alkyldextran-polyalcohol drug complexes

Abstract: A drug complex characterized in that a residue of a drug compound such as antineoplastic agents and a carboxy(C 1-4 )alkyldextran polyalcohol obtained by treating a dextran under conditions that enable substantially complete polyalcoholization are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Said complex is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Description: Technical Field The present invention relates to a drug complex which is useful as a medicament. More specifically, the present invention relates to a drug complex in which a carboxy(C 1-4 )alkyldextran polyalcohol that is a polysaccharide derivative and a drug compound such as antineoplastic agents or anti-inflammatory agents are bound to each other via a spacer. Background Art Antineoplastic agents, used for treatment of solid cancers such as lung cancer or digestive organ carcinomas and blood cancers such as leukemia, are systemically administered through routes of administration such as intravenous or oral administration, and then, are distributed to specific tumorous sites and inhibit or suppress the proliferation of cancer cells to exhibit their therapeutic efficacy. However, the systemically-administered antineoplastic agents are rapidly taken into livers and reticuloendothelial organs from blood, or rapidly excreted into urine, and accordingly, their blood concentrations may sometimes be lowered to allow the distribution into tumorous sites to be insufficient. In addition, common antineoplastic agents themselves have poor distribution-selectivity to tumorous sites (tumor selectivity), and therefore, the antineoplastic agents are uniformly distributed over various tissues and cells of the whole body, and act as cytotoxins also against normal cells and tissues, which results in problems of the appearance of adverse effects, e.g., emesis, pyrexia, or alopecia at an extremely high rate. Therefore, it has been desired to develop a means of efficiently and selectively distributing antineoplastic agents to tumorous sites. As one of such means, a process was proposed in which an antineoplastic agent is bound to a polysaccharide polymer to delay the disappearance of the antineoplastic agent from blood and to enhance selectivity to tumor tissues. For example, Japanese Patent Publication (KOKOKU) No. (Hei) 7-84481/1995 discloses a drug complex in which daunorubicin, doxorubicin, mitomycin C, bleomycin or the like is introduced into a carboxymethylated mannoglucan derivative by means of a Schiff base or an acid amide bond. As the mannoglucan derivative in the invention, carboxymethylated mannoglucan polyalcohols are also used. However, mannoglucan derivatives are too much branched and have complicated structures, and accordingly, it has been difficult to obtain a product with uniform quality suitable for manufacturing medicaments. In addition, International Patent Publication WO94/19376 discloses a drug complex in which a peptide chain (the number of amino acid residues: 1 to 8) is bound to a carboxyl group of a polysaccharide having carboxyl groups, and doxorubicin, daunorubicin, mitomycin C, bleomycin or the like is further bound by means of the peptide chain. As the polysaccharide having carboxyl groups, examples are given such as polysaccharides inherently having carboxyl groups in their structures (e.g., hyaluronic acid), and polysaccharides inherently having no carboxyl groups in their structures (e.g., pullulan, dextran, chitin, etc.) in which their hydroxyl groups are modified with carbonyl groups by introducing with carboxy(C 1-4 )alkyl groups or binding with a polybasic acid such as malonic acid or succinic acid by esterification. The drug complexes are structurally characterized in that a drug such as doxorubicin and the above-mentioned polysaccharide moiety are bound to each other by means of a spacer, and the complexes have higher antineoplastic activity compared to doxorubicin and reduced toxicity and adverse effects. As for technologies relating to drug complexes utilizing polyalcoholized polysaccharide derivatives as drug delivery carriers, some reports are available, for example, "Researches on polysaccharide-peptide-doxorubicin complexes-Correlations between stabilities of polysaccharide carriers in blood and their anti-neoplastic activities" (Abstracts of 10th Meeting of the Japan Society of Drug-Delivery System, 279, 1994); "Researches on polysaccharide-peptide-doxorubicin complexes - Pharmacokinetics and anti-neoplastic activity" (Abstracts of 9th Annual Meeting of Japanese Society for the study of xenobiotics, 292, 1994); Abstracts of 19th Seminar of Trends in Research and Development (held by The Organization for Drug A D R Relief, R&D Promotion and Product Review ), D-9, 1995; and "Researches on drug delivery to a tumor tissue by polysaccharide carriers" (Abstracts of 12th Colloid and Interface Technology Symposium, The Chemical Society of Japan, 51, 1995). Disclosure of the Invention An object of the present invention is to provide a drug complex capable of site-selectively delivering an active ingredient such as antineoplastic agents or anti-inflammatory agents to tumorous sites or the like. More specifically, the object of the present invention is to provide a drug complex which contains a drug compound such as antineoplastic agents or anti-inflammatory agents as a partial structure and can be retained in blood for a long period of time, and furthermore, can site-selectively deliver the drug compound to tumorous sites or inflammatory sites. In addition, another object of the present invention is to provide a method for preparing the drug complexes having the aforementioned features. In order to achieve the foregoing object, the present inventors attempted to improve the drug complex disclosed in the International Patent Publication WO94/19376. As a result, they found that, when a dextran derivative obtained by the carboxy(C 1-4 )alkylation of a polyalcoholized dextran is used as a polysaccharide moiety instead of the polysaccharides having carboxyl groups, high concentration of the medicament was retained for a long period of time after administration, and site-selectivity to tumorous sites or inflammatory sites can significantly be improved. They also found that, in these compounds, the main efficacy such as antineoplastic activity is remarkably enhanced, whereas toxicity is reduced. The present invention was achieved on the basis of these findings. The present invention thus provides a drug complex characterized in that a carboxy(C 1-4 )alkyldextran polyalcohol and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. According to other embodiments of the present invention, there are provided a medicament comprising the aforementioned drug complex; and a pharmaceutical composition comprising the aforementioned drug complex as an active ingredient, for example, preparations for injection or drip infusion in the form of lyophilized products filled in vials. Furthermore, according to another embodiment of the present invention, a method for preparing the aforementioned drug complex is provided. As preferred embodiments of the aforementioned invention, there are provided the above drug complex characterized in that the dextran polyalcohol that constitutes the carboxy(C 1-4 )alkyldextran polyalcohol is a dextran polyalcohol which is obtained by treating a dextran under conditions that enable substantially complete polyalcoholization; the above drug complex wherein the carboxy(C 1-4 )alkyldextran polyalcohol is carboxymethyldextran polyalcohol; the above drug complex wherein the drug compound is an antineoplastic agent or an anti-inflammatory agent; the above drug complex wherein the drug compound is an antineoplastic agent which concentration-dependently exhibits antineoplastic activity (an antineoplastic agent exhibiting more potent antineoplastic activity at a higher concentration: sometimes referred to as a concentration-dependent type antineoplastic agent in the present specification); the above drug complex wherein the drug compound is an antineoplastic agent which time-dependently exhibits antineoplastic activity (an antineoplastic agent exhibiting more potent antineoplastic activity at longer working times: sometimes referred to as a time-dependent type antineoplastic agent in the present specification); and the above drug complex wherein the antineoplastic agent is doxorubicin or (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H)-dione. In addition, as also preferred embodiments, there are provided the above drug complex wherein the spacer is a dipeptide represented by -X-Z- [the symbol "-X-Z-" means a residue which consists of a dipeptide that is formed by peptide bonding of a hydrophobic amino acid (X) and a hydrophilic amino acid (Z) being at the N-terminal side and the C-terminal side, respectively, and whose one hydrogen atom and one hydroxyl group are removed from the amino group at the N-terminus and the carboxyl group at the C-terminus, respectively], or wherein the spacer contains the dipeptide as a partial peptide sequence; the above drug complex wherein the hydrophobic amino acid is phenylalanine and the hydrophilic amino acid is glycine; the above drug complex wherein the spacer is (N-terminus)-Gly-Gly-Phe-Gly-; and the above drug complex wherein an introduced amount of the residue of the antineoplastic agent is in the range of from 1 to 15% by weight, preferably from 3 to 10% by weight, and more preferably from 5 to 6% by weight. As particularly preferred embodiments of the present invention, there are provided the above drug complex wherein N-terminus of a peptide represented by H 2 N-Gly-Gly-Phe-Gly-COOH is bound to a carboxyl group of carboxymethyldextran polyalcohol by means of an acid-amide bond and C-terminus of the peptide is bound to the 1-amino group of (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-10,13(9H,15H)-dione by means of an acid-amide bond; the above drug complex wherein the introduced amount of the (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-10,13(9H,15H)-dione residue is in the range of from 2 to 10% by weight; and the above drug complex wherein the carboxy(C 1-4 )alkyldextran polyalcohol is a carboxymethyldextran polyalcohol having a molecular weight in the range of from 5,000 to 500,000, preferably in the range of from 50,000 to 450,000, and more preferably in the range of from 200,000 to 400,000, and the degree of carboxymethylation per constitutive saccharide residue is in the range of from 0.01 to 2.0, preferably in the range of from 0.1 to 1.0, and more preferably in the range of from 0.3 to 0.5. According to another aspect of the present invention, a drug delivery carrier comprising the carboxy(C 1-4 )alkyldextran polyalcohol is provided. According to preferred embodiments of this aspect of the invention, a molecular weight of the carboxy(C 1-4 )alkyldextran polyalcohol is in the range of from 5,000 to 500,000, preferably in the range of from 50,000 to 450,000, and more preferably in the range of from 200,000 to 400,000, and the degree of carboxymethylation per constitutive saccharide residue is in the range of from 0.01 to 2.0, preferably in the range of from 0.1 to 1.0, and more preferably in the range of from 0.3 to 0.5. Carboxymethyldextran polyalcohol is provided as the most preferred carrier. From another aspect of the invention, there is provided a use of a carboxy(C 1-4 )alkyldextran polyalcohol for the manufacture of a drug complex which contains the carboxy(C 1-4 )alkyldextran polyalcohol bound to the residue of a drug compound. As preferred embodiments of the present invention, there are provided the use of the carboxy(C 1-4 )alkyldextran polyalcohol for the manufacture of a drug complex in which the residue of a drug compound and the carboxy(C 1-4 )alkyldextran polyalcohol are bound to each other by means of a spacer; and the use of the carboxy(C 1-4 )alkyldextran polyalcohol for the manufacture of a drug complex characterized in that the carboxy(C 1-4 )alkyldextran polyalcohol and the residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. Brief Explanation of the Drawings Fig. 1 shows the GPC chart of the drug complex of the present invention (prepared in Example 8). Fig. 2 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 8). Fig. 3 shows the GPC chart of the drug complex of the present invention (prepared in Example 9). Fig. 4 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 9). Fig. 5 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 10). Fig. 6 shows the GPC chart of the drug complex of the present invention (prepared in Example 15). Fig. 7 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 15). Fig. 8 shows the GPC chart of the drug complex of the present invention (prepared in Example 28). Fig. 9 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 28). Fig. 10 shows the GPC chart of the drug complex of the present invention (prepared in Example 29). Fig. 11 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 29). Fig. 12 shows the GPC chart of the drug complex of the present invention (prepared in Example 34). Fig. 13 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 34). Fig. 14 shows the GPC chart of the drug complex of the present invention (prepared in Example 39). Fig. 15 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 39). Fig. 16 shows the GPC chart of the drug complex of the present invention (prepared in Example 41). Fig. 17 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 41). Fig. 18 shows the GPC chart of the drug complex of the present invention (prepared in Example 44). Fig. 19 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 44). Fig. 20 shows the GPC chart of the drug complex of the present invention (prepared in Example 47). Fig. 21 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 47). Fig. 22 shows the GPC chart of the drug complex of the present invention (prepared in Example 55). Fig. 23 shows the ultraviolet absorption spectrum of the drug complex of the present invention (prepared in Example 55). Fig. 24 shows the pharmacokinetics of the drug complex of the present invention (prepared in Example 15). Each point in the figure represents an average value of three experiments. Best Mode for Carrying out the Invention The drug complex of the present invention is characterized in that a carboxy(C 1-4 )alkyldextran polyalcohol and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. The residue of a drug compound contained in the drug complex of the present invention is derived from a drug compound used for therapeutic and/or preventive treatment of diseases of mammals including humans as a medicament, for example, an antineoplastic agent, an anti-inflammatory agent, an antibacterial agent or the like, and the residue is composed of a partial structure of the drug compound. However, the drug compound which the residue is derived from is not limited to those mentioned above. In addition, as the drug compound, any compounds may be used so long as they have one or more reactive functional groups capable of participating in bond formation with a spacer (for example, amino group, carboxyl group, hydroxyl group, thiol group, ester group or the like). The term "drug compound" in the present specification also includes a prodrug compound which contains, as a part thereof, a major structure of a drug compound having pharmacological activity, per se, and can reproduce the compound in vivo . More specifically, the term "residue of drug compound" in the present specification means a partial structure derived from the drug compound existing in the compound after bond formation, assuming that a bond between the spacer and the residue of a drug compound is formed through a reaction of a reactive functional group of the drug compound and a reactive functional group of the spacer (e.g., dehydration condensation etc.). For example, when the drug compound is represented by D-NH 2 , D-COOH, D-COOR, D-OH, D-SH, D-CONH 2 , or D-NH-COOR (R is a lower alkyl group or the like), the residue of the drug compound is represented by D-NH- (D-NH-CO-Q etc.), D-CO- (D-CO-NH-Q, D-CO-O-Q, D-CO-S-Q, etc.), D-CO- (D-CO-NH-Q, D-CO-O-Q, D-CO-S-Q, etc.), D-O- (D-O-CO-Q, D-O-Q, etc.), D-S- (D-S-CO-Q, D-S-Q, etc.), D-CONH- (D-CO-NH-CO-Q etc.), and D-NH-CO- (D-NH-CO-O-Q, D-NH-CO-NH-Q, etc.), respectively (the parenthesized represents a bond between the spacer and the residue of the drug compound, wherein Q represents a remaining partial structure of the spacer excluding a reactive functional group). However, the sort of the bond between the spacer and the residue of the drug compound is not limited to those mentioned above. The residue of the drug compound may be bound to the N-terminal amino group or the C-terminal carboxyl group of the spacer, or alternatively, may be bound to a reactive functional group existing in an amino acid that constitutes the spacer. As the residue of the drug compound, for example, residues of antineoplastic agents such as doxorubicin, daunorubicin, mitomycin C, bleomycin, cyclocytidine, vincristine, vinblastine, methotrexate, platinum antineoplastic agents (cisplatin or derivatives thereof), taxol or derivatives thereof, camptothecin or derivatives thereof (antineoplastic agents described in Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994, preferably (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-(9H,15H)-dione disclosed in claim 2, or the like) may preferably be used. In addition, residues of steroidal anti-inflammatory agents such as hydrocortisone succinate and prednisolone succinate and nonsteroidal anti-inflammatory agents such as mefenamic acid, flufenamic acid, diclofenac, ibuprofen, and tinoridine are also preferred. As the spacer which binds to the residue of the drug compound, a spacer comprising one amino acid or a spacer comprising 2 to 8 amino acids that are peptide-bonded may be used. More specifically, the spacer has a form of a residue of one amino acid, which means a residue obtained by removing one hydrogen atom and one hydroxyl group from an amino group and a carboxyl group of the amino acid, respectively, or a residue of an oligopeptide comprising peptide-bonded 2 to 8 amino acids, which means a residue obtained by removing one hydrogen atom and one hydroxyl group from the N-terminal amino group and the C-terminal carboxyl group of the oligopeptide, respectively. Preferred spacers are residues of oligopeptides comprising 2 to 6 amino acids. The sort of the amino acid constituting the spacer is not particularly limited, and for example, L- or D-amino acids, preferably L- amino acids can be used, and β-alanine, ε-aminocaproic acid, γ-aminobutyric acid or the like may also be used as well as α-amino acids. These amino acids other than α-amino acids are preferably located close to the polysaccharide derivative. The bonding direction of the spacer is not particularly limited, and generally, the N-terminus of the spacer can be bound to a carboxyl group of the carboxy(C 1-4 )alkyldextran polyalcohol by means of an acid-amide bond, and the C-terminus of the spacer can be bound to an amino group of the drug compound. Alternatively, for example, where a lysine residue is incorporated as a constitutional unit of the peptide spacer, the α-amino group and the ε-amino group of the lysine residue are allowed to form respective acid-amide bonds with carboxyl groups of other amino acids so as to form N-terminuses at both ends of the peptide spacer, which enables bond formation with carboxyl groups of the drug compounds. Moreover, by incorporating one or more residues of diamine compounds or dicarboxylic acid compounds (e.g., residues of diamine compounds such as ethylenediamine or dicarboxylic acid compounds such as succinic acid) in a spacer as constitutional units, a spacer having either N-terminuses or C-terminuses at both ends may be utilized. The amino acid sequence of the spacer is not particularly limited. Preferably used spacers include, for example, a spacer being a residue of a dipeptide represented by -X-Z-, wherein X represents a residue of a hydrophobic amino acid and Z represents a residue of a hydrophilic amino acid; and X-Z- means a residue which consists of a dipeptide that is formed by a peptide bond between a hydrophobic amino acid (X) and a hydrophilic amino acid (Z) at the N-terminal side and the C-terminal side, respectively, and whose one hydrogen atom and one hydroxyl group are removed from the amino group at the N-terminus and the carboxyl group at the C-terminus, respectively, and a spacer containing a residue of the dipeptide as a partial peptide sequence. As the hydrophobic amino acid, for example, phenylalanine, tyrosine, leucine or the like can be used, and as the hydrophilic amino acid, for example, glycine, alanine or the like can be used. The spacer may have a repeated sequence of the dipeptide residue (for example, X-Z-X-Z-, -X-Z-X-Z-X-Z-, etc.). By using the spacer containing such dipeptide structure, the spacer can be hydrolyzed in tumorous sites or inflammatory sites, which is considered abundant in peptidase, to release the drug compound at high concentration in the sites. The partial structure formed between the spacer containing the above dipeptide and the drug compound by binding to each other is a preferred partial structure of the drug complex of the present invention. Where a concentration-dependent antineoplastic agent (e.g., doxorubicin) or the like is used as the residue of the drug compound, for example, a spacer composed of the above dipeptide residue represented by -X-Z- or a spacer containing the above dipeptide residue as a partial peptide sequence may most preferably be used. In addition, where a time-dependent type antineoplastic agent which requires a retained working time at over certain concentration is used as the residue of the drug compound, enhanced antineoplastic activity may sometimes be obtained by using the above spacer. Examples include the antineoplastic agents disclosed in the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994, preferably the antineoplastic agent disclosed in claim 2. Generally, the spacer should not be limited to those mentioned above, and it is necessary to choose an appropriate spacer from viewpoints of the mode of action of the antineoplastic agent, characteristics in pharmacokinetics or appearance of toxicity, releasability in vivo of the antineoplastic agent and the like. For carcinomas exhibiting rapid proliferation, it is generally preferred to choose the above spacer capable of releasing the drug compound at high concentration in a short time. Specific examples of the spacer are shown in the following table; however, the spacer used for the drug complexes of the present invention is not limited to those mentioned below, and it can be readily understood that one of ordinary skilled in the art can appropriately choose a spacer so as to achieve an optimum releasing rate of a drug compound. In the table, the left ends of peptide sequences are N-terminuses and the residues of drug compounds are bound to C-terminuses. D-Phe represents a D-phenylalanine residue and the other amino acids represent L-amino acids. The degrees of the releasing rates were judged from the degree of appearance of efficacy of drug complexes bound with doxorubicin against Walker 256 tumor-bearing rats, or from the free doxorubicin concentration at the tumorous sites of Walker 256 tumor-bearing rats. Among these spacers, a spacer which can release the drug compound at high concentration in a short time, e.g., (N-terminus)-Gly-Gly-Phe-Gly-, is preferably used for doxorubicin. Although the degree of polyalcoholization of the carboxy(C 1-4 )alkyldextran polyalcohol, that constitute the moiety of the polysaccharide derivative of the drug complex of the present invention, is not particularly limited, it is preferred that the dextran polyalcohol constituting the carboxy(C 1-4 )alkyldextran polyalcohol is a dextran polyalcohol obtained by treating a dextran under conditions which enable substantially complete polyalcoholization. For example, a dextran polyalcohol obtained by treating a dextran with large excess amounts of sodium periodate and sodium borohydride successively to achieve substantially complete polyalcoholization can preferably be used as a starting material for manufacturing the drug complex of the present invention. However, the method for the polyalcoholization of adextran is not limited to the method mentioned above, and any methods available to those skilled in the art may be applied. The sort of the dextran is not particularly limited, and the dextran may contain α-D-1,6-bonds at any rate. For example, dextrans containing α-D-1,6-bond at the rate of 85% or more, 90% or more, and 95% or more can be used. The molecular weight of the dextran is not particularly limited, and for example, dextrans having a molecular weight of from about 10,000 to about 2,000,000, preferably from about 50,000 to about 800,000 can be used. As the C 1-4 alkyl group constituting the carboxy(C 1-4 )alkyl group, a linear or branched C 1-4 alkyl group, specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group or the like can be used, and methyl group can preferably be used. The carboxy(C 1-4 )alkylation can be carried out, for example, by reacting a halogenated (C 1-4 )alkylcarboxylic acid such as chloroacetic acid, bromoacetic acid, α-chloropropionic acid, α-methyl-α-chloropropionic acid, β-chloropropionic acid, α-methyl-β-chloropropionic acid, α-chlorobutyric acid, β-chlorobutyric acid, or γ-chlorobutyric acid, preferably chloroacetic acid, with hydroxyl groups of the dextran polyalcohol to achieve partial or complete carboxy(C 1-4 )alkylation of the hydroxyl groups. For example, the dextran polyalcohol is dissolved in an inert solvent which does not participate in the reactions (e.g., water, N,N-dimethylformamide, or dimethyl sulfoxide) and the solution is added with a halogenated (C 1-4 )alkyl carboxylic acid or a salt thereof in the presence of a base (e.g., sodium hydroxide or potassium hydroxide), and then the mixture is allowed to react for several minutes to several days at a temperature under ice-cooling to about 100°C. The degree of introduction of the carboxy(C 1-4 )alkyl group may be easily controlled, for example, by suitably choosing the reaction temperature of the carboxy(C 1-4 )alkylation or the amount of the halogenated (C 1-4 )alkyl carboxylic acid or bases used as reagents, and these means are well-known to those skilled in the art. The degree of the carboxy(C 1-4 )alkylation for hydroxyl groups of the dextran polyalcohol is not particularly limited, and for example, the degree may be in the range of from 0.01 to 2.0, preferably from 0.1 to 1.0, and more preferably from 0.3 to 0.5 per residue of the constitutive saccharide. The molecular weight of the carboxy(C 1-4 )alkyldextran polyalcohol is from about 5,000 to 500,000, preferably from about 50,000 to 450,000, and more preferably from about 200,000 to 400,000 when determined by the gel filtration method. The aforementioned carboxy(C 1-4 )alkyldextran polyalcohol is useful as a drug delivery carrier. Drug complexes in which a drug compound and the carboxy(C 1-4 )alkyldextran polyalcohol are bound to each other are characterized in, for example, that they have excellent selectivity such as neoplastic selectivity and are capable of maintaining high blood concentration for a long period of time. As for the bond between the drug compound and the carboxy(C 1-4 )alkyldextran polyalcohol, for example, a method in which both are bound to each other directly by means of an ester bond, or alternatively, a method in which both are bound to each other by means of an appropriate spacer such as those mentioned above can be adopted. As for the drug complex bound by means of the spacer, the drug complex of the present invention can be prepared by binding the spacer, that is bound to a residue of a drug compound, to a carboxyl group of the carboxymethyldextran polyalcohol obtained as above. The bond between the spacer and the carboxyl group of the carboxymethyldextran polyalcohol can generally be formed by binding the N-terminal amino group of the spacer to a carboxyl group of the carboxymethyldextran polyalcohol by means of an acid-amide bond. However, the bond between the spacer and the carboxyl group of the carboxymethyldextran polyalcohol is not limited to that described above, and other chemical bonds and bonds utilizing one or more spacers may be used. For example, an acid anhydride may be formed between the C-terminal carboxyl group of the spacer and a carboxyl group of the carboxymethyldextran polyalcohol, or by using a diamine compound such as ethylenediamine as a spacer, each of the carboxyl groups may be bound by means of acid-amide bond to each of the amino groups of the diamine compound. When the N-terminal amino group of the spacer is bound to a carboxyl group of the carboxymethyldextran polyalcohol by means of an acid-amide bond, dehydration condensation agents ordinarily used for the synthesis of peptide chain, for example, N,N'-dicycloalkylcarbodiimides such as N,N'-dicyclohexylcarbodiimide (DCC), carbodiimide derivatives such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAPC), benzotriazole derivatives such as 1-hydroxybenzotriazole (HOBT), 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (EEDQ) and the like can be used. In addition, the reaction may also be performed by the activated ester method and the acid halide method. Although the amount of the residue of the drug compound introduced into the carboxymethyldextran polyalcohol is not particularly limited, the amount should be suitably chosen from the viewpoints of, for example, the physicochemical properties of the drug compound residue, and the pharmacokinetics, efficacy and toxicity of the drug complex of the present invention. Generally, the range of approximately from 0.1 to 30% by weight, preferably approximately from 1 to 15% by weight, and more preferably approximately from 3 to 10% by weight, and most preferably approximately from 5 to 6% by weight may be chosen. The ratio of the residue of the drug compound introduced into the carboxymethyldextran polyalcohol can be easily determined by, for example, the absorption spectrometric analysis. As an example of the method for manufacturing the drug complex of the present invention, the following scheme shows the preparing process for introducing the residue of the drug compound which is the antineoplastic agent disclosed in claim 2 of the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994; however, the drug complexes of the present invention and the methods for manufacturing thereof are not limited to those shown in the scheme. In the scheme below, the introduced amount of the residue of the drug compound is, for example, about from 1 to 15% by weight, preferably about from 2 to 10% by weight. In addition, among the constitutional units of the polyalcohols, only one constitutional unit that is introduced with one or two carboxymethyl groups is exemplified in the scheme below. However, it should be understood that the polysaccharide-derivative moiety of the drug complex of the present invention is not formed by the repetition of the aforementioned constitutional unit. It is known that the equilibrium of the aforementioned drug compound lies to the compound whose lactone ring is closed (the ring-closed compound) in an acidic aqueous medium (for example, approximately at pH 3), whereas the equilibrium lies to the compound whose lactone ring is opened (the ring-opened compound) in a basic aqueous medium (for example, approximately at pH 10), and the drug complex introduced with the residue corresponding to the ring-closed or ring-opened compound has similar antineoplastic activity. Accordingly, it should be understood that any of them falls within the scope of the present invention. When a reactant, whose lactone ring is opened, is present in the reaction system, the condensation reaction will progress between the carboxyl group derived from the lactone ring and the amino group derived from the spacer, which results in significant decrease of the reaction yield, and moreover, a desired drug complex cannot sometimes be uniformly obtained. Such side reaction can be avoided by selectively using the ring-closed compound as the reactant. That is, the side reaction can be reduced by converting sodium salt of carboxymethyldextran polyalcohol into the triethylammonium salt, and then condensing the N-terminal amino group of the spacer, which is bound to the residue of the drug compound described above, with a carboxyl group of the carboxymethyldextran polyalcohol in a non-aqueous system (in an organic solvent not containing water), which enables an efficient manufacture of the desired product. As the salt of the carboxymethyldextran polyalcohol that can be dissolved in organic solvents, for example, trialkylammonium salt such as triethylammonium salt or trimethylammonium salt, or salt of organic bases such as N-methylpyrrolidine, N-methylmorpholine, or dimethylaminopyridine (DMAP) can be used. As organic solvents, N,N-dimethylformamide, dimethyl sulfoxide or the like can be used. The drug complex of the present invention is characterized in that it can specifically exhibit desired pharmacological activity at a local site such as tumorous sites or inflammatory sites depending on the sort of the residue of the drug compound (e.g., the residue of the drug compound such as antineoplastic agents or anti-inflammatory agents), and can reduce toxicity inherent to the drug compound, per se. Although not intended to be bound by any specific theory, the polysaccharide-derivative moiety of the drug complex of the present invention (e.g., carboxymethyldextran polyalcohol) has quite excellent retention in blood and achieves high accumulation into tumorous or inflammatory sites, and hence is useful as a drug delivery carrier and allows the drug complex of the present invention to have neoplastic site-selectivity and inflammatory site-selectivity. Furthermore, it is considered that protease (peptidase) is expressed at tumorous sites or inflammatory sites, and accordingly, the spacer of the drug complex of the present invention is readily hydrolyzed to allow a released drug compound to exhibit its efficacy. A medicament containing the drug complex of the present invention may generally be filled in vials or the like in the form of a lyophilized product or other, and provided for clinical use as preparations for parenteral administration such as injections or drip infusions which are dissolved upon use. However, the form of pharmaceutical preparations of the medicament of the present invention is not limited to the aforementioned forms. For the preparation of the above pharmaceutical preparations, pharmaceutical additives available in the field of the art, for example, solubilizers, pH modifiers, stabilizers and the like, can be used. Although the dose of the medicament of the present invention is not particularly limited, it should normally be decided in view of the dose of the drug compound that constitutes the residue of the drug compound, the amount of the residue of the drug compound introduced into the drug complex of the present invention, the condition of a patient, the sort of a disease and the like. For example, where a drug complex of the present invention is administered parenterally, which is introduced with about 6% by weight of the residue of the antineoplastic agent disclosed in claim 2 of the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994, about 1 to 500 mg, preferably about 10 to 100 mg per m 2 of body surface area per day may generally be administered once a day, and the administration may preferably repeated every 3 to 4 weeks. Examples The present invention will be explained more specifically by examples; however, the scope of the present invention is not limited to the following examples. In the examples, "A-NH-" represents a residue of a drug compound wherein the drug compound has a lactone ring, such as the drug compound disclosed in claim 2 of the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994 (sometimes referred to as "DX-8951" in the examples), and the drug compound having a closed lactone ring is represented by A-NH 2 . An example includes the group represented by A-NH- in the above-described scheme in which a lactone ring is formed. In addition, A'-NH- represents that the lactone ring of the residue of a drug compound represented by A-NH- is either in the ring-closed form or ring-opened form, or alternatively, a mixture thereof, -DXR represents the residue derived from doxorubicin, and -D51-7059 represents the residue derived from the taxiol derivative shown in Example 55. In the examples, otherwise not specifically mentioned, the degree of carboxymethylation in carboxymethyldextran polyalcohol (the degree of substitution with carboxymethyl group per constitutive saccharide residue) was determined by converting the sodium salt of the carboxymethyldextran polyalcohol into the free acid form, dissolving the resulting acid in an aqueous 0.1N sodium hydoxide solution, and then titrating by using 0.1N hydrochloric acid. An aqueous solution of the sodium salt of the carboxymethyldextran polyalcohol was applied to a Bio-Rad AG50W-x 2 (H + form) column and the effluent was lyophilized and then used as a sample. The sample was dissolved in a prescribed excess amount of aqueous 0.1N sodium hydroxide solution and titrated with 0.1N hydrochloric acid using phenolphthalein as an indicator. The degree of carboxymethylation was calculated by using the following equation: Degree of carboxymethylation = 13.4(a-b)/[s·5.8(a-b)] wherein "s" is the weight of the applied sample (mg), "a" is the prescribed excess amount of aqueous 0.1N sodium hydroxide solution (ml), and "b" is the volume of 0.1N hydrochloric acid consumed for the titration (ml). The amount of introduced drug (percent by weight) was determined by the absorption spectroscopic analysis by using characteristic absorptions of the drug compound (approximately 362 nm). The gel filtration was performed under the following conditions: column: TSK gel G4000 PW XL ; eluent: 0.1M NaCl; flow rate: 0.8 ml/min; and column temperature: 40°C. Example 1: 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) Boc-Gly-Gly-Phe-Gly (600 mg) and N-hydroxysuccinimide (160 mg) were dissolved in N,N-dimethylformamide (20 ml) and cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (280 mg). To this solution, a solution of methanesulfonate of the drug compound described in claim 2 of the Japanese Patent Unexamined Publication (KOKAI) No. (Hei) 6-87746/1994 (600 mg, the compound described in Example 50 of the above-mentioned patent publication) and triethylamine (0.16 ml) dissolved in N,N-dimethylformamide (30 ml) was added, and the mixture was allowed to react at room temperature for 16 hours with stirring under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 10:1 solution containing 0.5% acetic acid) to give the title compound (1.0 g). 1 H-NMR (DMSO- d 6 ) δ :8.40 (d, 1H,J=8.3 Hz), 8.10-8.17 (m,2H), 7.91-8.01 (m, 1H), 7.78 (d,1H,J=10.75 Hz), 7.32 (s,1H), 6.94-6.96 (m,1H), 6.50 (s,1H), 5.57 (t,1H,J=4.5Hz), 5.43 (s,2H), 5.23 (s,2H), 3.77 (dd,2H,J=5.85Hz,J=8.80Hz), 3.70 (d,2H,J=4.40Hz), 3.65 (d,2H,J=5.35Hz), 3.56 (d,2H,J=5.85), 3.15-3.25 (m,2H), 2.40 (s,3H), 2.05-2.25 (m,1H), 1.86 (m,2H), 1.35 (s,9H), 0.88 (t,3H,J= 7.35). Mass (FAB); m/e 854 (M+1) Example 2: Synthesis of 3'-N-(Boc-Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) Boc-Gly-Gly-Gly-Phe (600 mg) and N-hydroxysuccinimide (160 mg) were dissolved in N,N-dimethylformamide (20 ml) and cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (280 mg). To this solution, a solution of methanesulfonate of DX-8951 (600 mg) and triethylamine (0.16 ml) dissolved in N,N-dimethylformamide (30 ml) was added and the mixture was allowed to react at room temperature for 16 hours with stirring under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 10:1 solution containing 0.5% acetic acid) to give the title compound (700 mg). 1 H-NMR (DMSO-d 6 ) δ :8.57 (d,1H,J=7.8Hz), 8.19 (d,1H), 8.05-8.07 (m,2H), 7.79 (d,1H,J=11.2Hz), 7.32 (s,1H), 7.10 (d,2H,J= 7.8Hz), 6.93-7.03 (m,4H), 6.51 (s,1H), 5.52-5.55 (m,1H), 5.44 (s,2H), 5.18 (d,1H,J= 18.5Hz), 4.84 (d,1H,J= 18.5Hz), 4.57-4.59 (m,1H), 3.57-3.71 (m,6H), 3.15-3.25 (m,2H), 3.00-3.02 (m,1H), 2.80-2.90 (m,1H), 2.40 (s,3H), 2.05-2.25 (m,1H), 1.86 (m,2H), 1.35 (s,9H), 0.88 (t,3H,J=7.35Hz). Mass (FAB); m/e 854 (M+1) Example 3: Synthesis of 3'-N-(Boc-Gly-Gly-Gly-Gly)-NH-A (A-NH 2 =DX-8951) . Boc-Gly-Gly-Gly-Gly (120 mg) and N-hydroxysuccinimide (39 mg) were dissolved in N,N-dimethylformamide (20 ml) and cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (70 mg). To this solution, a solution of methanesulfonate of DX-8951 (150 mg) and triethylamine (0.039 ml) dissolved in N,N-dimethylformamide (10 ml) was added, and the mixture was allowed to react at room temperature for 16 hours with stirring under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 10:1 solution) to obtain the title compound (100 mg). 1 H-NMR (DMSO-d 6 ) δ :8.40 (d,1H,J= 8.3 Hz), 8.10-8.17 (m,2H), 7.91-8.01 (m,1H), 7.78 (d,1H,J= 10.75 Hz), 7.32 (s,1H), 6.94-6.96 (m,1H), 6.50 (s,1H), 5.57 (t,1H,J= 4.5Hz), 5.43 (s,2H), 5.23 (s,2H), 3.77 (dd,2H,J= 5.85Hz,J= 8.80Hz), 3.70 (d,2H,J= 4.40Hz), 3.65 (d,2H,J= 5.35Hz), 3.56 (d,2H,J=5.85Hz), 3.15-3.25 (m,2H), 2.40 (s,3H), 2.05-2.25 (m,1H), 1.86 (m,2H),1.35(s,9H), 0.88 (t,3H,J= 7.35Hz). Mass (FAB); m/e 764 (M+1) Example 4: Synthesis of 3'-N-(Gly-Gly-Gly-Gly)-NH-A (A-NH 2 =DX-8951) trifluoroacetate 3'-N-(Boc-Gly-Gly-Gly-Gly)-NH-A (A-NH 2 =DX-8951) (79 mg) was dissolved in trifluoroacetic acid (3 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillation twice with methanol (30 ml) and twice with ethanol (30 ml), and then the residue was washed with ether to give the title compound (80 mg). 1 H-NMR (DMSO-d 6 ) δ :8.59-8.61 (m,1H), 8.50 (d,1H,J= 8.3Hz), 8.21-8.27 (m,2H), 7.91-8.01 (br,3H), 7.81 (d,1H,d=11.2Hz), 7.32 (s,1H), 6.50-6.52 (br,1H), 5.57-5.59 (m,1H), 5.43 (s,2H), 5.23 (s,2H), 3.80-3.82 (m,3H), 3.70-3.75 (m,3H), 3.15-3.25 (m,2H), 2.41 (s,3H), 2.05-2.25 (m,1H), 1.86-1.88 (m,2H), 0.88 (t,3H,J= 7.35Hz). Example 5: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol Dextran T2000 (10 g, Pharmacia, average molecular weight: 2,000,000) was dissolved in 0.1M acetate buffer (pH 5.5, 1,000 ml) and added with an aqueous solution (1000 ml) of sodium periodate (33.0 g). After stirring at 4°C for 10 days with shielding the light, the mixture was added with ethylene glycol (7.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (14 g) was added and dissolved, and the mixture was then stirred at room temperature overnight. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid, and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was subjected to ultrafiltration using a Biomax-30 membrane (Millipore) to remove the low molecular weight fraction. The polymer fraction was lyophilized to obtain dextran polyalcohol. After treating this dextran polyalcohol at pH 3.0 for one hour, the low molecular weight fraction was removed with Biomax-50 membrane, and subsequently, the polymer fraction was removed with Biomax-100 membrane, and the result was lyophilized to give purified dextran polyalcohol (2.0 g). The molecular weight of this substance was 220K (gel filtration, dextran standard). This purified dextran polyalcohol (1.8 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (10.5 g) in water (45 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (15 g) was added and dissolved under ice-cooling, and then the mixture was allowed to react at room temperature for 20 hours. After this reaction mixture was adjusted to pH 8 with acetic acid, the low molecular weight fraction was removed by ultrafiltration using a Biomax-10 membrane. The polymer fraction was lyophilized to give sodium salt of carboxymethyldextran polyalcohol (1.8 g). The molecular weight of this substance was 330K (gel filtration, dextran standard) and the degree of carboxymethylation was 0.8. The above sodium salt of carboxymethyldextran polyalcohol (300 mg) was dissolve in water, applied to a Bio-Rad AG50W-X2 (200-400 mesh, H + form) column (1.5 × 8.6 cm), and eluted with water. This effluent was added with triethylamine (0.5 ml) and lyophilized to give triethylammonium salt of carboxymethyldextran polyalcohol (380 mg). Portions of the sodium salt of carboxymethyldextran polyalcohol (each 300 mg) were treated with the column as described above to give triethylammonium salt of carboxymethyldextran polyalcohol (380 mg, 400 mg). Example 6: Synthesis of sodium salt of carboxymethyldextran polyalcohol The sodium salt of carboxymethyldextran polyalcohol (0.15 g) obtained in Example 5 above was added to an aqueous solution obtained by dissolving sodium hydroxide (1.05 g) in water (4.5 ml), and then dissolved at room temperature. To this solution, monochloroacetic acid (1.5 g) was added and dissolved under ice-cooling, and the mixture was allowed to react at room temperature for 18 hours. This reaction mixture was adjusted to pH 8 with acetic acid, added dropwise into 90 ml of methanol, and added with 3M aqueous sodium chloride (0.15 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were washed with methanol and then dissolved in water (5 ml), and added with 3M aqueous sodium chloride (0.15 ml). This aqueous solution was filtered through a Millipore filter (0.45 µm), and the filtrate was added dropwise to 35 ml of ethanol and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were washed with ethanol, dissolved in water, and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000). The inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and lyophilized to give sodium salt of carboxymethyldextran polyalcohol (0.18 g). The degree of carboxymethylation of this substance per saccharide residue was 1.2 (alkalimetry). Example 7: Synthesis of sodium salt of carboxymethyldextran polyalcohol The purified dextran polyalcohol (0.2 g) obtained in Example 5 was added to an aqueous solution obtained by dissolving sodium hydroxide (0.84 g) in water (6 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (1.2 g) was added and dissolved under ice-cooling, and the mixture was allowed to react at room temperature for 18 hours. The reaction mixture was adjusted to pH 8 with acetic acid, added dropwise to 120 ml of methanol, and then added with 3M aqueous sodium chloride (0.2 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were washed with methanol and then dissolved in water (5 ml), and added with 3M aqueous sodium chloride (0.2 ml). This aqueous solution was filtered through a Millipore filter (0.45 µm), and the filtrate was added dropwise to 35 ml of ethanol and the precipitate deposited was collected by centrifugation (3500 rpm, 8 minutes). The precipitates were washed with ethanol, dissolved in water, and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000). The inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and lyophilized to give sodium salt of carboxymethyldextran polyalcohol (0.20 g). The degree of carboxymethylation of this substance per saccharide residue was 0.4 (alkalimetry). Example 8: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Gly-Phe-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 5 (380 mg, the degree of carboxymethylation: 0.8) was dissolved in N,N-dimethylformamide (30 ml). To this solution, a solution of 3'-N-(Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt (49 mg) in N,N-dimethylformamide (5 ml), triethylamine (0.017 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (380 mg) were added successively, and then the mixture was allowed to react at room temperature overnight with stirring. This reaction mixture was adjusted to pH 10 with 1M aqueous sodium hydroxide and each of 5 ml portions of the mixture was added dropwise to 25 ml of ethanol. This mixture was added with 3M aqueous sodium chloride (1 ml) and diethyl ether (5 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in water and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000), and the inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and lyophilized. The resulting crude product was dissolved in water (30 ml), adjusted to pH 9 with 0.1M aqueous sodium hydroxide, and treated at 37°C for one hour. This treated solution was dialyzed as described above, and then the inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and lyophilized to give the title compound (289 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min), and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.25 mg/ml) are shown in Fig. 1 and Fig. 2, respectively. The content of the drug compound residue in the compound was 5.3% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 9: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The title compound (300 mg) was synthesized according to a similar manner to that of Example 8 by introducing trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A, which had been obtained by removal of the Boc group from 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (50 mg) in a manner similar to that of Example 4, into the triethylammonium salt of carboxymethyldextran polyalcohol (380 mg) obtained in Example 5. The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min), and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.19 mg/ml) are shown in Fig. 3 and Fig. 4, respectively. The content of the drug compound residue in the compound was 5.3% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 10: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Gly-Gly-NH-A' (A-NH 2 =DX-8951) The title compound (190 mg) was synthesized according to a similar manner to that of Example 8 by introducing trifluoroacetic acid salt of 3'-N-(Gly-Gly-Gly-Gly)-NH-A, which had been obtained through removal of the Boc group from 3'-N-(Boc-Gly-Gly-Gly-Gly)-NH-A (A-NH 2 =DX-8951) (41 mg) in a manner similar to that of Example 4, into the triethylammonium salt of carboxymethyldextran polyalcohol (380 mg) obtained in Example 5. The ultraviolet absorption spectrum of this compound (0.1M Tris buffer solution, pH 9.0, 0.34 mg/ml) is shown in Fig. 5. The content of the drug compound residue in the compound was 5.3% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 11: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice were prepared (7 mice per group) by subcutaneously transplanting 1 × 10 6 mouse fibrosarcoma Meth A cells into the right inguinal regions of BALB/c male mice (7-week old). On day 7, the drug complex of Example 9 dissolved in distilled water for injection was injected in the tail vein of the Meth A tumor-bearing mice every 4 days 4 times. On day 21 after the transplantation, tumor masses were excised and weighed to calculate the inhibition rate of tumor growth according to the following equation: inhibition rate of tumor growth (%) = [1 - (average tumor weight of the group administered with the test sample / average tumor weight of control group)] × 100. As a result, it was found that the drug complex of the present invention obtained in Example 9 exhibited remarkably enhanced antitumor activity compared to the drug compound, per se, without the spacer and the polysaccharide derivative, while showing no toxicity (weight loss). The polysaccharide derivative (Example 5), per se, and the drug compound introduced solely with the spacer (trifluoroacetic acid salt of H 2 N-Gly-Gly-Phe-Gly-NH-A (A-NH 2 =DX-8951) obtained by removing the Boc group from the compound of Example 1 according to the process of Example 4) were found to be not effective. Test compound Dose (mg/kg) Inhibition rate (%) Drug compound, per se 7.5 × 4 76 1.875 × 4 46 0.9375 × 4 36 Compound of Example 9 1.4 × 4 94 0.7 × 4 59 0.35 × 4 41 Example 12: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice (6 mice per group) were prepared according to a similar manner to that of Example 11 and the antitumor activity was compared to that obtained by single administration of the drug complexes of Examples 8 and 9 once on day 7. As a result, the degree of the antitumor activity was as follows: (Polysaccharide derivative)-Gly-Gly-Phe-Gly-NH-A' > (Polysaccharide derivative)-Gly-Gly-Gly-Phe-NH-A' > the drug compound, per se. The compound comprising the residue of the drug compound directly binding to a carboxyl group of the carboxymethyldextran polyalcohol of Example 5 without any spacer (the amount of the drug compound residue introduced: 6.2% by weight) was found to be not effective. Test compound Dose (mg/kg) Inhibition rate (%) Drug compound itself 60 77 20 59 Compound of Example 8 10 85 5 76 Compound of Example 9 5 98 2.5 87 Example 13: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol Dextran T500 (10 g, Pharmacia, molecular weight: 500K) was dissolved in 0.1M acetate buffer (pH 5.5, 1000 ml) and added with an aqueous solution (1000 ml) of sodium periodate (33 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (7.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide. Sodium borohydride (14 g) was added and dissolved, and then the mixture was stirred overnight. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then adjusted to pH 7.5 with 8M aqueous sodium hydroxide to give Solution 1. Separately, a series of procedures described above was performed using Dextran T500 (10 g, Pharmacia, molecular weight 500K) to obtain Solution 2. Furthermore, a series of procedures described above was repeated by using Dextran T250 (10 g each, Pharmacia, molecular weight 250K) to obtain Solution 3 and Solution 4. These Solutions 1-4 were combined and subjected to ultrafiltration using a Biomax-50 membrane to remove the low molecular weight fraction. The polymer fraction was lyophilized to give dextran polyalcohol (25 g). The molecular weight of this substance was 163K (gel filtration, pullulan standard). This dextran polyalcohol (11 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (46.2 g) in water (330 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (66 g) was added under ice-cooling and dissolved, and the mixture was allowed to react at room temperature overnight. This reaction mixture was adjusted to pH 9 with acetic acid and desalted by ultrafiltration using a Biomax-30 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (13 g). The molecular weight of this substance was 228K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.4. This sodium salt of carboxymethyldextran polyalcohol (600 mg) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, H + form) column (diameter: 44 mm, length: 210 mm), and eluted with water. This effluent was added with triethylamine (0.93 ml) and then lyophilized to give the title compound (690 mg). Example 14: Synthesis of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt The 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (79 mg) obtained in Example 1 was dissolved in trifluoroacetic acid (3 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillation twice with methanol (30 ml) and twice with ethanol (30 ml), and then washed with ether to give the title compound (80 mg). 1 H-NMR (DMSO-d 6 ) δ: 8.53 (d,1H, J=8.3Hz), 8.40-8.48 (m, 2H), 8.28 (d, 1H, J=8.3Hz), 7.95-8.07 (br, 3H), 7.81 (d, 1H, J=10.2Hz), 7.30-7.37 (m, 2H), 7.15-7.30 (m, 5H), 6.50-6.55 (br, 1H), 5.50-5.57 (m, 1H), 5.41 (d, 2H, J=7.82Hz), 5.25 (s, 2H), 4.55-4.62 (m, 1H), 3.55-3.92 (m, 6H), 3.15-3.25 (br, 2H), 2.98-3.03 (m, 1H), 2.73-2.82 (m, 1H), 2.40 (s, 3H), 2.05-2.25 (m, 1H), 1.84-1.92 (m, 2H), 0.88 (t, 3H, J=7.35Hz). Example 15: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The sodium salt of carboxymethyldextran polyalcohol obtained in Example 13 (400 mg) was converted into the triethylammonium salt (470 mg) and dissolved in N,N-dimethylformamide (30 ml). To this solution, a solution of trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) obtained in Example 14 (62 mg) in N,N-dimethylformamide (5 ml), triethylamine (0.02 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (470 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring and shielding the light. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. To the mixture, 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml) were added, and the precipitates deposited were collected by centrifugation. The precipitates were dissolved in 0.5M aqueous sodium chloride, adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling and then dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000). The inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (600 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh; solvent: 0.1 M NaCl; flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.1 mg/ml) are shown in Fig. 6 and Fig. 7, respectively. The content of the drug compound residue in the compound was 5.8% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 16: Synthesis of 3'-N-(Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt The 3'-N-(Boc-Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) (79mg) obtained in Example 2 was dissolved in trifluoroacetic acid (3 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillation twice with methanol (30 ml) and twice with ethanol (30 ml), and then the residue was washed with ether to give the title compound (80 mg). 1 H-NMR (DMSO-d 6 ) δ :8.62-8.66 (m, 2H), 8.23 (d, 1H, J=8.3Hz), 8.18-8.20 (m, 1H), 7.98-8.10 (br, 2H), 7.79 (d, 1H, J=10.7Hz), 7.32 (s, 1H), 7.09 (d, 2H, J=7.3Hz), 6.93-7.03 (m, 4H), 6.50-6.60 (br, 1H), 5.52-5.55 (m, 1H), 5.44 (s, 2H), 5.18 (d, 1H, J=18.5Hz), 4.80 (d, 1H, J=18.5Hz), 4.57-4.59 (m, 1H), 3.57-3.71 (m, 6H), 3.15-3.25 (m, 2H), 3.00-3.02 (m, 1H), 2.80-2.90 (m, 1H), 2.50 (s, 3H), 2.05-2.25 (m, 1H), 1.86-2.00 (m, 2H), 0.88 (t, 3H, J=7.35Hz). Example 17: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Gly-Phe-NH-A' (A-NH 2 =DX-8951) The sodium salt of carboxymethyldextran polyalcohol obtained in Example 13 (1.0 g) was converted into the triethylammonium salt (1.2 g) and dissolved in N,N-dimethylformamide (90 ml). To this solution, a solution of trifluoroacetic acid salt of 3'-N-(Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) obtained in Example 16 (158 mg) in N,N-dimethylformamide (15 ml), triethylamine (0.05 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.2 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring and shielding the light. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and then the precipitates deposited were collected by centrifugation. The precipitates were dissolved in 0.5M aqueous sodium chloride, adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000). The inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.4 g). The content of the drug compound residue in this compound was 5.2% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 18: Synthesis of Boc-Gly-Phe-Leu-OH H-Gly-Phe-Leu-OH (3.0 g) was added to 50% aqueous dioxane (48 ml) and ice-cooled. To this solution, 1N aqueous sodium hydroxide (9.45 ml) and a dioxane solution (24 ml) containing (Boc) 2 O (2.27 g) were added, and the mixture was stirred overnight. 1N hydrochloric acid (9.45 ml) was added to the reaction mixture and the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 5:1 solution) to obtain the title compound (2.5 g). Example 19: Synthesis of Boc-Gly-Phe-Leu-Gly-OBzl The Boc-Gly-Phe-Leu-OH obtained in Example 18 (2.4 g) and N-hydroxysuccinimide (656 mg) were dissolved in N,N-dimethylformamide (50 ml), cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (1.17 g) and stirred for 2 hours. To this solution, a N,N-dimethylformamide solution (40 ml), in which tosylate of H-Gly-OBzl (1.9 g) and triethylamine (0.79 ml) had been dissolved, was added and the mixture was allowed to react with stirring at room temperature for 16 hours. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 50:1 solution) to give the title compound (2.0 g). 1 H-NMft (DMSO-d 6 ) δ : 8.20-8.30 (m, 1H), 8.12 (d, 1H, J =8.3Hz), 7.83 (d, 1H, J =8.3Hz), 7.32-7.37 (m, 5H), 6.89-6.95 (m, 1H), 5.12 (s, 1H), 4.52-4.59 (br, 1H), 4.34 (dd, 1H, J =7.3Hz, J =15.1Hz), 3.93 (dd, 1H, J =5.5Hz, J =17.2Hz), 3.84 (dd, 1H, J =5.5Hz, J =17.2Hz), 3.54 (dd, 1H, J =5.9Hz, J =16.7Hz), 3.42 (dd, J =5.9Hz, J =16.7Hz), 3.00 (dd, 1H, J =4.4Hz, 13.7Hz), 2.78 (dd, 1H, J =8.8Hz, J =13.2Hz), 1.50-1.65 (m, 1H), 1.45 (t, 2H, J =7.3Hz), 1.36 (s, 9H), 0.86 (d, 3H, J =6.4Hz), 0.82 (d, 3H, J =6.4Hz). Example 20: Synthesis of Boc-Gly-Phe-Leu-Gly-OH The Boc-Gly-Phe-Leu-OBzl (1.7 g) obtained in Example 19 was dissolved in a mixed solution of ethyl acetate (30 ml) and methanol (30 ml), and added with 5% Pd-C (1.5 g) to perform catalytic reduction. The reaction mixture was filtered and the filtrate was evaporated to dryness under reduced pressure to give the title compound (1.15 g). Example 21: Synthesis of 3'-N-(Boc-Gly-Phe-Leu-Gly)-NH-A (A-NH 2 =DX-8951) The Boc-Gly-Phe-Leu-Gly-OH obtained in Example 20 (200 mg) and N-hydroxysuccinimide (58 mg) were dissolved in N,N-dimethylformamide (5 ml). After cooling at 4°C, N,N'-dicyclohexylcarbodiimide (104 mg) was added to the solution and dissolved. To this solution, a N,N-dimethylformamide solution (5 ml), in which methanesulfonate of DX-8951 (224 mg) and triethylamine (0.059 ml) had been dissolved, was added and the mixture was allowed to react with stirring at room temperature for 16 hours under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 10:1 solution containing 0.5% acetic acid) to give the title compound (200 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.35 (d, 1H, J =7.8Hz), 8.08-8.18 (m, 2H), 7.75-7.85 (m, 2H), 7.32 (s, 1H), 7.10 (d, 2H, J =6.8Hz), 7.08-7.13 (m, 3H), 6.85-6.95 (br, 1H), 6.40-6.65 (br, 1H), 5.52-5.55 (m, 1H), 5.46 (d, 1H, J =18.5Hz), 5.37 (d, 1H, J =18.5Hz), 5.24 (s, 2H), 4.44-4.52 (m, 1H), 4.15-4.25 (m, 1H), 3.68-3.72 (m, 2H), 3.40-3.52 (m, 2H), 3.15-3.25 (br, 2H), 2.85-2.95 (m, 1H), 2.65-2.75 (m, 1H), 2.40 (s, 3H), 2.05-2.25 (m, 1H), 1.80-1.91 (m, 2H), 1.50-1.65 (m, 1H), 1.45 (t, 2H, J =7.3Hz), 1.35 (s, 9H), 0.88 (t, 3H, J =7.4), 0.86 (d, 3H, J =6.4Hz), 0.82 (d, 3H, J =6.4Hz). Example 22: Synthesis of 3'-N-(Gly-Phe-Leu-Gly)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt The 3'-N-(Boc-Gly-Phe-Leu-Gly)-NH-A (A-NH 2 =DX-8951) (97 mg) obtained in Example 21 was dissolved in trifluoroacetic acid (3 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillation twice with methanol (30 ml) and twice with ethanol (30 ml), and then washed with ether to obtain the title compound (95 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.57 (d, 1H, J =8.3Hz), 8.47 (d, 1H, J =8.3Hz), 8.32 (d, 1H, J =7.8Hz), 8.17 (t, 1H, J =5.5Hz), 7.81-7.91 (br, 3H), 7.79 (d, 1H, J =10.7Hz), 7.32 (s, 1H), 7.21-7.23 (m, 5H), 7.12-7.17 (m, 1H), 6.45-6.55 (br, 1H), 5.57 (q, 1H, J =4.4Hz), 5.43 (d, 1H, J =16.1Hz), 5.34 (d, 1H, J =16.1Hz), 5.23 (s, 2H), 4.67 (dt, 1H, J =4.0 Hz, J =9.0 Hz), 4.31 (dd, 1H, J =8.5Hz, J =15.0 Hz), 4.0-4.4 (br, 1H), 3.74-3.76 (m, 2H), 3.56 (dd, 1H, J =6.0 Hz, J =16.0 Hz), 3.41 (dd, 1H, J =6.0 Hz, J =16.0 Hz), 3.17-3.19 (br, 2H), 3.02 (dd, 1H, J =4.0 Hz, J =14.0 Hz), 2.70 (dd, 1H, J =10.0 Hz, J =14.0 Hz), 2.40 (s, 3H), 2.05-2.15 (m, 1H), 1.85 (dt, 2H, J =7.0 Hz, J =14.0 Hz), 1.50-1.55 (m, 1H), 1.45 (t, 2H, J =6.0 Hz), 1.35 (s, 9H), 0.88 (t, 3H, J =7.4), 0.85 (d, 3H, J =6.4Hz), 0.80 (d, 3H, J =6.4Hz). Example 23: Synthesis of carboxymethyldextran polyalcohol-Gly-Phe-Leu-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 13 (690 mg) was dissolved in N,N-dimethylformamide (50 ml). To this solution, a solution of the trifluoroacetic acid salt of 3'-N-(Gly-Phe-Leu-Gly)-NH-A (A-NH 2 =DX-8951) (95 mg) obtained in Example 22 in N,N-dimethylformamide (10 ml), triethylamine (0.03 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (690 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation. The precipitates were dissolved in 0.5M aqueous sodium chloride, adjusted to pH 9 with 0.1M aqueous sodium hydroxide, and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000). The inner dialyzate solution was filtered through a Millipore filter (0.22 µm), and then the filtrate was lyophilized to obtain the title compound (600 mg). The content of the drug compound residue in this compound was 4.8% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 24: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol Dextran T500 (50 g, Pharmacia, molecular weight: 500K) was dissolved in 0.1M acetate buffer (pH 5.5, 5000 ml), and an aqueous solution (5000 ml) of sodium periodate (165.0 g) was added. After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (35.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide. Sodium borohydride (70 g) was added and dissolved, and then the mixture was stirred overnight. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then adjusted to pH 7.5 with 8M aqueous sodium hydroxide. The resulting solution was subjected to ultrafiltration using a Biomax-50 membrane to remove the low molecular weight fraction. The polymer fraction was lyophilized to obtain dextran polyalcohol (27.1 g). The molecular weight of this substance was 140K (gel filtration, pullulan standard). This dextran polyalcohol (5 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (21 g) in water (150 ml), and dissolved at room temperature. To this solution, monochloroacetic acid (30 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature overnight. This reaction mixture was adjusted to pH 8 with acetic acid and then desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (5.6 g). The molecular weight of this substance was 263K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.4. This sodium salt of carboxymethyldextran polyalcohol (2.0 g) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, H + form) column (diameter: 44 mm, length: 210 mm), and eluted with water. This effluent was added with triethylamine (4 ml) and lyophilized to obtain the title compound (2.2 g). Example 25: Synthesis of trimethylammonium salt of carboxymethyldextran polyalcohol The sodium salt of carboxymethyldextran polyalcohol (1.0 g) obtained in Example 24 was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, Me 3 N H + form) column, and eluted with water. This effluent was lyophilized to obtain the title compound (950 mg). Example 26: Synthesis of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) hydrochloride In a manner similar to that of Example 14, 3'-N-(Gly-Gly-Phe-Gly)-NH-A trifluoroacetic acid salt obtained from 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (400mg) was dissolved in water/MeOH (1:4), applied to a Bio-Rad AG 1-X8 (200-400 mesh, Cl - form) column (1.5 cm×8.6 cm), and eluted with the above solvent. This effluent was concentrated and then lyophilized to obtain the title compound (310 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.53 (d, 1H, J=8.5Hz), 8.46-8.48 (m, 1H), 8.37-8.39 (m , 1H), 7.95 (d, 1H, J=8.0Hz), 7.80 (s, 3H), 7.78 (d, 1H, J=11.1Hz), 7.34 (s, 1H), 7.14-7.24 (m, 5H), 6.50(s, 1H), 5.56-5.60 (m, 1H), 5.35-5.40 (m, 2H), 5.24 (s, 2H), 4.51-4.56 (m, 1H), 3.86 (dd, J=4.8, 13.5Hz, 1H), 3.68-3.79 (m, 3H), 3.54 (s, 2H), 3.15-3.22 (m, 2H), 3.01 (dd, J=5.6, 13.5Hz, 1H), 2.78 (dd, J=9.6, 3.5Hz, 1H), 2.41 (s, 3H), 2.12-2.23 (m, 2H), 1.81-1.89 (m, 2H), 0.88 (t, 3H, J=7.2Hz). Mass (FAB); m/e 753 (M+1) Example 27: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The trimethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 25 (0.1 g) was dissolved in N,N-dimethylformamide (6 ml). To this solution, a solution of the hydrochloride of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (24 mg) obtained in Example 26 in N,N-dimethylformamide (10 ml), triethylamine (5 µl), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (0.1 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-30 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to give the title compound (90 mg). The content of the drug compound residue in this compound was 11% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 28: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The trimethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 25 (0.1 g) was dissolved in N,N-dimethylformamide (6 ml). To this solution, a solution of the 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) hydrochloride (36 mg) obtained in Example 26 in N,N-dimethylformamide (10 ml), triethylamine (8 µl), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (0.1 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the precipitate deposited were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 12 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-30 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to give the title compound (80 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min), and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 36 µg/ml) are shown in Fig. 8 and Fig. 9, respectively. The content of the drug compound residue in the compound was 15% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 29: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Gly-Phe-NH-A' (A-NH 2 =DX-8951) Dextran T250 (20 g, EXTRASYNTHESE, average molecular weight: 250K) was dissolved in 0.1M acetic acid buffer (pH 5.5, 2000 ml) and added with an aqueous solution (2000 ml) of sodium periodate (66.0 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (14.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (28 g) was added and dissolved, and then the mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The low molecular weight fraction was removed from the resulting aqueous solution by ultrafiltration using a Biomax-30 membrane to obtain Retained solution 1 that did not pass through the membrane. Separately, Dextran T250 (50 g, EXTRASYNTHESE, average molecular weight: 250K) was dissolved in 0.1M acetate buffer (pH 5.5, 5000 ml) and added with an aqueous solution (5000 ml) of sodium periodate (165 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (35.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (70 g) was added and dissolved, and then the mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The low molecular weight fraction was removed from the resulting aqueous solution by ultrafiltration using a Biomax-30 membrane to obtain Retained solution 2 that did not pass through the membrane. Retained solutions 1 and 2 were combined, subjected to ultrafiltration using a Biomax-30 membrane to remove the low molecular weight fraction from the fraction, that had passed through Biomax-50 membrane, and lyophilized to obtain dextran polyalcohol (25.7 g). The molecular weight of this substance was 47K (gel filtration, pullulan standard). This dextran polyalcohol (5 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (35 g) in water (150 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (50 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 18 hours. This reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (7.2 g). The molecular weight of this substance was 127K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.8. This sodium salt of carboxymethyldextran polyalcohol (2.2 g) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, H + form) column (diameter: 44 mm, length: 210 mm) and eluted with water. This effluent was added with triethylamine (4 ml) and then lyophilized to give triethylammonium salt of carboxymethyldextran polyalcohol (2.69 g). This triethylammonium salt of carboxymethyldextran polyalcohol (2.67 g) was dissolved in N,N-dimethylformamide (200 ml). To this solution, a solution obtained by dissolving the trifluoroacetic acid salt of 3'-N-(Gly-Gly-Gly-Phe)-NH-A, which had been obtained by removing the Boc group according to the method similar to that of Example 16 from 3'-N-(Boc-Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) (350 mg) prepared in a similar manner to that of Example 2, and triethylamine (0.116 ml) in N,N-dimethylformamide (10 ml), and a solution obtained by dissolving 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (2.67 g) in N,N-dimethylformamide (10 ml) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. This reaction mixture was added with 3M aqueous sodium chloride (100 ml) and each of 8 ml portions of the mixture was added dropwise to each 30 ml of ethanol. To each mixture, 3M aqueous sodium chloride (1 ml) and diethyl ether (5 ml) were added, and the precipitates deposited were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were washed with acetone and then dissolved in water, and added with 3M aqueous sodium chloride (10 ml), and then adjusted to pH 9 with 0.1M aqueous sodium hydroxide, and further treated at 37°C for 1 hour. The treated solution was desalted by ultrafiltration using a Biomax-10 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to give the title compound (2.30 g). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.20 mg/ml) are shown in Fig. 10 and Fig. 11, respectively. The content of the drug compound residue in the compound was 5.8% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 30: Synthesis of triethylammonium saltofcarboxymethyldextran polyalcohol To a solution (2000 ml) of Dextran T10 (20 g, Pharmacia, average molecular weight: 10K) in 0.1M acetic acid buffer (pH 5.5) was added an aqueous solution (2000 ml) of sodium periodate (66.0 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (14.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (28 g) was added and dissolved, and the mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was subjected to ultrafiltration using a Biomax-5 membrane (Millipore) to remove the low molecular weight fraction, and the remaining solution that had not passed the membrane was passed through a Biomax-30 membrane. The resulting filtrate was lyophilized to obtain dextran polyalcohol (8.0 g). The molecular weight of this substance was 13K (gel filtration, pullulan standard). This dextran polyalcohol (3.7 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (25.9 g) in water (111 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (37 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 20 hours. This reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-5 membrane. The remaining solution that had not passed through the membrane was lyophilized to give sodium salt of carboxymethyldextran polyalcohol (6.2 g). The molecular weight of this substance was 37K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.9. This sodium salt of carboxymethyldextran polyalcohol (6.0 g) was dissolved in water, applied to a Bio-Rad AG50W-X2 (200-400 mesh, H + form) column, and then eluted with water. This effluent was added with triethylamine (9.3 ml) and then lyophilized to obtain the title compound (7.2 g). Example 31: Synthesis of triethylammonium salt ofcarboxymethyldextran polyalcohol The dextran polyalcohol (3.9 g) obtained in Example 30 was added to an aqueous solution obtained by dissolving sodium hydroxide (16.3 g) in water (117 ml), and dissolved at room temperature. To this solution, monochloroacetic acid (23.4 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 18 hours. This reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-5 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (5.0 g). The molecular weight of this substance was 28K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.5. This sodium salt of carboxymethyldextran polyalcohol (4.8 mg) was converted into the triethylammonium salt in a similar manner to that of Example 30 to obtain the title compound (5.6 g). Example 32: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol An aqueous solution (2000 ml) of sodium periodate (66.0 g) was added to a solution (2000 ml) of Dextran 4 (20 g, Funakoshi, average molecular weight: 4K-6K) in 0.1M acetic acid buffer (pH 5.5). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (14.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (28 g) was added and dissolved, and the mixture was stirred overnight at room temperature. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was subjected to ultrafiltration using a Biomax-3 membrane (Millipore) to remove the low molecular weight fraction. The filtrate obtained was lyophilized to give dextran polyalcohol (6.0 g). The molecular weight of this substance was 9K (gel filtration, pullulan standard). This dextran polyalcohol (2.7 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (18.9 g) in water (81 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (27 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 20 hours. This reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-5 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (4.2 g). The molecular weight of this substance was 20K (gel filtration, pullulan standard), and the degree of carboxymethylation was 0.9. This sodium salt of carboxymethyldextran polyalcohol (4.0 g) was converted into the triethylammonium salt in a similar manner to that of Example 30 to obtain the title compound (4.8 g). Example 33: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol The dextran polyalcohol (2.7 g) obtained in Example 32 was added to an aqueous solution obtained by dissolving sodium hydroxide (11.3 g) in water (81 ml), and dissolved at room temperature. To this solution, monochloroacetic acid (16.2 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 18 hours. This reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-5 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (2.7 g). The molecular weight of this substance was 16K (gel filtration, pullulan standard) and the degree of carboxymethylation was 0.5. This sodium salt of carboxymethyldextran polyalcohol (2.7 g) was converted into the triethylammonium salt in a similar manner to that of Example 30 to obtain the title compound (3.1 g). Example 34: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 30 (1.5 g) was dissolved in N,N-dimethylformamide (90 ml). To this solution, a solution of triethylamine (0.07 ml) and trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (210 mg) in N,N-dimethylformamide (40 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.5 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and then the precipitates deposited were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-3 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.3 g). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 65 µg/ml) are shown in Fig. 12 and Fig. 13, respectively. The content of the drug compound residue in the compound was 6.4% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer solution (pH 9.0). Example 35: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 31 (1.2 g) was dissolved in N,N-dimethylformamide (90 ml). To this solution, a solution of triethylamine (0.056 ml) and trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (168 mg) in N,N-dimethylformamide (30 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.2 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-3 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.0 g). The content of the drug compound residue in this compound was 4.8% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 36: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 32 (1.2 g) was dissolved in N,N-dimethylformamide (90 ml). To this solution, a solution of triethylamine (0.056 ml) and trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (168 mg) in N,N-dimethylformamide (30 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.2 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-3 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.0 g). The content of the drug compound residue in this compound was 5.9% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 37: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 33 (1.5 g) was dissolved in N,N-dimethylformamide (90 ml). To this solution, a solution of triethylamine (0.07 ml) and trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (210 mg) in N,N-dimethylformamide (40 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.5 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-3 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.3 g). The content of the drug compound residue in this compound was 4.6% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 38: Synthesis of Boc-Gly-Gly-Phe-Gly-NH-A (A-NH 2 =DW-8286) Boc-Gly-Gly-Phe-Gly (42 mg) and N-hydroxysuccinimide (12 mg) were dissolved in N,N-dimethylformamide (2 ml), and cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (22 mg). To this solution, a N,N-dimethylformamide solution (6 ml), in which hydrochloride of the compound represented by the following formula: [(1s,9s)-1-amino-5-chloro-9-ethyl-2,3-dihydro-9-hydroxy-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H]-dione: DW-8286] (50 mg) and triethylamine (0.01 ml) were dissolved, was added and the mixture was allowed to react with stirring and shielding the light at room temperature for 16 hours. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 10:1 solution containing 0.5% acetic acid) to obtain the title compound (27 mg). 1 H-NMR, (CDCl 3 ) δ: 8.10-8.20 (br, 1H), 7.95-8.05 (br, 1H), 7.70-7.80 (br, 2H), 7.50-7.60 (br, 1H), 7.40-7.50 (br, 1H), 7.10-7.25 (m, 5H), 7.05-7.15 (br, 1H), 5.85-5.95 (br, 1H), 5.50-5.60 (br, 1H), 5.40-5.50 (m, 1H), 5.25-5.35 (m, 1H), 5.05-5.15 (m, 1H), 4.90-5.00 (m, 1H), 4.70-4.80 (br, 1H), 4.10-4.25 (br, 2H), 3.60-3.90 (m, 4H), 3.10-3.40 (m, 3H), 2.95-3.05 (br, 1H), 2.15-2.30 (br, 1H), 1.75-1.90 (br, 2H), 1.39 (s, 9H), 0.80-1.00 (m, 3H). Example 39: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DW-8286) The triethylammonium salt of carboxymethyldextran polyalcohol (175 mg) obtained in Example 24 was dissolved in N,N-dimethylformamide (20 ml). To this solution, a solution of trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DW-8286) (29 mg), which had been obtained from 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (27 mg) prepared in Example 38 by removing the Boc group in a similar manner to that of Example 4, and triethylamine (9 µl) in N,N-dimethylformamide (5 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (175 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-30 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (135 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 99 µg/ml) are shown in Fig. 14 and Fig. 15, respectively. The content of the drug compound residue in the compound was 6.1% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 40: Synthesis of 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (A-NH 2 =DW-8089) Boc-Gly-Gly-Phe-Gly (163 mg) and N-hydroxysuccinimide (45 mg) were dissolved in N,N-dimethylformamide (10 ml), cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (79 mg). To this solution, a N,N-dimethylformamide solution (30 ml), in which tosylate of the compound represented by the following formula: [(1s,9s)-1-amino-9-ethyl-2,3-dihydro-9-hydroxy-1H,12H-benzo[de]pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-10,13(9H,15H)-dione: DW-8089] (170 mg) and triethylamine (0.054 ml) were dissolved, was added and the mixture was allowed to react with stirring at room temperature overnight under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 94:6 solution containing 0.5% acetic acid) to obtain the title compound (100 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.51 (d, 1H, J=8.5Hz), 8.41 (t, 1H, J=5.6Hz), 8.29 (s, 1H), 8.17 (d, 1H, J=8.0Hz), 8.03 (d, 1H, J=8.0Hz), 7.90 (dd, 1H, J=4.8, 5.6Hz), 7.79 (t, 1H, J=5.6Hz), 7.53 (d, 1H, J=7.2Hz), 7.36 (s, 1H), 7.13-7.25 (m, 5H), 6.94-6.95 (m, 1H), 5.60-5.63 (m, 1H), 5.36-5.47 (m, 2H), 5.21-5.30 (m, 2H), 4.42-4.47 (m, 1H), 3.63-3.96 (m, 3H), 3.51-3.59 (m, 3H), 3.31-3.40 (m, 1H), 3.09-3.21 (m, 1H), 3.02 (dd, 1H, J=4.8, 13.5Hz), 2.76-2.81 (m, 1H), 2.13-2.17 (m, 2H), 1.85-1.90 (m, 2H), 1.37 (s, 9H), 0.89 (t, 3H, J=8.0Hz). Mass (FAB); m/e 822 (M+1) Example 41: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-NH-A' (A-NH 2 =DW-8089) The triethylammonium salt of carboxymethyldextran polyalcohol (1.6 g) obtained in Example 24 was dissolved in N,N-dimethylformamide (60 ml). To this solution, a solution obtained by dissolving trifluoroacetic acid salt of 3'-N-(Gly-Gly-Phe-Gly)--NH-A (A-NH 2 =DW-8089), which had been obtained from 3'-N-(Boc-Gly-Gly-Phe-Gly)-NH-A (200 mg) prepared in Example 40 by removing the Boc group in a similar manner to that of Example 4, and triethylamine (0.07 ml) in N,N-dimethylformamide (20 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (1.6 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (25 ml), and the deposited precipitates were collected by centrifugation (2500 rpm, 8 minutes). The precipitates were washed with ethanol, then dissolved in water, added with 3M aqueous sodium chloride (20 ml), and adjusted to pH 9 with 0.1M aqueous sodium hydroxide. This solution was desalted by ultrafiltration using a Biomax-10 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (1.20 g). The result obtained by GPC analysis after dissolving the compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.26 mg/ml) are shown in Fig. 16 and Fig. 17, respectively. The content of the drug compound residue in the compound was 5.0% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer solution (pH 9.0). Example 42: Synthesis of Trt-Gly-Gly-Phe-Gly-OH Trt-Gly-Gly-Phe-Gly-OBzl (670 mg), 10% Pd-C (100 mg), and ammonium formate (200 mg) were added to DMF (5 ml) and stirred for three hours. The reaction mixture was filtered, the filtrate was evaporated to dryness under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 8: 1 solution) to obtain the title compound (300 mg). 1 H-NMR (CD 3 OD) δ : 7.16-7.45 (m, 20H), 4.66 (dd, 1H, J =9.8,5.4Hz), 3.93 (d, 1H, J =16.6Hz), 3.80 (d, 1H, J =17.6Hz), 3.78 (d, 1H, J =16.6Hz), 3.68 (d, 1H, J =17.1Hz), 3.23 (dd, 1H, J =14.2,5.4Hz), 2.90 (d, 1H, J =13.7Hz), 2.90 (s, 1H). Example 43: Synthesis of 3'-N-(Gly-Gly-Phe-Gly)-DXR hydrochloride Trt-Gly-Gly-Phe-Gly-OH (100 mg) and N-hydroxysuccinimide (22 mg) were dissolved in DMF (4 ml), and the mixture was added with N,N'-dicyclohexylcarbodiimide (40 mg) under ice-cooling and stirred at 4°C for 2 hours. To this solution, a solution of N-methylmorpholine (0.019 ml) and doxorubicin (DXR) hydrochloride (92 mg) dissolved in DMF (20 ml) was added, and the mixture was stirred at 4°C for 16 hours. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 20:1 solution). The resulting compound was dissolved in 75% acetic acid (1 ml) and stirred for 1 hour. Water (20 ml) was added, and the precipitated solid mass was removed by filtration, and then the filtrate was lyophilized and the resulting powder was dissolved in water (5 ml). This solution was passed through a AG-1X8 (Cl - form) column and eluted with water, and then the effluent was washed with dichloromethane, and the aqueous layer was lyophilized to obtain the title compound (40 mg). 1 H-NMR (CD 3 OD) δ : 7.95 (d, 1H, J =7.3Hz), 7.82 (t, 1H, J =7.8Hz), 7.54 (d, 1H, J =8.3Hz), 7.16-7.26 (m, 5H), 5.43 (d, 1H, J =3.4Hz), 5.14 (br, 1H), 4.72 (s, 2H), 4.42 (dd, 1H, J =8.3,6.8Hz), 4.30 (q, 1H, J =6.8Hz), 4.14-4.18 (m, 1H), 4.03 (d, 1H, J =16.6Hz), 4.02 (s, 3H), 3.86 (d, 1H, J =18.5Hz), 3.83 (d, 1H, J =17.1Hz), 3.75 (d, 1H, J =16.1Hz), 3.73 (d, 1H, J =16.1Hz), 3.62 (br, 1H), 3.58 (d, 1H, J =16.6Hz), 3.10-3.15 (m, 2H) 3.00 (d, 1H, J =18.6Hz), 2.94 (dd, 1H, J =14.2, 8.8Hz), 2.38 (d, 1H, J =14.2Hz), 2.18 (dd, 1H, J =14.2,4.4Hz), 1.94-2.00 (m, 1H), 1.71 (dd, 1H, J=12.7,4.4Hz), 1.28 (d, 3H, J =6.3Hz). Example 44: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-DXR The sodium salt of carboxymethyldextran polyalcohol (1.5 g) obtained in Example 24 was converted into the trimethylammonium salt (1.2 g) in a manner similar to that of Example 25, and then 400 mg of this salt was dissolved in N,N-dimethylformamide (24 ml). To this solution, a solution of 3'-N-(Gly-Gly-Phe-Gly)-DXR hydrochloride (76 mg) in N,N-dimethylformamide (24 ml), triethylamine (24 µl) and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (400 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.5 ml) and diethyl ether (20 ml), and the deposited precipitates were collected by centrifugation (3,500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and desalted by ultrafiltration using a Biomax-30 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (40 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 7.4, 36 µl) are shown in Fig. 18 and Fig. 19, respectively. The content of the drug compound residue in the compound was 6.0% (W/W) when determined based on the absorption at 480 nm in PBS (pH 7.4). Example 45: Synthesis of triethylammonium salt of carboxymethyldextran polyalcohol Dextran T150 (20 g, Pharmacia, average molecular weight: 150K) was dissolved in 0.1M acetate buffer (pH 5.5, 2000 ml) and added with an aqueous solution (2000 ml) of sodium periodate (66.0 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (14.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7.5 with 8M aqueous sodium hydroxide under ice-cooling. Sodium borohydride (28 g) was added and dissolved, and then the mixture was stirred at room temperature overnight. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid, and stirred at 4°C for 1 hour. The pH of the mixture was adjusted to 7.5 with 8M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was concentrated to 500 ml by ultrafiltration using a Biomax-5 membrane (Millipore) to obtain Solution 1. Separately, a series of procedures described above was performed using Dextran T110 (20 g) to obtain Solution 2. Solution 1 and Solution 2 were combined, and the combined solution was adjusted to pH 3.0 and incubated at 40°C for 4 hours, and then adjusted to pH 7 to obtain a solution containing the dextran polyalcohol with lowered molecular weight. The solution was passed through a Biomax-30 membrane and desalted by ultrafiltration using a Biomax-5 membrane, and then lyophilized to obtain dextran polyalcohol (4.6 g). The molecular weight of this substance was 17K (gel filtration, pullulan standard). This dextran polyalcohol (2.5 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (17.5 g) in water (75 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (25 g) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 20 hours. This reaction mixture was adjusted to pH 9 with acetic acid and then desalted by ultrafiltration using a Biomax-5 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (4.0 g). The molecular weight of this substance was 45K (gel filtration, pullulan standard), and the degree of carboxymethylation was 0.9. This sodium salt of carboxymethyldextran polyalcohol (3.7 g) was dissolved in water, applied to a Bio-Rad AG50W-X2 (200-400 mesh, H + form) column, and eluted with water. This effluent was added with triethylamine (5.8 ml) and then lyophilized to obtain the title compound (4.4 g). Example 46: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Gly-Phe-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 45 (4.4 g) was dissolved in N,N-dimethylformamide (300 ml). To this solution, a solution of triethylamine (0.19 ml) and trifluoroacetic acid salt of 3'-N-(Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951) (580 mg) in N,N-dimethylformamide (45 ml) and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (4.4 g) were added successively, and the mixture was allowed to react at room temperature overnight with stirring and shielding the light. This reaction mixture was adjusted to pH 10 with 1M aqueous sodium hydroxide, and then each of 5 ml portions of the mixture was added dropwise to each 25 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (1 ml) and diethyl ether (5 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in water and dialyzed against purified water using a dialysis membrane (Spectrapore 1, cut-off molecular weight; 6,000-8,000), and the inner dialyzate solution was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (3.4 g). The content of the residue of the drug compound in this compound was 4.6% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer solution (pH 9.0). Example 47: Synthesis of α-methylcarboxymethyldextran polyalcohol-Gly-Gly-Gly-Phe-NH-A' (A-NH 2 =DX-8951) The dextran polyalcohol (2 g) obtained in Example 45 was added to an aqueous solution obtained by dissolving sodium hydroxide (14 g) in water (60 ml) and dissolved at room temperature. To this solution, α-bromopropionic acid (19 ml) was added under ice-cooling and dissolved, and then the mixture was allowed to react at room temperature for 18 hours. The reaction mixture was adjusted to pH 8 with acetic acid and desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of α-methylcarboxymethyldextran polyalcohol (2.95 g). The molecular weight of this substance was 45K (gel filtration, pullulan standard). The degree of α-methylcarboxymethylation per saccharide residue was obtained according to the cases of carboxymethyldextran polyalcohol as follows. An aqueous solution of the sodium salt of α-methylcarboxymethyldextran polyalcohol was applied to a Bio-Rad AG 50W-X2 (H + form) column, and the effluent was lyophilized and used as a sample. This sample was dissolved in a prescribed excess amount of 0.1N aqueous solution of sodium hydroxide and titrated with 0.1N hydrochloric acid using phenolphthalein as an indicator. The degree of α-methylcarboxymethylation was obtained according to the equation: the degree of α-methylcarboxymethylation = 13.4(a-b)/[s-7.2(a-b)] wherein "s" is the amount of sample used (mg), "a" is the prescribed excess amount of 0.1N aqueous solution of sodium hydroxide (ml), and "b" is the amount of 0.1N hydrochloric acid consumed for the titration (ml). As a result, the degree of α-methylcarboxymethylation was found to be 0.8. This sodium salt of α-methylcarboxymethyldextran polyalcohol (2.2 g) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, H + form) column (diameter: 44 mm, length: 210 mm), and then eluted with water. This effluent was added with triethylamine (4 ml) and then lyophilized to give triethylammonium salt of α-methylcarboxymethyldextran polyalcohol (2.69 g). This triethylammonium salt of α-methylcarboxymethyldextran polyalcohol (2.68 g) was dissolved in N,N-dimethylformamide (60 ml). To this solution, a solution obtained by dissolving trifluoroacetic acid salt of 3'-N-(Gly-Gly-Gly-Phe)-NH-A (A-NH 2 =DX-8951), which had been obtained in a similar manner to that of Example 16 by removing the Boc group from 3'-N-(Boc-Gly-Gly-Gly-Phe)-NH-A (350 mg) synthesized similarly to that of Example 2, and triethylamine (0.116 ml) in N,N-dimethylformamide (10 ml), and a solution obtained by dissolving 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (2.68 g) in N,N-dimethylformamide (10 ml) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. This reaction mixture was added with 3M aqueous sodium chloride (40 ml), and each of 6 ml portions of the mixture was added dropwise to each 30 ml of ethanol. Each was added with 3M aqueous sodium chloride (1 ml) and diethyl ether (5 ml), and the precipitate deposited was collected by centrifugation (3500 rpm, 8 minutes). This precipitate was washed with acetone, then dissolved in water, added with 3M aqueous sodium chloride (10 ml), adjusted to pH 9 with 0.1M aqueous sodium hydroxide, and treated at 37°C for 1 hour. This treated solution was desalted by ultrafiltration using a Biomax-10 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (2.15 g). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (0.1M Tris buffer solution, pH 9.0, 0.21 mg/ml) are shown in Fig. 20 and Fig. 21, respectively. The content of the drug compound residue in the resulting product was 5.9% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer solution (pH 9.0). Example 48: Synthesis of 3'-N-(Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt A mixture of p-toluenesulfonic acid salt of Phe-Gly-OBzl (3.06 g), Boc-Gly-OH (1.10 g), N-hydroxysuccinimide (941 mg), N-methylmorpholine (0.725 ml), and N,N-dimethylformamide (40 ml) was cooled to 4°C, and added with N,N'-dicyclohexylcarbodiimide (1.56 g). The mixture was allowed to react overnight at room temperature with stirring, and then evaporated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 98:2 solution) to give Boc-Gly-Phe-Gly-OBzl (1.93 g). 1 H-NMR (DMSO-d 6 ) δ : 8.52 (dd, 1H, J=5.6, 6.4Hz), 7.97 (d, 1H, J=8.8Hz), 7.30-7.39 (m, 5H), 7.15-7.26 (m, 5H), 6.83 (t, 1H, J=5.6Hz), 5.14 (s, 1H), 4.52-4.57 (m, 1H), 3.87-3.96 (m, 2H), 3.57 (dd, 1H, J=5.6, 16.7Hz), 3.43 (dd, 1H, J=5.6, 16.7Hz), 3.01 (dd, 1H, J=4.8, 14.3Hz), 2.77 (dd, 1H, J=5.6, 14.3Hz), 1.37 (s, 9H). The resulting Boc-Gly-Phe-Gly-OBzl (1.78 g) was dissolved in ethyl acetate (60 ml) and subjected to catalytic reduction for 24 hours in the presence of 5%-Pd-C (1.8 g). The catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to obtain Boc-Gly-Phe-Gly-OH (1.41 g). 1 H-NMR (DMSO-d 6 ) δ : 8.35 (t, 1H, J=5.6Hz), 7.94 (d, 1H, J=8.8Hz), 7.15-7.26 (m, 5H), 6.85 (dd, 1H, J=5.6, 6.4Hz), 4.52-4.58 (m, 1H), 3.76 (d, 2H, J=5.6Hz), 3.56 (dd, 1H, J=6.4, 16.7Hz), 3.43 (dd, 1H, J=5.6, 16.7Hz), 3.03 (dd, 1H, J=5.0, 13.5Hz), 2.79 (dd, 1H, J=9.5, 13.5Hz), 1.37 (s, 9H). The Boc-Gly-Phe-Gly-OH (500 mg) obtained above and N-hydroxysuccinimide (161 mg) were dissolved in N,N-dimethylformamide (10 ml). To this solution, a N,N-dimethylformamide (50 ml) solution, in which methanesulfonate of DX-8951 (530 mg) and triethylamine (0.146 ml) were dissolved, was added. The mixture was cooled to 4 °C, added with N,N'-dicyclohexylcarbodiimide (268 mg), and allowed to react overnight with stirring at room temperature under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol =96:4 solution) to obtain 3'-N-(Boc-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (100 mg). 1 H-NMR (DMSO-d 6 ) δ: 8.39 (d, 1H, J=8.0Hz), 8.34 (t, 1H, J=5.6Hz), 7.98 (d, 1H, J=7.2Hz), 7.78 (d, 1H, J=10.3Hz), 7.33 (s, 1H), 7.13-7.24 (m, 5H), 6.80 (dd, 1H, J=5.6, 6.4Hz), 5.55-5.61 (m, 1H), 5.44 (d, 1H, J=16.0Hz), 5.41 (d, 1H, J=16.0Hz), 5.25 (s, 2H), 4.43-4.46 (m, 1H), 3.69-3.79 (m, 2H), 3.50 (dd, 1H, J=5.6, 16.7Hz), 3.41 (dd, 1H, J=5.6, 16.7Hz), 3.16-3.19 (m, 2H), 2.98 (dd, 1H, J=4.8, 14.3Hz), 2.79 (dd, 1H, J=9.5, 14.3Hz), 2.41 (s, 3H), 2.19-2.25 (m, 1H), 2.10-2.15 (m, 1H), 1.82-1.90 (m, 2H), 1.35 (s, 9H), 0.88 (t, 3H, J=8.0Hz). Mass (FAB); m/e 797 (M+1) The resulting 3'-N-(Boc-Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (100 mg) was dissolved in trifluoroacetic acid (3 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillations twice with methanol (30 ml) and twice with ethanol (30 ml), and then washed with ether to obtain the title compound (80 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.52-8.62 (m, 1H), 7.94 (s, 3H), 7.79 (t, 1H, J=11.1Hz), 7.34 (s, 1H), 7.15-7.27 (m, 5H), 6.52 (s, 1H), 5.57-5.61 (m, 1H), 5.36-5.46 (m, 2H), 5.24 (s, 2H), 4.66-4.70 (m, 1H), 3.69-3.81 (m, 2H), 3.61-3.68 (m, 1H), 3.40-3.47 (m, 1H), 3.15-3.23 (m, 1H), 3.01 (dd, 1H, J=4.0, 13.5Hz), 2.77 (dd, 1H, J=9.5, 13.5Hz), 2.12-2.23 (m, 2H), 1.81-1.91 (m, 2H), 0.89 (t, 3H, J=7.2Hz). Mass (FAB); m/e 697 (M+1) Example 49: Synthesis of 3'-N-(Phe-Gly)-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt Boc-Phe-Gly (771 mg) and N-hydroxysuccinimide (300 mg) were dissolved in N,N-dimethylformamide (10 ml). To this solution, a N,N-dimethylformamide (50 ml) solution, in which methanesulfonate of DX-8951 (1058 mg) and triethylamine (0.293 ml) were dissolved, was added. The mixture was cooled to 4°C, and then added with N,N'-dicyclohexylcarbodiimide (494 mg) and allowed to react with stirring at room temperature overnight under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol =98:2 solution) to obtain 3'-N-(Boc-Phe-Gly)-NH-A (A-NH 2 =DX-8951) (1.20 g). 1 H-NMR (DMSO-d 6 ) δ: 8.29 (d, 1H, J=8.0Hz), 8.21 (t, 1H, J=4.8Hz), 7.76 (d, 1H, J=10.3Hz), 7.32 (s, 1H), 7.13-7.25 (m, 5H), 6.92 (d, 1H, J=7.2Hz), 6.49 (s, 1H), 5.56-5.61 (m, 1H), 5.44 (d, 1H, J=15.9Hz), 5.38 (d, 1H, J=15.9Hz), 5.25 (s, 2H), 4.08-4.12 (m, 1H), 3.78 (d, 1H, J=4.8Hz), 3.16-3.25 (m, 2H), 2.99 (dd, 1H, J=4.0, 13.5Hz), 2.72 (dd, 1H, J=10.3, 13.5Hz), 2.40 (s, 3H), 2.09-2.35 (m, 2H), 1.80-1.91 (m, 2H), 1.16 (s, 9H), 0.88 (t, 3H, J=8.0Hz). Mass (FAB); m/e 741 (M+1) The 3'-N-(Boc-Phe-Gly)-NH-A (170 mg) obtained above was dissolved in trifluoroacetic acid (4 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillations twice with methanol (10 ml) and twice with ethanol (10 ml), and then washed with ether to obtain the title compound (100 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.88 (t, 1H, J=4.8Hz), 8.68 (d, 1H, J=8.7Hz), 8.05-8.15 (m, 3H), 7.79 (d, 1H, J=11.1Hz), 7.26-7.36 (m, 5H), 6.52 (d, 1H, J=7.2Hz), 5.57-5.62 (m, 1H), 5.43 (d, 1H, J=15.9Hz), 5.38 (d, 1H, J=15.9Hz), 5.19-5.28 (m, 1H), 4.10-4.18 (m, 1H), 3.93 (dd, 1H, J=4.8, 16.7Hz), 3.82 (dd, 1H, J=4.8, 16.7Hz), 3.17-3.24 (m, 2H), 3.14 (dd, 1H, J=4.8, 13.5Hz), 2.95 (dd, 1H, J=8.0, 13.5Hz), 2.42 (s, 3H), 2.14-2.25 (m, 2H), 1.83-1.91 (m, 2H), 0.89 (t, 3H, J=8.0Hz). Mass (FAB); m/e 640 (M+1) Example 50: Synthesis of 3'-N-Gly-NH-A (A-NH 2 =DX-8951) trifluoroacetic acid salt Methanesulfonate of DX-8951 (530 mg) and triethylamine (0.28 ml) were dissolved in N,N-dimethylformamide (10 ml), cooled to 4°C, and added with N-hydroxysuccinimide ester of Boc-Gly (327 mg). The mixture was allowed to react with stirring at room temperature overnight under light-shielded conditions. This reaction mixture was evaporated to dryness under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol =98:2 solution) to obtain 3'-N-(Boc-Gly)-NH-A (A-NH 2 =DX-8951) (500 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.38 (d, 1H, J=8.3Hz), 7.77 (d, 1H, J=10.7Hz), 7.31 (s, 1H), 6.89-6.91 (m, 1H), 6.49 (s, 1H), 5.55-5.59 (m, 1H), 5.45 (d, 1H, J=16.1Hz), 5.38 (d, 1H, J=16.1Hz), 5.27 (d, 1H, J=19.0Hz), 5.18 (d, 1H, J=19.0Hz), 3.50-3.62 (m, 2H), 3.15-3.19 (m, 2H), 2.41 (s, 3H), 2.18-2.24 (m, 1H), 2.08-2.12 (m, 1H), 1.81-1.91 (m, 2H), 1.31 (s, 9H), 0.87 (t, 3H, J=8.0Hz). Mass (FAB); m/e 593 (M+1) The 3'-N-(Boc-Gly)-NH-A (100 mg) obtained above was dissolved in trifluoroacetic acid (2 ml) and allowed to stand for one hour. The solvent was evaporated, and the residue was subjected to azeotropic distillations twice with methanol (10 ml) and twice with ethanol (10 ml), and then washed with ether to obtain the title compound (70 mg). 1 H-NMR (DMSO-d 6 ) δ: 8.88 (d, 1H, J=8.8Hz), 8.08 (s, 3H), 7.81 (d, 1H, J=11.2Hz), 7.34 (s, 1H), 6.52 (s, 1H), 5.63-5.67 (m, 1H), 5.45 (d, 1H, J=16.7Hz), 5.40 (d, 1H, J=16.7Hz), 5.36 (d, 1H, J=19.1Hz), 5.25 (d, 1H, J=19.1Hz), 3.56 (s, 2H), 3.11-3.19 (m, 2H), 2.43 (s, 3H), 2.23-2.28 (m, 1H), 2.11-2.19 (m, 1H), 1.81-1.91 (m, 2H), 0.88 (t, 3H, J=8.0Hz). Mass (FAB); m/e 493 (M+1) Example 51: Synthesis of trimethylammonium salt of carboxymethyldextran polyalcohol Dextran T500 (50 g, Pharmacia, molecular weight: 500K) was dissolved in 0.1M acetate buffer (pH 5.5, 5000 ml) and added with an aqueous solution (5000 ml) of sodium periodate (165.0 g). After stirring at 4°C for ten days with shielding the light, the mixture was added with ethylene glycol (35.0 ml) and stirred overnight. The reaction mixture was adjusted to pH 7 with 8M aqueous sodium hydroxide. Sodium borohydride (70 g) was added and dissolved, and the mixture was stirred overnight. The reaction mixture was ice-cooled, adjusted to pH 5.5 with acetic acid and stirred at 4°C for one hour, and then, adjusted to pH 7.5 with 8M aqueous sodium hydroxide. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain dextran polyalcohol (20.2 g). The molecular weight of this substance was 159K (gel filtration, pullulan standard). This dextran polyalcohol (7.5 g) was added to an aqueous solution obtained by dissolving sodium hydroxide (31.5 g) in water (225 ml) and dissolved at room temperature. To this solution, monochloroacetic acid (45 g) was added under ice-cooling and dissolved, and the mixture was allowed to react at room temperature overnight. This reaction mixture was adjusted to pH 8 with acetic acid and then desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was lyophilized to obtain sodium salt of carboxymethyldextran polyalcohol (8.5 g). The molecular weight of this substance was 274K (gel filtration, pullulan standard), and the degree of carboxymethylation was 0.4. This sodium salt of carboxymethyldextran polyalcohol (2.0 g) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, H + form) column (diameter: 44 mm, length: 210 mm), and eluted with water. This effluent was added with triethylamine (4 ml) and then lyophilized to obtain the title compound (2.2 g). Example 52: Synthesis of carboxymethyldextran polyalcohol-Gly-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 51 (200 mg) was dissolved in N,N-dimethylformamide (7 ml). To this solution, a solution of the trifluoroacetic acid salt of 3'-N-(Gly-Phe-Gly)-NH-A (A-NH 2 =DX-8951) obtained in Example 48 (41 mg) in N,N-dimethylformamide (5 ml), triethylamine (0.014 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (100 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.0 ml) and diethyl ether (25 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (190 mg). The content of the drug compound residue in this compound was 4.5% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer (pH 9.0). Example 53: Synthesis of carboxymethyldextran polyalcohol-Phe-Gly-NH-A' (A-NH 2 =DX-8951) The sodium salt of carboxymethyldextran polyalcohol obtained in Example 24 (2.5 g) was dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, Et 3 N H + form) column, and eluted with water. This effluent was lyophilized to give triethylammonium salt of carboxymethyldextran polyalcohol (2.5 g). This triethylammonium salt of carboxymethyldextran polyalcohol (200 mg) was dissolved in N,N-dimethylformamide (12 ml). To this solution, a solution of the trifluoroacetic acid salt of 3'-N-(Phe-Gly)-NH-A (A-NH 2 =DX-8951) (42 mg) obtained in Example 49 and triethylamine (0.016 ml) in N,N-dimethylformamide (5 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (200 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring and shielding the light. This reaction mixture was added with water (300 ml) and subjected to ultrafiltration using a ultrafiltration membrane 10K (Filtron). The remaining solution that had not passed through the membrane was adjusted to pH 10 with 0.1N aqueous sodium hydroxide, and passed through a filtration membrane (0.16 µm, Filtron). The filtrate was desalted by ultrafiltration using a Biomax-50 membrane, and then filtered through a Millipore filter (0.22 µm) and lyophilized to obtain the title compound (180 mg). The content of the drug compound residue in this compound was 6.1% (W/W) when determined based on the absorption at 362 nm in 0.1 M Tris buffer solution (pH 9.0). Example 54: Synthesis of carboxymethyldextran polyalcohol-Gly-NH-A' (A-NH 2 =DX-8951) The triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 51 (370 mg) was dissolved in N,N-dimethylformamide (10 ml). To this solution, a solution of the trifluoroacetic acid salt of 3'-N-Gly-NH-A (A-NH 2 =DX-8951) obtained in Example 50 (57 mg) in N,N-dimethylformamide (3 ml), triethylamine (0.027 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (185 mg) were added successively, and then the mixture was allowed to react at room temperature overnight with stirring. Each of 5 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. The mixture was added with 3M aqueous sodium chloride (2.0 ml) and diethyl ether (25 ml), and the deposited precipitates were collected by centrifugation (3500 rpm, 8 minutes). The precipitates were dissolved in 0.5M aqueous sodium chloride and adjusted to pH 9 with 0.1M aqueous sodium hydroxide under ice-cooling. The resulting aqueous solution was desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (290 mg). The content of the drug compound residue in this compound was 0.5% (W/W) when determined based on the absorption at 362 nm in 0.1M Tris buffer (pH 9.0). Example 55: Synthesis of carboxymethyldextran polyalcohol-Gly-Gly-Phe-Gly-D51-7059 Boc-Gly-Gly-Phe-Gly-OH (200 mg) was dissolved in trifluoroacetic acid (4 ml) and stirred for 1.5 hours. The solvent was evaporated, and the residue was subjected to azeotropic distillations twice with methanol (10 ml) and twice with ethanol (10 ml) and washed with ether to obtain trifluoroacetic acid salt of Gly-Gly-Phe-Gly-OH (225 mg). 1 H-NMR (DMSO-d 6 ) δ : 8.48 (dd, 1H, J=5.6, 5.6Hz), 8.59 (dd, 1H, J=5.6, 6.4Hz), 8.29 (d, 1H, J=4.8Hz), 7.23-7.26 (m, 4H), 7.16-7.20 (m, 1H), 4.58 (ddd, 1H, J=4.8, 4.8, 10.4Hz), 3.89 (dd, 1H, J=5.6, 16.7Hz), 3.76-3.79 (m, 2H), 3.67 (dd, 1H, J=5.6, 16.7Hz), 3.56 (s, 2H). The trifluoroacetic acid salt of Gly-Gly-Phe-Gly-OH (200 mg) obtained above was dissolved in water (10 ml), added with triethylamine to adjust the pH to 9.0, then added with a solution of 9-fluorenylmethyl N-hydroxysuccinimidylcarbonate (200 mg) in acetonitrile (5 ml), and stirred at room temperature for four hours while maintaining the pH in the range of 8.0 through 8.5 by using triethylamine. The reaction mixture was added with 1.5N hydrochloric acid (50 ml), and the deposited precipitates were collected by filtration, washed with water, and purified by silica gel column chromatography (eluent: dichloromethane:methanol = 4:1 solution) to obtain Fmoc-Gly-Gly-Phe-Gly-OH (151 mg). 1 H-NMR (DMSO-d 6 ) δ: 8.28-8.32 (m, 1H), 8.08-8.12 (m, 1H), 7.85-7.89 (m, 2H), 7.68-7.72 (m, 2H), 7.57-7.65 (m, 1H), 7.38-7.43 (m, 2H), 7.29-7.34 (m, 2H), 7.20-7.25 (m, 4H), 7.14-7.17 (m, 1H), 4.45-4.52 (m, 1H), 4.26-4.30 (m, 2H), 4.19-4.24 (m, 1H), 3.77 (dd, 1H, J=5.6, 16.7Hz), 3.58-3.69 (m, 4H), 3.42-3.52 (m, 1H), 3.06 (dd, 1H, J=4.0, 13.5Hz), 2.78 (dd, 1H, J=4.0, 13.5Hz). The Fmoc-Gly-Gly-Phe-Gly-OH obtained above (24 mg), the taxol derivative represented by the following formula: [D51-7059: 9,10-O-(2-aminoethylidene)-13-O-[3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenyl]-propanoyl-10-deacetyl-9-dihydrobaccatin III] (20 mg), and N-hydroxysuccinimide (7 mg) were dissolved in N,N-dimethylformamide (1 ml). This solution was cooled to 4°C and then added with N,N'-dicyclohexylcarbodiimide (9 mg), and the mixture was allowed to react at room temperature overnight with stirring. This reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 96:4 solution) to obtain Fmoc-Gly-Gly-Phe-Gly-D51-7059 (21 mg). 1 H-NMR (CDCl 3 ) δ : 8.06 (d, 2H, J=8.1Hz), 7.75 (d, 2H, J=8.1Hz), 7.18-7.61 (m, 23H), 7.62 (dd, 1H, J=7.2, 8.0Hz), 6.07 (dd, 1H, J=7.9, 8.8Hz), 5.98 (d, 1H, J=4.8Hz), 5.63 (d, 1H, J=8.8Hz), 5.00-5.40 (m, 4H), 4.92 (s, 1H), 4.60-4.69 (m, 2H), 4.41 (d, 2H, J=6.4Hz), 4.35 (d, 1H, J=8.0Hz), 4.29 (d, 1H, J=8.0Hz), 4.21 (t, 1H, J=7.5Hz), 3.96-4.07 (m, 3H), 3.73-3.86 (m, 4H), 3.37-3.41 (m, 1H), 3.19-3.23 (m, 1H), 3.00 (dd, 1H, J=8.0, 13.5Hz), 2.85-2.89 (m, 3H), 2.29 (s, 3H), 2.05-2.40 (m, 4H), 1.57 (s, 3H), 1.56 (s, 3H), 1.53 (s, 3H), 1.40 (s, 9H), 1.22 (s, 3H). Mass (FAB); m/e 1413 (M+Na) The Fmoc-Gly-Gly-Phe-Gly-D51-7059 obtained above (21 mg) was dissolved in dichloromethane (1.8 ml) and added with piperazine (0.2 ml), and then the mixture was allowed to react at room temperature for 1 hour. This reaction mixture was purified by silica gel column chromatography (eluent: dichloromethane:methanol = 94:6 solution) to obtain Gly-Gly-Phe-Gly-D51-7059 (16 mg). 1 H-NMR (CDCl 3 ) δ : 8.10 (d, 2H, J=8.1Hz), 7.89-7.94 (m, 1H), 7.62 (dd, 1H, J=7.2, 8.0Hz), 7.45-7.50 (m, 2H), 7.17-7.42 (m, 12H), 7.10-7.16 (m, 1H), 6.97 (dd, 1H, J=5.6, 6.4Hz), 6.08 (dd, 1H, J=8.0, 8.7Hz), 6.02 (d, 1H, J=4.8Hz), 5.62 (d, 1H, J=11.1Hz), 5.23-5.30 (m, 1H), 5.23 (d, 1H, J=7.2Hz), 5.10 (s, 1H), 4.98-5.00 (m, 1H), 4.60-4.63 (m, 1H), 4.38 (d, 1H, J=8.8Hz), 4.33 (d, 1H, J=8.8Hz), 4.13 (s, 1H), 4.04 (dd, 1H, J=5.6, 16.7Hz), 3.93 (dd, 1H, J=5.6, 16.7Hz), 3.82 (d, 1H, J=7.2Hz), 3.73-3.82 (m, 2H), 3.43-3.49 (m, 1H), 3.30-3.38 (m, 2H), 3.24 (dd, 1H, J=6.4, 14.3Hz), 3.04 (dd, 1H, J=8.0, 14.3Hz), 2.89-3.07 (m, 3H), 2.30 (s, 3H), 2.01-2.50 (m, 4H), 1.70 (s, 3H), 1.62 (s, 3H), 1.61 (s,3H), 1.40 (s, 9H), 1.26 (s, 3H). Mass (FAB); m/e 1169 (M+1) The Gly-Gly-Phe-Gly-D51-7059 synthesized according to the above method (33 mg) was dissolved in N,N-dimethylformamide (0.5 ml). To this solution, a solution of the triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 24 (180 mg) in N,N-dimethylformamide (7 ml), and 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (180 mg) were added successively, and the mixture was allowed to react at room temperature overnight with stirring. Each of 4 ml portions of this reaction mixture was added dropwise to each 10 ml of ethanol. Each was added with 3M aqueous sodium chloride (2.0 ml) and diethyl ether (25 ml), and the deposited precipitates were collected by centrifugation (2500 rpm, 8 minutes). The precipitates were washed with ethanol, then dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, Na + form) column (diameter: 15 mm, length: 85 mm), and eluted with water to obtain Solution 1. Separately, Gly-Gly-Phe-Gly-D51-7059 (10 mg) was dissolved in N,N-dimethylformamide (0.5 ml), and then added successively with a solution of the triethylammonium salt of carboxymethyldextran polyalcohol obtained in Example 24 (60 mg) in N,N-dimethylformamide (5 ml) and a solution of 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroxyquinoline (60 mg) in N,N-dimethylformamide (0.25 ml), and the mixture was allowed to react at room temperature overnight with stirring. This reaction mixture was added dropwise to 10 ml of ethanol, and then the resulting mixture was added with 3M aqueous sodium chloride (2.0 ml) and diethyl ether (25 ml), and the precipitates deposited were collected by centrifugation (2500 rpm, 8 minutes). The precipitates were washed with ethanol, then dissolved in water, applied to a Bio-Rad AG 50W-X2 (200-400 mesh, Na + form) column (diameter: 15 mm, length: 85 mm), and eluted with water to obtain Solution 2. Solution 1 and Solution 2 were combined and then desalted by ultrafiltration using a Biomax-50 membrane. The remaining solution that had not passed through the membrane was filtered through a Millipore filter (0.22 µm) and then lyophilized to obtain the title compound (208 mg). The result obtained by GPC analysis after dissolving this compound in 0.1M aqueous sodium chloride (column: TSK Gel PW-4000XL, Tosoh, solvent: 0.1 M NaCl, flow rate: 0.8 ml/min) and the ultraviolet absorption spectrum of the compound (methanol:water = 10:1 solution, 1.69 mg/ml) are shown in Fig. 22 and Fig. 23, respectively. The content of the drug compound residue in the compound was 5.3% (W/W) when determined based on the absorption at 240 nm in a methanol:water = 10:1 solution. Example 56: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice (6 mice per group) were prepared according to a similar manner to that of Example 11 and the antitumor activity of the drug complex of Example 15 was examined by single administration in a similar manner to that of Example 12. As a result, the drug complex of Example 15 exhibited remarkably enhanced antitumor activity and broader effective dose-range compared to the drug compound itself of Example 12. Test compound Dose (mg/kg) Inhibition rate (%) Compound of Example 15 10 100 5 99 2.5 95 1.25 83 Example 57: Antitumor activity of the drug complex of the present invention SC-6 tumor-bearing nude mice (5 mice per group) were prepared by subcutaneously transplanting a piece of SC-6 human gastric tumor block into the right inguinal regions of nude mice (BALB/c-nu/nu, male). On day 27 after the transplantation, the drug complex of Example 15 dissolved in distilled water for injection was given as a single intravenous administration and its antitumor activity was compared to that of the drug compound, per se. As a result, the drug complex of Example 15 exhibited higher antitumor activity compared to the drug compound, per se, whereas there was no death due to toxicity. Test compound Dose (mg/kg) Inhibition rate (%) Numbers of died mice/mice used Drug compound, per se 60 98 2/5 15 61 0/5 Compound of Example 15 8 100 0/5 2 71 0/5 Example 58: Antitumor activity of the drug complex of the present invention Human lung cancer QG-90-bearing nude mice (5 mice per group) were prepared according to a similar manner to that of Example 57. On day 16 after the transplantation, the drug complex of Example 15 dissolved in distilled water for injection was given as a single intravenous administration and its antitumor activity was compared to that of the drug compound, per se. As a result, the drug complex of Example 15 exhibited remarkably enhanced antitumor activity and broader effective dose-range compared to the drug compound, per se. Test compound Dose (mg/kg) Inhibition rate (%) Numbers of died mice/mice used Drug compound, per se 50 65 0/5 12.5 51 0/5 Compound of Example 15 7 98 0/5 1.75 97 0/5 Example 59: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice (6 mice per group) were prepared according to a similar manner to that of Example 11, and the antitumor activity of the drug complex of Example 41 was examined in the cases of single administration in a similar manner to that of Example 12, and its antitumor activity was compared to that of the drug compound, per se. As a result, the drug complex of Example 41 exhibited remarkably enhanced antitumor activity and broader effective dose-range compared to the drug compound, per se. Test compound Dose (mg/kg) Inhibition rate (%) Drug compound, per se 100 64 50 56 25 34 Compound of Example 41 25 99 12.5 95 6.25 81 3.125 61 Example 60: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice (6 mice per group) were prepared according to a similar manner to that of Example 11, and the antitumor activity was examined according to a similar method to that in Example 12 by single administration of the drug complexes of Examples 29, 46, and 47, respectively. As a result, all of the drug complexes exhibited high antitumor activity and broader effective dose-range. Test compound Dose (mg/kg) Inhibition rate (%) Compound of Example 29 30 99 20 99 10 89 5 79 Compound of Example 46 100 94 80 92 40 82 20 75 Compound of Example 47 100 96 80 94 40 97 20 75 Example 61: Antitumor activity of the drug complex of the present invention Meth A tumor-bearing mice (6 mice per group) were prepared according to a similar manner to that of Example 11, and antitumor activity of the drug complex of Example 44 was examined according to a similar method to that of Example 12 by single administration, and its antitumor activity was compared to that of the drug compound (Doxorubicin), per se. As a result, the drug complex of Example 44 exhibited remarkably enhanced antitumor activity and broader effective dose-range compared to the drug compound, per se. Test compound Dose (mg/kg) Inhibition rate (%) Numbers of died mice/mice used Drug compound, per se 20 - 6/6 10 64 0/6 5 39 0/6 Compound of Example 44 40 96 0/6 20 96 0/6 10 87 0/6 5 76 0/6 Example 62: Pharmacokinetics of the drug complex of the present invention Meth A tumor-bearing mice were prepared according to a similar manner to that of Example 11, the drug complex of Example 15 was given as single administration in a similar manner to that of Example 12 (10 mg/kg: calculated as the drug compound), and the change of the drug complex concentration in various tissues was determined. As a result, the drug complex of Example 15 was found to have extremely long retention of blood level, high distribution in tumor tissues, and high tumor selectivity against liver and small intestine. The results are shown in Fig. 24. Industrial Applicability The drug complex of the present invention that is introduced with a residue of a drug compound such as antineoplastic agents is characterized in that it has excellent selectivity to tumorous sites so as to exhibit high antineoplastic activity and also achieves reduced appearance of toxicity.

Claims: A drug complex characterized in that a carboxy(C 1-4 )alkyldextran polyalcohol and a residue of a drug compound are bound to each other by means of a spacer comprising an amino acid or a spacer comprising peptide-bonded 2 to 8 amino acids. The drug complex according to claim 1, characterized in that the dextran polyalcohol that constitutes the carboxy(C 1-4 )alkyldextran polyalcohol is a dextran polyalcohol which is obtained by treating a dextran under a condition that enables substantially complete polyalcoholization. The drug complex according to claim 1 or claim 2, wherein the carboxy(C 1-4 )alkyldextran polyalcohol is carboxymethyldextran polyalcohol. The drug complex according to any one of claims 1 to 3, wherein the drug compound is an antineoplastic agent or an anti-inflammatory agent. The drug complex according to claim 4, wherein the drug compound is an antineoplastic agent which concentration-dependently exhibits antineoplastic activity. The drug complex according to claim 4, wherein the drug compound is an antineoplastic agent which time-dependently exhibits antineoplastic activity. The drug complex according to claim 4, wherein the antineoplastic agent is doxorubicin or (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13(9H,15H)-dione. The drug complex according to any one of claims 5 to 7, wherein the spacer is a dipeptide represented by -X-Z- wherein "-X-Z-" represents a residue which consists of a dipeptide that is formed by peptide bonding of a hydrophobic amino acid (X) and a hydrophilic amino acid (Z) being at the N-terminal side and the C-terminal side, respectively, and whose one hydrogen atom and one hydroxyl group are removed from the amino group at the N-terminus and the carboxyl group at the C-terminus, respectively, or wherein the spacer contains the dipeptide as a partial peptide sequence. The drug complex according to claim 8, wherein the hydrophobic amino acid is phenylalanine and the hydrophilic amino acid is glycine. The drug complex according to claim 9, wherein the spacer is (N-terminus)-Gly-Gly-Phe-Gly-. The drug complex according to any one of claims 5 to 10, wherein an introduced amount of the residue of the antineoplastic agent is in the range of from 1 to 15% by weight. The drug complex according to any one of claims 5 to 10, wherein an introduced amount of the residue of the antineoplastic agent is in the range of from 3 to 10% by weight. The drug complex according to any one of claims 5 to 10, wherein an introduced amount of the residue of the antineoplastic agent is in the range of from 5 to 6% by weight. The drug complex according to claim 1, wherein the N-terminus of a peptide represented by H 2 N-Gly-Gly-Phe-Gly-COOH is bound to a carboxyl group of a carboxymethyldextran polyalcohol by means of an acid-amide bond and C-terminus of the peptide is bound to the 1-amino group of (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-10,13(9H,15H)-dione by means of an acid-amide bond. The drug complex according to claim 14, wherein the introduced amount of (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-10,13(9H,15H)-dione residue is in the range of from 2 to 10% by weight. The drug complex according to claim 14 or claim 15, wherein the carboxy(C 1-4 )alkyldextran polyalcohol is a carboxymethyldextran polyalcohol having a molecular weight in the range of from 5,000 to 500,000 and the degree of carboxymethylation is in the range of from 0.01 to 2.0. The drug complex according to claim 14 or claim 15, wherein the carboxy(C 1-4 )alkyldextran polyalcohol is a carboxymethyldextran polyalcohol having a molecular weight in the range of from 50,000 to 450,000 and the degree of carboxymethylation is in the range of from 0.1 to 1.0. The drug complex according to claim 14 or claim 15, wherein the carboxy(C 1-4 )alkyldextran polyalcohol is a carboxymethyldextran polyalcohol having a molecular weight in the range of from 200,000 to 400,000 and the degree of carboxymethylation is in the range of from 0.3 to 0.5. The drug complex according to claim 14, wherein the introduced amount of (1S,9S)-1-amino-9-ethyl-5-fluoro-2,3-dihydro-9-hydroxy-4-methyl-1H,12H-benzo[de]-pyrano[3',4':6,7]indolizino[1,2-b]-quinoline-10,13(9H,15H)-dione residue is in the range of from 5 to 6% by weight, the molecular weight of carboxy(C 1-4 )alkyldextran polyalcohol is about 228,000, and the degree of carboxymethylation is about 0.4. A drug delivery carrier for binding a drug compound which comprises a carboxy(C 1-4 )alkyldextran polyalcohol. The drug delivery carrier according to claim 20, wherein the molecular weight of the carboxy(C 1-4 )alkyldextran polyalcohol is in the range of from 5,000 to 500,000, and the degree of carboxymethylation is in the range of from 0.01 to 2.0. The drug delivery carrier according to claim 20, wherein the molecular weight of the carboxy(C 1-4 )alkyldextran polyalcohol is in the range of from 50,000 to 450,000, and the degree of carboxymethylation is in the range of from 0.1 to 1.0. The drug delivery carrier according to claim 20, wherein the molecular weight of the carboxy(C 1-4 )alkyldextran polyalcohol is in the range of from 200,000 to 400,000, and the degree of carboxymethylation is in the range of from 0.3 to 0.5. The drug delivery carrier according to any one of claims 20 to 23, wherein the carboxy(C 1-4 )alkyldextran polyalcohol is a carboxymethyldextran polyalcohol. Process for the manufacture of a drug complex according to any of claims 1-19 containing carboxy(1-4C)alkyl-dextran-polyalcohol bound to a residue of a drug characterized by using a carboxy(1-4C)alkyl-dextran-polyalcohol which is bound to a residue of a drug compound. Process according to claim 25 wherein the carboxy(1-4C)alkyl-dextran-polyalcohol is bound to the drug by means of a spacer or without a spacer.

Inventors: IKEDA MASAHIRO, INOUE KAZUHIRO, KUGA HIROSHI, KUMAZAWA EIJI, SUSAKI HIROSHI, TOGO AKIKO, IKEDA, MASAHIRO, INOUE, KAZUHIRO, KUGA, HIROSHI, KUMAZAWA, EIJI, SUSAKI, HIROSHI, TOGO, AKIKO, IKEDA, Masahiro, Daiichi Pharmaceutical Co., Ltd., INOUE, Kazuhiro, Daiichi Pharmaceutical Co., Ltd., KUGA, Hiroshi, Daiichi Pharmaceutical Co., Ltd., KUMAZAWA, Eiji, Daiichi Pharmaceutical Co., Ltd., SUSAKI, Hiroshi, Daiichi Pharmaceutical Co., Ltd., TOGO, Akiko, Daiichi Pharmaceutical Co., Ltd.
Applicants: DAIICHI SEIYAKU CO, DRUG DELIVERY SYSTEM INST LTD, DAIICHI PHARMACEUTICAL CO., LTD., DRUG DELIVERY SYSTEM INSTITUTE, LTD.
Application year: 1997
Main classification: A61K47
IPC codes: A61K47