipitate, it was homogenized with a homogenizer, and ethanol was added to 80/0, and after stirring for 30 minutes, it was filtered with filter paper. After 500 liters of sodium chloride saturated with 80% ethanol was added to the obtained residue, the mixture was homogenized with a homogenizer, and sodium chloride saturated ethanol was added to make the mixture liters. After stirring for 30 minutes, it was filtered with filter paper. This process is repeated until the absorbance at 26 nm of the filtrate becomes 0 (typically 5 times). The obtained residue was dissolved in 5 liters of 2M sodium chloride, and the insoluble matter was removed by centrifugation, and then it was injected to 100 ml of DEAE which was equilibrated with 2m sodium vaporized in advance_ 赛 路 洛 凡 八 _ 800 column. The fraction was concentrated to 2 liters with an external filter with a molecular weight of 100,000 hollow fibers, and the solution was replaced with 2 mM sodium chloride by external filtration. This solution was centrifuged and the resulting supernatant was freeze-dried to obtain 22.9 g of seaweed-derived fucoidan. Reference Example 10 (1) 50 grams of dried stone cauliflower was cut with scissors. Suspend in 500 ml of 80% ethanol, place at 25 ° C for 3 hours, and filter with filter paper. The obtained residue was suspended in 1 liter of 30 mM sodium linate buffer solution (pH 6.5) containing 100 mM sodium chloride, and was placed at 95 ° C for 2 hours. Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention () 49 Stainless steel screen filter with aperture 106 / zm. The above phosphate steel buffer solution was added to the aforementioned filtrate, adjusted to 3 liters, and then 5 g of activated carbon was added, and the mixture was stirred at 25 ° C for 1 night, and then centrifuged. The obtained supernatant was concentrated to 200 ml with an external-limiting filter equipped with a hollow fiber having a molecular weight of 100,000, and then the solution was exchanged with the external-limiting filter to prepare a 10 mM chlorinated steel solution. The insoluble matter in the solution was removed by centrifugal separation, and then dried in a cold state to obtain 2.3 g of a dried matter divided by a sulfated polysaccharide derived from a flower of cauliflower. (2) According to the method described in Reference Example 10- (1), 4.4 g of a sulfated polysaccharide derived from a turnip was prepared from 50 g of the dried turnip. In the same manner, 1.0 g of a sulfated polysaccharide derived from amaranth was prepared from dried acerola. (3)-① 1 kg of dried "Lessonia nigrescence" powder was suspended in 80% ethanol, placed under 25 for 3 hours, and filtered through a paper towel. The obtained residue was suspended in 20 liters of 30 mM sodium phosphate buffer (pH 6.5) containing 100 mM sodium vaporization, and was placed at 95 ° C for 2 hours, and then made of stainless steel with a pore size of 106 / zm. Sieve filtration. To the obtained filtrate, 100 g of activated carbon, 2.4 liters of ethanol, and 6,000 U of commercially available brown bath dissociation enzyme K were added, and the mixture was centrifuged at 25 C for 2 hours, and then centrifuged. The obtained solution was concentrated to 1.2 liters using an external filter with a molecular weight of 100,000 hollow fibers. The insoluble matter was removed by centrifugation, and it was left at 5 ° C for 24 hours. The resulting precipitate was removed by centrifugation, and the resulting supernatant was subjected to solution exchange with an external filter to prepare a 100 mM sodium chloride solution. The temperature of the supernatant was cooled to below 40 ° C, and the pH was adjusted to 2.0 'with a salt, and the resulting sink was removed by centrifugation. The resulting supernatant was adjusted to a pH of 80 with sodium hydride and concentrated to 2 -52. This paper size is in accordance with the Chinese National Standard (CNS) A4 specification (21〇X 297 public 11228991 A7 B7 V. Description of the invention ( ) After 50 liters, replace the solution with 20 mM sodium chloride with an out-of-limit filter. The insoluble matter in the solution was removed by centrifugation, and freeze-dried to obtain 41 g of sulfonium-derived sulfated polysaccharides. (3) -② 6 g of the above cold-rolled dried product was dissolved in 600 ml of 20 mM imidazole buffer solution (pH 6.0) containing 100 mM sodium chloride, and injected for equilibration with the same buffer solution beforehand. In a 5 liter DEAE-Seloflav A-800 column, wash with 10 liter of the same buffer, and dissolve at a concentration of 100 mM to 1600 mM of sodium chloride to dissolve. Dissolve the liquid used The volume is 13 liters, and the fractionation is 500 ml per tube. In the dissolution division, 250 mM, 530 mM, and 700 mM of chloride steel are dissociated and divided, and each is dialyzed with 500 ml of pure water and cold-rolled to dry. The cold-dried products are named DEAE 33, DEAE 37, and DEAE 40. 57 mg, 24 mg, and 62 mg were obtained respectively. Reference Example 11 5 kg of sea cucumber was disassembled, the internal organs were removed, and the body wall was collected. 200 g of wet weight of each body wall was added with 500 ml of acetone and treated with a homogenizer. After filtration, the residue was washed with acetone until the coloring matter disappeared. The residue was dried by suction to obtain 140 g of dried matter. On top of the dried matter, 2.8 liters of 0.4M saline solution was added. Treat at 100 ° C for 1 hour. Filter and wash the residue with 0.4M brine to obtain 3.7 liters of extract. To this extract, add 5% cetylpyridinium chloride until the precipitation disappears, and then The resulting precipitate was separated by centrifugation. The precipitate was suspended in 0.4M saline and then centrifuged again. After adding 1 liter of 4M sodium chloride to the obtained precipitate, the mixture was treated with a homogenizer and added while stirring 4升 之 _-53- The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention () 51 Ethanol, after stirring for 1 hour, filter through filter paper and get a precipitate. The precipitate is 80% B Suspension filtration was repeated until the absorbance at 260 nm of the supernatant became 0. The obtained precipitate was suspended in 2 liters of 2M saline, and then the insoluble matter was removed by centrifugation. Use a membrane with a molecular weight of 30,000 or more to remove it. The filter device was used for ultrafiltration of the supernatant, and after desalting completely, it was dried in the cold to obtain 3.7 g of seaweed-derived fucoidan. Reference Example 12 500 mg of agar agar powder (manufactured by Naco Vegetables) was suspended in 100 ml of Distilled water, heat and dissolve the agar. Thereafter, it was cooled to 45 ° C and kept at 45 ° C. To this agar solution, 2 ml of X50 / 3 agarase buffer (manufactured by FMC: with agarase) was added, and then 100 / zl of 1U // Z1 stone agarase (manufactured by FMC) was added. . The solution was incubated at 45 ° C for 24 hours, and 2.5 times the amount of ethanol was added. After cooling, the solution was centrifuged and the precipitate was recovered. The precipitate was dried and dissolved in 20 ml of distilled water. This solution was freeze-dried and prepared into a powdered agar pectin fraction. Reference Example 13 (1) Ten grams of dried bacteria of Spirulina platensis were suspended in 100 ml of chloroform, and the insoluble fraction was recovered by filtration, and repeated 5 times. Thereafter, it was suspended in 100 ml of ethanol and filtered, and the insoluble fraction was recovered and repeated 3 times. The insoluble fraction obtained by this procedure was completely removed with ethanol, and suspended in 100 ml of distilled water. After the distilled water was kept at 60 ° C for 1 hour, the supernatant was centrifuged. The supernatant was filtered, and 2.5 times the amount of ethanol was added to the filtrate. After cooling to -20 ° C, it was separated at a low temperature. _-54- This paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention () 52 The heart was separated to obtain the temple; The Shen Dian was dissolved with steamed hall water, and was aged for a while, and was prepared into a powdery form containing spirulina-derived sulfated polysaccharides. (2) 20 grams of dried spirulina powder (sold by Spirulina Research Institute) was added to a homogenizer (manufactured by Nippon Seiki Co., Ltd.), 400 ml of acetone was added, and the mixture was homogenized at 8000 rpm for 10 minutes. The homogenate was filtered through filter paper to obtain a residue. The residue was washed with acetone and repeated three times in the same manner as the previous procedure to obtain a residue washed with acetone. In the same manner as described above, the acetone washing residue was washed with acetone, and then washed four times with 90% ethanol and four times with 80% ethanol to obtain an ethanol washing residue. To the ethanol-washed residue, 600 ml of 30 mM phosphate buffer (pH 7.0) containing 100 mM sodium chloride and 10% ethanol was added, and the mixture was stirred at room temperature for 18 hours. This mixture was centrifuged at 10,000 rpm for 40 minutes to obtain a supernatant. The insoluble matter mixed in the supernatant was filtered through filter paper to obtain a crude extract (filtrate). The obtained crude extract was concentrated to 300 ml with an external-limiting filter equipped with a hollow fiber having a molecular weight of 10,000, and then 2 liters of 100 mM sodium chloride containing 10% ethanol was added for external-limiting filtration. Thereafter, the solvent was replaced with a 10 mM imidazole-hydrochloric acid buffer solution (pH 7.0) containing 10% ethanol and 50 mM sodium chloride to obtain 240 ml of a spirulina polymer fraction. This spirulina polymer was divided and added to a DEAE-Seloflav A-800 column (Φ) previously equilibrated with 10 mM imidazole-hydrochloric acid buffer (pH 7.0) containing 10% ethanol and 50 mM sodium chloride (Φ 3 X 14.2 cm), wash the column with 360 ml of the same buffer, and dissolve in a gradient of 0.05M (200 ml) to 2M (200 ml) sodium chloride. The eluent was 10 ml per tube. _-55- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) In the dissociation division, divisions 14 to 30 are named as the spiral sulfuric acid polysaccharide division -I (SSP-I), divisions 69 to 77 for spirulina sulfate polysaccharide division-II (SSP-II), divisions 78 to 83 for spirulina sulfate polysaccharide division -III (SSP-III), and divisions 84 to 99 Spirulina sulfate polysaccharide division-IV (SSP-IV). 88 卩 -I, SSP-II, SSP-III, and SSP-IV were sufficiently dialyzed against distilled water and lyophilized to obtain 200 mg, 260 mg, 100 mg, and 60 mg of each. (3) Suspend 10 g of dried bacteria of Chlorella vulgaris in 100 ml of chloroform, filter, recover insoluble fractions, and repeat 3 times. Thereafter, it was suspended in 100 ml of ethanol and filtered, and the insoluble fraction was recovered and repeated 3 times. The insoluble fraction obtained by this procedure was completely removed with ethanol, and suspended in 100 ml of distilled water. After the suspension was kept at 60 ° C for 1 hour, it was filtered. 2.5 times the amount of ethanol was added to the filtrate, and after cooling to -20 ° C, the precipitate was obtained by centrifugation at low temperature. The precipitate was dissolved in distilled water and freeze-dried to prepare a powdered division containing chlorated sulfate-derived polysaccharides. (4) 20 grams of dried Chlorella powder (sold out: Chlorella) is added to a homogenizer (manufactured by Seiki Co., Ltd.), 400 ml of acetone is added, and the mixture is homogenized at 8000 rpm for 10 minutes . The homogenate was filtered through filter paper to obtain a residue. The residue was washed with acetone and repeated three times in the same manner as the previous procedure, and the acetone washing process was obtained. In the same manner as described above, the acetone washing residue was washed with acetone, and then washed four times with 90% ethanol and four times with 80% ethanol to obtain ethanol washing residues. On the ethanol washing residue, add 600 liters containing 100 mM sodium chloride and _-56- This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 V. Description of the invention Q) 10% ethanol in 30 mM phosphate buffer (pH 7.0) was stirred at room temperature for 18 hours. This mixture was centrifuged at 10,000 rpm for 40 minutes to obtain a supernatant. The insoluble matter mixed in the supernatant was filtered through filter paper to obtain a crude extract (filtrate). The obtained crude extract was concentrated to 310 ml with an external-limiting filter equipped with a hollow fiber having a molecular weight of 10,000, and 3 liters of 100 mM sodium chloride containing 10% ethanol was added for external-limiting filtration. Thereafter, the solvent was replaced with a 10 mM imidazole-hydrochloric acid buffer solution (pH 7.0) containing 10% ethanol and 50 mM sodium chloride to obtain 203 ml of a spirulina polymer fraction. This Chlorella macromolecule was divided and added to a DEAE-Seloflav A-800 column equilibrated with 10 mM imidamine-hydrochloric acid buffer (pH 7.0) containing 10% ethanol and 50 mM sodium chloride. (Φ 3 X 14.2 cm), wash the column with 297 ml of the same buffer, and dissolve it in a gradient of 0.05M (200 ml) to 2M (200 ml) of vaporized steel. The eluent was 10 ml per tube. In the dissociation division, divisions 63 to 68 are designated as Chlorococcus sulfate polysaccharide division-I (CPS-I), and divisions 69 to 75 are classified as Chlorococcus sulfate polysaccharide division-II (CPS-II). CPS-I and CPS-II were fully dialyzed with distilled water and lyophilized to obtain 140 mg and 200 mg of each. (5) Grind the commercially available sagebrush (Altemisia princeps pampan: manufactured by Hanban Hanfangdo), and suspend 10g of sagebrush powder in 100ml of chloroform, filter and recover the insoluble fraction, and repeat 3 times. . Thereafter, it was suspended in 100 ml of ethanol and filtered. The insoluble fraction was recovered and repeated 5 times. The insoluble fraction obtained in this process was completely removed with ethanol, and suspended in 100 ml of distilled water. After the suspension was kept at 60 ° C for 1 hour, the paper size was adapted to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ^). A 2.5-fold amount of ethanol was added to the filtrate, and after cooling to -20 ° C, centrifugation was performed at a low temperature to obtain a supernatant of the wormwood tree. The precipitate was dissolved in distilled water and freeze-dried to prepare a powdered sagebrush-derived thiolated polysaccharide. (6) 50 grams of dried mountain wormwood leaves (sold: made by Sakamoto Hankatado) were added to a homogenizer (manufactured by Nippon Seiki Co., Ltd.), 500 ml of acetone was added, and the mixture was homogenized at 8000 rpm for 10 minutes. The homogenate was filtered through filter paper to obtain a residue. The above procedure was repeated twice, and the obtained residue of 100 g of Artemisia japonica leaves was put into a homogenizer, 500 ml of acetone was added, and the mixture was homogenized at 8000 rpm for 10 minutes. The homogenate was filtered through filter paper to obtain a residue. This procedure was repeated 4 times to obtain the acetone washing residue. Further, similar to the washing with acetone, washing with 90% ethanol 4 times and washing with 80% ethanol 4 times were obtained, and the residual inspection of ethanol washing was obtained. To the ethanol-washed residue, 5 liters of 30 mM phosphate buffer (pH 8.0) containing 100 mM sodium chloride and 10% ethanol were added, and stirred at room temperature for 19 hours. The insoluble matter mixed in the supernatant was filtered through filter paper to obtain a crude extract (filtrate). The obtained crude extract was concentrated to 2 liters using an external-limiting filter equipped with a hollow fiber having a molecular weight of 10,000, and 10 liters of 100 mM sodium chloride containing 10% ethanol was added to perform external-limiting filtration. Thereafter, it was concentrated to 500 ml, and the solvent was replaced with a 10 mM imidazole-hydrochloric acid buffer solution (pH 7.0) containing 10% ethanol and 50 mM sodium chloride. This liquid was transferred to a beaker, 1 g of activated carbon was added, and after stirring at room temperature for 40 minutes, it was centrifuged at 10,000 rpm for 40 minutes. The activated carbon mixed in the supernatant was filtered through filter paper and removed. In this way, the height of 560 milligrams of Artemisia sylvestris leaves is obtained -58- This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ^) Molecular division. This mountain wormwood leaf was divided into macromolecules and added to a DEAE · Seloflav A-800 column equilibrated with 10 mM imidazole-hydrochloric acid buffer (pH 7.0) containing 10% ethanol and 50 mM sodium chloride in advance ( Φ 3 · 5 X 31 cm), the column was washed with 940 ml of the same buffer solution, and then dissolved in a gradient of 0.05M (600 ml) to 2M (600 ml) sodium chloride. The eluent was 10 ml per tube. In the dissociation division, division numbers 180 to 202 are named as mountain wormwood leaf acid polysaccharide division (YAP), and division numbers 203 to 270 are mountain wormwood leaf sulfated polysaccharide division (YSP). YAP was fully dialyzed against distilled water and freeze-dried to obtain 250 mg. In order to further classify the sulfonated polysaccharides of the wormwood tree, the sulfonated polysaccharides of the wormwood tree are divided into 3 liters of 10 mM imidazole-hydrochloric acid buffer solution (pH 10) containing 10% ethanol and 100 mM sodium chloride. 7.0) Perform dialysis. The dialyzed sulfated polysaccharide (327 ml) was added to the equilibrated DEAE-Seloflav A-800 column (Φ3 × 14.2 cm) with the same buffer. The column was washed with 273 mL of buffer, and then dissolved in a gradient of 0.1M (200 mL) to 2M (200 mL) of sodium chloride. The eluent was 5 ml per tube. In the dissociation division, division numbers 140 to 154 are named as Suaeda sulphate polysaccharide division-I (YSP-I), and division numbers 155 to 200 are Suaeda sulphate polysaccharide division-II (YSP-II). YSP-1 and YSP-II were each sufficiently dialyzed against distilled water and freeze-dried to obtain 20 and 130 mg, respectively. To YSP-II (119.4 mg), 59.7 ml of 10 mM imidazole-hydrochloric acid buffer (pH 7.0) containing 10% ethanol and 0.2 M sodium chloride was added, and the solution was stirred overnight at room temperature to dissolve. Dissolved YSP-II is added in -59 with the same buffer.- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 _______ B7 _ V. Description of the invention &) Balanced DEAE -Sailu Luofan A-800 column (Φ2 · 5χ 10 · 2 cm). After washing the column with 200 ml of a buffer solution, the column was dissolved in a gradient of 0.2 M (100 μL) to 1 M (100 μL) of chloride steel. The eluent was 5 liters per tube. In the dissociation division, division numbers 54 to 70 are named as the sulphated polysaccharides of mountain wormwood leaves-Ι-2 (YSP-II-2), and division numbers 71 to 90 are the assimilated polysaccharides on wormwood leaves-Π-3 ( YSP-II-3), and the division numbers 91 to 120 are the sulfated polysaccharides of mountain wormwood leaves_Π-4 (YSP-II-4). YSP-II-2, YSP-II-3 and YSP-II-4 were each sufficiently dialyzed against distilled water and freeze-dried 'to obtain 39.5 mg, 61 mg, and 57.3 mg of each. (7) The commercially available edible bitter gourd is ground with a stirrer, and the ground product is freeze-dried to obtain a dried bitter gourd. 10 g of dried bitter gourd were suspended in 100 ml of chloroform, filtered, and the insoluble fraction was recovered and repeated 3 times. Thereafter, it was suspended in 100 ml of ethanol and filtered. The insoluble fraction was recovered and repeated 3 times. The insoluble fraction obtained in this process was completely removed with ethanol, and suspended in 100 ml of distilled water. After the suspension was kept at 60 ° C for one hour, the suspension was passed through the reactor. Add 2.5 times the amount of ethanol to the filtrate and cool to -20. (: Then, the precipitate was obtained by centrifugation at low temperature. The precipitate was dissolved in distilled water, cold-rolled to dry, and prepared into powdered sulfated polysaccharide-containing divisions. (8) Five commercially available aloe leaves were recovered. The transparent mesophyll portion was dried cold / east. This lyophilized 481 g of aloe mesophyll was suspended in 100 ml of distilled water. The suspension was kept at 60 ° C for 1 hour and then filtered. Add 2.5 times the amount of ethanol in the filtrate, after cooling to -20 ° C, the precipitate was obtained by centrifugation at low temperature. The precipitate was dissolved in distilled water and freeze-dried to prepare a powder containing sulfuric acid derived from aloe mesophyll. -60 of this polysaccharide-This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 ________ V. Description of the invention Is Γ ~ ^ ~ Division. On the other hand, the transparent mesophyll is recovered by the above method. After the portion, the remaining green leaf surface was ground and lyophilized. The cold quasi-dried material (3.43 g) was suspended in 100 ml of aerosol, filtered, and the insoluble fraction was recovered and repeated 3 times. , Hanging Float in 100 ml of ethanol and filter, recover its insoluble fractions, and repeat 3 times. The insoluble fractions obtained in this process are completely removed with ethanol 'suspended in 100 ml of distilled water. The suspension is at 60 ° After incubating for 1 hour at C, it was filtered. 2.5 times the amount of ethanol was added to the solution to be 'cooled to -20 C' and centrifuged at low temperature to obtain the precipitate. The precipitate was dissolved in distilled water, freeze-dried, and prepared Classification of powdered sulfated polysaccharides containing aloe vera leaf surface. Reference Example 14 (1) 200 mg (1.1 mmol) of D-(+)-glucose was dissolved in 10 ml of pyridine 'chamber After adding 1.05 g (6.6 mmol) of Pyridine Sulfur Trioxide Complex (Pyr · SO3: Tokyo Chemical Industry) at room temperature, place it at room temperature for several minutes, and stir at 60 ° C for 1 hour. Dilute the reaction solution with water. After adjusting the pH to near neutral with a saturated barium hydride aqueous solution, it was dried and solidified under reduced pressure. A small amount of water was added to the obtained concentrate to dry and solidify under reduced pressure. This process was repeated once more. The obtained Add a small amount to the concentrate The water 'was centrifuged to remove the precipitate of barium sulfate, and the resulting supernatant was injected into a cation exchange column (Amber's special IRA-120 (Na +) (Orge)). As a result, the obtained tube was The column was directly divided and concentrated under reduced pressure to prepare 700 mg of sulfated D-(+)-glucose sodium salt. (2) 240 mg (1.3 mmol) of D-(+)-galactose was dissolved in 10 ml of pyridine -61- This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 —_ B7 _ V. Description of the invention) 'Add Pyr * S〇3l.〇5 grams (6.6¾ at room temperature) (Moore) and then 'place at room temperature for a few minutes and then at 60. (: Stir for 1 hour. Below, the same procedure as in Reference Example 14- (1) was used to prepare 406 g of sulfated 0-(+)-galactose sodium salt. (3) D-(+)-mannose 200 mg (1.3 mmoles) was dissolved in 10 ml of pyridine. 'Added at room temperature? 5 ^ * 8〇31.〇5 g (6.6 mmoles)' Placed at room temperature for a few minutes, then at 60 Stir for 1 hour at ° C. Following this, use the same procedure as in Reference Example 14- (1) to prepare 700 g of sulfated D-(+)-mannose sodium salt. (4) 205 mg (0.57 mmol) of maltose It is dissolved in 10 ml of pyridine, and it is added at the temperature of 71? §03 816 g (5.2 millimoles), then it is placed at room temperature for several minutes, and then stirred at 60 ° C for 1 hour. Below, use 520 mg of sulfated maltose sodium salt was prepared in the same procedure as in Reference Example 14- (1). (5) 200 mg (0.4 mmol) of maltotriose was dissolved in 10 ml of pyridine, and Pyr was added at room temperature. 700 mg (4.4 mmol) of S03, then left at room temperature for several minutes, and then stirred at 60 ° C for 1 hour. Below, the same procedure as in Reference Example 14- (1) was used to prepare sulfated malt III Sugar sodium salt 420 mg. (6) Sea and algae 250 mg (0.73 mmol) was dissolved in 10 ml of Edian, 1.1 g (7 mmol) of Pyr · SO3 was added at room temperature, and it was left at room temperature for several minutes, and then stirred at 60 ° C for 1 hour. Below, the same procedure as in Reference Example 14- (1) was used to prepare 750 mg of sulfated trehalose sodium salt. (7) 222 mg (0.62 mmol) of lactose was dissolved in 10 ml of pyridine, and Pyr was added at room temperature. · After 785 mg (4.9 mmol) of SO3, place it at room temperature for several minutes, and stir at 60 ° C for 1 hour. Hereinafter, the same procedure as in Reference Example 14- (1) was used to prepare the sulfated lactose sodium salt. 476 mg. (8) Dissolve 220 mg of sugar (0.62 mmol) in 10 ml of p-bite, chamber-62- This paper is in accordance with China National Standard (CNS) A4 (210X297 mm) 1228991 A7 B7 V. Description of the invention) After adding 785 g (4.9 mmol) of Pyr · SO3 at room temperature, place it at room temperature for several minutes and stir at 60 ° C for 1 hour. Hereinafter, 481 mg of sulfated sucrose sodium salt was prepared in the same manner as in Reference Example 14- (1). (9) Dissolve 370 mg (1.08 mmol) of lactulose in 10 ml of pyridine, add 1.3 8 g (8.8 mmol) of Pyr · SO3 at room temperature, and then place at room temperature for several minutes Then, it was stirred at 6 ° C for 1 hour. Hereinafter, 1 g of sulfated lactulose steel salt was prepared in the same mud procedure as in Reference Example 14 · (1). (10) 379 mg of melibiose (0 · 9 Mmol) was dissolved in 10 ml of pyridine, and 1.43 g (9.0 mmol) of Pyr · SO3 was added at room temperature, then it was left at room temperature for several minutes, and then stirred at 60 ° C for 1 hour. The following is for reference Example 14- (1): The same procedure was used to prepare 950 g of sulfated melibiose sodium salt. (11) 150 mg (1.0 mmol) of D-(+)-xylose was dissolved in 10 ml of pyridine. After adding 770 mg (4.8 mmol) of Pyr · SO3 at room temperature, leave it at room temperature for several minutes, and then stir at 60 X: for 1 hour. The following is the same procedure as in Reference Example 14- (1). 35 mg of sulfated (+)-xylose sodium salt was prepared. (12) 200 mg (1.2 mmol) of 2-deoxy-glucose was dissolved in 10 ml of pyridine, and Pyr · S was added at room temperature. 3 920 mg (5.8 mmoles) Let it stand at room temperature for several minutes, and then at 60. (: Stir for 1 hour. Below, the same procedure as in Reference Example 14- (1) was used to prepare sulfated 2-deoxyglucose sodium salt 500. (13) Dissolve 150 mg (0.83 mmol) of sorbitol in 10 ml of pyridine, and add 955 mg (6 mmol) of Pyr · SO3 at a temperature, and place it in a chamber m. Then, it was stirred for 1 hour at 60 C. Hereinafter, the same procedure as in Reference Example j4- (1) was used to prepare sulfated 0 · (+ &gt; sorbitan sodium salt 570 mg.) (14) Cellulose 147 Mg (.43 mmol) was dissolved in 5 liters of dimethyl sulfoxide, added at 1 ° C? 71: 80,657 g (4.13 mmol), and then left at room temperature for several minutes, Stir at 6 (rc for more than 1 hour. Below, with reference _ -63- This paper is again applicable to China National Standard (CMS) A4 specification (21〇X 297 public reply) &quot; — 1228991 A7 B7 V. Description of the invention &amp;) Example 14- (1) The same procedure was used to prepare 230 g of sulfated cellobiose sodium salt. (15) 62 mg (0.18 mmol) of isomaltose was dissolved in 5 ml of pyridine and added at room temperature. Pyr After 275 mg (1.73 mmol) of SO3, it was left at room temperature for several minutes, and then stirred at 60 ° C for 1 hour. Hereinafter, the same procedure as in Reference Example 14- (1) was used to prepare sulfated isomaltose sodium salt. 162 g. (16) Dissolve 293 mg (0.86 mmol) of melibiose in 5 ml of pyridine, add 1310 mg (8.22 mmol) of Pyr · SO3 at room temperature, and leave at room temperature for several minutes. , And stir at 60 ° C for 1 hour. Hereinafter, 835 mg of sulfated sucralose sodium salt was prepared by the same procedure as in Reference Example 14_ (1). (17) Dissolve 315 mg (0.875 mmol) of palatinose in 5 liters of pyridine, add 1.34 g (8.4 mmol) of Pyr · SO3 at room temperature, and then place at room temperature for several minutes. Stir at 60 ° C for 1 hour. Hereinafter, 845 mg of sulfated palatinose sodium salt was prepared by the same procedure as in Reference Example 14- (1). (18) Dissolve 56 mg (0.31 mmol) of a-D-talose in 5 ml of pyridine, add 300 mg (1.9 mmol) of Pyr · SO3 at room temperature, and then place at room temperature for several minutes , And stirred at 60 ° C for 1 hour. Hereinafter, 150 g of sulfated d-talose sodium salt was prepared by the same procedure as in Reference Example 14- (1). (19) Treat 7 g of α-cyclodextrin complete acetamate with a mixture of anhydrous acetic acid and sulfuric acid (49: 1) to obtain a complete acetamate of maltohexose, and place it in ethanol to Sodium methanolate (NaOM) was deacetylated to obtain 1.5 g of maltohexose. 79 mg (0.83 mmol) of maltohexose and 1.33 g of piperidine sulfate were dissolved in 5 ml of dimethyl sulfoxide (DMSO) and stirred at 8 (rc for 2 hours. The reaction solution was cooled. After that, it was placed in a dialysis membrane with a molecular weight of 1000, and dialyzed for 2 days. The obtained dialysis internal solution was injected into cation-64. X 297 Public Love) Order

1228991 A7 B7 V. Description of the invention L) Exchange column (Amberlite IRA-120 (Na +) (Orge)). As a result, the obtained column was directly divided and concentrated under reduced pressure to prepare 167 mg of sulfated malt sodium hexose salt. (20) Treating 2.2 g of methycyclodextrin with acetic acid and sulfuric acid in a mixed solution (49 ·· 1) to obtain a complete ethyl acetate of maltoheptose, which is placed in ethanol. Deacetylation with NaOMe gave 0.5 g of maltoheptose. 20 mg (0.83 mmol) of maltoheptose and 325 g of sodium sulfate were dissolved in 5 ml of DMSO, and stirred at 80 ° C for 2 hours. The following is the same as in Reference Example 14_ (19) Process to prepare sulfated maltoheptose steel salt 4 5.6 mg. (2 1) The complete acetamate of maltohexose was stirred in dichloromethane in the presence of trichloroacetonitrile and calcium carbonate to obtain an imidized salt of maltohexose. The imide salt of acetylated maltohexose and dodecyl alcohol were placed in dichloromethane, and the reaction was carried out using trimethylsilyl trifluoromethanesulfonate as a catalyst. Deacetate to obtain lauryl-maltohexose. After dissolving 370 mg (0.32 mmol) of lauryl-malt hexose in 10 ml of DMSO and stirring at 80 ° C for 2 hours, the following procedure is the same as that of Reference Example 14- (19). Preparation of 700 mg of sulfated lauryl maltohexose sodium salt. (22) Dissolve 276 mg of Dian powder in 10 ml of DMSO, add 2.76 g of Pyr · SO3 at room temperature, and stir at 8 ° C for 2 hours. After cooling the reaction solution, add acetone to make it insoluble After washing with methanol several times, it was diluted with water and injected into a cation exchange column (Amberlite ira 120 (Na +) (Orge)). As a result, the obtained column was directly divided into -65. -

1228991 A7 B7 V. Description of the invention ^) Concentrated under reduced pressure to prepare 350 mg of sulfated sodium starch salt. (23) Dissolve 111 mg of curdlan in 5 ml of DMSO, add 1 · 11 g of Pyr · S03 at room temperature, and stir at 80 ° C for 2 hours. After the reaction solution was cooled, acetone was added, and the resulting insoluble matter was diluted with water, and its pH value was neutralized with saturated sodium bicarbonate water. Then, the dialysis membrane with a molecular weight of 1,000 was dialyzed for 1 day. The obtained dialysate was injected into a cation exchange column (Amberlite IRA-120 (Na +) (Orge)), and then dried under reduced pressure to prepare 180 mg of sulfated cardel blue sodium salt. (24) Dissolve 267 mg of pectin in 5 ml of DMSO, add 2.67 g of Pyr · S03 at room temperature, and stir at 80 ° C for 2 hours. After the reaction solution was cooled, 384 mg of sulfated pectin sodium salt was prepared by the same procedure as in Reference Example 14- (23). Example 1 (1) MRC-5 cells (CCL 171: manufactured by Otsumoto Pharmaceutical Co., Ltd., code. 02-021) suspended in DME medium containing 10% bovine fetal serum at a concentration of IX 105 cells / ml ) 500 // 1, add a 48-well cell culture plate, and incubate at 37 ° C in the presence of 5% carbon dioxide for 24 hours, then replace the medium with DME medium containing 1% bovine fetal serum. Thereafter, alginans derived from Cageale kumbu described in Reference Example 1- (1) as a sample were added to a final concentration of 1, 10, and 100 # g / ml, and after further culture for 24 hours, the culture medium was recovered. Then, a Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00) was used to determine the amount of HGF in the culture medium. The control group added the same distilled water as the sample. The HGF content of the control group is -66- This paper size is applicable to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ^) 7.2 ng / ml. The value is taken as 100%, and the HGF production in each sample addition zone is shown in Table 1. All experiments were performed twice, and the average value was used. Table 1 The production amount of algal-derived algal HGF derived from Cage-meal Kumbu (/ zg / ml) (%) 0 100 1 214 10 339 100 339 There was a statistically significant increase in HGF production. In addition, compared with the case of adding heparin or low-molecular-weight heparin, it also significantly increased the amount of HGF production, showing that the alga derived from Kumbu is more confirmed than the so-called heparin induced by HGF production so far. Or a low-molecular-weight heparin having an average molecular weight of about 5000 has a higher HGF production-promoting activity. (2) The same conditions as in Example 1- (1) were used to measure I division, II division, and III division prepared by the method described in Reference Example 1- (2); 7- 12SFd-F; 6-2S prepared by the method described in Reference Example 4; wakame-derived alginans prepared by the method described in Reference Example 6; and lime algae derived by the method described in Reference Example 7 Algin; its respective HGF produces a defamatory effect. The results are shown in Tables 2 ~ 4. 〇-67- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention "Table 2 Sample concentration HGF production (/ zg / ml) (%) 1 167 I division 100 234 1 208 II division 100 359 1 146 III division 100 291 (HGF production amount of the control group is 8.3ng / ml) Table 3 Samples of concentration HGF production amount (/ zg / ml ) (%) 1 148 Lime-algae-derived fucose 10 246 100 335 1 179 Wakame-derived fucose 10 250 100 291 1 149 7-12SFd-F 10 276 100 339 (HGF production in the control group is 8.6 ng / ml) -68- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention Table 4 Sample concentration (/ zg / ml) HGF production (% ) 6-2S 10 100 112 246 (HGF production in the control group is 9.9 ng / ml). Divided from alga derived from Cages Kumbu, that is, derived from U-fucoid, F-fucoid, and lime-algae. Of the fucoidan, wakame-derived fucoidan, F-fucoidan-derived 7-12SFd_F, and U-fucoidan-derived 6-2S, each of them was confirmed. Strong HGF has a defamatory effect. In addition, the macanbu-derived oscillating polysaccharides described in Reference Example 1- (1), the "Lessonia nigrescence" -derived oscillating polysaccharides described in Reference Example 7, and " Derived from Ascophyllum nodosum, fucoidan, the acid decomposition product described in Reference Example 8, and the division of A to F were also confirmed to have a strong defamatory effect on HGF. (3) -① A 2% solution of the alga-derived fucoidan derived from Cageme kumbu prepared by the method described in Reference Example 1- (1) was prepared to pH 3 with citric acid or sulfuric acid, and each was heated at 100 ° C. Then, the water-decomposing solution was prepared after 30 minutes, 1 hour, 2 hours, and 4 hours, and the HGF production induction effect was measured under the same conditions as in Example 1- (1). A 10-fold dilution of the acid decomposition solution was used as the sample. -69- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) Table 5 Sample heating time HGF production amount (%) Undecomposed liquid 448 Sulfuric acid decomposed liquid 30 Minutes 364 1 hour 385 2 hours 368 4 hours 345 undecomposed solution 480 citric acid decomposition solution 30 minutes 402 1 hour 429 2 hours 397 4 hours 341 (HGF production of the control group is 8.6 ng / ml) (3) -② The citric acid of the alga-derived fucoidan derived from Cageale kumbu prepared in Example 1- (3) -① was heat-treated for 4 hours in the presence of the citric acid and gel-filtered. That is, a 1.5-liter column filled with Toyo pearl HW40 C was equilibrated with water, and then 10 ml of a heat-treated product of fucoid derived from Cageme kumbu was injected thereinto, and thereafter, the flow rate was 1 ml / min. Dissolve with water below. The first 680 ml was directly dissociated, and thereafter it was divided every 14 ml to obtain a gel filtration fraction of the heat-treated product. TLC (solvent, butyl acetic acid: acetic acid: water = 3: 4: 3, -70-) This paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) 1228991 A7 B7 V. Invention Explanation k) The detection agent is ositol alcohol sulfuric acid) for analysis, and according to the form of point crushing, collect gel divisions of 12 to 13, 16 to 17, 26 to 40, and freeze-dry. The obtained cold bundle dried product was re-dissolved in water to have a concentration of 100 mg / ml, and the HGF produced a slurring effect under the same conditions as in Example 1- (1). As a result, HGF production-inducing activity was confirmed in each of the divisions of 12 to 13, and 16 to 17. The structure of 12 to 13 is determined. The analytical value is consistent with the analytical value of the compound represented by formula (VIII) described in the pamphlet of International Publication No. 97/26896. Therefore, gluconic acid and mannose were confirmed. The sugar polymer has HGF production-inducing activity.

(VIII) (4) Preparation of a commercially available dextran sodium sulfate (Sigma) solution 'was used to measure the HGF-producing effect according to the method described in Example 1-(1). As shown in Table 6, sodium dextran sodium has an HGF production-inducing effect. -71- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) 1228991 Α7 Β7 V. Description of the invention Table 6 Gluconate sodium sulfate concentration HGF production (average molecular weight) (UR / ml) (%) 1 588 10 10 655 100 787 1 395 8 thousand 10 573 100 695 1 398 5 thousand 10 421 100 565 (HGF production of the control group is 6.7 ng / ml) (5) Preparation of commercially available λ-red The solution of algin (manufactured by Nakola) was measured for the induction of HGF production according to the method described in Example 1- (1). As shown in Table 7, λ · red algae has a detrimental effect on HGF production. Table 7 Lambda algal HGF production (&quot; g / ml) (%) 1 152 10 140 (HGF production of the control group is 13.4 ng / ml) (6) -① Preparation of commercially available brown acid ( The solution of swelling property (manufactured by Wako Pure Chemical Industries, Ltd.) was measured for its action to induce HGF production according to the method of Example 1 (1). As shown in Table 8, the 'brown medicine system exhibited its action to induce HGF production. -72- The standard of this paper is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of invention) Table 8 Alginic acid HGF production (/ zg / ml) _ (%) __ 1 125 10 154 100 327 (HGF production in the control group was 7.3 ng / ml) (6) -② Similarly, review alginic acid (swellable, Wako Pure Chemical Industries, Ltd. · Sample ①), alginic acid (non-swellable, Wako Pure Chemicals Co., Ltd .: sample ②), alginic acid (100 ~ 150 cp, Wako Pure Chemicals Co., Ltd .: sample ③), alginic acid (30 ～ 400cp, Wako Pure Chemical Co., Ltd .: sample ④), alginic acid (500 ~ 600 cp, Wako Pure Chemical Industries, Ltd. sample ⑤) HGF-producing activity. As shown in Table 9, all of the samples ① to ⑤ could defame the generation of HGF. Based on the above, it is apparent that the alginic acid solution of the acidic polysaccharide has HGF-producing activity. Table 9 Production amount of HGF in concentration (%) Sample ① Sample ② Sample ③ Sample ④ Sample ⑤ 10 154 138 115 127 104 100 327 158 184 152 187 (The amount of HGF generated by the control group of samples ① and ② is 7.3 ng / ml, The amount of HGF produced by the control group of samples ③, ④, and ⑤ is 6.7 ng / ml) (6) -③ Similarly, review the production of HGF by pectin (manufactured by Nakola) -73- This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention As shown in Table 10, pectin can induce the production of HGF. Based on the above, it is apparent that the pectinic acid of the acidic polysaccharide has an HGF production-inducing activity. Table 10 Sample concentration (// g / ml) HGF production (%) Pectinic acid 1 145 10 218 100 684 (HGF production in the control group is 5.91 ng / ml) (7) Review of salmon sperm DNA (Niger Lloyd's Corporation) HGF's defamatory activity. DNA was added to a final concentration of 1, 10, 100 / zg / ml. As shown in Table 11, salmon sperm DNA has HGF-producing activity. Table 11 Sample concentration HGF production amount (/ zg / ml) (%) 1 110 Salmon sperm DNA 10 182 100 285 (HGF production amount of the control group is 9.9 ng / ml) (8) Preparation Prepared in Reference Examples 9, 11 According to the method described in Example 1- (1), the seaweed and sea cucumber-derived algal solution were measured for their HGF production defamatory effect. As shown in Table 12, each of the alginans had an HGF production-inducing effect. -74- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7

V. Description of the invention Q Table 12 Sample concentration (/ zg / ml) HGF production amount (%) 1 282 Sea cucumber-derived algin 10 10 356 100 495 1 218 Sea-derived algin 10 10 279 100 307 (Control group The amount of HGF produced was 7.77 ng / ml. (9) Preparation of Sulfate-derived Sulfated Polysaccharides (Sample ①) prepared from Reference Example 10, Sudder-derived Sulfated Polysaccharides (Sample ②), and Feather Vegetable-derived Sulfate The solution of the modified polysaccharide (sample ③) was measured for its HGF-producing effect according to the method described in Example 1- (1). Add samples ① and ③ to make the final concentration 1, 10, 100 // g / ml, and add samples ② to make the final concentration 10, 100 // g / ml. As shown in Table 13, samples ① to ③ could induce HGF production. -75- This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 1228991 A7 B7

V. Description of the invention Q Table 13 Sample concentration (// g / ml) HGF production amount (%) 1 100 sample ① 10 177 100 169 sample ② 10 117 100 198 1 116 sample ③ 10 207 100 228 (HGF of the control group Yield: 7.3 ng / ml) (10) In the same manner as in Example 1- (1), review the "Lessonia nigrescence" -derived flocculation prepared in Reference Example 10- (3). The HGF of sugar (sample ①), DEAE 33 (sample ②), DEAE 37 (sample ③), and DEAE 40 (sample ④) produce defamatory activity. Samples were added so that the respective final concentrations became 1, 10, 100 / zg / ml. As shown in Table 14, samples ① to ④ could induce HGF production. -76- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention "Table 14 1 Degree (βg / m \) HGF production (%) Sample ① Sample ② Sample ③ Sample ④ 138 105 235 121 10 167 221 253 254 100 331 265 261 295 (HGF production amount of the control group is 11.5 ng / ml) (11) In the same way as in Example 1- (1), review the reference example HGF production of sulfated seaweed galactan according to 3- (2), agar pectin described in Reference Example 12, chondroitin sulfate B (manufactured by Biochemical Industry Co., Ltd.) and chondroitin sulfate D (manufactured by Biochemical Industry Co., Ltd.) Defeat activity. Add samples to make the final concentrations of 1, 10, and 100 vg / ml. As shown in Tables 15 to 17, chondroitin sulfate can lead to the production of HGF. Table 15 Sample concentration 1 10 100 (of the control group The amount of HGF produced is 4.3 ng / ml) The amount of sulfated seaweed galactan HGF produced (%) 194 355 429 -77- This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 1228991 A7 B7 5 、 Explanation of the invention Table 16 Sample concentration (&quot; g / ml) Agar pectin 1 10 100 HGF production (%) 117 121 256 (control The amount of HGF produced by the control group is 6.7 ng / ml) Table 17 Sample concentration _ (βξ / τηΐ) The amount of HGF produced (%)

Chondroitin sulfate B

(The HGF production amount of the control group is 11.9 ng / ml) (12) In the same manner as in Example 1- (1), review the reference examples 3_ (ι), 13- (3), 13- (5), 13 -(7), 13_ (8), Spirulina-derived sulfated polysaccharides, Chlorococcus-derived sulfated polysaccharides, Mountain wormwood-derived sulfated polysaccharides, Momordica charantia-derived sulfated polysaccharides, and aloe mesophyll-derived ones HGF production inducing activity of sulfated polysaccharides and sulfated polysaccharides derived from the surface of aloe leaves. Spirulina-derived sulfated polysaccharides and mountain wormwood-derived sulfated polysaccharides were added so that their final concentrations became 1, 10, 100 // g / ml. In addition, green ball, algae-derived sulfated polysaccharide, bitter gourd-derived sulfated polysaccharide, and reed-78- this paper standard universal towel national time scale (CNS) M specifications (⑽㈣7 public)-1228991 A7 B7 V. Description of invention ς ) 76 Sulfose-derived polysaccharides derived from aloe vera and Sulfate-derived polysaccharides derived from the surface of aloe leaves make their respective final concentrations of 1, 10, 100, 1000 / zg / ml. As shown in Tables 18 to 20, spirulina-derived sulfated polysaccharides, chlorella-derived sulfated polysaccharides, mountain wormwood-derived sulfated polysaccharides, momordica-derived sulfated polysaccharides, aloe mesophyll-derived sulfated polysaccharides, and Sulfated polysaccharides derived from the surface of aloe vera can all blame HGF production. Table 18 Sample concentration (/ zg / ml) HGF production (%) 1 149 Spirulina-derived sulfated polysaccharide 10 293 100 398 1 108 Chlorococcus-derived sulfated polysaccharide 10 149 100 175 1000 396 (of the control group HGF production amount is 7.9 ng / ml) -79- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of invention () 77 Table 19 Sample concentration HGF production amount (/ zg / ml) (%) 1 137 Mountain wormwood-derived sulfated polysaccharide 10 284 100 265 (HGF production amount of the control group is 12.7 ng / ml) Table 20 Sample concentration HGF production amount (/ zg / ml) ( %) 1 111 10 104 Bitter melon derived sulfated polysaccharide 100 133 1000 190 1 111 10 125 Aloe mesophyll-derived sulfated polysaccharide 100 150 1000 401 1 106 10 125 Aloe leaf surface-derived sulfated polysaccharide 100 120 1000 328 (Control group The HGF production amount is 8.7 ng / ml) (13) In the same way as in Example 1- (1), review the reference example 13- (2). 80- This paper size applies the Chinese National Standard (CNS) A4 (210X 297 mm) 1228991 A7 B7 V. Description of the invention Q) Spirulina divides SSP-I (Sample ①), SSP-II (Sample ②), SSP-III (Sample ③), and SSP-IV (Sample ④). Each sample was added so that the final concentrations became 1, 10, and 100 g / ml. As shown in Table 21, samples ① ~ ④ can all induce the generation of HGF. Table 21 Concentration (/ zg / ml) Sample ① Production amount of HGF (%) Sample ② Sample ③ Sample ④ 1 240 165 141 218 10 243 152 270 282 100 302 212 280 351 (The HGF production amount of the control group is 7.3 ng / ml) (14) In the same way as in Example 1- (1), review the CSP-I (sample ①) and CSP-II (sample ②) of the Chlorococcus aureus extract prepared in Reference Example 13- (4). HGF produces inducing activity. Add sample ① to make the final concentration 10, 100 # g / ml, and add sample ② to make the final concentration 100 / zg / ml. As shown in Table 22, samples ① and ② can induce the production of HGF. -81- This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) A7 B7

1228991 V. Description of the invention) Table 22 Sample concentration HGF production (^ g / ml) _ (%) 111 173 Sample ① 10 100 Sample ② 100 175 (HGF production of the control group is 11.4 ng / ml) (15 ) Review the YAP division (Sample ①), ysp · 1 division (Sample ②), and YSP-II division of the wormwood extract prepared in Reference Example 13- (6) in the same way as in Example 1- (1) (Sample ③), ysp-ii-2 division (sample ④), ysp-ii-3 division (sample ⑤), YSP-II-4 division (sample ⑥) HGF production inducing activity. Each sample was added so that the final concentration became 1, 10, and 100 V g / ml. As shown in Tables 23 and 24, samples ① to ⑥ can all induce the generation of HGF. Especially in YSP-II division (sample ③), YSP-II-3 division (sample ④), and YSP_II-4 division (sample ⑤), it is confirmed that there is a strong defamatory activity of HGF. -82- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (21 × 297 mm) 1228991 A7 B7 V. Description of the invention ^ 0) Table 23 Sample concentration HGF production (&quot; g / ml) (% ) Sample ① 10 121 100 266 Sample ② 1 104 10 148 100 381 Sample ③ 1 328 10 386 100 390 (The HGF production amount of the control group is 11.5 ng / ml) Table 24 The production amount of concentration HGF (%) (// g / ml) Sample ④ Sample ⑤ Sample ⑥ 1 152 290 226 10 462 383 322 100 475 321 314 (The HGF production amount of the control group is 7.7 ng / ml) (16) The same as in Example 1- (1) Methods: Review the sulfated maltose sodium salt, sulfated maltotriose sodium salt, sulfated lactose sodium salt, sulfated sucrose sodium salt, sulfated trehalose sodium salt, sulfated grape-83- Paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of the invention) Sodium sugar, sodium lactulose sulfate, sodium melibiose sulfate, sodium galactose sulfate Salt, sulfated mannose sodium salt, sulfated xylose sodium salt, sulfated 2- Deoxy-glucose sodium salt, sulfated sorbitol sodium salt, sulfated cellobiose sodium salt, sulfated isomaltose sodium salt, sulfated melibiose sodium salt, sulfated palatinose steel salt, sulfated tarot Sugar steel salt, sulfated malt hexose steel salt, sulfated malt heptose sodium salt, sulfated lauryl maltohexose sodium salt, sulfated starch sodium salt, sulfated cardel blue sodium salt, sulfated fruit HGF of gum sodium produces defamatory activity. Add each sample to the final concentration of 1, 10, 100 / zg / ml, or 10, 100, 1000 # g / ml, or 100 / z g / ml. The control group added the same amount of steaming water as the sample. In addition, the non-sulfurized sugars were each measured for their HGF production-inducing activity with their sulfated sugars and the same concentration. As shown in Tables 25 to 34, sulfated oligosaccharides and sulfated monosaccharides can induce the production of HGF. In addition, the unsulfated sugars cannot defame the production of HGF. Furthermore, as a result of sulfating the sodium salt of lauryl maltohexose, it was found that even if the sugar was modified with lipids, it retained the HGF production-inducing activity. Table 25 Sample concentration (/ zg / ml) HGF production amount (%) 1 142 Sulfated maltose steel salt 10 273 100 439 1 151 Sulfated maltotriose sodium salt 10 286 100 387 (HGF production amount of the control group is 8.7 ng / ml) -84- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of invention k) Table 26 Sample concentration HGF production (/ zg / ml) (%) Sulfated lactose sodium salt 1 118 10 185 100 410 Sulfated sucrose sodium salt 1 173 10 355 100 501 Sulfated glucose sodium salt 1 178 10 377 100 864 (The amount of HGF produced by the control group is 5.5 ng / ml ) Table 27 Production sample of HGF concentration (/ zg / ml) (%) 1 277 Sulfated haitang sugar steel salt 10 447 100 421 (HGF production of control group is 4.3 ng / ml) -85- This paper size Applicable Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention ^

Binding

Table 28 Sample concentration (# g / ml) HGF production amount (%) Sulfated galactose sodium salt 100 166 (HGF production amount of the control group is 12.7 ng / ml) Table 29 Sample concentration HGF production amount (/ zg / ml) (%) Sulfated mannose steel salt 1 112 10 175 100 456 (HGF production of the control group is 6.2 ng / ml) -86- This paper size applies to China National Standard (CNS) A4 (210 X 297) (%) 1228991 A7 B7 V. Description of invention) Table 30 Sample concentration HGF production (/ zg / ml) (%) Sulfated lactulose sodium salt 10 139 100 376 1000 583 Sulfated melibiose sodium salt 10 240 100 403 1000 667 Sulfated xylose sodium salt 10 110 100 112 1000 284 10 127 Sulfated 2-deoxy-glucose sodium salt 100 102 1000 239 Sulfated sodium sorbitol 10 112 100 203 1000 335 (HGF production of control group Amount is 5.9 ng / ml) -87- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of invention (85) Table 31 Sample concentration HGF production (%) Sulfated cellobiose sodium salt 10 100 100 143 1000 546 Sulfated isomaltose sodium salt 10 134 100 301 1000 477 Sulfated sucralose steel salt 10 127 100 203 1000 379 Sulfated palatinose steel salt 10 132 100 278 1000 519 (The HGF production amount of the control group is the sulfated cellobiose sodium salt 11.1 ng / ml, sulfated isomaltose steel salt is 11.3 ng / ml, sulfated sucrose sodium salt and sulfated palatinose sodium salt are 8.6 ng / ml.) Table 32 Sample concentration HGF production (/ zg / ml) (%) Sulfated talose sodium salt 10 112 100 263 1000 494 (The HGF production amount of the control group is 9.5 ng / ml) -88- This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 1228991 A7 B7 V. Description of the invention ^ Table 33 Sample concentration (/ zg / ml) HGF production (%) Sulfated maltohexose steel salt 10 407 100 571 1000 761 Sulfated heptose maltose Salt 10 341 100 486 1000 706 Sulfated sodium lauryl maltohexose sodium salt 10 289 100 371 1000 359 (HGF production of the control group is 8.15 ng / ml) -8 9-This paper size applies to Chinese National Standards (CNS) A4 specification (210 X 297 mm) 1228991 V. Description of invention table 34

Sulfurized card transfer blue steel salt sulfated pectin steel salt HGF production amount (%) 10 781 100 864 1 00 0804 10 359 100 503 .1000 617 10 721 100 780 1000 648 Example 2 In the same way as in Example 检讨, we reviewed the multiplication effect of the kumbu-derived glycosaminoglycan and prostaglandin described in Reference Example Mυ on the induction of hgf. 1 Effect That is, the multiplication of the alga-sugar, PGEi (manufactured by Wako Pure Chemical Industries, Ltd.), and Jiang _ α (manufactured by Gene Saim Co., Ltd.) was simultaneously added to review the effects of its defamatory activity. Fucoidan was added to a final concentration of 1, ^ 1 10, 100 # g / ml. PGE ^ was added to a final concentration of 0.1, 1 &quot; M, and i, ττ was added from 1 to IL-la to a final concentration of 1 ng / ml. The control group added &lt; hot water in the same scene as the sample. Compare each with Dangan or PGE !, IL-1 α, and ^ t flat candle when added, check -90-

1228991 A7

This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 1228991 A7 B7 V. Description of the invention Multiplication effect. At the same time, 7-12SFd-F, PGEi, and IL-1 α were added to review the multiplicative effect of its HGF-induced slurring activity. Each of 7-12SFd-F was added to a final concentration of 1, 10, 100 / zg / ml. PGEi and IL-1 α were added to 7-12SFd-F-added cells, respectively. That is, PGEHt was added to a final concentration of 0.1 and 1 βM, and IL-1 α was added to a final concentration of 01 and 1 ng / ml. For the negative control group, add the same amount of distilled water as the sample. Then, compare each with 7-12SFd-F or PGEi, IL-1 α when added separately, and review the multiplication effect. The Hgf content is only expressed in 100% for the negative control group with the addition of distilled water. The results are shown in Tables 37 and 38. All experiments were performed three times and the average value was used. Table 37 7-12S Fd-F added amount (&quot; g / ml) 0 1 10 100 PGEl added amount (βΜ) 0.1, HGF production amount (〇 / 0) 100 123 120 158 218 309 219 365 (of the control group HGF production is 5.1 ng / ml) 170 216 317 382 -92- 1228991 A7 B7

V. Description of the invention L Table 38 7-12S 1L-1 α Addition (ng / ml) Fd-F 0 0.1 1 Addition (/ zg / ml) HGF production (%) 0 100 130 151 1 140 168 159 10 191 154 208 100 203 255 222 (HGF production in the control group is 5.1 ng / ml) Example 3 (1) The DMEM medium containing 10% bovine fetal serum was suspended at a concentration of IX 105 cells / ml KG-1-C cells (Glioma: sold by the Human Science Promotion Foundation) 500, added to a 48-well cell culture plate, cultured at 37 ° C in the presence of 5% carbon dioxide for 1 night, and then replaced the medium DMEM medium containing 1% bovine fetal serum. Thereafter, the test sample was added, and after further culture for 20 hours, the culture medium was recovered, and the HGF ELISA kit described in Example 1 was used to measure the amount of HGF in the culture medium. Each of the test materials was added so that the final concentration of the algal derivative derived from Caladium kumbu described in Reference Example 1_ (1) was 1, 10, 100 # g / ml, and the final concentration of heparin (manufactured by Wako Pure Chemical Industries, Ltd.) was adjusted. The concentration was 1, 10 / zg / ml. In addition, the control group added the same amount of distilled water as the sample. All experiments were performed 3 times, and the average value was used. The results are shown in Table 39. In Table 39, the HGF production of the control group is shown as 100%. -9 3-This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention L) The cell population to which the algal sample is added, all of which are better than the control group with distilled water The amount of HGF produced is a statistically significant increase. Furthermore, compared with those who added heparin, the amount of HGF produced also increased. Based on the above facts, it has been shown that the algal polysaccharide has a higher HGF production-promoting activity than that of HGF that has been confirmed to induce heparin production. Table 39 Sample concentration HGF production (// g / ml) (%) Cangbu kumbu-derived algal 1 1 194 10 285 100 351 Heparin steel salt 1 176 10 215 (HGF production in the control group is 4 · 4 ng / ml) (2) HL-60 cells (pre-myeloid leukemia cells · ATCC CCL-240) 500 suspended in RPMI1640 medium containing 10% bovine fetal serum at a concentration of 1 X 105 cells / ml // 1, add a 48-well cell culture plate. Thereafter, 10 nM of 12_0_tetradecylcyclopropenyl alcohol 13-acetate (manufactured by TPA GIBCO BRL) was added, and the test sample was also added at the same time. After 20 hours of addition, the medium was recovered and the amount of HGF in the medium was measured using an HGF ELISA kit. Each of the test materials was added so that the final concentration of the algal-derived fucoidan derived from the genus Kumbu of Reference Example 1- (1) was 1, 10, 100 # g / ml, and the final concentration of heparin was 1, 10 / / g / ml. All experiments were performed 3 times, and then the average was adopted. _-94 -__ This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7. 5. Means of invention description. The results are shown in Table 40. In Table 40, the HGF production scale of the control group is 100%. All the cell populations to which the fucoidan sample was added were statistically meaningfully increased compared to the HGF production in the control group to which distilled water was added. Furthermore, compared with those who added heparin, the amount of HGF produced also increased. Based on the above facts, it has been shown that the algal polysaccharide has a higher HGF production-promoting activity than that of HGF that has been confirmed to induce heparin production. Table 40 Sample concentration of HGF production (&quot; g / ml) (%) Algae-derived algae poly 1 191 Sugar 10 342 100 490 Heparin sodium salt 1 140 10 189 (HGF production of control group is 0.4 ng / ml) Example 4 MRC-5 cell solution 500 // 1 suspended in DME medium containing 10% bovine fetal serum at a concentration of 1 X 105 cells / ml was added to a 48-well cell culture plate. After 24 hours incubation at ° C and 5% carbon dioxide, the medium was replaced with DME medium containing 1% bovine fetal serum. Thereafter, the medium was recovered, and the HGF ELISA kit was used to measure the amount of HGF in the culture medium. Further, after washing the cells with PBS, dissolve them _-95-_ This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) Solution at 500 // Cell lysis buffer 1 (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% Triton X100, 1 mM PMSF, 1 / zg / ml pepstatinA, 1 # g / ml leupeptin). Furthermore, in order to completely dissolve it, after ultrasonic treatment, centrifugation and preparation of a supernatant (cell extract) were performed, and the HGF concentration in the culture medium was the same, and the amount of HGF in the cells was measured. The algae polysaccharide derived from Klebsiella kumbu described in Reference Example 1- (1) of the test material was added to a final concentration of 1, 10, 100 // g / ml. The control group added the same amount of distilled water as the sample. All experiments were performed twice, and the average value was used. The results are shown in Table 41. As shown in Table 41, the HGF amount of the alga-sugar concentration-dependent cell population of the cell-supplemented sample was a statistically significant increase over the control group added with distilled water. On the other hand, the amount of HGF in the cells is reduced in dependence on the concentration of fucoidan. Second, the total amount of HGF inside and outside the cell is dependent on the concentration of fucoidan. Based on this fact, it is shown that the algal polysaccharide has the activity of promoting the production of HGF and the function of promoting the release of HGF from the cells. ) Control group of total amount of cells in culture medium 4.2 5.7 9.8 1 9.3 3.2 12.5 10 15.9 0.9 16.8 -9 6-This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention

100 16.9 0.4 17.3 Example: In a dme medium containing 10 A of bovine fetal serum, 500 MRC-5 cell suspension suspended at a concentration of lx cells / liter was added to a 48-well cell culture plate at 37t: In the presence of 5% carbon dioxide, the culture medium is replaced with DME medium containing 1% bovine fetal serum after 24 hours of culture, and then 'samples' are added and further tested at 0, 0.5, 1, 2, 4, 8, 12 After 24 hours incubation, the medium was recovered, and the amount of HGF in the medium was measured using an HGF ELISA kit. The reference example of the test material was added. __ (i) The fucoidan derived from the genus Kumbu was added to a final concentration of 10 "g / ml. In the control group, the same amount of steam as the sample was added. Table 42. As shown in Table 42, compared to the control group, the HGF production amount of the cell population added with the algal test sample increased statistically in a time-dependent manner. Based on this fact, the alginan was shown to have a high degree of HGF production-promoting activity, and at the same time, the amount of HGF production does not increase regularly. Table 42

Incubation time (hours) 0.5 2 12 24

______- 97- This paper size applies Chinese National Standard (CNS) A4 size (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) MRC-5 cells (CCL 171: Big Book) Code: 02-021) 500 / ^ 1, manufactured by the pharmaceutical company, added to a 48-well cell culture plate, cultured at 37 ° C and 5% carbon dioxide for 24 hours, and then replaced the culture medium with a bovine fetus containing 1% DME medium for serum. Thereafter, samples were added and further cultured at 0, 0.5, 1, 2, 4, 8, 12, 24, 48, and 72 hours, and then the culture medium was recovered, and a Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (Funkoshi Co., Ltd., Code: RS-0641-00) to determine the amount of HGF in the culture medium. Further, after recovering the culture medium, washing the cells with PBS, and lysing them in a 500 W lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 // g / ml pepstatin A, 1 // g / ml leupeptin). In order to completely dissolve it, after the ultrasonic treatment, the supernatant (cell extract) is prepared by centrifugation, and the HGF concentration in the culture medium is the same as that in the culture medium to measure the amount of HGF in the cells. The kumbu-derived fucoidan described in Reference Example 1- (1) was added to a final concentration of 10 # g / ml. For the negative control group, add the same amount of distilled water as the sample. The HGF concentration in the medium of the algal polysaccharide-added group was statistically significant in a time-dependent manner compared with the negative control group of distilled water. On the other hand, although the amount of HGF in the cells of the fucoidan-added group decreased to 4 hours after the addition, the amount of HGF remained at a certain low value thereafter. As for the negative control group with the addition of distilled water, there was no such change, and it was always an increasing trend. Based on this fact, it has been shown that the algal polysaccharide has the activity of freeing HGF from the cells and the activity of promoting the production of HGF, and at the same time, the amount of HGF production is increased at regular intervals. These results are shown in Tables 43 to 45. -98- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention k) Table 43 Timing changes of the amount of HGF in the medium 0 0.5 1 2 4 8 12 24 48 72 HGF production (ng / well) Control group 0 0.11 0.19 0.29 1.07 1.56 2.34 3.46 7.45 10.5 Added algal 0.51 0.46 1.23 2.86 4.00 6.70 9.15 12.4 22.8 29.3 Table 44 Timed changes in the amount of HGF in the culture medium (hours) 0 0.5 1 2 4 8 12 24 48 72 HGF production (ng / well) Control group 0.51 0.52 0.66 0.56 0.71 0.63 0.86 0.73 1.02 1.20 Adding algin 0.88 0.66 0.45 0.46 0.25 0.29 0.20 0.20 0.18 0.23 Table 45 Timed change of total HGF amount in culture time (hours) 0 0.5 1 2 4 8 12 24 48 72 HGF production amount (ng / well) Control group 0.51 0.63 0.85 0.84 1.78 2.19 3.19 4.19 8.47 11.6 Added algin 1.39 1.12 1.68 3.31 4.25 7.00 9.35 12.6 22.9 29.5 (3) MRC-5 cells (CCL 171: 1) suspended in DME medium containing 10% bovine fetal serum at a concentration of 1 X 105 cells / ml 'Code. 02-021) 500 // 1 (made by Daiyakumoto Pharmaceutical Co., Ltd.), add a 48-well cell culture plate, incubate at 37 ° C and 5% carbon dioxide for 24 hours, and then replace the -99- The standard is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of the invention &) The medium is DME medium containing 1% bovine fetal serum. Thereafter, samples were added and further cultured at 0, 0.5, 1, 2, 4, 8, 12, 12, 24, 48, and 72 hours, and then the culture medium was recovered, and a Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (Funkoshi Co., Ltd., Code: RS-0641-00) to determine the amount of HGF in the culture medium. Furthermore, after recovering the culture medium, washing the cells with PBS, and lysing them in a 500 // 1 cell lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 / zg / ml pepstatinA, 1 / zg / mlleupeptin). In order to completely dissolve it, after the ultrasonic treatment, the supernatant (cell extract) is prepared by centrifugation, and the HGF concentration in the culture medium is the same as that in the culture medium to measure the amount of HGF in the cells. 7-12 SFd-F was added to a final concentration of 10 / zg / ml. For the negative control group, add the same amount of distilled water as the sample. The HGF concentration in the medium of the 7-12 SFd-F addition group was statistically meaningfully time-dependently increased compared to the negative control group to which distilled water was added. On the other hand, the amount of HGF in the cells of the 7-12 SFd-F addition group will decrease in a short time after the addition, but will increase afterwards. As for the negative control group with the addition of distilled water, there is no such change, but it is always increasing. Based on this fact, it was shown that the 7-12S Fd-F has the activity of freeing HGF from cells and the activity of promoting the production of HGF, and at the same time, the amount of HGF production does not increase regularly. It then becomes a certain low value. These results are shown in Tables 46 to 48. -100- This paper size applies to China National Standard (CNS) A4 (210X297 mm)

Binding

1228991 A7 B7 V. Description of the invention) 146 Timed change of the amount of HGF in the medium _ Culture time (hours) 0 0.5 1 2 4 8 12 24 48 72 ____HGF production (ng / well) _

Control group 0.14 0.33 0.36 0.63 1.29 1.60 2.54 3.89 7.99 13.3 Add 7-12S ^ 0.48 1.82 2.16 2.53 3.12 4.01 5.84 9.82 17.0 23.5

Fd-F _Table 47 Timing changes of the amount of HGF in the medium Culture time (hours) 0 0.5 1 2 4 8 12 24 48 72 _ _ The amount of HGF produced (ng / well) _

Control group 2.65 3.11 2.73 2.77 2.31 2.82 2.80 4.61 5.36 6.74 Add 7-12S 2.79 1.78 1.65 1.31 1.06 1.31 1.07 1.56 2.66 3.09

Fd-F Table 48 Timing change of total HGF content in culture medium and cells _ culture time (hours) 0 0.5 1 2 4 8 12 24 48 72 HGF production (ng / well)

Control group 2.79 3.43 3.09 3.39 3.60 4.41 5.34 8.50 13.3 20.2 Add 7-12S 3.26 3.60 3.81 3.84 4.18 5.31 6.91 11.4 19.7 26.6

Fd-F -101 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) (4) DME medium containing 10% bovine fetal serum is IX 105 cells / ml suspended MRC-5 cells (CCL 171: manufactured by Dainippon Pharmaceutical Co., Ltd. 02-021) 500 // 1, added to a 48-well cell culture plate, 37 ° C, 5% After 24 hours of culture in the presence of carbon dioxide, the medium was replaced with DME medium containing 1% bovine fetal serum. After that, a sample was added and cultured for another 24 hours. This medium was recovered, and the amount of HGF in the medium was measured using a Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00). Furthermore, after washing the cells with PBS, they were lysed in a 500 / zl cell lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 eg / ml pepstatinA, 1 // g / ml leupeptin). In order to completely dissolve it, after the ultrasonic treatment, the supernatant (cell extract) was prepared by centrifugation, and the amount of HGF in the cells was measured in the same manner as the concentration of HGF in the culture medium. Add 7-12 SFd-F to a final concentration of 1, 10, 100 # g / ml. For the negative control group, add the same amount of distilled water as the sample. All experiments were performed 3 times, and then the average value was used. As a result, as shown in Table 49, the HGF concentration in the culture medium of the 7-12 SFd-F addition group was statistically significant compared to the negative control group to which distilled water was added, and the 7-12 SFd-F concentration was statistically significant. On the other hand, the amount of HGF in the cells of the 7-12 SFd-F addition group was 7-12 SFd-F concentration-dependently reduced. Based on this fact, it was shown that the 7-12 SFd-F has the activity of freeing HGF from cells and the activity of promoting HGF production. The results are shown in Table 49. -102- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 _—__ B7 V. Description of the invention () 100 -1249 7-12SFd-F Timing HGF production 7- 12 SFd-F added amount (// g / ml) 0 1 10 100 ____HGF production amount (ng / well) 5.66 8.46 17.1 22.0 6.28 6.04 4.15 1.59 total amount in cells 11.9 14.5 21.3 23.6 Example 6 (1) In a DME medium containing 10% bovine fetal serum, MRC-5 cells 500 // 1 suspended at a concentration of IX 105 cells / ml were added to a 48-well cell culture plate in the presence of 37 ° C and 5% carbon dioxide. After 24 hours of culture, the medium was replaced with DME medium containing 1% bovine fetal serum. Thereafter, cyclohexamethyleneimine (protease inhibitor · manufactured by Nakola Co., Ltd.) was added to a final concentration of 0, 1, 10 # g / ml, and further, a test substance was added, and then cultured 2 4 hour. This medium was recovered, and the HGF ELISA kit was used to measure the amount of HGF in the medium. Alginans derived from Cageale kumbu described in Reference Example 1- (1) were added to a final concentration of 1, 10, 100 β g / ml. The control group added the same amount of distilled water as the sample. All experiments were performed twice, and the average value was used. The results are shown in Table 50. In Table 50, the amount of HGF produced by the control group is shown as 100%. As shown in Table 50, by adding cycloheximide, the concentration of HGF in the medium of the cycloheximide-added group was dependent on the concentration of cycloheximide, and the inhibition rate was similar to that without addition. In the control group of fucoidan, the inhibition caused by cycloheximide is to the same extent, and the concentration of cycloheximide is according to _-103- This paper standard applies to China National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention () 101 Existingly suppressed. Based on this fact, it was shown that the HGF-producing line of fucoidan is involved in protein synthesis. Table 50__ Addition of Cyclohexanimide derived from Cages Kumbu (# g / ml) Algae_0_1_10_ (/ ^ g / ml) Ratio of HGF production to control group Control group 100 35 27 1 226 110 72 10 317 130 110 100 456 206 127 (HGF production in the control group was 7.3 ng / ml) (2) The DME medium containing 10% bovine fetal serum was suspended at a concentration of 1 X 105 cells / ml MRC-5 cells (CCL 171: manufactured by Daiyoshimoto Pharmaceutical Co., Ltd. 02-021) 500 // Add 48-well cell culture plates, incubate at 37 ° C and 5% carbon dioxide for 24 hours, and then This medium was replaced with DME medium containing 1% bovine fetal serum. Thereafter, cycloheximide (a protein synthesis inhibitor: manufactured by Nakola Co., Ltd.) was added to a final concentration of 0, 1, 10 // g / ml, and a test material was further added, followed by culturing for another 24 hours. This medium was recovered, and the Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00) was used to determine the amount of HGF in the medium. After washing the cells with PBS, the cells were dissolved in a cell lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 / zg / mi pepStatinA) , 1 / zg / ml leupeptin). Further ______- 104- —__ This paper size is in accordance with China National Standard (CNS) A4 (210X297 mm) 1228991 A7 B7 V. Description of invention k) step, in order to completely dissolve it, after ultrasonic treatment , Centrifuge and prepare the supernatant (cell extract), which is the same as the HGF concentration in the culture medium, and measure the amount of HGF in the cells. The amount of HGF produced in the negative control group is shown in 100%. The inhibition rate is based on the amount of HGF produced when only 7-12SFd-F at each concentration is added, and the inhibition rate (%) of the cycloheximidine addition division is calculated. 7-12SFd-F was added to a final concentration of 1, 10, 100 / zg / ml. For the negative control group, add the same amount of distilled water as the sample. All experiments were performed 3 times and the average value was used. As a result, as shown in Tables 51 and 52, by adding cycloheximide, the total amount of HGF in the medium of the 7-12SFd-F addition group or the total amount of HGF in the cells and the medium was all the same. Cyclohexanimide concentration decreased dependently. Based on this fact, it was shown that the HGF production-inducing line of 7-12SFd-F is involved in protein synthesis. Table 5 1 Inhibition of HGF production induction (in culture medium) _ Cycloheximide addition amount (# g / ml)

7-12S 0 10

Fd-F HGF production amount:% / Inhibition rate when no cycloheximide is added as 100%:% Addition amount (/ zg / ml) 0 100/0 40/60 40/60 1 124/0 61 / 51 39/69 10 216/0 88/59 53/75 100 265/0 117/56 74/72 Table 52 Inhibition of HGF production (total in cells and in culture medium) -105- This paper size applies to China Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention (^ 3) Cyclohexanimine addition amount (// g / ml)

7-12S Fd-F 0 10 10 Addition amount HGF production amount:% / Inhibition rate when no cyclohexamethyleneimine is added as 100%:% 0 100/0 31/69 27/73 1 104/0 31 / 70 25/76 10 128/0 38/70 28/78 100 137/0 47/66 37/73 (/ zg / ml) (3) DME medium containing 10% bovine fetal serum was used to IX 105 cells MLC-5 cells (CCL 171: made by Dainippon Pharmaceutical Co., Ltd., 02-021) 500 // 1 at a concentration of 1 / ml, added to a 48-well cell culture plate, at 37 ° C, in the presence of 5% carbon dioxide After 24 hours of culture, the medium was replaced with DME medium containing 1% bovine fetal serum. Thereafter, actinomycin D (RNA synthesis inhibitor: manufactured by Sigma) was added to a final concentration of 0, 0.1, and 1 / zg / rrU, and further samples were added, followed by culturing for another 24 hours. This medium was recovered, and the Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00) was used to determine the amount of HGF in the medium. The amount of HGF produced in the negative control group is shown in 100%. Inhibition rate is based on the amount of HGF produced when only alginans of various concentrations are added, and the inhibition rate (%) divided by the addition of actinomycin D is calculated. Fusarium derived from Cageale kumbu described in Reference Example 1- (1) was added to a final concentration of 1, 10, 100 / zg / ml. Negative control group -106- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) Distilled water with the same amount as the sample is added. All experiments were performed twice, and the average value was used. As a result, as shown in Table 53, by adding actinomycin D, the amount of HGF in the culture medium of the algal-sugar-added group inhibited the concentration of actinomycin D in a dependent manner. Based on this fact, it is shown that the HGF production of algal polysaccharides may be involved in the synthesis of RNA, not just the HGF from the free cells. Table 53 Addition amount of actinomycin D (/ zg / ml) Production amount of algal polysaccharide HGF derived from Cageale kumbu 0 0.1 1:% / Inhibition rate without addition of actinomycin D as 100%:% 0 100 / 0 79/21 83/17 1 244/0 138/43 119/51 10 343/0 224/35 239/30 100 492/0 341/31 285/42 (4) will contain 10% bovine fetal serum In DME medium, MRC-5 cells (CCL 171: manufactured by Dainippon Pharmaceutical Co., Ltd., 02-021) 500 were suspended at a concentration of IX 105 cells / ml in a 48-well cell culture plate at 37 ° C. In the presence of 5% carbon dioxide, after 24 hours of culture, the medium was replaced with DME medium containing 1% bovine fetal serum. Thereafter, actinomycin D (RNA synthesis inhibitor: manufactured by Sigma) was added to a final concentration of 0, 0.1, 1 / zg / ml, and further samples were added, followed by culturing for another 24 hours. Recover this medium and then use Quantikine Human -107- This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 _ B7 V. Description of the invention k)

Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00) to measure the amount of HGF in the culture medium. Furthermore, after washing the cells with PBS, they were lysed in a 500 // 1 cell lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 / zg / ml pepstatinA, 1 / zg / ml leupeptin). Further, in order to completely dissolve it, after ultrasonic treatment, centrifugal separation and preparation of a supernatant (cell extract), the same as the determination of the HGF concentration in the culture medium, to determine the amount of HGF in the cells. The amount of HGF produced in the negative control group is shown in 100%. The inhibition rate is based on the amount of HGF produced when only 7-12SFd-F of each concentration is added, and the inhibition rate (%) of the addition of actinomycin D is calculated. 7-12SFd-F was added to a final concentration of 1, 10, and 100 g / ml. For the negative control group, add the same amount of distilled water as the sample. All experiments were performed 3 times, and the average value was used. As a result, as shown in Tables 54 and 55, by adding actinomycin D, whether the total amount of HGF in the medium of the 7-12SFd-F addition group or the total amount of HGF in the cells and the medium was actinomycetes. The concentration of bacteriocin D decreases in a dependent manner. Based on this fact, it is shown that the HGF-producing line of 7-12SFd-F may be involved in the synthesis of RNA, and not only HGF derived from cells. -108- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 1228991 A7 B7 V. Description of invention k) Table 54 Inhibition of HGF production (in culture medium) Addition of actinomycin D ( / zg / ml) 7-12S Fd_F (# g / ml) 0_0Λ_1_ HGF production:% / Inhibition rate when no actinomycin D is added as 100% ·% 0 100/0 1 130/0 10 225 / 0 100 295/0 76/24 80/20 95/27 96/26 182/19 152/32 212/28 187/48 Table 55 Inhibition of HGF production (total in cell and medium) Actinomycin D Added amount (# g / ml)

7-12S

Fd-F (/ zg / ml) 0_0Λ_1_ HGF production:% / Inhibition rate when no actinomycin D is added as 100%:% 0 100/0 1 98/0 10 113/0 100 126/0 61 / 39 59/41 64/35 61/38 83/27 71/37 91/28 81/36 Example 7 (1) A 7-week-old male Wistar rat was used, and part of the liver was surgically removed as follows. That is, the rats were laparotomy under ether anesthesia, and about 30% of the liver was ligated with surgical sutures at the base of the blood vessel before resection. -109- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention k) The suture needle is used to suture the open abdomen. Immediately after the excision was completed, the first-time administration of the alga-derived fucoid derived from the genus Kumbu described in Reference Example 1- (1) was followed by intraperitoneal administration at an hourly interval. In the control group, saline was administered into the abdominal cavity. After hepatectomy, the rats were anesthetized at 24 hours or 72 hours, blood was collected from the abdominal aorta, and the plasma of 0.1% ethylenediaminetetraacetic acid disodium salt was centrifuged. The HGF ELISA kit (manufactured by the Special Immunology Research Institute) was used to measure the amount of HGF in plasma. As shown in Table 56. The numbers in the table indicate the mean standard error of the mean, and the numbers in () indicate the number of rats in each group. In addition, * in the table indicates that when compared with the control group, it has a statistically significant difference when the risk rate is 5% or less. Table 56 __________ Dosing amount of test sample HGF concentration in plasma (ng / ml) __ (mg / kg) 24 hours and 72 hours ± 0.02 (3) Kumbu-derived fucoidan 0.1 0 · 04 ± 0 · 12 (4) 0.52 ± 0 · 06 (5) * 0.65 ± 0.18 (4) 0.64 ± 0.09 与 * and control group Compared with the group, the algal administration group tended to increase the amount of HGF in plasma after 24 hours of hepatectomy, and a statistically significant increase after 72 hours. Based on the above 'algalans are produced by defamating HGF, in addition to the need for surgery, liver disease ’, in addition to promoting rapid regeneration of the liver after surgery,

1228991 A7 B7 V. Description of the Invention (^ 8) It is also very useful in restoring liver function. (2) A 7-week-old male Wistar rat was used, and partial liver resection was performed by surgical treatment as follows. That is, the rats were laparotomy under ether anesthesia, and about 30% of the liver was ligated with surgical sutures at the base of the blood vessel before resection. A suture needle is used to suture the open abdomen. The enzyme-treated F-fucoidan prepared in Reference Example 2- (4) was administered immediately after the excision was completed, and then administered orally twice in the morning and evening. The control group was administered physiological saline. Twenty-four hours after hepatectomy, the rats were anesthetized and blood was collected from their abdominal aorta, and the plasma of 0.1% ethylenediaminetetraacetic acid disodium salt was centrifuged. The HGF ELISA kit (produced by the Special Immunology Research Institute) was used to measure the amount of HGF in the plasma. As shown in Table 57. The numbers in the table indicate the mean standard error of the mean, and the numbers in () indicate the number of rats in each group. In addition, * in the table indicates a group having a statistically significant difference in the case of a risk rate of 1 ° / 0 or lower compared with the control group. Table 57 Plasma HGF concentration (ng / ml) Group 24-hour physiological saline 0 · 184 ± 0 · 33 (6) Enzyme-treated F-algalan (1 g / kg / day) 0 · 505 ± 0 · 97 * (5) -111- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X 297 mm) 1228991 A7 ____B7 V. Description of the invention Compared with the control group, the enzyme-treated F-fucoidan administration group After 24 hours of liver resection, there was a statistically significant increase. Based on the above-mentioned alginans and 7-12SFd-F high-contained oscillating glycans, which induce HGF production, in liver diseases that require surgery, in addition to promoting rapid regeneration of the liver after surgery, and remaining liver It is also extremely useful in restoring functions. Example 8 In a DMEM medium (manufactured by GIBCO BRL) containing 10% bovine fetal serum (FBS: manufactured by Biotech Corporation), insulin-type cells were proliferated in the presence of 50/0 carbon dioxide at 37 ° C. Hs68 cells (ATCC CRL-163 5) of a human neonatal foreskin epithelial cell line expressing h-IGF-1, which is one of the factors, are cultured in a culture vessel until saturation, and the cells are suspended in a trypsin-EDTA solution From the above culture medium, 3 x 03 / well 'was injected into each well of a 96-well microtiter plate at 200 // 1. After 5 to 7 days of culture, at the point when the cells are almost saturated in the incubator, discard the culture medium, and refer to Reference Example 1- (2) containing 0, 12.3, 37, 111, 333, 1000, or 3000 / zg / ml. I division, π division, ΠI division, or the algal derivative derived from C. melanoglossus described in Reference Example (1), the above medium was added to 200 // 1 / well. The culture supernatant was periodically recovered at the i, 4, 12, and 24 hours according to a 24-hour time course, and the h-IGF production of Hs68 cells was measured by the h-IGF_1 ELISA kit (manufactured by Dyknotics). active. As shown in Tables 58 to 61. The control group is a group without added samples. ------- Tue 11 2 · This paper ruler Qi Gong Family (CNS) M specification (Can χ tear public treasure) 1228991 A7 B7 V. Description of the invention L) Table 58 h. -IGF-1 concentration of raw fucoidan (ng / ml) 1 hour 4 hours 12 hours 24 hours Control group 4.3 2.9 4.1 4.5 12.3 22.9 14.7 10.5 11.8 37 17.5 13.9 10.8 11.4 111 14.6 13.7 10.3 7.8 333 13.8 17.6 9.4 7.7 1000 13.9 14.7 14.6 7.5 3000 15.9 14.0 14.0 7.2 Table 59 h-IGF-1 concentration (/ zg / ml) (ng / ml) in I-division medium 1 hour 4 hours 12 hours 24 hours Control group 6.8 5.4 5.0 5.0 12.3 13.9 10.5 7.6 7.3 37 19.0 11.7 8.3 10.1 111 20.4 11.0 9.5 9.9 333 18.7 12.2 10.9 10.3 1000 17.7 13.2 12.7 11.3 3000 19.0 12.1 13.1 11.7 -113 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 V. Description of the invention () 111 Table 60 Concentration of h-IGF-I (// g / ml) (ng / ml) in the II divided medium 1 hour 4 hours 12 hours 24 hours Control group 4.3 2.9 4.1 4.5 12.3 18.5 10.2 6.9 7.0 37 20.1 9.9 9.2 9.2 111 20.0 11.1 9. 8 8.9 333 16.3 12.7 9.7 9.2 1000 17.0 12.2 10.0 8.8 3000 17.9 11.3 10.0 7.6 Table 61 Concentration of h-IGF-I (ng / ml) in III divided medium 1 hour 4 hours 12 hours 24 hours Control group 4.3 2.9 4.1 4.5 12.3 16.5 10.9 8.5 8.6 37 16.7 10.2 11.1 8.4 111 11.8 11.5 8.6 6.9 333 9.6 11.2 8.0 5.9 1000 7.9 10.4 10.6 6.6 3000 7.1 9.4 9.7 6.2 _-114- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) 1228991 A7 B7 V. Description of the invention \ 12) As shown in Table 5 8 ~ 61, the phytosan derived from the genus Kumbu, I division, jj division, and III division are shown to have h-IGF-1 defamation. active. h-lGF. 1 produces a defensive activity ', which shows that it has the highest value in the first hour by adding a sample of 12 to 100 / z g / ml. In addition, in each sample, it was confirmed that there was no toxicity or proliferation-inhibitory activity on Hs68 cells. In addition, regarding other acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, and their salts described in the reference examples, it was confirmed that the same h-IGF-1 had a defamatory activity. Example 9 Rat fibroblast LM cells (ATCC CCL-1.2) were suspended to 1.5 × 105 cells / ml in Ml 99 medium containing 0.5% Baker protein gland (manufactured by Difco), and then 96 Well plates were inoculated sterilely at 0.1 ml. After 3 days of culture, the medium was removed and replaced with M199 medium containing 5% bovine serum albumin (manufactured by Sigma). Alkaline-derived fucoidan derived from Cageale kumbu described in Reference Example ι_ (ι) was added to a final concentration of .0, 62 5, 25, and 1000 Vg / ml, and cultured for 24 hours. The control group was those who added distilled water. After the completion of the cultivation, the ngf concentration in the culture solution was measured by an enzyme analysis method (NGF Emax Immuno Assay System: manufactured by the American company). The NGF production scale of the control group was 100%. All experiments were performed twice and the average value was used. The results are shown in Table 62. As shown in Table 62, the Kageme-derived yamose-derived yamose system promoted the production of nerve proliferation factors in L-M cells in a concentration-dependent manner. Even its fractions show the same activity. In addition, the other acidic polysaccharides, their decomposed products, acidic oligosaccharides, acidic monosaccharides, and their salts' described in the reference example also have the same NGF-producing effect. --- --___- 115- The paper size is suitable for China® Standard (CNS) A4 specification (21GX297 public director) 1228991 A7 B7 V. Description of invention ί 13) Table 62 Sample concentration HGF production (/ zg / ml) (%) Kumbu derived algae poly 62.5 117 Sugar 250 166 1000 179 (The HGF production amount of the control group is 155 pg / ml) Similarly, the I division, II division, Promoting activity of III division of nerve proliferation factor production, and confirming the activity of each division. The results are shown in Table 63. In addition, other acidic polysaccharides, their degradation products, acidic oligosaccharides, acidic monosaccharides, and their salts described in the reference examples also have the same NGF production-inducing effect. Table 63 Sample concentration NGF production (/ zg / ml) (%) I division 250 505.6 500 619.6 1000 806.5 II division 250 664.5 500 864.5 1000 1137.4 III division 250 1021.1 500 1187.0 1000 1265.0 Order

-116- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention "4" (The amount of NGF produced by the control group is 50.03pg / ml) Example 10 (1) Male C3H / He mice were purchased from SLC, Japan, and were used for experiments starting from 5 weeks of preparation. The algal derivatives derived from Cageme kumbu prepared in Reference Example 1_ (1) were suspended and dissolved in ethanol. 3%, and applied to the back of rats (200 β 1 each). The control group was similarly coated with ethanol. The administration was performed once a day for 8 consecutive days. On the 9th day of administration, the The skin was peeled off, and the HGF activity in the skin was measured by an ELISA kit (Special Immunology Research Institute). The results are shown in Table 64. The numbers in the table represent the average of 5 cases (standard error. Extracted from the skin The HGF activity was significantly higher in this algal-coated group than the control group, and it was confirmed that the alga-coated Hgf produced a defamatory effect. Table 64 HGF activity in skin (ng / g tissue) Control group (N = 5) Fucoidan coated group (N = 5) 16.3 1 ± 2.86 104.46 ± 4.05 Mean earth standard The quasi deviation (2) compares the cosmetic lotion of the present invention described in Example 26- (1) described below with a control lotion that does not contain alginans, and randomly performs functionalization on 25 adults and females aged 20 to 35 Check. As a result, confirm the number of people who are more effective __ -117- This paper ruler Qi Cai ® A4 specification (—297 public reply) 1228991 A7 B7 V. Description of the invention (15) is shown in Table 65. Table 65 _ Muscle The smoothness of the moist Zhan muscle The tightness of the muscle The lotion of the present invention 21 19 16 The lotion of the control group 5 6 9 Based on the above results, it is shown that the defensive action of hgf of alginans is accompanied by alginans The lotion of the present invention has excellent muscle wetness, smoothness, and tightness. Example 11 (1) 98 mg of F-algalan prepared by the method described in Reference Example 1- (2) Dissolved in 5 ml of DMSO, added 980 mg of pyridine sulfuric acid at room temperature, and stirred at 80 ° C for 2 hours. After the reaction solution was cooled, it was dialyzed against a dialysis membrane with a molecular weight of 1,000 for 2 days. The obtained dialysate was For injection in a cation X exchange column (Amberlite IRA_120 (Na +)), and 98 mg of F-algalan high sulfate was prepared by drying under reduced pressure. (2) 7-12SFd-F34 mg prepared by the method described in Reference Example 2 was dissolved in 4 ml of DMSO, and thereafter, 98 mg of 7-12SFd-F34 high sulfate was prepared in the same procedure as in Example 丨 Gas ”. (3) In the same way as in Example 1, review F-Han prepared in Example 丨 丨 Gas. High Sulfate of Glycan (Sample ①), Example 丨 丨 _ (2) High Sulfate of 12SFd-F (Sample ②), F-Fucoidan Prepared by Reference Example 1- (2) ), And HGF production-inducing activity of 7-12SFd-F high sulfate (sample ④) prepared in Reference Example 2. Add their respective samples so that their final concentration becomes 1, 10, 100 # g / ml. The control group adds the same amount of steam as the sample. __ -118- This paper size applies the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 1228991 A7 B7 V. Description of the invention $ 16) Hall water. The results are shown in Table 66. In Table 66, the HGF production amount of the control group is 100%. All experiments were performed twice, and the average value was used. As shown in Table 66, samples ① to ④ all lead to the generation of HGF. Further, among the high sulfates, the HGF-producing activity was increased compared with those without high sulfuric acid treatment. Based on this fact, it was clearly shown that the naturally occurring sulfated sugar, which also undergoes sulfate treatment, can significantly enhance the HGF production-inducing activity. The sulphuric acid content was quantified by adding 10.2 ml (1 to 10 mg / ml) of IN HC to each sample and heating at 105 ° C for 4 hours, taking 0.1 ml of it and adding 0.1N HC1 solution 1.9 to it. 1 ml of 0.25 ml of 1% barium chloride-0.5% gelatin solution was left for 20 minutes, and then the absorbance at 500 nm was measured. The calibration line uses the IN HC1 solution of 0, 1, 3, 5, 7, 10, 15, 20 mM sodium sulfate as the standard sample, and then calculates the sulfuric acid content of each sample from the reduction line (S03 conversion). This calibration curve is shown in Figure 2 and the sulfuric acid content of each sample is shown in Table 67. Table 66 HGF production in concentration (%) Sample ① Sample ② Sample ③ Sample ④ 1 346 192 312 192 10 715 214 493 229 100 794 499 598 355 (HGF production in the control group is 8.15 ng / ml) -119- Paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention Table 67 Sulfuric acid content of the sample (S03 conversion,%) F-Algin 40 F-Algin Sulfate 47 7-12SFd-F 40 High sulfate of 7-12SFd-F 48 Example 12 NHDF cells (human) suspended in a DMEM medium containing 10% bovine fetal serum at a concentration of IX 105 cells / ml Normal skin fibroblasts: 500 // 1 (manufactured by Bio Wittaker), 48-well cell culture plates were added and cultured for 24 hours. Thereafter, the medium was replaced with a DMEM medium containing 1% bovine fetal serum, and 10 nM of tetradecylcyclopropenyl benzyl alcohol 13-acetate (TPA: manufactured by GIBCO BRL) and a test substance were added. Twenty hours after the addition, the medium was recovered and the Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit (manufactured by Funakoshi Corporation, Code. RS-0641-00) was used to determine the amount of HGF in the medium. The amount of HGF produced in the negative control group is shown in 100%. The algal polysaccharide described in Reference Example 1- (1) was added to a final concentration of 1, 10, 100 eg / ml. Heparin was added to a final concentration of 1, 10 / zg / ml. For the negative control group, add the same amount of distilled water as the sample. For culturing experiments, at the same time as the sample is added, 10 nM of TPA is added. All experiments were performed 3 times and the average value was used. As a result, as shown in Table 68, all the cell groups added with fucoidan had statistically significant increase in the amount of HGF produced compared with the negative control group added with distilled water. Further 'It also has a significant increase in HGF production compared to the heparin-added group __ -120- This paper standard Tongcai Guo® Home Scale (CNS) A4 specification (referred to as X 297 public love) 1228991 A7 B7 V. Invention Description) Plus. Based on this fact, it was shown that the algal polysaccharide described in Reference Example 1- (1) has a higher activity to promote HGF production than the heparin which has been confirmed to defame HGF. Table 68 Concentration of heparin algal (// g / ml) 0 100 100 1 950 1140 10 2170 2470 100-2770 (however, the HGF production amount of the control group is 0.20ng / ml) Example 13 will contain 10% of cattle Hs68 cells (human neonatal foreskin cells: ATCC CRL-1635 manufactured by Dainippon Pharmaceutical Co., Ltd.) suspended in a concentration of IX 105 cells / ml in fetal serum DMEM medium 500 // Add 48-well cell culture plates and culture 24 hours. Thereafter, the medium was replaced with a DMEM medium containing 1% bovine fetal serum, and 10 nM of TPA and a test substance were added. It should be noted that the control group without the addition of TPA and only the sample was also performed at the same time. The medium was recovered and the amount of HGF in the medium was measured using a Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit. After washing the cells with PBS, they were dissolved in 500 / zl of cell lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 / zg / ml pepstatinA, 1 / zg / ml leupeptin). Furthermore, in order to completely dissolve it, the supersonic-121- this paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention) After centrifugation and centrifugation, The supernatant (cell extract) was prepared, and the HGF concentration in the culture medium was the same, and the amount of HGF in the cells was measured. 7-12SFd-F prepared in Reference Example 2- (3) was added to a final concentration of 0.1, 1, 10, 100 / zg / ml. Add the same amount of steamed surface water to the negative control group. All experiments were performed 3 times and the average value was used. The results are shown in Tables 69 to 71. In the absence of added TPA, significant HGF production cannot be confirmed. However, when TPA was added, the amount of HGF in cells decreased 7-12SFd-F concentration-dependently, while the amount of HGF and total HGF in culture medium increased 7-12SFd-F concentration-dependently. Further, the total HGF amount is a statistically significant increase over the control group without the addition. In addition, the increase in the amount of HGF when such an mRNA is increased is very significant when compared with a small amount of mRNA when the TPA is not treated. Based on this fact, it has been shown that 7-12SFd-F can promote the transcription of mRNA, and when a large amount of HGF is required, it can significantly promote the release and production of HGF. Table 69 HGF content in Hs68 / 7-12SFd-F medium (pg / well) 7-12SFd-F without TPA lOnM TPA 0 ND 65.54 0.1 ND 71.04 1 ND 99.25 10 ND 226.14 100 ND 260.49 ND means the detection limit is below- 122- This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A7 B7 V. Description of invention (20) Table 70 HGF view (pg / well) in Hs68 / 7- 12SFd-F medium 7- 12SFd-F without TPA 1〇πΜ TPA (/ zg / ml) 0 98.62 155.65 0.1 87.60 151.99 1 62.47 142.17 10 ND 120.70 100 ND 95.67 ND is the detection limit shown in Table 71 Hs68 / 7_12SFd-F Full HGF amount (pg / and ) 7-12SFd-F without TPA 10nM TPA 0 g / ml) 0 221.19 0.1 223.02 1 241.42 10 346.84 100 356.05 Example 14 will contain 10 ° /. MRC-5 cells (CCL 171: made by Dainippon Pharmaceutical Co., Ltd. 02-021) suspended in a 2.5 × 105 cell / ml concentration in DMEM medium of bovine fetal serum was added to a 6-well cell culture plate. Incubate at 37 ° C for 24 hours in the presence of 5% carbon dioxide. After that, the paper was replaced with -123-. This paper size is in accordance with the Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7. V. Description of the invention21) The medium is dmem medium containing 1% bovine fetal serum, Incubate for another 22 hours. Thereafter, the respective culture media were replaced with 7-12SFd-F of Reference Example 2- (3) at a final concentration of 100 // l / ml, and LM heparin at a final concentration of 1 / zl / ml (Celsus Labs) (Produced), and prostaglandin EKPGEDC dissolved in dimethyl sulfene at a final concentration of 1 vi / mi (manufactured by Kosuke Pharmaceutical Co., Ltd.) and other culture fluids. The control group used DMSO-added medium. It should be noted that all of the agents of each medium were added to 1%. Then go to * -step for culture, and extract the whole RNA at 0, 2, 4, 6, 8, 10, 12, 24 hours. The entire RNA was extracted using RNeasy Mini Kit (manufactured by QIAGEN). For RT-PCR, the RNA PCR kit ver.2.1 (manufactured by Takara Shuzo Co., Ltd., R019A) was used. 〇Reverse transcription reaction Beij ij heat-denatured the entire RNA, and then used random primers (N6) (manufactured by Takara Shuzo Co., Ltd., 3801). 10 minutes at 42 ° C, 30 minutes at 42 ° C, and 5 minutes at 99 ° C. In order to detect the mRNA of HGF, the primers described in Sequence Number 1 of the Sequence Listing are used as meaning primers, and the primers described in Sequence Number 2 of the Sequence Listing are used as antisense primers. The amplified product of this primer was 41 5 bp. In order to perform a semi-quantitative experiment, the / 5-activin of the house keeping gene is detected. For primers, the primers described in sequence number 3 of the sequence list are used as meaning primers, and the primers described in sequence number 4 of the sequence list are used as antisense primers. The amplified product of this primer is 275 bp. PCR was performed using PJ9600 (manufactured by Parkin Elma). The PCR cycle was 2 minutes at 94 ° C, re-denaturation at 94 ° C for 30 seconds, pairing at 59 ° C for 30 seconds, extended reaction at 72 ° C for 60 seconds, and 24 cycles. After the reaction, 2% agar gel electrophoresis and ethidium bromide staining were performed, and the gel was observed under UV irradiation. Can be detected on all samples -124- This paper size applies to China National Hazel Standard (CNS) A4 (210X297 mm)

Binding

1228991 A7 B7 V. Description of the invention \ 22) The mRNA of the HGF. Compared with the control group, the defamation of PGEii mRNA can be confirmed, but the induction of 7-12SFd-F and LM heparin mRNA cannot be confirmed. Based on this fact, it can be clearly found that in the state where mRNA of HGF is frequently transcribed, the addition of 7-12SFd-F and LM heparin will not promote the transcription of HGF mRNA, proving that 7-12SFd-F and LM heparin will not Caused excessive defamation of HGF. Example 15 The Hs68 cells used in Example 13 were changed to NHDF cells (human normal skin fibroblasts: manufactured by Bio Whittaker). The rest were the same as in Example 13, and among the NHDF cells investigated, 7-12SFd-F HGF produces defamatory activity. The results are shown in Tables 72 to 74. In the absence of added TPA, the amount of HGF in the cells was 7-12SFd-F concentration-dependently decreased, and the amount of HGF and total HGF in the culture medium was 7-12SFd-F concentration-dependently increased. Further, the amount of whole HGF is a statistically significant increase over the control group without addition. Based on this fact, it has been shown that even in the case of a small amount of HGF mRNA, such as in the absence of TPA, both the release of HGF on the cell surface and the synthesis of HGF can be promoted at the same time. Furthermore, when TPA was added, the amount of HGF in the cells was 7-12SFd-F concentration-dependently decreased, while the amount of HGF and total HGF in the culture medium was 7-12SFd-F concentration-dependently increased. Further, the total HGF amount was a statistically significant increase over the control group without the addition of 7-12SFd-F. In addition, the increase in the amount of HGF when such mRNA is increased is very significant when compared with a small amount of mRNA when no TPA is added. Based on this fact, it is proved that 7-12SFd-F can promote the release and production of HGF in small amounts when the mRNA is small, and if -125- this paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) i order

1228991 A7 B7 V. Description of the invention \ 23) When mRNA is promoted to transcription and a large amount of HGF is required, it significantly promotes the release and production of HGF. Table 72 Amount of HGF in NHDF / 7-12SFd-F medium (ng / well) 7-12SFd-F No TPA ΙΟηΜ TPA (# g / ml) 0 ND 0.39 1 0.05 0.68 10 0.18 1.22 100 0.385 1.625 ND means detection The following table shows the amount of HGF in NHDF / 7-12SFd-F cells (ng / well). 7-12SFd-F No TPA ΙΟηΜ TPA (/ zg / ml) 0 0.185 0.24 1 0.145 0.19 10 0.075 0.12 100 0.025 0.055 -126 -This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 __ B7 V. Description of the invention (24) ^ 24 NHDF / 7-12SFd-F Full HGF amount (ng / well) 7] 2SFd-F without TPA ΙΟηΜ TPA 0 0.63 1 0.195 0.87 10 0.255 1.335 __100 0.41 1.68 Example 16 NHDF cells suspended in a DMEM medium containing 10% bovine fetal serum at a concentration of 2.5 × 105 cells / ml (human normal Skin fibroblasts) were added to 6-well cell culture plates every 2 ml, and cultured at 37 ° C for 24 hours in the presence of 5% carbon dioxide. Thereafter, the medium was replaced with a DMEM medium containing 1% bovine fetal serum, and 10 nM of tetradecylcyclopropenyl alcohol 13-acetate (manufactured by TPA ·· GIBCO BRL) and Reference Example 2_ were added. (3) Prepare 7-12SFd-F test material so that its final concentration becomes 100 # g / ml. In addition, the division without adding TPA and only adding 7-12-SFd-F was performed at the same time. After further culture, the total RNA was extracted at 4, 6, 8, and 10 hours. All RNA was extracted using RNeasy Mini Kit (manufactured by QIAGEN). RT-PCR was performed in the same manner as in Example 14 except that 28 cycles were used. After the reaction, 2% agar gel electrophoresis and ethidium bromide staining were performed, and the gel was observed under UV irradiation. As a result, when TPA is not added, the transcription amount of HGF mRNA is very small, but due to the addition of 7-12SFd-F, within 4 hours after the addition, it can be ___ -127- This paper size applies to China Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ') A considerable increase in the amount of transcription of mRNA was seen. When TPA and 7-12SFd-F were added, compared with TPA alone, the amount of HGF mRNA was significantly increased within 4 hours after the addition, but at 6 hours, the amount of HGF mRNA was significantly increased. 12SFd-F was not much different. That is, it is necessary for 7-12SFd-F system HGF. When mRNA transcription is actively performed, it obviously promotes the transcription, but then the promotion effect disappears. Based on this fact, it can be clearly found that 7-12SFd-F can induce the production of HGF at the moment necessary for HGF, and thereafter, it will not defame the production of excess HGF. Example 17 HL60 cells (human premyeloid leukemia cells) suspended at a concentration of 5 × 105 cells / ml in RPMI 1640 medium containing 10% bovine fetal serum were suspended in 1% bovine fetal serum In RPMI 1640 medium, 500 # 1 of each was added to a 48-well cell culture plate. Thereafter, 10 nM TPA and test material were added. Incubate for 24 hours after the addition. The same applies to the grouping of samples without adding TP A and only adding samples. The culture medium was recovered, and the Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit was used to determine the amount of HGF in the culture medium. Further, after washing the cells with PBS, they were lysed in a 500 / zl lysis buffer (50 mM HEPES pH 7.4, 10 mM EDTA, 0.1% TritonXIOO, 1 mM PMSF, 1 // g / ml pepstatinA, 1 # g / ml leupeptin). Further, in order to completely dissolve it, after ultrasonic treatment, centrifugal separation and preparation of a supernatant (cell extract), the same as the determination of the HGF concentration in the culture medium, to determine the amount of HGF in the cells. 7- ____- 128- prepared in Reference Example 2- (3) This paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention &amp; 26) 12SFd-F added The final concentration was 1, 10, 100 / zg / ml. For the negative control group, add the same amount of distilled water as the sample. All experiments were performed 3 times, and the average value was used. The results are shown in Table 7 5-7. As a result, when TPA was not added, the amount of HGF in the cells did not change with the concentration of 7-12SFd-F. Although the amount of HGF in the medium was increased at 100 β g / ml, there was no significant change due to the concentration of 7-12SFd-F. In addition, when TPA was added, the amount of HGF in the cells did not change due to the concentration of 7-12SFd-F, but the whole was low. On the other hand, the amount of HGF and total HGF in the culture medium increased significantly depending on the concentration of 7-12SFd-F. Further, the total HGF amount was a statistically significant increase over the control group without the addition of 7-12SFd-F. In addition, the increase in the amount of HGF when such an mRNA is increased is very significant compared with the case of a small amount of mRNA when there is no TPA treatment. Based on this fact, it is shown that the transcription of 7-12SFd-F is promoted in mRNA, and when a large amount of HGF is required, it can obviously promote the HGF release and significantly promote the production of HGF. Table 75 Amount of HGF in HL60 / 7-12SFd-F medium (pg / well) 7-12SFd-F without TPA ΙΟηΜ TPA 0 76.74 261.60 1 67.10 295.94 10 78.54 464.55 100 162.85 843.84 _ -129- This paper is for Chinese country 榡Standard (CNS) A4 specification (210X297 mm) 1228991 Α7 Β7 V. Description of invention ί27 Table 76 HGF amount in HL60 / 7-12SFd-F cells (pg / and) 7-12SFd-F (/ zg / ml) No TPA ΙΟηΜ TPA 0 294.12 83.37 1 276.67 89.39 10 236.30 67.09 100 257.04 85.77 Table 77 HL60 / 7-12SFd-F total HGF amount (pg / well) 7-12SFd-F (// g / ml) without TPA ΙΟηΜ TPA 0 370.85 344.97 1 343.77 385.32 10 314.84 531.64 100 420.26 929.60 Example 18 RPMI 1640 medium containing 10% bovine fetal serum was suspended at a concentration of 5X 105 cells / ml in HL60 cells and suspended in 1% bovine fetal serum RPMI In 1640 medium, another 2 ml of each was added to a 6-well cell culture plate. Thereafter, 7-12SFd-F prepared in Reference Example 2- (3) was added with 10 nM of TPA to a final concentration of 100 eg / ml. The same applies to the grouping of the zones without the addition of τρα and only the samples. In addition, the division of TPA and addition of only 7-12-SFd-F is performed simultaneously. Further cultivation, -130- This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 1228991 A7 B7 __ V. Description of the invention \ 28)

The total RNA was extracted at 4, 6, 8, and 10 hours. The entire RNA was extracted using RNeasy Mini Kit (manufactured by QIAGEN). RT-PCR was performed in the same manner as in Example 14 except that 32 cycles were used. After the reaction, 2% agar gel electrophoresis and ethidium bromide staining were performed, and the gel was observed under UV irradiation. As a result, when TPA was not added, the transcription amount of HGF mRNA was very small, but due to the addition of 7-12SFd-F, a considerable increase in the transcription amount of mRNA was seen within 4 hours after the addition. On the other hand, by adding TPA, the mRNA amount of HGF increased significantly at any time point. When TPA and 7-12SFd-F were added, compared with TPA alone, the amount of HGF mRNA was significantly increased within 4 hours after the addition, but at 6 hours, the amount of HGF mRNA was significantly increased. 12SFd-F was not much different. That is, it is necessary for 7-12SFd-F system HGF. When the transcription of mRNA is actively performed, it obviously promotes the transcription, but then the promotion effect disappears. Based on this fact, it can be clearly found that 7-12SFd-F can defame the production of HGF at the moment necessary for HGF, and thereafter, it will not induce the production of excess HGF. Example 19 (1) A commercially available chrysanthemum was freeze-dried to obtain a chrysanthemum freeze-dried product. 10 g of the inulin powder obtained by pulverizing the freeze-dried product of the inulin was suspended in 1000 ml of chloroform, filtered, and the insoluble fraction was recovered and repeated 3 times. In this way, the insoluble ethanol obtained was completely removed, and resuspended in 100 ml of distilled water. This distilled water was kept at 60 ° C. for 1 hour, and then filtered. Add 2.5 times the amount of ethanol, and cool to -20 ° C, then leave it at -131- at a low temperature. This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of invention \ 29) The precipitate was isolated from the heart. This precipitate was dissolved in distilled water and freeze-dried to obtain a powdered sugar-containing fraction and an inulin extract. (2) In the same manner as in Example 1- (1), review the HGF-producing activity of the inulin extract prepared in Example 19- (1). Add the sample so that the final concentration becomes 1, 10, 100 # g / ml. The negative control group was added with the same amount of distilled water as the sample, and the HGF content of the negative control group was expressed as 100%. The results are shown in Table 78. All experiments were performed twice and the average value was used. As shown in Table 78, inulin extracts blame HGF production. Table 78 Inulin extract (/ zg / ml) HGF production amount (%) 1 125 10 148 100 314 (However, the HGF production amount of the control group is 8.21 ng / ml) Example 20 In accordance with Example 1- (1 ) The same method was used to determine the HGF-producing activity of the supernatant of the wormwood tree prepared in Reference Example 13- (5). However, the division of the supernatant of mountain wormwood is based on the amount of 1/100 of the medium added. The results are shown in Table 79. That is, even if the wormwood extract is subjected to ethanol precipitation without being precipitated, it has obviously HGF-producing activity. Based on this fact, it is considered to be active even in the low-molecular fraction that is not precipitated during the ethanol precipitation. -132- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7, Description of invention () 130 Table 79 Addition amount of HGF produced by the supernatant of mountain wormwood (%) 0 100 Add 1 463/1000 (However, the HGF production amount of the control group is 4.31 ng / ml) Example 21 (1) 50 g of dried mountain wormwood leaves (sold: Hanban Hankatado) are added to the homogenizer ( 500 ml of chloroform was added, homogenized at 8000 rpm for 10 minutes, and then filtered with filter paper to obtain a residue. The above operation was repeated twice, and the obtained residue of 100 g of Artemisia sylvestris leaves was added to a homogenizer, followed by addition of 500 ml of chloroform, homogenization at 8000 rpm for 10 minutes, and filtration with a filter paper to obtain a residue. The above operation was repeated 4 times to obtain an acetone washing residue. The residue was washed with acetone in the same manner as with acetone, and washed with 90% ethanol 4 times and 80% ethanol 4 times to obtain an ethanol-washed residue. The above operation was performed again from the beginning to obtain a total of 200 g of ethanol washing and examination of the leaves of mountain wormwood. (2) To the ethanol washing residue, add 10 liters of 30 mM phosphate buffer (pH 8.0) containing 100 mM sodium chloride and 10% ethanol, and stir at room temperature for 19 hours. Filter through a filter paper to obtain a crude extract (filtrate). The obtained crude extract was concentrated to 2 liters with an external-limiting filter that excludes hollow fibers with a molecular weight of 10,000, and 20 liters of 100 mM sodium chloride containing 10% ethanol was added for external-limiting filtration. After that, it was concentrated to 668 ml, 1 g of activated carbon was added, and it was dropped at room temperature for 30 minutes, and then centrifuged at 10,000 rpm. _-133 -__ This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) ) 1228991 A7 B7 V. Description of the invention () 131 Separated for 40 minutes to remove activated carbon. The trace amount of activated carbon remaining in the supernatant was removed with No. 5c filter paper. 66.8 ml was taken from the activated carbon treatment solution, and it was sufficiently dialyzed against distilled water, followed by freeze-drying to obtain 670 mg of a dried product. This dried material was named as mountain wormwood leaf polymer partition (YPS). The remaining 601.2 ml of activated carbon treatment solution was added to the out-of-limit filtration device, and the solvent was replaced with 10% ethanol and 50 mM sodium chloride and 10 mM imidazole hydrochloride buffer solution (pH 7.0) to obtain the solvent-exchanged mountain wormwood. Macromolecular division of leaves. (3) Substitute this solvent for the high molecular weight of mountain wormwood leaves and add to DEAE-Seloflavin A equilibrated with 10 mM imidazole-hydrochloric acid buffer (pH 7.0) containing 10% ethanol and 50 mM sodium chloride. -800 column (Φ 4 · 05 X 37 · 8 cm). After washing the column with 1200 ml of the same buffer, the column was dissolved in a gradient of 0.1M (1000 ml) to 2M (1000 ml) sodium chloride. The eluent is 30 ml per tube. In the dissociation division, division numbers 13 to 33 are named as the high molecular division of mountain wormwood leaf-I (YPS-I), and division numbers 69 to 78 are high molecular division of mountain wormwood leaf-II (YPS-II), and the division number 79 to 137 are the macromolecular division-III (YPS-III) of mountain wormwood leaves. YPS-I, YPS-II, and YPS-III were sufficiently dialyzed against distilled water to obtain 530 mg, 420 mg, and 380 mg of each freeze-dried product. (4) In order to further classify YPS-III, 200 mg of YPS-III is dissolved in 5 mM imidazole-hydrochloric acid buffer (pH 8.0) containing 4M sodium hydrochloride, and added to the balance with the same buffer solution. Phenyl-Seloflav A-800 column ((/) 3.1 · 14.3 cm). After washing with 200 ml of the same buffer, each was dissolved with 5 ml of imidazole-hydrochloric acid buffer (pH 8.0) containing 200 ml of 1 M sodium chloride, 200 ml of distilled water, and 200 ml of ethanol. _-134- This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention ς 2) The dissolution solution is 10 ml per tube. In the dissociation division, the division numbers 1 to 32 are named as Shan wormwood polymer division-ΙΙΙ-1 (YPS-III-1), and the division numbers 33 to 53 are named as Shan wormwood polymer division-ΙΙΙ-2 (YPS-III -2), and division numbers 54 to 66 are named as Shan wormwood polymer division-III III-3 (YPS-III-3). YPS-III-1, YPS-III-2 and YPS-III-3 were each fully dialyzed with water and freeze-dried to obtain 20.11 mg, 32.59 mg and 113.75 mg of each. (5) Using the same method as in Example 1- (1), determine the fractions, extracts, YPS (sample ①), YPS- HGF of 1 (Sample ②), YPS-II (Sample ③), and YPS-III (Sample ④) produced defamatory activity. The results are shown in Table 80. The results show that the fractions of these extracts of wormwood tree have HGF-producing activity. -135- This paper size is in accordance with China National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of invention 3) Table 80 Sample concentration HGF production (/ zg / ml) (%) Sample ① 0 100 1 214 10 267 100 215 Sample ② 0 100 1 121 10 113 100 260 Sample ③ 0 100 10 129 100 243 Sample ④ 0 100 1 232 10 323 100 272 (However, the HGF production amount of the control group is 8.43 ng / ml ) (6) In the same manner as in Example 1- (1), determine the fractions of the wormwood extract prepared in Example 21- (4), YPS-III-1 (sample ①), YPS_III-2 (Sample ②), HPS of YPS-III-3 (Sample ③) produced slander activity. The results are shown in Table 81. The results show that the fractions of these extracts of wormwood tree have HGF-producing activity. _-136-_ This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 1228991 A7 B7 V. Description of the invention L) Table 81 Addition (// g / ml) Sample ① HGF production (%) Sample ② Sample ③ 0 100 100 100 1 188 290 247 10 181 304 217 100 348 295 243 (HGF production in the control group is 8.26 ng / ml) Example 22 The cage described in Reference Example 1- (1) 30 grams of fucoidan derived from mesh kumbu was dissolved at room temperature by stirring with 12 liters of distilled water. This suspension was centrifuged at 10,000 X g for 40 minutes, and the supernatant was collected. This was subjected to aseptic filtration with a membrane filter (0.22 // m) (manufactured by Millipore) to obtain 21.4 g of a freeze-dried product. This was designated as Takara kumbu fucoidan Bf (hereinafter referred to as fucoidan Bf). In the same manner as in Example 1- (1), the HGF production-inducing activity of algal Bf (sample ①) was measured. The results are shown in Table 82. The experiments were performed twice, and the average value was used. As a result, it was shown that fucoidan Bf has HGF-producing activity. -137- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1228991 A7 B7 V. Description of invention \ 35) Table 82 Addition amount HGF production (%) (Ag / ml) Sample ① 0 100 1 209 10 333 100 377 (However, the HGF production amount of the control group is 9.17 ng / ml) Example 23 (1) 500 g of dried cage mesh kumbu was finely cut. After washing with 10 liters of 80% ethanol, put it in 50 liters of 10% ethanol containing 1 mM potassium chloride, stir at 25 ° C for 3 days, and filter through a stainless steel mesh with a mesh size of 32 # m To obtain a liquid volume of 45 liters. After 34 liters of the filtrate was heated at 80 ° C for 3 hours, it was cooled to 50 ° C. While keeping the liquid temperature at 50 ° C, the solution was concentrated using an external filter OMEGA (manufactured by Felt Wheel Co., Ltd.) with a molecular weight of 10,000. Further, 5 L of distilled water heated to 50 ° C was used for desalting, 200 ml of the same distilled water was added, the circuit was washed twice, and then recovered to obtain 1.5 liters of concentrated liquid. It was cold-bundled and dried to obtain 8.2 g of F-rich kotosan. (2) In the same manner as in Example 1- (1), the HGF production-inducing activity of the F-Hch alginan (sample ①) prepared in Example 23- (1) was measured. The results are shown in Table 83. The results show that F-rich algin has HGF production-inducing activity. 0 -138- This paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) 1228991 A7 B7 V. Description of the invention "36" Table 83 Adding amount HGF production (%) (/ zg / ml) Sample ① 0 100 1 117 10 186 100 244 (However, the HGF production of the control group is 9.60 ng / ml) Example 24 A sample containing 10% bovine fetal serum In DMEM medium, NHDF cells (human normal skin fibroblasts) suspended at a concentration of IX 105 cells / ml were suspended in 10% bovine fetal serum in DMEM medium, and each 5 0 0 # 1 was added to 4 8 Well cell culture plate, incubate for 24 hours. Thereafter, the culture medium was replaced with 1% bovine fetal serum in DMEM medium, and 10 # g / ml or 100 // g / ml of Minoridine (manufactured by Wako Pure Chemical Industries, Ltd.) and the test materials were added. In addition, when F-rich algalan was added, Minoridine 1 // m / ml was also added for experiments. In the same manner, the same procedure was performed in the case where the sample was added without adding minoladine. This medium was recovered and the Quantikine Human Hepatocyte Growth Factor (HGF) ELISA kit was used to determine the amount of HGF in the medium. The fucoidan Bf prepared in Example 22, the F-rich fucoidan prepared in Example 23, and the 7-12SFd-F prepared in Reference Example 2- (3) were added to a final concentration of 1, 10, 100 / zg / ml. In addition, algal polysaccharide Bf was added to a final concentration of 0.1 g / ml. For the negative control group, add the same amount of distilled water as the sample. All experiments were performed 3 times, and the average was adopted. _-139- This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Explanation of the invention () 137 value. The results are shown in Tables 84 to 86. As a result, the amount of HGF in the medium at the time of no addition of minola increased dependently on the concentrations of algal Bf, F-rich algal, and 7-12SFd-F, and it was statistically higher than that of the control group without addition. Meaningful increase. Based on this, it was proved that even in the case of a small amount of mRNA of HGF such as non-Minoridine treatment, it can simultaneously promote the release of HGF on the cell surface and the synthesis of HGF. In addition, the amount of HGF in the medium at the time of addition of Minor increased dependently on the concentrations of algal Bf, F-rich algal, and 7-12SFd-F, and was statistically significant compared to the control group without addition. increase. In addition, the increase in the amount of HGF when such mRNA is increased is very significant compared with the small amount of mRNA when treated with non-allidine. Based on this fact, it is shown that when the fucoidan Bf, F-rich fucoidan, and 7-12SFd-F have a small amount of mRNA, they can promote the release and production of HGF in a small amount, and when a large amount of mRNA exists and a large amount of HGF is required It can obviously promote the release of HGF and significantly promote the production of HGF. Table 84 NHDF / fucoidan Bf medium HGF concentration (pg / ml) Fucoidan Bf (&quot; g / ml) 10 / zg / ml Minodine 100 // g / ml 0 ND 126.04 148.83 0.1 300.20 307.00 478.90 1 428.83 448.17 624.60 10 791.93 799.90 794.20 100 729.33 709.97 860.23 ND means the detection limit is below _-140- This paper scale is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of invention Table 85 NHDF / F-dch algal culture medium HGF concentration (pg / ml) F-rich algal (/ zg / ml ) Minolidine Minolidine 1 / zg / ml Minolidine 10 # g / ml Minolidine 100 / zg / ml 0 NDNDNDND 1 132.75 NTNT 203.03 10 316.90 239.90 310.20 434.10 100 369.33 372.70 372.70 537.87 ND means the detection limit the following. N.T. said it would not evaluate. Table 86 Concentrations of HGF in NHDF / 7-12SFd-F medium (pg / ml) 7-12SFd-F (// g / ml) Minoridine 10 Minoridine 10 / zg / ml Mineridine 100 // g / ml 0 NDND 137.20 1 228.73 164.00 378.30 10 345.93 376.07 450.83 100 439.67 483.20 820.10 ND represents the limit of detection. Example 25 In mice (CDF1 female 7 weeks old, weighing about 20 kg), intraperitoneal administration of galactose Amine (20 mg / mouse) and LPS (lipopolysaccharide: 0.03 # g / mouse) to make a model of lethality caused by violent hepatitis, and review the life-sustaining effect caused by the alginans described in Reference Example 1- (1) . Alginate was prepared to 10% in distilled water, and then used at an amount of 10 ml / kg body weight (1 g / kg alginan) 1 hour before and 1 hour after the simultaneous administration of galactosamine and LPS. 2 compulsory oral administrations. The control group also administered distillation _-141-_ This paper size applies Chinese National Standard (CNS) A4 (210X 297 mm) 1391228991 A7 B7 V. Description of the invention (water. Survival rate 72 hours after the start of the experiment The control group was treated as t, but the algal administration group was 7 out of 8 cases. Algae obviously had its prolonged effect. In the surviving cases, its serum biochemical value There is also an improvement effect. The results are shown in Table 87. Table 87

Group whole bilirubin GPT (U / 1) G0T (U / 1) (bilirubin) --------- (mg / dl) Control group 385 613 io 233 ± 53 Fucoidan administration group 94 ± 22 Example 26 (1) Cut 500g of kumbu finely, wash it with 10 liters of go% ethanol, and place it in a 40 cm inner container with 50 liters of 10% 1 mM potassium gasification In ethanol, it was stirred at 25 ° C for 2 days at a speed of 120 revolutions per minute, and then the fucoidan was extracted. The extract was filtered through a stainless steel metal mesh with a mesh of 3 2 // m to prepare an algal polymer. Sugar solution. 1 liter of palm oil solution prepared by dissolving 1 gram of palm oil (made by Kao Corporation, for cosmetics) in 1 liter of ethanol, adding this palm oil to 46 liters of medicinal glycan solution, and stirring at the same time, and further Add 1 liter of glycerin to make a lotion. (2) To the algal solution prepared in Example 26- (1), gelatin and perfume were added so that the final concentration became 0.02%, and a gelatin-based lotion was obtained. _ -142- This paper size applies the Chinese National Standard (CNS) A4 specification (21〇 × 297 &gt; price ^) 1228991 A7 B7 V. Description of the invention (14〇) In addition, the same collagen can be used to obtain collagen Protein lotion 0 Industrial availability The present invention provides an effective medicine for diseases requiring growth factor production, which contains a substance having a growth factor-producing activity. The medicinal system has in vivo HGF production inducing activity, h-iGF production inducing activity, ngf • neurotrophic factor production inducing activity, etc., and it is required to produce these growth factors such as hepatitis, diabetes, cancer, and neurological diseases Disease; a or preventive agent is extremely useful. &quot; μ Further, use of acidic polysaccharides, sulfated polysaccharides, such as algin, dextran sodium sulfate, chondroitin sulfate highly contained in shark cartilage extracts having destructive effects by growth factors, their decomposition products, acidity Those who choose oligosaccharides with acidic monosaccharides or their salts can also be made into food and drink and taken as daily food and drink, which can improve the symptoms of the two diseases that require growth factors. The present invention can also provide materials having the same physiological function. Therefore, it is a functional food selected from the acidic polysaccharides, sulfated polysaccharides, such as algal, decomposed products, acid oligosaccharides, acidic monosaccharides, and salts thereof as active ingredients, which are used in the present invention having an HGF production-inducing effect The functional feed is a functional food or drink, or a feed thereof, which is useful for maintaining the constancy of the body, by inducing an action by its growth factor. The present invention can also provide HGF production-inducing life; it can be extremely useful in skin health management, etc. using cosmetics. Furthermore, the present invention also provides an itching transfer inhibitor. … -143- The paper size is suitable for S S home materials (CNS) A4 size (21GX 297 public love) 1228991

V. Description of the Invention (41) In addition, the present invention also provides a growth factor-producing agent, which is extremely useful in the research of the function of growth factors and the screening of medicines for diseases related to growth factors. Sequence Listing &lt; 110 &gt; Takara Shuzo &lt; 120 &gt; Therapeutic

&lt; 130 &gt; 00-028-PCT &lt; 150 &gt; JP 11-108067 &lt; 151 &gt; 1999-4-15 &lt; 150 &gt; JP 1 1-108499 &lt; 151 &gt; 1999-4-15 &lt; 150〉 JP 11 -114542 &lt; 151 &gt; 1999-4-22 &lt; 150 &gt; JP 11-129163 &lt; 151 &gt; 1999-5-10 &lt; 150 &gt; JP 1 1-142343 &lt; 151 &gt; 1999-5-21 -144- present The paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 1228991 A7 B7 V. Description of invention 2) &lt; 150 &gt; JP 1 1-154662 &lt; 151 &gt; 1999-6-2 &lt; 150 &gt; JP 1 1-200982 &lt; 151 &gt; 1999-7-14 &lt; 150 &gt; JP 11-275231 &lt; 151 &gt; 1999-9-28 &lt; 150〉 JP 1 1-375606 &lt; 151 &gt; 1999-12-28 &lt; 150 &gt; JP 2000-99941 &lt; 151 &gt; 2000-3-31 &lt; 160 &gt; 4 &lt; 210〉 1 &lt; 211 &gt; 23 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &gt; &lt; 223 &gt; primer &lt;; 400 &gt; 1 -145- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Order

1228991 A7 B7 V. Description of the invention L) gtgaatactg cagaccaatg tgc 2 3 &lt; 210 &gt; 2 &lt; 211 &gt; 25 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &gt; &lt; 223> primer &lt; 400 &gt; 2 cacagacttc gtagcgtacc tctgg 2 5 &lt; 210 &gt; 3 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &gt; &lt; 223> primer &lt; 400 &gt; 3 caagagatgg ccacggctgc t 2 1 &lt; 210 &gt; 4 &lt; 211 &gt; 22 &lt; 212 &gt; DNA &lt; 213 &gt; Artificial Sequence-146- This paper size applies Chinese National Standard (CNS) A4 specifications (210 x 297 mm) 1228991 A7 B7 V. Description of the invention) &lt; 220 &gt; &lt; 223 &gt; Introduction &lt; 400 &gt; 4 22 tccttctgca tcctgtcggc aa -147- This paper size applies Chinese National Standard (CNS) A4 (210x 297 mm)

Claims (1)

122 | View) 7. Patent No. 84 * A8 Replacement of Chinese patent application scope (November 1993) ^ 6. Application for patent Fan Yuan 1. A type that needs to induce hepatocyte proliferation factor, insulin-like proliferation factor and / or nerve A therapeutic or preventive agent for diseases caused by growth factors, which is characterized by containing sulfated polysaccharides derived from algae, sulfated polysaccharides derived from mountain wormwood, sulfated polysaccharides derived from bitter gourd, sulfated polysaccharides derived from aloe vera, sea cucumber Derived algin, dextran sodium sulfate, chondroitin sulfate B, chondroitin sulfate D, sulfated starch, sulfated curdlan, sulfated pectin, alginate highly sulfated, alginic acid , Pectin, hyaluronic acid, DNA, pectinic acid, agar pectin, their enzymes or acid degradation products, sulfated oligosaccharides, sulfated glucose, sulfated galactose, sulfated xylose, sulfuric acid Chemical 2 _ deoxy-glucose, sulfated talose, sulfated mannose, sulfated sugar alcohols and their selected groups as the active ingredient. 2. 3. The therapeutic or prophylactic agent according to item 1 of the application, wherein the algae-derived sulfated polysaccharide is fucoidan. For example, the application of the therapeutic or preventive agent in the first item of the patent scope, wherein the sulfated oligosaccharide is composed of sulfated maltose, sulfated lactose, sulfated sucrose, sulfated trehalose, sulfated lactulose, sulfated, ,,, 、 Bulgur monosaccharide, Sulfated cellobiose, Sulfated isomaltose, Sulfated-oligosaccharides, Saccharinized palatinose, Sulfated maltotriose, Sulfated maltosan, Hexose , Sulfated wheatgrass nasty sugar 'Sulfated lauryl maltohexose, represented by the following formula ⑴, compounds, and compounds represented by the following formula (II): ^ ^,% Sulfated oligosaccharide: 63836-931I26.DOC This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 9 9 8 2 2 8 8 8 8 A BCD (Where R is OH or 0S03H) Η Η ο Ti TJ r 'R (where R is OH or OS03H). 4. The therapeutic or preventive agent according to item 1 of the patent application scope, further comprising a group consisting of interleukins, prostaglandin E1, prostaglandin E2, and compounds of the following formulae (II) to (V) Selected substances: 63836-93H26.DOC -2 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 A8 B8 C8 D8 hole, patent application rV ϋ-l0h (III) iOOH s (IV) (V) 5. — A food for inducing the production of hepatocyte proliferation factor, insulin-like proliferation factor and / or nerve growth factor, which contains sulfated polysaccharide derived from algae, sulfated derived from mountain wormwood Polysaccharides, bitter melon-derived sulfated polysaccharides, aloe-derived sulfated polysaccharides, sea cucumber-derived alginans, dextran sodium sulfate, chondroitin sulfate B, chondroitin sulfate D, sulfated starch, sulfated cardelin (cur dl an), sulfated pectin, alginate hypersulfate, alginic acid, pectin, hyaluronic acid, DNA, pectinic acid, agar pectin, their enzymes or acid degradation products, sulfuric acid Huadu 63836-931126.DOC This paper size applies to China National Standard (CNS) A4 (210X297 mm) 1228991 Αδ B8 C8 Sugar, sulfated glucose, sulfated galactose, deacidified xylose, sulfated 2-deoxy. Glucose 'sulfated talose, sulfated mannose, sulfated sugar alcohols, and their salts The choice. 6. The food with the scope of the patent application, wherein the sulfated polysaccharide derived from the class is a phytosaccharide. 7. The food with the scope of the patent, where the sulfated oligosaccharides are chemicalized by Shi Fan Maltose, Sulfated lactose, Sulfate sulfate, Sulfated sucrose, Sulfated lactulose, Sulfated melibiose, Sulfated cellobiose, Sulfated isomalt, Sulfated sucrose, Sulfated palatin Sugar, sulfated maltotriose, sulfated maltohexose, sulfated maltoheptose, sulfated lauryl maltohexose, a compound represented by the following formula ⑴, and a compound represented by the following formula (Π) Selected sulfated oligosaccharides in the group of compounds: : Θ: \ β (I) (Where R is OH or 0S03H) -4- 63836-931126.DOC This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1228991 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 1228991 9. A beverage for inducing hepatocyte proliferation factor, insulin-like proliferation factor and / or nerve growth factor production, comprising algae-derived sulfated polysaccharide, mountain wormwood-derived sulfated polysaccharide, and balsam pear-derived sulfated Polysaccharides, aloe-derived sulfated polysaccharides, sea cucumber-derived alginans, gluconate. Sodium sulfate polysaccharides, chondroitin sulfate B, chondroitin sulfate D, sulfated starch, sulfated cardel blue (curd 1 a η), Sulfated pectin, alginate highly sulfated, alginic acid, pectin, hyaluronic acid, DNA, pectinic acid, agar pectin, their enzymes or acid degradation products, sulfated oligosaccharides, Group consisting of sulfated glucose, sulfated galacto-sugar, sulfated xylose, sulfated 2-deoxy-glucose, sulfated talose, sulfated mannose, sulfated sugar alcohols, and their salts The choice. 10. The beverage according to item 9 of the patent application scope, wherein the algae-derived sulfated polysaccharide is algal. 11. The beverage according to item 9 in the scope of the patent application, wherein the sulfated oligosaccharide is composed of mashed maltose, sulfated lactose, sulfated sucrose, sulfated trehalose, sulfated lactulose, sulfated melibiose, sulfuric acid Cellulose diose, gallate isomaltose, sulfated melibiose, sulfated palatinose, sulfurized maltobiose, sulfated maltohexose, sulfated maltoheptose, sulfur 63836-931126. DOC This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 male cage) 9 9 8 2 2 8 8 8 8 A Β c D 6. Application scope of patents Acidified lauryl malt hexose, with the following formula ( The sulfated oligosaccharide selected in the group consisting of the compound represented by I) and the compound represented by the following formula (II): Η (where R is OH or 0S03H) Ο ο ΤΑ Η I (wherein R is OH or OS03H). 12. As for the food item under the scope of patent application No. 9, which further contains the white paper 63836-931126 DOC This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 Substances selected from the group consisting of ABCD Fan Qi, prostaglandin E1, prostaglandin E2, and compounds of the following formulae () II) to (v): 〇human-OH —〇H (III) Η, CH—CH2 —CH2 ~ C—NH—CH—C—NH—CH, —COOH: OOH II (IV) (V) 13. Feeds for inducing the production of hepatocyte proliferation factors, tolinoid-like proliferation factors and / or nerve growth factors, which contain sulfated polysaccharides derived from algae, sulfated polysaccharides derived from mountain wormwood, and bitter gourd Derived sulfated polysaccharides, aloe-derived sulfated polysaccharides, sea cucumber-derived alginans, dextran sodium sulfate, chondroitin sulfate B, chondroitin sulfate 0, sulfated starch, sulfated cardanol blue (c 11 rd 1 a η), sulfated pectin, alginate 63636-931126.DOC This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 9 9 8 2 2 AB c D Sulfated body, alginic acid, pectin, hyaluronic acid, DNA, pectinic acid, agar pectin, their enzymes or acid degradation products, sulfated oligosaccharides, sulfated glucose, sulfated galactose, Selected by the group consisting of sulfated xylose, sulfated 2-deoxy-glucose, sulfated talose, sulfated mannose, sulfated sugar alcohol, and their salts. 14. The feed according to item 13 of the application, wherein the algae-derived sulfated polysaccharide is algal. 15. The feed according to item 13 of the application, wherein the sulfated oligosaccharide is composed of sulfated maltose, sulfated lactose, sulfated sucrose, sulfated trehalose, sulfated lactulose, sulfated melibiose, sulfuric acid Cellulose diose, sulfated isomaltose, sulfated melibiose, sulfated palatinose, sulfated maltotriose, sulfated maltohexose, sulfated maltoheptose, sulfated lauryl malt Hexose, sulfated oligosaccharides selected from the group consisting of compounds represented by the following formula (I) and compounds represented by the following formula (II): 63836-931126.DOC This paper size applies Chinese national standards ( CNS) A4 size (210 X 297 mm) 9 9 8 2 2 8 8 8 8 AB c D 々, patent application scope R Η (where R is OH or 0S03H) (Wherein R is OH or OS03H). 16. The feed according to item 13 of the patent application scope, further comprising a substance selected from the group consisting of interleukins, prostaglandin E 1, prostaglandin E 2 and compounds of the following formulae (BI) to (V) ： 63836-931126.DOC _1〇 This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm) 9 9 8 2 2 A BCD patent application scope (III) Η 2 N—C H—C Η 2—C Η 2—C—N Η—C Η—C—N Η—C Η2—C Ο Ο Η iOOH OH CH, (IV) s -c-c2h5 (V) 17. —A kind of liver cell proliferation factor, insulin-like proliferation factor and / or nerve growth factor for defamatory cosmetics, which contains sulfated polysaccharide derived from algae, derived from mountain wormwood Sulfated polysaccharides, bitter melon-derived sulfated polysaccharides, aloe-derived sulfated polysaccharides, sea cucumber-derived alginans, dextran sodium sulfate, chondroitin sulfate B, chondroitin sulfate D, sulfated starch, sulfated cardelin (Curd 1 a η), sulfated pectin, alginate hypersulfate, alginic acid, pectin, hyaluronic acid, DNA, pectinic acid, agar pectin, their enzymes or acid decomposition Material, sulfuric acid 63836-93II26.DOC -11- This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) A8 ! 228991 Sulfurized oligosaccharides, sulfated grape vinegar, sulfated galactose, sulfated xylose, sulfated 2-deoxy · glucose, sulfated talose, sulfated mannose, gallate sugar alcohol or their salts The selected group. 18. The cosmetic according to claim 17 in which the lysine-derived thiolated polysaccharide is algalan. 19. The granulated material according to item 17 of the application, wherein the acid oligosaccharide is composed of sulfated maltose, sulfated lactose, sulfated sucrose, sulfated trehalose, sulfated lactose homosaccharide, and 4 acidified melibiose , Sulfated cellobiose, sulfated isomaltose, sulfated melibiose, sulfated palatinose, sulfated maltobiose, sulfated maltohexose, sulfated maltoheptose, sulfated lauryl sulfate Malted hexose, a sulfated oligosaccharide selected from the group consisting of a compound represented by the following formula ⑴ and a compound represented by the following formula (II): (Where R is 0H or 0S03H) (I) 63836-931126.DOC-1 2- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 20. Rushen Ge (III) -C H—C—NH—C -C 〇〇 H 13- (Equation φ τ ′ R is OH or 0S03H). The cosmetic of the 17th patent scope of the τ meal, which further contains a group consisting of Jibaiyin, body, cheeks, prostaglandin E 1, prostaglandin E 2 and compounds of the following formulas (m) to (V) Selected substances: 〇-OH -OH CH—CH2—CH2—〇 Ι II COOH 〇 (iy) 63836-931126.DOC This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 1228991 、 Applicable patent scope (V) -〇-c-c2h £ -〇-c-c9h (21 · If the cosmetic material in the scope of patent application No.17, it is a lotion, lotion bath, cream, mask , Bath preparation, face wash, bath soap or cleanser. Glucoside 22 · —a liver cell proliferation factor, insulin-like proliferation factor and / or nerve growth factor production regulator, which is characterized by containing sulfuric acid derived from algae Polysaccharides, Susan-derived sulfated polysaccharides, Momordica charantia-derived sulfated polysaccharides, Aloe-derived sulfated polysaccharides, sea cucumber-derived alginans, sodium glycan sulfate, chondroitin sulfate B, chondroitin sulfate D, sulfated One powder, sulfated cardan blue (curd 丨 an), sulfated pectin, alginate highly sulfated, alginic acid, pectin, hyaluronic acid, DNA, pectin, agar pectin, Their enzymes or acid degradation products, sulfated oligosaccharides, sulfated glucose, sulfated galactose, sulfated xylose, sulfated 2 · deoxy-glucose, sulfated talose, sulfated mannose, sulfated Sugar alcohol and The selected one in the group formed by the salt of the same type. 23. If the hepatocyte proliferation factor, insulin-like proliferation factor, and / or nerve growth factor production regulator of the patent application scope item 22, the sulfate derived Polysaccharide is phytosan. 24. For example, hepatocyte proliferation factor and insulin-like increase in item 22 of the patent application scope 63836-931126.DOC -14- ^ 991 991 A8 B8 C8 D8 patent application scope Gene and / or nerve growth factor production A regulator, wherein the acid oligosaccharide is composed of sulfated maltose, sulfated lactose, sulfated saccharose, sulfated sea, fucose 'sulfated lactulose, sulfated melibiose, sulfated cellobiose, and sulfuric acid: Isomaltose, sulfated melibiose, sulfated palatinose, disproportionated maltotriose, sulfated maltohexose, sulfated maltose, sulfated lauryl maltohexose, the following and the following formula ( II) The compounds represented by () are not deficient in the sulfated oligosaccharides: (Where R is 0H or 0S03H) (I) 63836-931126.DOC -15- This paper size is applicable to China National Standard (CNS) A4 specification (210X 297 mm) 8 8 8 8 ABCD 1228991 (Wherein R is OH or OS03H). 25. For example, the hepatocyte proliferation factor, the sequelae factor and / or the nerve growth factor production regulator of the scope of the patent application No. 17, wherein the -... Selected substances in the group consisting of compounds of 1:12 and (IΠ) to (V): containing formula. I) Η, Ν—CH—CHS—CH2—C—NH—CH—C—NH—CH2—COOH. II COOH 〇 (iy) 63836-93ll26.DOC -16- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 8 8 8 8 A B c D 1228991 6. Scope of patent application C 2 cI o = c H 2 cI cyo 63836-931126.DOC This paper size applies to China National Standard (CNS) A4 (210X297 mm)