TWI240629B - Hematopoietic arabinogalactan composition - Google Patents

Abstract

Purified arabinogalactan compositions isolated from the roots of Astragalus membranaceus, and arabinogalactan protein compositions having a weight average molecular weight of at least 100 kiloDaltons isolated from these purified arabinogalactan compositions, are capable of reconstitution into aqueous intravenously injectable formulations; and are useful for stimulating hematopoiesis, inducing the proliferation or maturation of megakaryocytes, stimulating the production of IL-1beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF, or G-CSF, stimulating the production or action of neutrophils, treating neutropenia, anemia, or thrombocytopenia, accelerating recovery from exposure (e.g. accidental or non-therapeutic exposure, as well as therapeutic exposure) to cytotoxic agents or radiation, treating cachexia, emesis, or drug withdrawal symptoms, or modifying biological responses or protecting hepatic cells in hepatitis B, in a mammal when intravenously administered to the mammal.

Description

1240629 A7 B7 V. Description of the Invention (/) Fapon Field · The present invention relates to an arabinose galactan. In particular, the present invention relates to an arabinose galactan isolated from the roots of P. chinensis and an arabinose galactan having an average molecular weight of at least 100 KD and isolated from these arabinose galactan compositions or intermediates thereof. Sugar galactan protein composition. BACKGROUND OF THE INVENTION Radix Astragali is the root of dwraga / ⑽ membra and cews Bge. Var. Mongholicus (Bge) Hsiao or A. membranaceus (Fisch) Bge · (Fabaceae) after drying. Yellow buttercup is a well-known ancient Chinese herb. It is officially recorded in the Chinese Pharmacopoeia and is mainly used as a strong agent for the treatment of nephritis and diabetes. Usually used as a decoction or as "tea" alone, or in the traditional herbal shi-ka-ron (composed of Lithospermum erythrorhizon and Ligusticum wallachii) Ren-shen-yang-rong-tang (which consists of twelve herbs including Radix Astragali) is used in combination with other plants. [See by W. "Chinese Drugs of Plant Origin" edited by Tang and G · Eisenbrand, Section 26, page 19M97, titled "Astragalus membranaceus (Fisch) Bge. '', Springer Verlag, Berlin, 1992] ° Astragalus decoction, and a solution prepared from the alcoholic precipitate of the decoction, are injected. It is known to improve the symptoms of gastric and duodenal ulcers and increase the white blood cell index of patients with chronic hypoleukocytosis. ——！ ----- Potential (please read the precautions on the back before filling this page) --Order ------ • Line reference · Printed by the staff of the Intellectual Property Bureau of the Ministry of Economic Affairs Consumer Cooperatives This paper is applicable to the paper China National Standard (CNS) A4 specification (210 X 297 mm) '' Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 1240629 A7 ___B7 V. Description of the invention (>) Read by Η.-Μ. Chang and Ρ_ Ρ ·- But · But et al. "Pharmacology and Applications of Chinese material Medica", 'p. 1041-1046, title "Huang Qi", World Scientific Publishing Co., Singapo re, 1987]. It is known that Huangmin decoction, purified low-molecular weight part (ie, the part with molecular weight between 25,000-35,000), and decoction containing astragalus medicinal mixture can also restore the immunity of the local immune response system due to foreign limb transplant Reactivity (D._T.chu et al., "Immunotherapy with Chinese medicinal herbs. I ...", J. Clin. Lab. Immunol., 25, 1 19-123 (1988)), and reverse the cause loop Immunosuppressive response induced by phosphatidamine (D.-T. Chu et al., "Immunotherapy with Chinese medicinal herbs II ..", J. Clin. Lab. Immunol., 25, 125-129 (1988) ) To promote cytotoxicity caused by rIL-2 in LAK cells (D.-T. Chu et al., "Fractionated extract of dWraga / w membranaceus' \ J. Clin. Lab. Immunol., 25, 183-187 (1988)), Promoting the immune response in immunosuppressive mice [KS Zhao et al., `` Enhancement of the immune response in mice by Astragalus membranaceus extracts '', Immunopharmacology, 20, 225-234 (1990)], Stimulation list Nuclear cell response [Y. sun et al ·, "preliminary observation on the effects of the Chinese medicinal herbs ... J. Biol. Response Modifiers, 2, 227-237 (1983)], and stimulate the bone marrow hematopoietic ability of mice [M. Rou et al., "The effect of Radix astragali on mouse marrow hemopoiesis" , J. Trad. Chin. Med ·, 3 (3), 199-204 (1983); S.-I. Miura et al ·, "Effect of a traditional Chinese herbal medicine… Int. J. This paper standard applies to China National Standard (CNS) A4 Specification (210 X 297 mm). ----- (Please read the precautions on the back before filling out this page) Order ----- 1240629 A7 B7 Employees ’Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs Printed 5. Description of Invention (;)

Immunopharmacol ·, 7 (11), 771-780 (1989); and Y. Ohnishi et al ·, "Effects of Juzen-taiho-toh (TJ-48) ···", Exp. Hematol ·, 18, 18- 22 (1990)].

U.S. Patent No. 4,843,067 to Liu discloses a pharmaceutical composition 'which is composed of a polysaccharide containing xanthophyll (which can be obtained by extracting from or dWraga) and angelica polysaccharide. The astragalus polysaccharide can be obtained by extracting water from astragalus root powder or precipitating with alcohol. Verbiscar U.S. Patent No. 5,2868,467 discloses an immunomodulating polysaccharide from the iragMani / zaWragac plant of tragacanth, which is prepared at low temperature to "maintain the integrity of the polysaccharide structure, No chemical or configuration changes. " U.S. Patent No. 5,336,506 to Josephson et al. Discloses a complex formed by botanical polysaccharides such as arabinose galactan (isolated from larch (lar / x and mannan), etc. Agents that deliver agents to cellular receptors that are capable of carrying out the cell-killing action. U.S. Patent No. 5,1,969, Adams et al. Discloses a particularly fine arabinose galactose suitable for use in density gradient separation processes. Glycan products. June et al. US Patent No. 5,478,576 discloses a purified arabinose galactan (also from Lar / x, its lysate, and its modifications, etc.), which can also be used to deliver pharmaceuticals to Target cell receptor capable of carrying out cell cyst effect. Lewis et al. US Patent No. 5,589,591 discloses an endotoxin-free polysaccharide, such as arabinogalactan, dextrin, mannan, and acacia ; It is made from an impure polysaccharide by ultrafiltration. 6 The paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) " --------- ^ --- - ----- (Please read the notes on the back before filling this page) 1240629 A7 B7 V. Description of the invention (Φ) Prepared by first passing a film that can remove the low molecular weight part, leaving the filtrate, and then passing Another thin film that removes higher molecular weight fractions still leaves a filtrate fraction. However, these references above all focus on the polysaccharide fraction (ie, arabinogalactan) in the product, and may use arabinose that can be excluded Technology of galactoprotein. Arabinogalactan protein printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs is also found in flowering plants and widely in higher plants. Arabinogalactan proteins (AGPs ) 'Sometimes also known as arabinogalactan peptides, are glycoproteins that contain a high proportion of carbohydrates and low amounts of protein (usually less than 10%), although AGPs containing high amounts of protein are also known. Among the hydroxyproline-rich glycoproteins isolated from plants, AGPs are characterized by a low protein content and their ability to interact with β-glucosyl Yarif reagents, namely 1,3,5- -(4-β-glucosylfuranoxyphenylazo) -2,4,6-trihydroxybenzene, binding ability [JH yariv et al., Biochem. J ·, 85, 383-388 (1962); RL Anderson et al ·, Aust · J · plant physiol ·, 4,143-158 (1977)]. AGPs are part of gum arabic (ie, a gum exudate of gum arabica senega /) and are often used as Used as emulsifier, prevent crystallizer, and flavor from being added to food. From Nicotiana alata, Nicotiana

And comm's method of isolating the AGP gene from mi and other plants is disclosed in US Patent No. 5,646, 〇29 filed by Chen et al. For a detailed discussion of AGP, please refer to "Proteglycans and related compounds in plant cells" by E.A. Nothnagel, Int. Rev. cytology, 174, 195-291 (1997). 7 This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 a7 B7 V. Description of the invention () These documents mentioned above are based on References are incorporated into the present invention. Summary of the Invention A first aspect of the present invention provides a purified arabinose galactan composition isolated from Huang Min's root. A second aspect of the present invention provides an arabinose galactan protein composition having a mean molecular weight of at least 100 KD and a purified arabinose galactan composition isolated from the first aspect of the present invention. In. A third aspect of the present invention provides an arabinose galactan formulation for intravenous injection, which comprises a pharmaceutically effective amount of the purified arabinose galactan composition of the first aspect of the present invention, or The arabinogalactan protein composition of the second aspect of the present invention, and an adjuvant solution for intravenous injection. A third aspect of the present invention provides a treatment by administering the purified arabinose galactan composition of the first aspect of the present invention, or the arabinose galactan protein composition of the second aspect of the present invention for treatment. Methods for mammalian diseases (such as stimulating hematopoiesis, triggering proliferation of mature megakaryocytes, stimulating IL-ip, [L-6, TNF-α, IFN-γ, GM-CSF, or G-CSF production, stimulating neutrophil The formation or effect of white blood cells, the treatment of too few neutrophils, anemia, or too few platelets, accelerates the exposure (such as accidental or non-therapeutic exposure, and exposure under pharmaceutical treatment) to cytotoxic substance treatment or radiation Recovery after irradiation, treatment of cachexia, vomiting, or drug withdrawal symptoms, or to improve the biological response or protect the liver of patients with hepatitis B. 8 This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm Γ " ---- U ------------- (Please read the notes on the back before filling out this page) 1240629 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs fc) dirty cells) The method includes injecting a pharmaceutically effective amount of the purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention into the mammal being treated. In particular, a third aspect of the present invention is an arabinose galactan formulation that can be injected intravenously; or combined with at least one other agent (such as a agent that can stimulate hematopoietic). A fifth aspect of the present invention provides a Method for preparing the purified arabinose galactan composition of the first aspect of the present invention and the arabinose galactan protein composition of the second aspect of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a human cancer patient After receiving chemotherapy, if there is no further treatment, and the arabinose galactan composition purified according to the present invention, or when treated with G-CSF, the average leukocyte count after treatment varies with the number of days. Figure 2 shows human cancer After the patient receives chemotherapy, if there is no further treatment, and the arabinose galactan composition purified according to the present invention, or when treated with G-CSF, the total symptoms after treatment will not change. Fig. 3 does not show the number on the Karnofsky performance index. Detailed description of the invention Definition "Arabinose galactan protein" or "AGP" can usually be β-glucose Precipitated by Yariv reagent and a highly saccharified protein, the carbohydrates account for at least 50% of the molecular weight, and the main carbohydrate composition is arabinose and galactose, and the arabinose residue is mostly located 9 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ---- U ---- ^ --------- (Please read the precautions on the back before filling in this Page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 A7 B7 V. The invention description (β) end. It can specifically react with AGPs monoclonal antibody MAC207. "Arabinose galactan protein composition" means a composition comprising at least 70%, in particular at least 80%, and more particularly at least 90% by weight of the composition of arabinose galactan as described above Protein, and related arabinose galactans and other polysaccharides. The "purified arabinose galactan composition" is a composition comprising arabinose galactan protein (as described above) and related arabinose galactan and other polysaccharides. "Mammal" includes human and non-human mammals, such as pets (cats, dogs, etc.) and domestic animals (cows, horses, sheep, goats, pigs, etc.). "Disease" includes any unhealthy condition of an animal, including unhealthy conditions caused by medical treatment (eg, side effects), such as a disease state, and its blood-reinforcing effect is curative, especially including the "pharmacological and Disease states described in the "Usage" section. "Pharmaceutically acceptable adjuvant" means an adjuvant that is useful for the preparation of a pharmaceutical composition, is generally safe, non-toxic, and preferred, and includes adjuvants that can be used in veterinary medicine and human medicine. Such adjuvants can be in the form of a solid, liquid, semi-solid, or aerosol composition, and a gaseous form. "Pharmaceutically acceptable amount" means a drug amount which, when administered to the body of an animal to treat a disease, is sufficient to effectively treat the disease. "Treatment" of a disease includes preventing the infection of an animal that has no signs of disease (preventive treatment), suppressing the disease (slowing or inhibiting the development of the disease), providing relief from the symptoms or side effects of the disease (including mitigation therapy), and 10 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ---------- ^ --------- ^^^ 1 (Please read the back first Please pay attention to this page and fill in this page again) 1240629 B7 Printed by the Consumers ’Cooperative of the Ministry of Intellectual Property Bureau of the Ministry of Education 5. Description of the invention (Solving the disease (deteriorating the disease). The glycogalactan composition is defined as described above, which is isolated from Huang Qi (jWMga / like root, and preferably isolated from the root of Astragalus membranaceus Bge. Var. Mongholicus Hsiao or (Fisch) Bge .; and more Fortunately, the roots of astragalus (children's plant, especially the former) growing in Inner Mongolia or Shanxi Province of China; and the roots of the plant are preferably biennial yellow buttercups. It has a typical sugar composition (the methanol of the composition Extracts The trimethylsilyl derivative was judged in the GLC analysis), which contained about 5-15% (molar percentage), especially 10% (molar percentage) of arabinose (Ara); 1.5 ° /. Ear percentage), especially Rha below 1% (mole percentage); GalA up to about 4% (mole percentage); Gal between about 3% and 7% (mole percentage); and about 70% to Glc between 90% (percent of mole); where the ratio of Ara: Gal is not less than 1.5: 1; especially not less than 1.75: 1; and especially not less than 3: 1; its ash content is not more than 2 % (Weight percentage); heavy metal content is not higher than 10ppm; and hydroxyproline content is not higher than 0.1%, especially not higher than 0.05%. It contains almost no endotoxin (ie, according to the manufacturer's manual After the endospecy test [Seikagaku corporation, Tokyo, Japan]), its content is less than 1.0 EU / mg, especially less than 0.8 EU / mg, more specifically less than 0.5 EU / mg, Preferably less than 0.3 EU / mg); soluble in water up to at least 20 mg / ml, and the pH of the aqueous solution is between about 4.5 to 6.5; and the average molecular weight is between 20 and 60 kD, especially It is between 25 and 40 ---- K ---- ^ --------- (Please read the precautions on the back before filling out this page) 1240629 a7 B7 V. Description of the invention () kD, and preferably between 27 and 35 kD. For convenience, "PAGC" is used to represent this substance. Preparation of purified arabinose galactan composition The purified arabinose galactan composition is co-extracted (co- with or without alkali metal salts, especially potassium dihydrogen phosphate or sodium dihydrogen phosphate). extract) # Under the conditions, hot water (temperature is generally not lower than 80 ° C, especially not lower than 90 °; especially about 100 ° C), at this temperature, yellow buttercup (△ ga / such as sun Dry roots (generally, the dried roots are washed with ultra-filtered water under aseptic conditions, and then rinsed with a sterile solution such as 70% alcohol, then the roots are cut into thin slices and air-dried under aseptic conditions, hereinafter referred to as "" "Drink chips") for a period of time, and repeat the extraction steps as many times as necessary, so that the arabinogalactan protein and related polysaccharides that the root desires can be dissolved as much as possible (generally at about 100 ° C, extracted three times, 3 hours each time). All steps performed after the preparation of root fragments are performed in a sterile environment using sterile equipment and reagents. The hot water extract is concentrated (concentrated under vacuum at 60-70 ° C to about 1 liter / Kilograms of dried roots), then low-carbon Alcohol (such as alcohol, the final concentration of 70% at room temperature) precipitation. The lower carbon number alcohols are used to wash these low carbon number alcohol precipitates (usually three times with 95% alcohol) , And suspended in water at an appropriate concentration for further processing (generally 18-20% weight / volume). After that, the water-insoluble substances in the suspension are removed, for example, by low-carbon alkanol (about 35% ethanol) After the precipitation is removed, the lower alkanol precipitate (for example, 35% alcohol precipitate) is used for further precipitation with a high concentration of low-carbon alkanol, such as 80% alcohol, especially 60-70 % Of alcohol, will contain arabinose galacto 12 This paper size applies to Chinese National Standard (CNS) A4 specifications (210 X 297 mm) --------- ^ --------- Γ Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 A7 B7 V. Description of the invention (/ 0) 'Λ glycan protein and related polysaccharides arabinose galactan composition The crude product precipitated out. The precipitate was dissolved in water again and dried (spray-dried 'to avoid excessive heating) to isolate the crude product of the arabinose galactan composition. The crude product of this composition is generally a light yellow powder 'soluble in water' at a concentration of at least 100 mg / ml, especially at least 200 mg / ml, the dry weight lost by drying is less than about 15%, and the endotoxin content Below 0.5 ', especially below 0.3 EU / mg. The crude product of the arabinogalactan composition was further purified by ion exchange chromatography. Dissolve it in water, or adjust the solution after the precipitate is dissolved to an appropriate concentration (usually about 2%), and then perform ultrafiltration to remove the low molecular weight part to reduce the solution volume (for example, to exclude the molecular weight at 5 kD The following ultrafiltration system (5K MWCO UF system) is used for filtration). After ultrafiltration, the supernatant liquid is passed through a cation exchange column (for example, SP Sepharose cation exchange column, equilibrated with 20 mM NaOAc buffer, pH 5.20), and the distillate is packed into the anion exchange tube. In a column (for example, a Q Sepharose anion exchange column, equilibrated with the same NaOAc buffer). The liquid flowing out from the anion exchange column can be directly used to prepare the arabinogalactan protein composition of the second aspect of the present invention, and can be concentrated and dried to form a suitable arabinogalactan protein composition. The intermediate product is used directly to prepare a purified arabinose galactan composition. When preparing the purified arabinose galactan composition, a microfiltration membrane (for example, a filter membrane of 0.ΐμπι) capable of filtering bacteria can be used for ultrafiltration to remove salts and reduce the solution volume (for example, 8K MWCO UF system). Concentrate the ultrafiltration solution after ultrafiltration (50-60 ° C, 20-26%) 13 In the standard paper of this paper, 闘 家 鲜 (CNS) A4 娜 (21 () x 297 公 爱) '----- ---- ^ --------- '(Please read the notes on the back before filling out this page) Printed clothing 1240629 A? _ B7 by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs丨), followed by precipitation with a low-carbon alkanol (about 80-90% ethanol). Further washing the precipitate (for example, three times with absolute alcohol) and drying (60-70 ° C vacuum oven) to obtain a purified arabinose galactan composition. Arabinose galactan protein composition The definition of arabinose galactan protein composition of the present invention is the arabinose galactan protein composition isolated from the root of a membra-like membra as described above; and Var. Mongholicus (Bge) Hsiao ^ A. (Fisch) Bge. Is preferably isolated from the root of membranaceus Bge. Var. Mongholicus (Bge) Hsiao ^ A. (Fisch) Bge .; The former; and the root of the plant is preferably from biennial astragalus. It has a sugar composition that is typically about 45 ° to 75% (mole percent), especially about 50% to 70% (mole percent) Arabinose (Ara); Rha between 2% and 4% (percent of moles); GalA between about 4% and 6% (percent of moles); between about 8% and 25% (percent of moles); In particular, Gal between 10% and 20%; and Glc between approximately 5% and 25% (molar percentage); wherein the ratio of Ara: Gal is not less than 2: 1; especially not less than 3: 1; And especially not less than 4 ·· 1; its ash content is not higher than 2% (weight percent); heavy metal content is not higher than 10 ppm; and hydroxyproline content is not higher than 0.2%, especially not less than 0.3%. It contains almost no endotoxin (as defined above); it can be dissolved in water at a concentration of at least 20 mg / ml, and the pH of the aqueous solution is between about 4.5 to 6.5 ; And the average molecular weight is not less than 100 kD, especially between 150 and 350 kD. It contains about 95% carbohydrates (including carbohydrates that can saccharify arabinose galactan protein core) , And about 14 paper sizes are applicable to Chinese National Standard (CNS) A4 specification mo X 297 mm) --------- ^ -------- (Please read the notes on the back before filling This page) 1240629 A7-B7 V. Description of the invention (1205% protein. Hydroxyproline, which accounts for about 20% of its total amino acids, is a characteristic feature of arabinogalactan protein. For convenience, the following are all "AGPC" is used to represent this substance. Preparation of arabinogalactan protein composition The arabinogalactan protein composition of the present invention is composed of the aforementioned arabinogalactan by a 100 K MWCO ultrafiltration system Or the distillate obtained from the purification step of the ion exchange column (or the distillate The solid intermediate after shrinking and drying) was further purified. The distillate obtained from the anion exchange column in the above "Preparation of arabinogalactan protein composition" was directly added to a 100 K MWCO ultrafiltration system The filtrate remaining in this 100 K MWCO ultrafiltration system is further concentrated and precipitated with a low carbon number alkanol, or further washed and dried, which are similar to the preparation of purified arabinose galactan composition. The arabinose galactan protein composition was obtained. Pharmacology and use

The advantageous activity of the purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention has been confirmed in several tests, and it is known that It has the following uses. Treatment of neutropenia in chemotherapy patients 1. To produce cytokine immunity and hematopoietic systems from activated human peripheral blood mononuclear cells (PBMCs) requires the interaction of several cytokines to be activated, which is tested in Example 3. The ability of PAGC to induce cytokine production in vitro was demonstrated. PAGC can activate human PBMC after PHA activation, and release IL-Ιβ, IL-6, TNF-α, IFN-γ, GM-CSF obviously and dose-dependently. 15 This paper size applies to Chinese National Standard (CNS) A4 specifications. (210 X 297 mm) (Please read the notes on the back before filling out this page) tr --------- Printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 A7 ------------- B7 V. Description of the Invention (, ')) and G-CSF. It is known that three cytokines, IL-6, GM-CSF, and G-CSF, can affect the production and / or activation of neutrophils in vitro and in vivo. It is known that IL-6 itself or together with other cytokines can stimulate megakaryocyte maturation in the bone marrow and restore the number of platelets in the peripheral blood of mice and non-human primates. These data show that PAGC can stimulate patients with bone marrow suppression to make neutrophils and restore their platelet count by making cytokines related to hematopoietic function. 2. Recovery of GM-CFC progenitor cells in mice treated with fluorinated uracil. Example 5 is a test model of PAGC's short-term, mouse, and in vitro hematopoietic cells. Fluorinated uracil is widely used to remove progenitor cells in mouse bone marrow and colony forming units in culture (CFU-C) in cell culture. Since unactivated stem cells are not affected by fluorinated uracil, the treated mice will recover along a known and predictable time curve [AM Yeager et al., UThe effects of 5 -fluorouracil on hematopoiesis: studies of murine megakaryocyte-CFC, granulocyte-macrophage-CFC, and peripheral blood cell levels '', Exp. Hematol., 11, 944-952 (1983)]. From the table in Example 5, it can be seen that the amount of GM-CFC in each mouse also increased with the increase of the dose of PAGC on the fourth day after the uracil fluoride treatment. When the dose of PAGC administered was 200 mg / kg, the average increase in GM-CFC per mouse was 3.3 times that of the control group (ρ <0.01); if it was treated with 100 mg / kg PAGC, each The average increase of GM-CFC per mouse is 16 paper sizes of the control group of rats, which is applicable to China National Standard (CNS) A4 (210 X 297 mm) --------- Order ------ ---. (Please read the notes on the back before filling out this page) 1240629 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (outside) 1.8 times (p <0.01); if it is 50 mg / For the treatment of kg of PAGC, the average increase of GM-CFC per mouse is not far from that of the control group. These data show that PAGC can promote the recovery of bone marrow generation cells (GM-CFC) in bone marrow-suppressed mice induced by fluorinated uracil. PAGC can increase the number of peripheral white blood cells in bone marrow-suppressed mice. 3. Resume the number of peripheral white blood cells in the mice that received sublethal doses of radiation 値 irradiate BALB / c mice with sublethal doses of radiation and then inject subcutaneous saline or various doses according to the procedure of Example 6 PAGC into mice. Compared with normal rats, the number of WBCs in the rats exposed to radiation decreased to 12% of that in the normal rats on the day after radiation exposure. Compared to mice injected with saline alone, treatment with PAGC increased the total number of WBCs in the mice. In mice treated with 100 or 300 mg / kg PAGC, the total number of WBCs in the body was 7-9 days earlier than that of rats injected with normal saline alone, and returned to 80% of normal rats (normal: 6000-10000 WBC). / mm3 blood). In the old rats treated with PAGC, the WBC count returned to normal after about 22-23 days, while the rats injected with saline only had 46% of the normal count at this time. In addition, peripheral blood smears can be used to learn about different WBCs. From this information, the absolute 値 of neutrophils and lymphocytes can be calculated. Compared with mice injected with saline alone, PAGC treatment increased the absolute number of neutrophils. It can also increase the absolute number of lymphocytes. 4 · Number of white blood cells in patients receiving chemotherapy 値 17 This paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 males) ----. (Please read the precautions on the back before filling this page)- --Order ---- 1240629 A7 ___ B7 V. Description of Invention (X,) All Phase II clinical trials were completed in the People's Republic of China. The trial analyzed the data of a small group of patients whose WBC number was less than 3 X 109 WBC / L when participating in the experiment: 168 patients were treated with pAGC, 59 patients were treated with G-CSF, and another 23 The patient was not receiving any treatment. The treatment process is detailed in Example 9. As shown in Fig. 1, 'PAGC can stably increase the number of WBCs in patients after receiving chemotherapy', and this increase can continue to the 14th day. Although the administration of G-CSF 'can increase the WBC faster, it cannot be sustained, and the WBC number in the patient's body will begin to decrease after the 7th day. Compared with the control group who did not receive any treatment, both groups of treatment groups returned WBC count to normal. Compared with the control group that did not receive any treatment, the number of WBCs in the PAGC treatment group could reach a significant difference on the 10th and 14th days; but on the 14th day, the PAGC group and the G-CSF group had two groups.値 There is no significant difference. The above results show that the use of PAGC as an adjuvant for lung cancer, gastrointestinal cancer and breast cancer patients receiving chemotherapy is not only safe but also tolerable by patients. PAGC treatment can restore the number of WBCs in chemotherapy patients. In addition, no serious side effects were found in the clinical treatment with PAGC. Treatment of Chemotherapy Patients with Low Platelet Cells 1. Resume the number of peripheral platelet cells in rats that received sublethal doses of radiation. On day 0, irradiate BALB / c mice with sublethal doses of radiation, and then follow the examples Step 6 is treated with physiological saline or various doses of PAGC. Compared with normal mice, the number of WBCs of rats exposed to radiation will decrease to exactly 18 days after radiation exposure. The paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) ( Please read the notes on the back before filling out this page) II --------- Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 A7 B7 4) 7% of Chang rats. Mice treated with subcutaneous injection of 100 or 300 mg / kg PAGC can significantly increase the number of peripheral platelet cells in the old body. Compared with mice that received saline injection only, PAGC could induce platelet cell numbers to return to 80% of normal mice 5-6 days earlier than the control group (normal: 8-12 X 106 platelets / mm3 blood). ). ^ PAGC-treated mice returned to normal about 24-25 days after radiation exposure, while rats injected with saline only returned 72% of normal numbers. These results show that PAGC is a potent agent that promotes platelet development and is therefore quite useful for treating too few platelets. In the same way, rats treated with 100 and 250 mg / kg of AGPC during a 20-day course of treatment improved their red blood cells and platelet numbers compared to the control group when tested at all time points. ; Shows that PAGC has the same effect in this model system. 2. Proliferation of bone marrow megakaryocytes and mature PAGC. It can accelerate the recovery of bone marrow suppression in the animal model of bone marrow suppression induced by radiation irradiation, as described in the previous paragraph; this shows that PAGC can stimulate the proliferation of bone marrow megakaryocytes and / Or mature. This possibility was investigated using the in vitro liquid culture system (Liqid Culture System) described in Example 4. From the dose titration curve, we know that the optimal PAGC dose in this model is 100-200 micromg / ml, and the ED50 is 30-40 micromg / ml. This study shows that PAGC alone can promote the proliferation and / or maturation of bone marrow megakaryocytes in vitro. In addition, PAGC also works synergistically with a suboptimal dose of IL-3 (50 pg / ml) to increase acetylcholinesterase (AchE) content in a dose-dependent manner. Made by 200 micrograms / milligrams 19 This paper size is applicable to China National Standard (CNS) A4 specifications (210 X 297 public love) --------- ^ --------- (Please read first Note on the back, please fill out this page again) 1240629 A / B7 V. Description of the invention () The AchE content obtained in the cell culture treated with 1 liter of PAGC and 50 pg / ml of IL-3 is equivalent to the optimal dose AchE content in IL-3 treated cultures. Appropriate data shows that PAGC can improve the response of bone marrow megakaryocytes to lower doses of 1L_3, or that IL_3 can increase the response of bone marrow megakaryocytes to PAGC. Because chemotherapy or radiation can damage cells and tissues, including cells that can produce cytokines, patients who receive this treatment will have lower levels of endogenous cytokines. Such a low cytokine content will not be able to support the normal function of the hematopoietic system 'and therefore cannot produce a sufficient number of hematopoietic cells to restore the suppressed bone marrow function. Therefore, PAGC is the best substance to repair this situation. The results of this study show that PAGC can promote the proliferation and / or maturation of bone marrow megakaryocytes in the absence of endogenous cytokines. As shown above, PAGC can stimulate the number of peripheral blood platelets to return to normal, and this effect seems to be achieved by inducing the proliferation and / or maturation of bone marrow megakaryocytes. This data suggests that PAGC may be useful in treating hypoplasia due to bone marrow suppression. 3. Increasing the number of platelet cells after chemotherapy. The second phase clinical trial is as described in Example 9. The data of a small group of patients participating in the experiment when their WBC number was less than 4 X 109 WBC / L and platelet number was less than 90 X 10 / L were analyzed in the trial: 54 patients received PAGC treatment . The platelet count of these patients increased to more than 100 × 109 / L on day 7, and continued to increase to day 14, as shown in Table 9. These data show that PAGC can increase platelet counts in these chemotherapy patients. Improving the quality of life of cancer patients 20 scales applicable to China National Standard (cnS) A4 specifications (210 X 297 mm) " ^ (Please read the precautions on the back before filling out this page) — Order · Consumption by the Intellectual Property Bureau of the Ministry of Economic Affairs Cooperative printed by the Intellectual Property Bureau of the Ministry of Economic Affairs. Consumption printed by the cooperative of the employees. Cooperative printed 1240629 A7 __B7 V. Description of the invention (d) The first phase clinical trial is as described in Example 9. As described in Example 9, the number of improving chemotherapy symptoms and Karnofsky performance index (Karnofsky performance index) was used as the basis for evaluating the quality of life of all patients participating in the trial. Record and calculate symptoms caused by chemotherapy during treatment, including fatigue and burnout, discomfort, night sweats, shortness of breath, and lack of appetite. As shown in Figure 2, as the treatment progressed, the PagC group showed the fastest curative effect, which can be seen from the decrease in the symptom index and its faster return to normal number (number = 値) than the G-CSF group. In addition, compared with the G-CSF group, the PAGC group also showed a more significant improvement than the statistics during the period of 10 days to 14 days (P < 0.001). However, there were no significant statistical differences between the G-CSF group and the control group (without any treatment) throughout the 14-day monitoring period. These data show that PAGC improves symptoms in chemotherapy patients, and in this regard, G-CSF seems to have no effect. Analyze the symptom improvement index of a small group of patients with a Karnofsky performance index below 70 before treatment. Compared with the G-CSF group and the control group not receiving any treatment, the PAGC group can significantly improve symptoms, and the statistical differences are ρ < 0.001 and p < 0.0001, respectively, as shown in FIG. 3. Patients in most PAGC groups had higher indices than the other two groups. Preventing too few neutrophils in cancer patients undergoing chemotherapy In the previous paragraph, PAGC is known to be effective in treating neutropenia caused by chemotherapy. These data show that PAGC is equally effective in preventing and treating too few neutrophils, and clinical trials are currently expected in the People's Republic of China. Too little neutrophil cells in the treatment of cancer patients receiving radiation exposure 21 This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) " (Please read the precautions on the back before filling this page) tr 'A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 V. Description of the Invention (q) The preceding pharmacological data also show that PAGC can effectively recover the neutrophilic leukocytosis caused by radiation exposure. Clinical trials in the People's Republic of China have begun to understand PAGC in treating patients with non-Harkin's lymphoma cancer who have received neutropenia after radiation exposure. Anemia in cancer patients treated with chemotherapy. BALB / c mice were irradiated with a sub-lethal dose (4.25 Gy) of radiation, and then treated with physiological saline or various doses of PAGC according to the procedure of Example 6. Compared with normal rats, the number of RBCs in the rats exposed to radiation will drop to 55% of that in normal rats on day Π after irradiation. On the 17th day, the rats treated with PAGC could obtain a relatively high RBC count, while the rats injected with saline only still had a low count at this time. Mice treated with subcutaneous injection or 300 mg / kg PAGC can significantly increase the number of peripheral RBC cells in the old body. Compared with mice receiving saline injection only, PAGC can induce RBC to return to 80% of normal mice 4-6 days earlier than the control group (normal 値: 8 · 5-11 X 106 RBC / mm3 blood) . In rats treated with PAGC, their RBC counts returned to normal in about 20-22 days, while rats injected with physiological saline only had 65% of normal counts at this time. These results show that PAGC is a very effective agent that promotes the development and / or migration of red blood cell cells, and is therefore very useful for treating anemia caused by radiation exposure or chemotherapy. In the same manner, rats treated with AGPC at 100 and 250 mg / kg during the 20-day course of treatment "improved their red blood cell and platelet numbers when tested at all time points compared to the control group"; 22 1 This paper size applies to China National Standard (CNS) A4 (210 X 297 public love) " (Please read the precautions on the back before filling this page)

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 A / B7 V. Description of Invention (/) PAGC has the same effect in this model system. The second phase of the clinical trial in Example 9 was designed to investigate the recovery of WBC in chemotherapy patients. Therefore, the condition is to perform an analysis test based on the number of WBCs. At present, it is planned to investigate clinical trials for treating anemia with PAGC and anemia caused by chemotherapy in PRC (People's Republic of China). Moving peripheral blood cells alone or together with G-CSF to treat patients receiving peripheral blood cell transplants and including hematopoietic stem cells and cells such as BFU-E (bUrst-fomming unit -erythroid) that produce cell populations, GM-CFC (Generating granulocyte macrophage colonies), and CFU-Mix (a mixture that produces cell colonies) all contain CD4 antigen on the progeny cells. The analysis of CD34 * cells by flow cytometry provides the best way to calculate the graft composition. As early as 1975, the description of the existence of hematopoietic cells (PBPCs) in the peripheral blood system of humans has been proposed. These peripheral blood progenitor cells account for only a small fraction of the total number of cells because most of the progenitor cells are located in the bone marrow. In 1976, it was first suggested that during the recovery period after chemotherapy, the number of hematopoietic cells in the human peripheral blood system would increase. Recently, it has been reported that colony stimulating factor G-CSF and GM-CSF can directly increase the number of PBPCs. Compared with single use, the combined use of cell population stimulating factors during chemotherapy can significantly increase the number of PBPCs. G-CSF is currently used to move PBPCs in human autologous and allogeneic transplants. Compared with traditional bone marrow transplantation, transplantation of PBPC can make transplantation faster. If used in combination with chemotherapy or other cytokines, the number of PBPCs produced by G-CSF treatment can be significantly increased. Use 23 paper sizes separately. Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) '--------- ^ --------- (Please read the notes on the back first (Fill in this page again) A7 1240629 ____B7___ 5. Description of the Invention (,. 丨) The ability of PAGC or G-CSF to cooperate to induce the movement of PBPC is detailed in Example 7. As shown in the table results in Example 7, PAGC can increase the amount of GM-CFC in the cycle by about 6 times. In addition, when PAGC and G-CSF are used together, the amount of GM-CFC can be increased by about 83 times. This increase is much higher than the 39-fold increase when G-CSF is used alone. The results showed that PAGC could increase the amount of circulating GM-CFC, or synergize with G-CSF to increase the amount of circulating GM-CFC in normal mice. PAGC can also increase the amount of circulating BFU-E by about 3 times, as shown in the table, and cooperate with G-CSF to increase the amount of circulating BFU-E by about 9.5 times. This increase is much higher than the 4.5-fold increase when G-CSF is used alone. In a similar experiment in mice treated with cyclophosphamide, the number of CD34 + Lin cells increased compared to untreated mice '. Agents such as PAGC that work synergistically with G-CSF to increase the number of PBPCs are also effective. Such synergy can reduce the cost of obtaining PBPC cells from a donor. In addition, this type of combined treatment is also helpful when patients receiving transplantation do not respond well to G-CSF alone, or patients who cannot use chemical conversion. Similarly, AGPC is also effective for transplantation. Treatment of cachexia One of the most common side effects of chemotherapy and radiation exposure is the loss of appetite and weight loss. Example 8 shows that PAGC can increase the weight of mice treated with the chemotherapeutic agents cyclophosphamide and fluorinated uracil. Compared to mice treated with cyclophosphamide alone, PAGC-treated mice ' have less weight loss and can recover their original weight faster. However, these differences are not statistically significant. 24 This paper is suitable for the size of the national fresh (CNS) A4 secret (210 X 297 meals 1 '' a * U --------- (Please read the precautions on the back before filling out this page) Ministry of Economy Printed by the Consumer Property Cooperative of the Intellectual Property Bureau 1240629 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the Invention (π) As mentioned above, PAGC can obviously improve the quality of life of patients in Phase II clinical trials. The parameter is appetite. The results of this study with a mouse model show that PAGC can help improve cachexia in patients. It is a kind of physical waste and malnutrition caused by chronic diseases such as cancer or cancer treatment. And G -CSF combined treatment of cancer patients receiving bone marrow suppression therapy to promote the recovery of neutrophil cells and reduce the amount of G_CSF. The previous discussion showed that PAGC can stimulate the production of cytokines, especially G_CSF produced by human peripheral blood mononuclear cells; and Can promote the recovery of GM_CFC and surrounding WBC numbers in bone marrow suppression animal models caused by radiation exposure, and enable WB in vivo in patients with cancer in the second phase of clinical trials after chemotherapy C 値 returned to normal. These results show that PAGC can indirectly act on the hematopoietic system by manufacturing a variety of endogenous cytokines, and these cytokines can cooperate with each other to restore the number of neutrophils. At the same time, PAGC and IL can also -3 works synergistically to promote the proliferation / maturation of bone marrow megakaryocytes. In addition, PAGC administration is not only safe, but can be tolerated by patients in clinical trials. Serious side effects such as bone headache, muscle pain, headache when using G-CSF , Fatigue, nausea, vomiting, diarrhea, etc. were not found during the administration of PAGC. This synergy with the above shows that PagC can be used in combination with G-CSF to reduce the amount of exogenous G-CSF and promote the acceptance of bone marrow suppression Recovery of the number of neutrophils in the treated cancer patients. After high-dose cytotoxic treatment and autologous or allogeneic hematopoietic cell transplantation, the paper size of this paper applies Chinese National Standard (CNS) A4 (210 X 297 mm) installed --------- tr --------- (Please read the precautions on the back before filling out this page) 1240629 Employees' cooperation on intellectual property of the Ministry of Economic Affairs Print A7 B7 V. Description of the invention (4) Combination of G-CSF treatment to promote the recovery of neutrophil leukocytes At present, many high-dose chemotherapy and / or radiation exposure and supportive blood cell (BPC) transplantation are used to treat many Cancer patients, such as breast cancer, lymphoma, and multiple bone marrow cancer. Transplantation of BPC can accelerate the recovery of hematopoietic function. G-CSF is usually used after transplantation of BPC to accelerate the recovery of the number of neutrophils to prevent infection due to infection. Fever caused by too few neutrophils, shortened the length of hospital stay, and reduced the amount of antibiotics. As shown in the second phase clinical trial of Example 9, PAGC can restore the WBC number of chemotherapy cancer patients; this and the pharmacological effects summarized in the previous paragraph show that the combined use of PAGC and G-CSF can accelerate the recovery of neutropenia after transplantation of BPC The number of sexual white blood cells is very useful. Improve and modify the bioreactivity of hepatitis B carriers and protect liver cells. Cytokines play a very important role in fighting viral infections. Cytokines are produced by cells associated with the immune system, such as macrophages; CD4 + and CD8 + T lymphocytes have a more direct effect on individuals' recovery from infections such as hepatitis B virus (HBV). From animal models to human studies, it is clear that cellular immune responses may play a role in addressing HBV infection and its pathology. In acute HBV infection, a strong multi-cell immune response is required. The release characteristics of type 1 cytokines are that IL-2 and INF-γ are produced by CD4 + T lymphocytes; and IL-2 and INF-γ are used to induce and maintain cellular immunity, which is important for combating viral infections. It is quite important [c. A. Biron, "cytokines in the generation of immune response to, and regulation of, virus infection", Cur. Opin. Immunol., 6, 530-538 (1994)]. CD4 + 26 This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) --------- ^ --------- ^^^ 1 (Please read the Note: Please fill in this page again) 1240629 A7 B7 V. Description of the invention (A) and cytokines released by CD8 + cells also play a very important role in downregulation of HBV replication. If there is a defect in the acute response, it becomes a chronic HBV infection. These results suggest that enhancing type 1 responses or enhancing the production of appropriate cytokines in localized areas of the liver may be very useful in treating chronic HBV infection [M.J. Koziel, Sem. Liver Disease, 19 (2), 157-161 (1999)]. PAGC is made from traditional Chinese medicine plants (like cews Far · (AM)) and has long been used to stimulate the immune and hematopoietic system. It is widely used to treat patients with various types of anemia, whose disease is very similar to that of bone marrow suppression induced by chemotherapy or radiation (in addition to too few neutrophils, too few platelets and anemia). In addition, AM is known to stimulate rat pancreatic cell proliferation in vitro, and this cell proliferation phenomenon is positively correlated with dose; it can also increase natural killer cells in pancreatic cells of animals inoculated with S-180 sarcoma cells (Natural killer (NK) activity; and increase cytotoxic T lymphocytes (CTL) activity. Cytokines produced by CTL can control viral infections in the body, and INF-γ and INF-a produced by virus-specific CTL can increase the ability of CTL to eliminate virus infection [LG Guidotti et al., "Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice '', Proc. Natl · Acad. Sci. USA, 91, 764-3768 (1994)]. In addition, as described above, PAGC can stimulate humans after being activated with PHA. PBMC manufactures IL-1β, IL-6, TNF-α, TNF-γ, GM-CSF, and G-CSF. These results show that PAGC can indirectly affect the production of cytokines by regulating cytokine production 2Ί This paper is applicable to China Standard (CNS) A4 specification (210 X 297 mm) ----------- (Please read the precautions on the back before filling out this page)-Order ---- Φ. Intellectual Property of the Ministry of Economic Affairs Printed by the Bureau ’s Consumer Cooperatives 1240629 A7 B7 Printed by the Intellectual Property Bureau of the Ministry of Economy ’s Consumer Cooperatives 5. Printed on the invention () Immune system. Crude extracts made by AM have been used to treat patients with chronic hepatitis to reduce their internal health High IgG levels and lower ALT 値, improve Patients' immune and liver function [Y · Liu, "therapeutic effect of oral solution from Astragalus in the treatment of 70 chronic hepatitis B patients", Jiang Su Chung Yao, 15 (12), 38 (1994)]. In addition, it is known The fraction of AM has the ability to increase immune function as described above. These results show that PAGC can be used to improve and modify the bioreactivity of hepatitis B carriers and protect liver cells. E vaccine adjuvants for patients with hepatitis B were prepared The resulting polysaccharide has been used as an adjuvant for hepatitis B vaccine to treat chronic hepatitis B. It is known to convert hepatitis B e-antigen (HBeAg) to be blood-negative and eliminate hepatitis B virus DNA (HBV- DNA) has a satisfactory effect [SM · Wu et al., "The therapeutic observation on the combined Polyporus polysaccharide with hepatitis B vaccine in the treatment of chronic hepatitis J. Chin. Infectious Disease, 13 (3), 187-189 (1995); Η · Z · Shu et al ·, "The therapeutic observation on the Polyporus polysaccharide with large dose of hepatitis B vaccine in the treatment of 64 cases of chronic hepatitis B patients ", Med. J. NDFSC, 6 (4), 21 1-212 (1996)]. It is known that the extract made by AM can convert hepatitis B e antigen (HBeAg) and anti-HBc core antigen (anti HBc) to blood sac negativity, and remove hepatitis B virus DNA from patients with hepatitis B ( HBV-DNA) [CK Liu et al., "Clinical and experimental studies on effects of chronic 28 This paper is sized to the Chinese National Standard (CNS) A4 (210 x 297 mm) ^ --------- (Please read the precautions on the back before filling this page) 1240629 A7 B7 V. Description of Invention (A) Hepatitis B treated with Astragli composita ", Chung Kuo Chung His I Chieh Ho Tsa Chin, 16 (7), 394-397 ( 1996); P. L. Chen et al., "Polysaccharide from Astragalus in treating 33 cases of chronic active hepatitis B patients", New Drugs Clin. Remedies, 11 (2), 75-76 (1991)]. The results show that PAGC may be used as a vaccine adjuvant for patients with hepatitis B. The symptoms of withdrawal are generally seen when patients with narcotic withdrawal and palsy symptoms begin to withdraw from the use of narcotics. From the perspective of Traditional Chinese Medicine (TCM) In terms of The symptom of withdrawal is Qi (energy) deficiency. According to the observation of Chinese medicine practitioners, if Qi can be strengthened, the drug withdrawal process can be accelerated. One of the results of the clinical trial of PAGC in Example 9 is that it can improve cancer chemotherapy patients. Quality of life. The quality of life is assessed by assessing the improvement of chemotherapy-related symptoms; these include fatigue and exhaustion, discomfort, cold sweats, shortness of breath, and lack of appetite. These symptoms are typically "qi" deficiency A manifestation is also a typical manifestation of the symptoms of withdrawal as considered by traditional Chinese medicine. Therefore, in addition to strengthening the "qi" of patients, PAGC can also treat the symptoms of withdrawal of patients who want to quit using anesthetic drugs. Prevention and treatment of chemotherapy Nausea and vomiting are the most common side effects of chemotherapy and / or radiation exposure in cancer patients with radiation or radiation. Although the current chemotherapy or radiation technology has been greatly improved, a significant proportion of patients will experience nausea. Therefore, the industry is also continuously looking for ways to reduce the side effects of chasing. Although the market Many such chewing-resistant drugs (such as serotonin receptor antagonists, corticosteroids, and dopamine 29) This paper size applies to China National Standard (CNS) A4 (210 X 297 public love) 丨 —— 丨- ---- (Please read the precautions on the back before filling this page) Order --- Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (J ) Receptor antagonists), however, these drugs also have other side effects of their own. Symptoms associated with these drugs are mild headaches, constipation, inability to fall asleep, sleeplessness, involuntary vibrations and quiescence of muscles and tongue. Although the neuropharmacology of nausea is currently unclear, approaches related to the goal of complete control of nausea include making patients as comfortable and comfortable as possible, and providing patients with treatments that reduce hospitalization and bed time, thereby promoting patients' quality of life. Clinical trials conducted in China have shown that PAGC is beneficial to chemotherapy patients, especially to improve their quality of life. The results from these studies and the patients participating in the study support the conclusion that PAGC can improve the quality of life of patients, which shows that PAGC may play some roles in preventing and treating the nausea caused by chemotherapy. Reduce or replace the amount of erythropoietin used in dialysis patients. EPOGEN (Epoetin alfa, erythropoietin) was approved in 1989 for the treatment of chronic kidney failure associated with anemia in patients with dialysis. This medicine allows patients to live a more normal and active life. Prior to the advent of EPOGEN, 90% of dialysis patients had anemia, which often caused patients to feel tired and weak, and thus affected their ability to work. Today, most dialysis patients receive EPOGEN at the same time to increase or maintain their red blood cells. During clinical trials, severe side effects associated with EP0GEN are most commonly seen as hypertension, headache, stroke, nausea / vomiting, and muscle thrombosis; in general, physicians will advise patients to reduce the amount of EPOGEN if these side effects occur. PAGC research has shown that it can promote the recovery of the number of red blood cells around the body of rats exposed to sub-lethal doses of radiation. It is true that this paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) ----- ----- ^ --------- ^^^ 1 (Please read the notes on the back before filling in this page) 1240629 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs J) As shown in Example 6. In the same way, mice 'treated with 100 and 250 mg / kg AGPC during a 20-day course of treatment' improved their red blood cell and platelet numbers when tested at all time points compared to the control group; show PAGC has the same effect in this model system. In addition, as shown in Example 7, PAGC can also increase the amount of circulating BFU_E, and cooperate with G-CSF to increase the amount of circulating BFU_E in normal mice. In addition, the number of TER-119 + cells in the peripheral blood drawn by PAGC-treated normal mice and cyclophosphamide-treated mice increased significantly. The TER-119 antigen system appears on the surface of red blood cells from the early period of red blood cells to mature red blood cells. It shows that the increase in the number of TER_119 + cells means that PAGC can stimulate the differentiation, proliferation and maturation of red blood cell cells in the bone marrow, and promote the migration of these cells to the surrounding blood. All these results show that PAGC promotes the production and maturation of red blood cells in a mouse-based study. Because the use of PAGC in clinical trials is not only safe, and has never seen any serious side effects, PAGC may reduce or even replace EPOGEN to treat anemia in patients with dialysis. From these results, it can be seen that when an animal or human patient is deliberately exposed to radiation and cytotoxic agents, this treatment can accelerate the recovery of the animal or human patient compared to an untreated animal or human patient, and At the same time, PAGC will also accelerate the recovery of animal or human patients from injuries caused by exposure (ie, accidental or ineffective exposure) to radiation and cytotoxic agents. In accordance with the procedure of Example 6, in the same way during a 20-day course of treatment, 31 paper sizes apply the Chinese National Standard (CNS) A4 Regulations (21 × x 297 public love) ---- U ---- ^- -------- (Please read the notes on the back before filling out this page) 1240629 Printed by A7 B7, Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, V. Invention Description), 100 and 250 mg / kg of AGPC Compared with the radiation control group, the treated mice were able to improve their number of red blood cells and platelets when tested at all time points; it was shown that PAGC had the same effect in this model system. If discussed in conjunction with other PAGC data studied in this article, AGPC and PAGC are equally effective and therefore suitable for the various pharmaceutical applications of PAGC discussed. Pharmaceutical Formulation and Administration Generally speaking, the pharmaceutically effective amount of the purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention will be Intravenous injections are administered to an individual, either alone or together with at least one other agent, particularly one that stimulates hematopoiesis. A pharmaceutically effective amount will vary from other factors depending on the disease, its severity, the age and health of the individual being administered. For stimulation of hematopoiesis, including megakaryocyte proliferation or maturation, stimulation of IL-Ιβ, IL-6, TNF-α, INF-γ, GM-CSF or G-CSF, stimulation of neutrophil production or action, For the treatment of too few neutrophilic leukocytes, anemia or too few platelet cells; for humans of general body shape and body weight, the pharmaceutically effective star of the purified arabinose galactan composition of the first aspect of the present invention is between 50 to 100 mg / day, especially about 100 to 500 mg / day, especially about 250 mg / day. For the treatment of cachexia, nausea, or withdrawal symptoms, or to improve bioreactivity or protect liver cells in patients with hepatitis B, a dose similar to the above is also a pharmaceutically effective amount. Because the arabinose galactan protein composition of the present invention itself contains higher quality arabinose galactan protein, it is expected that its medicinal properties should be stronger, so its pharmacy is 32. The paper standard is applicable to the CNS A4 specifications ⑽ x 297 public love) ------- ---------- ^ --------- (Please read the precautions on the back before filling this page) 1240629 Α7 Β7 Fifth, the invention description u. ) The effective amount will be lower. For example, between 10% and 50% of the pharmaceutically effective amount of the purified arabinose galactan composition. A skilled artisan should be able to determine, without further experimentation, how much of a composition of the invention should be administered to a particular disease based on the facts disclosed in this specification and its own technology. Generally, the purified arabinose galactosaccharide composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention will be administered by intravenous injection in a pharmaceutical formulation. The formulation will include the purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention, and an adjuvant solution suitable for intravenous injection. Suitable adjuvant solutions for intravenous injection are well known to those skilled in the art. For these and methods of formulating, refer to Alfonso AR: Remington's Pharmaceutical Science, 17th ed., Mack Publishing Company, Easton, PA, 1985. Suitable adjuvant solutions for intravenous injection include water, physiological saline, aqueous glucose and the like. Generally, if administered as a hematopoietic agent, the purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention will be injected intravenously. It can be administered by way of injection, especially by continuous injection for several minutes or continuous injection for one or several hours, such as continuous injection for 15 minutes. The content of the compound of the present invention in the composition will vary depending on the type of composition, the size of the unit dose, the type of adjuvant, and other conventional factors. Generally speaking, the composition may finally contain the compound of the present invention from 0.001% to 10% by weight, preferably between 0.01% and 1%. The paper size is applicable to the Chinese National Standard (CNS) A4 specification ( 210 X 297 mm) (Please read the notes on the back before filling out this page) Binding --- Printed by the Employees 'Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1240629 Printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 (Y) The rest are adjuvants. The purified arabinose galactan composition of the first aspect of the present invention or the arabinose galactan protein composition of the second aspect of the present invention can also be selectively combined with at least one other agent capable of treating diseases Administration, especially other agents that stimulate hematopoiesis, such as heme-producing hormone, thrombopoietin, granulocyte community stimulating factor (G-CSF) and the like. Examples The invention is further illustrated by the following non-limiting examples. All purified arabinogalactan compositions and arabinogalactan protein compositions were analyzed by size exclusion chromatography. The procedure for size exclusion chromatography is as follows:

Shimadzu HPLC system, equipped with SCL-10A system controller, LC-10AD pump, DGU-4A exhaust, RID-6A refractive index detector, and SPD-10AV UV detector, and uses 0.2 N-NaCl equilibrated GS-701 and GS-620 columns (shodex Ashipak, 7.6 X 500 mm) were analyzed. The sample load was 80 μ§ (40 μΐ sample solution at a concentration of 2 mg / ml), and the sample was washed out at a rate of 1 ml / min. A calibration curve was prepared with standards of different concentrations; the calibration curve was then used to determine the molecular weight. The average molecular weight of the sample (Mπ ^ Σ ^ ΜΟ / ΣΑί) was determined from the calibration curve using Shimadzu SEC software version 2.4. The sugar content and the composition of the PAGC and AGPC of the present invention were determined by GLC analysis of trimethyl sand methyl glycoside derivatives. In this method, first apply multiple paper sizes to Chinese National Standard (CNS) A4 (210 X 297 mm) --------- ^ --------- (Please read first Note on the back, please fill out this page again) 1240629 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7___ V. Description of the invention (ρ) Methanolation of sugar in hydrochloric acid-methanol, followed by trimethyl silicon derivative (TMS ) To produce volatile monosaccharide derivatives. After elimination, the derivatives were analyzed by gas-liquid chromatography (GLC), which was performed using a DB-1 column equipped with a flame ion detector (FID). The myo-insitol was used as an internal standard to analyze sugar composition and composition together with the composition sample. A chroma analyzer was used to analyze the content of hydroxy couric acid. The sample was hydrolyzed with hydrochloric acid and then treated with sodium perborate (a boron solution in sodium hydroxide), hydrochloric acid and dimethylaminobenzaldehyde. The optical density of the final solution was analyzed on a colorimeter. As for the content of hydroxycoamino acid, it was determined from the calibration curve of various hydroxycoamino acid concentrations prepared in the same way. Example 1 Preparation of arabinogalactan composition Step A. "Drink chips" procedure 300 kg of dried Huang Mincao aws) roots were made into chips, and any contaminated parts were removed, and rinsed under aseptic conditions. It was scrubbed with ultra-filtered water, then immersed in 70% alcohol overnight, cut into thin pieces about 3-5 mm thick, and dried in a sterile oven at 60-70 ° C. These dried "chips" lose about 15% of the water lost from baking. Step B. The crude extract of the arabinose galactan composition is 200 kg of "fragments" made in step A, with UF water (deionized water ultrafiltered with a 10K MWCO UF system) at 100 ° C Extract 3 times for 3 hours each. The extract was concentrated under reduced pressure to about 200 liters at 60-70 ° C. Add 95% alcohol to the concentrate to make the final alcohol concentration 70%, and stir at room temperature for 15 minutes to precipitate the polysaccharide. Decant the supernatant and rinse the pellet 3 times with 95% alcohol. Suspend the precipitate in UF water 35 I paper size applicable to Chinese National Standard (CNS) A4 specification (210 X 297 mm) " " _ --------- ^ -------- * (Please read the precautions on the back before filling out this page) 1240629 Printed by the Consumer Property Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 5. In the description of the invention (A), the concentration is about 18-20% (detected by the refractive index), and then Add 95% alcohol 'to bring the final alcohol concentration to 35%. Centrifuge the alcohol suspension 'discard the precipitate' and add 95% alcohol again and stir to a final alcohol concentration of 70%. The precipitate was collected and dissolved in UF water. After spray drying, the crude product of the arabinose galactan composition was obtained. The water lost due to drying weighs about < 15%. The endotoxin content is about < 0.3 EU / mg. Step C. Purification of the arabinose galactan composition 3.5 kg of the crude product of the arabinose galactan composition prepared in step B was dissolved in UF water to 2% (175 liters). The solution was filtered with a 5K MWCO UF system to a final volume of 35-40 liters. The concentration of the concentrate was adjusted to a buffer solution of 20 mM NaOAc by adding a 1.0 M NaOAc buffer pH 5.2 buffer solution, ρΗ5.2. The solution was loaded into a Q Sepharose cationic resin exchange column, and a 3-3.5-fold volume of distillate was collected. The collected liquid flowing from the Q Sepharose cation resin exchange column was filtered through a 0.1 μm filter membrane, and then ultra-filtered with an 8K MWCO UF system. The remaining liquid was concentrated in a concentration system at 50-6 ° C to 20-26%, and then anhydrous alcohol was added for precipitation. The final alcohol concentration was 80-90%. The precipitate was rinsed with anhydrous alcohol 3 times, and then at 60- The purified arabinose galactan composition can be obtained by drying at 70 ° C. The purified arabinose galactan composition is a white powder, which is soluble in water, physiological saline and 5% glucose water at a concentration of 20 mg / ml, and its water content is £ 6.0%. The composition contains 4.0% ash, S10 ppm of heavy metal, iO.l EU / mg of endotoxin. The pH of the composition aqueous solution is between 4.5 and 6.5. Composition Sugar content ^ 85% (with glucose as standard, 36 paper sizes are applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) ---------------- -(Please read the notes on the back before filling out this page) 1240629 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (w) Detected by the cresol-sulfuric acid method), and Ai * a: Gal ratio 11.5: 1 (obtained from GLC analysis of the TMS-methyl glycoside derivative of the composition). Example 2 Preparation of arabinose galactan protein The liquid collected in the Q Sepharose cationic resin exchange column in Example 1 and Step C was ultra-filtered using a 100K MWCO UF system. The liquid remaining after the ultra-filtration was further concentrated, and then anhydrous alcohol was added for precipitation. The final concentration of alcohol is 80-90%. The precipitate is washed three times with anhydrous alcohol, and then dried at 60-70 ° C to obtain a purified arabinose galactan protein composition. Purified arabinose galactopolymer The glycoprotein composition is a white powder that is soluble in water, physiological saline and 5% glucose water at a concentration of 20 mg / ml, and the pH of its aqueous solution is between 4.5 and 6.5. The composition contains heavy metals in ppm, within Toxin £ 0.5 EU / mg, Ara: Gal ratio 22 ·· 1, and containing 0.2% hydroxyproline. The average molecular weight of the composition is 100kD. Example 3 From activated human peripheral blood mononuclear cells Preparation of Cytokines Human peripheral blood mononuclear cells (PBMCs) were prepared according to the method described by Boyum [A. Boyum, "Isolation of mononuclear cells and granulocytes from human blood ...", Scan. J. Lab. Invest., 97, 77 -89 (1968)]. About 25ml / donor of human blood buffy coat sample was obtained from the blood bank of Stanford University Medical Center. Each buffy coat sample was taken at room temperature. Resuspend gently in a total volume of 100 ml, calcium-free, magnesium-free Hank's balanced salt solution (HBSS, Gibco). Put 25 ml of cell suspension into 15 ml η table paper size applicable to China National Standard (CNS) A4 specifications (210 X 297 Public Love 1 " ----- III ^ · I ------ I (Please read the precautions on the back before filling this page) 1240629 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of Invention (p)

Ficoll-Paque (Pharmacia LKB biotechnlogy, Inc.) was centrifuged in a 50 ml centrifuge tube with a Beckman GPR desktop centrifuge (GH-3.7 rotor) at 15 ° C for 30 minutes at 400 x g. After centrifugation, the PBMC suspension between the interfaces was transferred to another 50 ml centrifuge tube, resuspended in 45 ml HBSS, and centrifuged at 15 ° C for 10 minutes at 354 X g. The supernatant was discarded, and the cell pellet was resuspended in 45 ml of HBSS, and centrifuged at 265 X g for 10 minutes at 15 ° C. The cell pellet was resuspended in 10 ml of X-vivo tissue culture substrate (Bio Whittaker, MD) and the number of cells was counted. Polystyrene tubes (Falcon # 2057, Becton Dickson) and PBMC from two different people were used in the following experiments. Dilute PBMC to 4 X 106 / ml in the presence of 0.5 ml of phytohexin P (PHA-P, Pharmacia 27-3707-01) at a final concentration of 0.3 pg / ml. Mix 1 ml of cell suspension with 0.5 One milliliter of one of the solutions of the composition of the present invention was cultivated together. The total volume in each tube is 2 ml. Another cell solution treated with PHA alone was used as the control group. Incubate at 37 ° C and 7% C02 for 24 hours. Centrifuge these tubes in a Beckman GPR tabletop centrifuge (GH-3.7 rotor) at 15 ° C for 10 minutes at 1600 X g to collect the supernatant. , Store at -70 ° C before analysis. Cytokines are measured using commonly used ELISA reagent kits, such as human cytokines IL-Ιβ, IL-6, TNF-α, GM-CSF, and G-CSF (R & D Systems, MN) and human INF- γ (Endogen, MA). The optical density of each well was read with a microplate-ready instrument (Thermo max, Molecular Devices, CA). After calculation by software, the cytokine content (pg / ml) contained in the above mash was expressed. All results are based on samples on 38 paper sizes. Applicable to China National Standard (CNS) A4 (210 X 297 mm). Packing—U—Order —-------- (Please read the notes on the back before filling This page) 1240629 PAGC ELISA (S / C) pg / ml IL-1 11-6 TNF IFN GM-CSF G-CSF 25 9.1 11.8 4.9 3.1 6.5 49.9 10 4.3 5.9 2.3 1.2 2.1 16.5 A7 B7 V. Description of the invention (祚) Control group ratio (S / C), where S is the amount of cytokines produced by stimulating PBMC with PHA and test samples, and C is the amount of cytokines produced by stimulating PBMC with PHA alone. The following table summarizes that PAGC can increase the amount of cytokines produced by activated human PBMCs. Example 4 Proliferation / maturity of bone marrow megakaryocytes This experiment was performed with G3H / HeJ male mice 9-14 weeks old. The liquid culture analysis used to analyze the maturation of megakaryocytes is an in vitro test that can investigate the proliferation / maturity of bone marrow megakaryocytes (peripheral platelet generation cells). For detailed methods, see SA Burstein, "Interleukin 3 promotes maturation of murine megakaryocytes in vitro", Blood Cells, 11,469-479 (1986). First, normal mouse bone marrow mononuclear cells were isolated and suspended at room temperature. Deactivate the endogenous acetylcholinesterase (AchE) in a matrix containing 0.5 mM diisopropyl fluoride phosphate (DFP, sigma, St. Louis, MO) for 20 minutes. Wash the cells, Resuspend in 5% FCS-IMDM (Gibco BRL, Gaithersburg, MD) and place it in a tissue culture plastic bottle at a concentration of 4 X 106 / ml. The stromal cells and megakaryocytes will adhere to the bottom of the bottle to isolate them. Come out. Incubate the tissue culture flask containing resuspended bone marrow cells at 37 ° C, 5% CO2 for 1.5 hours. Collect those cells that are not adhered to the tissue flask, and place them at 1 x 106 / ml. The concentration is suspended in 1% Nutridoma SP (Boehringer mannheim, 39. This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 x 297 mm) K ^ --------- (Please read the note on the back first (Please fill in this page for matters) Member of Intellectual Property Bureau, Ministry of Economic Affairs Co-op printed 1240629 A7 B7 V. invention is described in (V])

Indianapolis, IN) -IMDM for analysis. Add cells to a 96-well, U-shaped tissue culture dish, with 105 cells per well, with a total volume of 0.2 ml, containing various PAGC concentrations, and with or without 50 pg / ml mouse recombinant IL- 3 (R & D Systems, Minneapolis, MN). These cultures were incubated at 37 C, 5% C02 for 7 days. PAGC activity on megakaryocytes is determined by analyzing the increase in AchE activity, and it is a very specific cell marker for megakaryocytes in dental animals. After 7 days' the culture plate was centrifuged and the supernatant was discarded. Add the first solution (0.2% Triton X-100, ImM EDTA, 0.12 mM NaCl, 50 mM HEPES, pH 7.5) to each culture well, and 0.2 ml, 20 μΐ of 6.27 mM thiothioacetate iodide Test (sigma, St. Louis, MO) (final thioacetate iodide test concentration is 0.57 mM). Incubate the tissue culture plate at 37 ° C for 4 hours, and then take out 10 μΐ of the reaction mixture from each well and place it into a 96-well black plate (Labsystems, Helsinki, Finland), and then add 10 μ1, 0.4 mM Coumarinphenylmaleimide, CMP, Molecular probes Inc., Eugene, OR in DMSO and 0.2 ml of a second solution (5 mM sodium acetate, ImM EDTA, 0.2 % Triton X-100, pH 5.0). Gently shake the culture plate to mix the liquid evenly. The emitted fluorescence intensity was measured in a fluorometer using an excitation light filter of 390 nm and an emission filter of 460 nm (Fliioroskan II, Labsystems, Helsinki, Finland). This fluorescence intensity is directly proportional to the amount of AchE produced by the cultured megakaryocytes. PAGC concentrations between 12.5 pg / ml and 400 pg / ml (peaks at a concentration of 200 | Lig / ml) can increase the number of megakaryocytes cultured, and PAGC concentrations between 12.5 pg / ml and 40 paper sizes Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) ----------- 螓 & (Please read the notes on the back before filling this page) Order --- SI. Economy Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs and printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs and printed by 1240629 A7 ^ __ B7 V. Description of the invention (0) 400 pg / ml (when the peak appears at a concentration of 200 pg / ml) IL-3 at 50 Pg / ml works together to increase the number of megakaryocytes cultivated (far more than 50 to 200 pg / ml). Example 5 Reconstitution of GM-CFC generation cells in mice treated with fluorinated uracil. On day 0, 150 mg / kg of fluorinated urine [I sigma] was injected into BALB / c. Female mice were intraperitoneally; and on day 1-3, physiological saline, various concentrations of PAGC or 100 pg / kg of recombinant human G-CSF (Neupogen, Amgen) were injected subcutaneously. And on the 4th day, the experimental mice were sacrificed. Bone marrow was collected from female mice. After calculation, 5 X 104 white blood cells were cultured in 35 mm culture plates. Each culture plate was filled with 1 ml of complete methylcellulose medium and prokaryotic cells. Pokeweed mitogen spleen cell conditioned medium is a source of community stimulating factors (StemCell Technologies, Inc). After 6-7 days of incubation at 37 ° C, cell populations with more than 50 cells were evaluated with a Nikon Diaphot microscope (30-60x). The following table shows that PAGC can promote the recovery of GM-CFC generation cells in mice treated with uracil fluoride. Treatment of physiological PAGC PAGC PAGC G-CSF saline 50 mg / Kg 100 mg / Kg 200 mg / Kg 100 pg / Kg GM-CFC 601 608 1075 2020 1196 / femur Example 6 Restoration of rats exposed to sublethal doses of radiation Peripheral white blood cell count: 41 This paper is sized for Chinese National Standard (CNS) A4 (210 X 297 mm) ^ --------- (Please read the precautions on the back before filling this page) 1240629 A7 B7 V. Description of the invention (0) This experiment was performed on female BALB / c mice with an average weight of 20 grams. Five days before each experiment, 40 mg / L of neomycin (neomycin, Sigma, St. Louis, MO) was added to the unacidified mash of rats. Six mice were randomly selected from the control group or the experimental group, and irradiated with 4.25 Gy X-rays (250 KVP, 0.35 mm Cu filter, Philips, Germany) on day 0. After radiation exposure, the number of white blood cells and blood platelets around the mice was lower than that of normal mice, while the number of red blood cells was slightly lower than normal. PAGC was injected subcutaneously at 100 and 300 mg / Kg. The first 5 days (from day 0 to day 4) were given once a day, and then three times a week for three consecutive weeks; the first dose was administered within 4-5 hours after radiation exposure. A total of 14 doses of PAGC were administered. The control group was subcutaneously injected with 0.1 ml of physiological saline. During the experiment, blood was drawn from the tail vein of the mice twice a week, and blood samples were stored in EDTA-coated tubes (Sarstedt, Germany) and counted with a Serono 9010+ cell counter (Serono Baker Diagnostics Inc., Allentown, PA). ) To calculate and analyze the number of peripheral white blood cells, platelets and red blood cells, and the hemoglobin content. Compared with the control group, 100 and 300 mg / Kg PAGC significantly (ρ < 0.01) promoted the recovery of white blood cells in mice from 17 to 30 days (after the experiment) after irradiation; (Ρ < 0.05, general ρ < 0.01) promotes the recovery of rat platelet cells from 14 to 25 days after radiation exposure; it is also obvious (ρ < 0.05, generally ρ < 〇.〇 1) Promote the recovery of red blood cells in mice from 14 to 25 days after irradiation. During the 20-day study period, applying AGPC at 100 and 300 mg / Kg in the same manner, no matter at which time point the test was performed, the old $ 42 paper after radiation exposure could be improved to the Chinese National Standard (CNS) A4 specification ( 210 x 297 mm) " (Please read the notes on the back before filling out this page) f -------------------- Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs Consumer Cooperatives 1240629 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (w) The recovery of red blood cells and platelets in the body shows that it has the same benefits as PAGC. Example 7 PAGC alone or with granulocyte colony stimulating factor (G-CSF) —moving peripheral blood generation cells to allow 8-10 week old BALB / c mice to freely access acidified water and food. Normal mice were treated for 7 days, once a day as follows: physiological saline (200 μ subcutaneous injection), PAGC (100 mg / Kg, subcutaneous injection), G-CSF (100 pg / Kg, subcutaneous injection) or PAGC + G_CSF (100 mg / Kg PAGC + 100 pg / Kg G-CSF, subcutaneous injection). The injection volume of each mouse was about 200 μ1. There are five mice in each group. After seven days of the above treatment, mice were injected intraperitoneally with 20 units of heparin (Elkins-Sinn, Inc., Cherry Hill, NJ) on the eighth day, and then the rats were sacrificed by inhaling C02 for 30 minutes, and cardiac puncture was performed. Peripheral blood was collected. UFicoll-Paque (pharmacia biotech AP, Uppsala, Sweden) density centrifugation was used to isolate peripheral blood mononuclear cells, rinsed twice with phosphate buffered saline, resuspended in culture medium, and calculated the number of cells with a cytometer. Peripheral blood mononuclear cells between 2.5 x 104 and 1 x 105 were cultured in 35 mm culture plates, and 1 ml of complete methylcellulose medium and Recombinant IL-3 + IL-6 stem cell factor (Stem cell Technologies Inc., Vancouver, B.C.). After 7-14 days of incubation at 37 ° C, cell populations with more than 50 cells were evaluated with a Nikon Diaphot microscope (30-150 times). The formation of GM-CFC and BFU-E (burst-forming unit-erythroid) was evaluated. The following table shows that PAGC and G-CSF can increase normal rats. The paper size is applicable to Chinese National Standard (CNS) A4 (210 X 297 mm). &Quot; " " .—U— ^ ------ --1 (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economy 1240629 A7 _______ B7 V. Description of the invention (d) GM-CFC and BFU-E numbers of the body disk fj ring Said. Physiological saline PAGC 100 mg / Ka G-CSF 100 μβ / Kg PAGC, 100 mg / Kg G-CSF, 100 pg / Kg GM-CFC, 100 / ml 0.8 4.6 30 64 BFU-E, 100 / ml 1.0 3.1 4.5 9.5 In another similar experiment, rats were treated with 200 mg / kg of cyclophosphamide, and then treated with physiological saline or 100 or 300 mg / kg of PAGC for 11 days. PBMCs were collected and resuspended into 2 X 107 Cells / ml, with fluorescein isothiocyanate-anti-CD34 and PE-cell line markers (CD3, CD4, CD6, CD19, CDllb, GR-1, CD41 and Ding 61: -119) (PhannaCia, San Diego, CA) for staining and analysis with a fluid cytometer (FACSCalibur, Becton Dickson, San Jose, CA). It can be seen that PAGC accelerates the movement of CD34 * Lin_ cells into the surrounding blood. Example 8 PAGC can restore the weight of mice treated with fluorinated uracil or cyclophosphamide. This experiment was performed with female BALB / C rats> 10 weeks old. Ten mice were randomly divided into 5 groups: normal control group, cyclophosphamide (CY) -treated group, fluorpyrimidine (FU) -treated group, CY + PAGC-treated group, or FU + PAGC- Processing group. In the normal control group, physiological saline was injected intraperitoneally on day 0, and then physiological saline was injected subcutaneously from day 1 to day 12. For the cyclophosphamide (CY) -treated group or CY + PAGC-treated group, the intraperitoneal injection of 200 mg / kg of cyclophosphamide was performed on day 0, and then from day 1 to day 12, It is a subcutaneous injection of saline or 200 mg / kg of PAGC. For the fluorinated uracil (FU) -treatment group or 44 paper sizes, the Chinese National Standard (CNS) A4 specification (210 X 297 mm) applies -n hi nnn One: mouth, an I n (Please read the note on the back first Please fill in this page again) 1240629 A7 V. Description of invention u &); FU + PAGC-treatment group, 150 mg / kg of FU was injected intraperitoneally on day 0, and then from day 1 to day 12, It is a subcutaneous injection of saline or 200 mg / kg of PAGC. The rats were weighed once on day 0 and then again every other day until day 12. The results showed that CY + PAGC-treated and FU + PAGC-treated mice had the least weight loss and recovered their original weight faster than mice treated with CY or FU alone. Example 9 PAGC human clinical trial conducted in China PAGC human clinical trial conducted in China was conducted in accordance with the regulations of the Ministry of Health of China. In the first phase of clinical trials, PAGC was diluted with normal saline and administered intravenously to 32 normal volunteers, and was continuously perfused for 7 days. No serious clinical side effects were found after three clinical doses (250 mg / day). The second phase of the clinical trial was to evaluate whether PAGC was helpful in reducing the incidence of low white blood cells (< 4 X 109 WBC / L) caused by chemotherapy in patients with lung, gastrointestinal or breast cancer. A total of 487 patients from six medical centers participated in this clinical trial, of which 328 patients belonged to the PAGC treatment group, 84 patients belonged to the G-CSF treatment group, and 75 patients in the control group. During the entire 14-day chemotherapy period, if the patient has a WBC below 4 X 109 WBC / L at any time, the patient will be included in any of the three groups. For the first group of patients, 250 mg of PAGC was dissolved in 500 ml of physiological saline, and then intravenously injected into the patient once a day for 7 consecutive days. Except for the 7 days that PAGC was administered, the patients were continuously observed for another 7 days. G-CSF treatment 45 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 X 297 mm) (Please read the precautions on the back before filling this page) ---- Order -------- -Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs and printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs and printed by 1240629 A7 B7 On day 'except 5 days of injection' continue to observe the patient for 9 days. As for the control group, other drugs that strengthen the blood system will not be given after chemotherapy, and the patients will be observed the next day. In this way, the WBC, RBC, and platelet counts of all three groups of patients were observed n days after treatment. At the same time, the effect of improving the quality of life of patients was also reviewed by using drugs to improve the patients' chemotherapy symptoms and Karnofsky performance index. Symptoms related to chemotherapy include fatigue and burnout, discomfort, night sweats, shortness of breath, and lack of appetite, and are determined by a qualified Chinese medicine practitioner. The score for each item is as follows: 0-no symptoms, 1-mild symptoms, 2-moderate symptoms and 3-severe symptoms. Therefore, the worst case will score 15 points. The Karnofsky performance index is the method WHO uses to assess general health. Figure 1 shows the daily changes in the number of white blood cells after chemotherapy; Figure 2 shows the daily changes in total symptom scores after chemotherapy; Figure 3 shows the score (PAGC) expressed by Karnofsky performance index Compared with G-CSF: U = 18.36, P <0.01; PAGC compared with control group: U = 15.62, ρ < 0.0.00). The table below shows the changes in mean platelet counts and days after chemotherapy. All results show that treatment with 250 mg of PAGC for 7 days does indeed promote the recovery of WBC and platelet cell numbers, improve the symptoms caused by chemotherapy, and improve the cardiology of chemotherapy patients. The overall performance index of Novsky was statistically significantly better than that of the control group; and it was generally better than the effect of 5 days of treatment with 75 pg of G-CSF. 46 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) " ---------- Order ----------- (Please read the precautions on the back before (Fill in this page) 1240629 A7 __ B7 、 Explanation of the invention (〇 >) Platelet, 109 / L, PAGC-treatment group patients (η = 54) Day 0 Day 4 Day 7 Day 10 Day 14 65 ± 21 87 soil 61 * 118 soil 94 ** 149 soil 107 ** 178 soil 111 ** 氺 ρ < 0,05, ** ρ < 0 · 001 The present invention has been described by way of examples, but those skilled in the art are watching After completing this description, it will be understood that there are many equivalent technologies that can be applied to the present invention, but these equivalent applications should still belong to the scope of the present invention. (Please read the precautions on the back before filling out this page) Order --- Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 47 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Claims (1)

1240629 A8 B8 C8 D8 6. Application scope of patent 4. Purified arabinose galactan composition as described in item 1 of the scope of patent application, in which astragalus refers to biennial yellow buttercup heart membranaceus) 〇5. As for the scope of patent application The purified arabinose galactan composition 'wherein the arabinose / galactose ratio is at least h5. 6. The purified arabinose galactan composition ' according to item 丨 of the scope of the patent application, wherein the endotoxin content does not exceed 1.0 EU / mg. 7 · —Arabic sugar galactan composition for intravenous injection, which comprises: (a) —a therapeutically effective amount of a purified arabinose galactan composition as described in item 1 of the patent application range · , And (b) — an aqueous vehicle solution for intravenous injection. 8 · -Arabic arabinose for treating intravenous administration by administering a purified arabinose galactan composition as described in any one of claims 1 to 6 or a water-soluble intravenously as described in claim 7 A glycogalactan composition to a mammal capable of treating a disease state, wherein the disease state can be treated by a method selected from the group consisting of: stimulating hematopoiesis, causing proliferation or maturation of megakaryocytes, Stimulate the production of 11-1β ·, IL-6, TNF-oc, IFN-γ, GM-CSF, or G = CSF, stimulate the production of neutrophils or their effects, treat neutrophil hypoplasia, anemia, Or hypoplatinism, which accelerates the recovery of individuals from exposure to cytotoxic agents or radiation, treats cachexia, nausea, or drug withdrawal symptoms, and improves bioreactivity or protects liver cells in patients with hepatitis B, including patent applications such as Purified 2 papers of any of the items 1 to 6 are in accordance with China National Standard (CNS) A4 (210 X 297 Mod Love) (Please read the precautions on the back before writing this page) Ordering line ... 1240629 S C8 D8 VI. Application scope of patent Arabian sugar galactan composition or Arabic sugar galactan composition for intravenous injection such as the scope of patent application No. 7 i stomach g7jc14. 9. The pharmaceutical composition according to item 8 of the patent application scope, wherein the composition can stimulate hematopoiesis, trigger the proliferation or maturation of megakaryocytes, and stimulate the production of IL 1β, IL-6, TNF-α, IFN-γ, GM -CSF, or G-CSF, hit rf, private " produce neutrophilic leukocytes or its effect, or treat neutrophilic leukemia ^ Seeking __ stagnation, treating anemia, or treating thrombocytopenia. 10. The pharmaceutical composition according to item 8 of the patent application, wherein the mammal is a human. 11. The pharmaceutical composition according to item 10 of the patent application, which is used for treating bone marrow depression. " 12. The pharmaceutical composition according to item 11 of the patent application, wherein the myelosuppression is caused by cancer chemotherapy or radiation therapy. Stomach 13. The pharmaceutical composition according to any one of claims 7 to 9, which further comprises the administration of at least one other agent. 14. The pharmaceutical composition according to item 13 of the scope of patent application, wherein at least one of the other agents refers to a medicine capable of stimulating hematopoiesis. 15. The medical music composition according to item 14 of the patent application, wherein at least one of the other agents is selected from the group consisting of heme generator, thrombopoietin, granulocyte community stimulating factor 'or IL-3. 16. · A method for preparing a purified arabinose galactan composition having a weight-average molecular weight of at least dultene, which comprises: (a) an extract containing 3 (please (Please read the precautions on the back before filling this page). ¾, II: This paper size is applicable to Chinese National Standard (CNS) A4 (210 χ 297 public love) 1240629 Pirate C8 D8 Γ-^-VI. Application for patent Arabic sugar A water-soluble extract of the galactan composition; (b) adding a sufficient amount of a low-carbon alkanol to the water-soluble extract of step (a) to precipitate the arabinose galactan composition, and Separating the precipitated arabinose galactan composition; (c) dissolving the arabinose galactan composition precipitated in step (b) in water to form a solution containing the arabinose galactan composition; (d) processing step (c) the solution containing the arabinogalactan composition in order to remove any material having a molecular weight of less than 100 μl Dalton; (e) using an ion exchange chromatography column To purify the arabinogalactan group containing step (d) The solution was; and the composition of the solution (f) from Step ⑷ purified arabinose containing arabinogalactan for separating the intravenous injection of purified arabinose galactan composition. 17. · A method of manufacturing an arabinose galactan composition as claimed in item 16 of the scope of patent application, the composition having a weight average molecular weight of at least 100 仟 Dor, comprising: (a) purifying arabinose The aqueous solution of the lactose composition was subjected to ultrafiltration using an ultrafiltration system capable of removing a molecular weight of less than 100 dauer; and (b) composed of arabinose galactan separated from the retentate in step (a). Thing. 4 (Please read the precautions on the back before filling this page) * 11: This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm)