WO1998024453A1

WO1998024453A1 - Remedies for myelopathy

Info

Publication number: WO1998024453A1
Application number: PCT/JP1997/004477
Authority: WO
Inventors: Kenji Okajima; Yuji Taoka; Yoji Ezure
Original assignee: Nippon Shinyaku Co., Ltd.
Priority date: 1996-12-05
Filing date: 1997-12-05
Publication date: 1998-06-11

Abstract

Preventives or remedies for myelopathy containing as the active ingredient Lewis sugar chain derivatives represented by general formula (I), wherein G represents hydroxy or acetamido; B represents oxygen or -A-R-substituted nitrogen; one of L and E represents fucosyl while another represents galactopyranosyl sialate (2→3) or galactopyranosyl; and M represents hydrogen, hydroxy or ethylgalactosyl bonded at the 3-position.

Description

Specification

Spinal cord disorder drug

The present invention relates to a preventive or therapeutic agent for spinal cord disorders and pathological conditions derived therefrom, comprising a Lewis-type sugar chain derivative as an active ingredient. Background art

Cyaryl Lewis X

Sialyl Lewis X represented by the above structural formula is composed of tetrasaccharides of sialic acid, galactose, fucose, and N-acetyltilcosamine. In addition, as an isomer thereof, sialyl Lewis A, in which fucose is bonded to the 4-position of N-acetylacetylcosamine and sialylgalactose is bonded to the 3-position, is also widely present in human tissues. These sugar chains exist as minor components on the cell surface and are involved in various cell activities.

For example, inflammation and blood clot formation associated with inflammation, rheumatism, asthma, infectious diseases, immune diseases, AIDS, cancer, and other diseases are caused by the adhesion of white blood cells and cancer cells to vascular endothelial cells (cell adhesion) as one step. I do. Such cell adhesion is mainly due to the ganglioside replacement paper present on the cell surface (Rule 26). Interactions between Lewis-type and sialyl-Lewis-type glycan ligands and a protein called reselectin present on the surface of leukocyte cells and E- and P-selectin expressed on the surface of vascular endothelial cells and platelets Is known (“Yumi of Medicine”, Vol.174, No.1, 36-40 (1995), etc.). This cell adhesion plays a role related to the roots of life activities such as immunity, cancer, and aging. Recently, research on the elucidation of the mechanism and application to medicine has been actively conducted.

Applicants have found that the compound according to the present invention, the Lewis-type sugar chain molanolin derivative, inhibits cell adhesion of leukocytes by binding to selectin. A patent application was filed as a prophylactic / therapeutic agent for rheumatism, asthma, and immune diseases (WO 93/15098). As for natural Lewis-type sugar chain derivatives, applications such as International Publication WO94 / 05152 and International Publication WO95 / 04751 have been filed, and there are descriptions on anti-inflammatory agents, therapeutic agents for immunological diseases, and anti-cancer agents.

However, there have been no reports that Lewis-type glycan derivatives are effective for the prevention and treatment of spinal cord disorders.Furthermore, there are no known preventive or therapeutic methods using Lewis-type glycan derivatives for spinal cord disorders. Not been.

The present invention provides a Lewis-type sugar chain derivative as a new or previously unknown novel preventive or therapeutic agent for spinal cord disorder (hereinafter referred to as a preventive or therapeutic agent).

Spinal cord injury is caused by spinal cord injury, spinal cord surgery, and spinal cord ischemia-reperfusion injury, resulting in severe sequelae and complications such as paralysis of motor function and impairment of spinal cord tissue.

For example, one of the serious complications is paraplegia associated with surgery such as thoracic aortic aneurysm, thoracoabdominal aortic aneurysm, or dissecting aortic aneurysm requiring descending aortic blockade. Once paraplegia develops, its prognosis and recovery are extremely poor, and the patient will be forced to undergo a new fighting illness with mental and physical distress.Prevention of postoperative paraplegia during the above surgery Greatest effort and great care is taken. However, due to the diversity of blood circulation to the spinal cord, its effects have not been sufficient.

Therefore, a replacement form for the prevention and treatment of spinal cord disorders such as motor dysfunction and tissue disorders (Rule 26) Is strongly desired. Disclosure of the invention

As a result of intensive efforts by the present inventors to solve the above-mentioned problems, a composition comprising a compound represented by the following general formula or a pharmaceutically acceptable salt thereof as an active ingredient is effective in preventing and treating spinal cord disorders. It was found to be effective, and the invention was completed.

The present invention relates to a prophylactic / therapeutic agent for spinal cord disorders comprising a Lewis-type sugar chain derivative represented by the following general formula [I] as an active ingredient.

[I]

In the formula, G is a hydroxyl group or acetamide, B is an oxygen atom or a nitrogen atom substituted with -A-R, and one of L and E is fucoh. The other is lanosyl, and the other is sialic acid (2 → 3). Lanosil or Lactohi. Is lanosyl, and M represents hydrogen, a hydroxyl group, or tyrka'lactopyranoside (the bonding position is the 3-position).

—A— is one (CH2) m—,-(CH2) n— NR ^e —CO— O—, — CO—O—, one (CH ₂ ) n—CO—O—, -C ₂ H ₄ ( OC ₂ H ₄ ) p— OCH 2— C 0— 0—,

-C 2 H ₄ (OC 2H4) _z —NR ^e —CO—0_ or 1 (CH ₂ ) n—O—, R ^e represents a hydrogen atom or lower alkyl, m is an integer of 0 to 12 And n represents an integer of 2 to 12. p represents an integer of 0 to 3; z represents an integer of 1 to 4;

R is

Replacement form (Rule 26) (In the formula, R ^a and R ^b are the same or different and each represents a linear or branched, saturated or unsaturated aliphatic hydrocarbon group or a saturated or unsaturated acyl group. ).

In the general formula [I], when B is a nitrogen atom, the compounds according to the present invention include those represented by the following general formula [Π].

[II]

In the formula, w and Y are different from each other, one represents galactopyranosyl and the other represents fucopyranosyl. In this galactobilanosyl, the hydrogen atom of the 3-position hydroxyl group is

0

-S0 ₃ H, - CH ₂ COOH or one P- R ^c

I

R ^d

Wherein R ^e and R ^a are the same or different and each represents a lower alkyl, a lower alkenyl, or a hydroxyl group.

-A-R is the same as the above, or represents a combination of A and R, and each of which may be substituted, represents alkyl, alkenyl, alkynyl, alkoxycarbonyl, or aralkyl.

Further, the Lewis-type sugar chain derivative according to the present invention includes a sialyl Lewis-type sugar chain derivative represented by either of the following general formulas [III] or [IV].

Replacement form (Rule 26)

[HI]

In the above formula, —A—R are taken together to form a straight-chain or branched-chain alkyl having 1 to 30 carbons, alkenyl having 3 to 30 carbons or 3 to 3 carbons. Ring with alkynyl having 0, alkoxycarbonyl having 2 to 30 carbon atoms, alkoxyalkoxyalkyl having 3 to 30 carbon atoms, alkoxyalkoxyalkoxyamide alkyl having 5 to 30 carbon atoms, or alkoxy having 1 to 20 carbon atoms Represents benzyl which may be substituted. V and Q are different from each other, one represents sialic acid (2 → 3) galactobilasyl and the other represents fucopyranosyl.

[IV]

In the above formula, M represents a hydroxyl group or I tilka 'lactobilant' (bonding position is 3-position). V and Q are the same as above.

Hereinafter, the present invention will be described in detail.

In the present invention, examples of the “lower alkyl” include linear or branched ones having 1 to 6 carbon atoms. Representative examples include methyl, ethyl, propyl, isopropyl, butyl, Isobutyl and hexyl.

In the present invention, the term "saturated or unsaturated aliphatic hydrocarbon" includes linear or branched C1-C30, preferably linear C12-C20 alkyl or Alkenes can be mentioned, for example, pentyl, hexyl, octyl, decyl, dodecyl,

Replacement form (Rule 26) Tetradecyl, palmityl, stearyl, icosanyl, docosanil, tetracosanil, hexacosanyl, octacosanil, isohexyl, 9-dodecenyl, 9-tetradecenyl, 9-hexadecenyl, 6-octadecenyl, oleyl, 9-docoenyl, 13-docoenyl , Y-linolenyl and α-linolenyl.

In the present invention, examples of the "saturated or unsaturated acyl" include straight-chain or branched-chain acyl having 1 to 30 carbon atoms, preferably straight-chain having 12 to 20 carbon atoms. Examples include: valeryl, isovaleryl, hexanoyl, octanoyl, decanoyl, lauroyl, myristoyl, palmitoyl, stearoyl, oleoil, 6-octadecenoyl, 13-docosenoyl, arakidoyl, elaidyl, 9,12-noctadeyl. , 9,12-Octadecatrienol and 9,12,15-Octadecatrienol. Of these, oil is preferred. It should be noted that some unsaturated aliphatic hydrocarbon groups or unsaturated acyl groups have 異性 and 異性 isomers, both of which are included in the present invention.

In the present invention, examples of the “lower alkenyl” include straight-chain or branched-chain ones having 2 to 6 carbon atoms. Representative examples thereof include butyl, aryl, propyl, and isopropyl. , 2-butul, 2-pentyl and 2-hexenyl.

In the present invention, examples of the “alkyl” represented by Α and R together include a linear or branched alkyl having 1 to 30 carbon atoms, such as methyl, ethyl, propyl, isopropyl, and the like. butyl, t- butyl, iso- butyl, sec- butyl, hexyl, Okuchiru, Desi Le, lauryl, myristyl to, Kisadeshiru, stearyl, eicosyl, 2-Tetoradeshi to Le can be mentioned Kisadeshiru like, butyl, _three to Preference is given to ethyl butyl, octyl, decyl, lauryl, myristyl, hexadecyl, stearyl, eicosyl and 2-tetradecylhexdecyl.

The alkyl represented by these A and R as 緖 represents a C 2-6 acyl, a C 2-6 alkoxycarbonyl, a cyano, a lower alkyl group rubamoyl, a nitro, a C 2-6 carbon acylamino, a lower Alkylthio, hydroxyl, aryloxy with 6 to 8 carbon atoms, and replacement paper (Rule 26) Is a substituted or unsubstituted benzene ring, or one or more substituents such as a hydroxyl group, lower alkoxy having 1 to 6 carbon atoms, lower alkyl, halogen, cyano, lower alkyl group, rubamoyl, nitro, acylamino having 2 to 6 carbon atoms, lower alkylthio. Or substituted by carboxy or phenyl lower alkyl. Examples thereof include propionylmethyl, norrelylethyl, vivapropylpropyl, methoxycarbonylbutyl, ethoxycarbonylpentyl, propoxycarbylhexyl, and 3- Cyanopropyl, methylcarbamoylethyl, propyl-lubamoylpentyl, 6-nitrohexyl, acetamidomethyl, butyrylaminoethyl, methylthiopropyl, ethylthiobutyl, propylthiopentyl, butylthiohexyl, 2- Droxityl, 2,3-dihydroxypropyl, 5-hydroxypentyl, 2,4,6-trihydroxyhexyl, 2-phenoloxybutyl, 4-phenoxybutyl, 6-phenoxyhexyl, P-trifluoromethylphenethyl 4- (m-dimethylaminophenyl) butyl, 5- (m-cyanophenyl) pentyl, 6- (p-pothamobylphenyl) hexyl, 3- (2,4-dinitrophenyl) propyl In particular, (3,4-dihydroxyphenyl) propyl, (4-hydroxy-3-methoxyphenyl) propyl, P-methylbenzyl, m-bromobenzyl, P-hexyloxybenzyl, m- ( Propionylaminomethyl) benzyl, P- (valerylaminoethyl) phenethyl, 4- (3-methylthio-4-hydroxyphenyl) butyl, P-carboxybenzyl are preferred.

Further, the “alkyl” represented by A and R together includes an alkyl substituted with a 5-membered unsaturated heterocyclic ring which is unsubstituted or substituted with lower alkyl. As a 5-membered unsaturated heterocyclic ring, thiophene, furan, pyrrol and imidazole are preferred, and for example, furfuryl, 5-methyl-furfuryl, 2-tur and 5-methyl-2-tur are preferred.

In the present invention, examples of “alkenyl” represented by A and R as — include alkenyl having 3 to 30 carbon atoms, and are preferably aryl, oleyl, vaccenyl, linoleyl, and arachidonyl.

In the present invention, examples of the “alkyl” represented by A and R together include alkynyl having 3 to 30 carbon atoms. Examples thereof include 2-probyl, 3-butul, and 2-o replacement paper (Rule 26). ) Cutinyl, 9-decinyl, 9-octadecynyl, 9-pentacoshell and the like.

... In the present invention, examples of "alkoxycarbonyl" represented by A and R as-include those having 2 to 30 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, butoxycarbonyl, and octylo. Xicarbonel, tesiloxycarbonyl, pentadecyloxycarbonyl and the like are preferred.

In the present invention, examples of “aralkyl” represented by A and R together include benzyl which may be substituted with alkoxy having 1 to 20 carbon atoms, such as methoxybenzyl, propoxybenzyl, and pentyl. Preferred are hydroxybenzyl, heptoxybenzyl, nonyloxybenzyl, pendecyloxybenzyl, tridecyloxybenzyl, pentadecyloxybenzyl, heptadecyoxybenzyl, eicosiloxybenzyl and the like, with hexyloxybenzyl being particularly preferred.

Further, as "aralkyl" represented by A and R together, a benzene ring is unsubstituted, or as at least one substituent, a hydroxyl group, a lower alkoxy having 1 to 6 carbon atoms, a lower alkyl, a halogen, a cyano, a lower alkyl. Examples include carbamoyl, nitro, C2 to C6 acylamino, lower alkylthio or carboxy-substituted C7 to C20 phenyl lower alkyl.

For example, m-methoxyphenyl, P-trifluoromethylphenethyl, 4- (m-dimethylaminophenyl) butyl, 5- (m-cyanophenyl) pentyl, 6- (p-pothamoylphenyl) ) Hexyl and 3- (2,4-dinitrophenyl) propyl are preferred, and (3,4-dihydroxyphenyl) propyl, (4-hydroxy-3-methoxyphenyl) propyl, P-methylbenzyl, m -Bromobenzyl, P-hexyloxybenzyl, m- (propionylaminomethyl) benzyl, P- (valerylaminoethyl) phenethyl, 4- (3-methylthio-4-hydroxyphenyl) butyl, P-carboxy Benzyl is preferred.

The compound according to the present invention can be used for treatment as it is, but can be used in the form of a pharmaceutically acceptable salt by a known method. In the present invention, "a pharmaceutically acceptable replacement sheet (Rule 26) Salts of mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, P-toluenesulfonic acid, benzenesulfonic acid And salts of organic acids such as ^ tansulfonic acid.

Furthermore,

0

-S0 ₃ H, -CH ₂ COOH or —— P— R ^c

(R ^c and R ^d are the same as those described above). In the compound [I] of the present invention, for example, alkali metal salts such as lithium salt, sodium salt and potassium salt, magnesium salt, calcium salt, and barium salt Alkali earth metal salts can be mentioned.

For example, the hydrochloride can be obtained by dissolving the compound of the present invention in an alcohol solution of hydrochloric acid.

Specific examples of the compound of the present invention include the following.

0- / 3-D-force 'Lactohi. Lanosyl- (l → 3) -O-C (a-L-fucopyranosyl)-(1 → 4)]-Ν- (2,3-Hy's (oley / reoxy)). Mouth hi. ) 1,5-S'-Doxy-1,5-imid D-g / Recitol

0- (3-0-s W- /? -D-force, lactovilanosyl)-(1 → 3) -0- [("-lefcoviranosyl)-(1 → 4)] -Ν- (2,3- Bis (oleix) F. mouth pill) -1,5-oxy-1,5-imino-D-q ', tol,

0- (3-0-S Ι β -D-force * Lactohi.lanosyl)-(1-3) -0- [(a-L-fucopyranosyl)-(1 → 4)] -N- (2,3 -Bis (Sai Reiki) F. Mouth pill)-1,5-Sixoxy-1,5-imino-D-co, Lentol sodium salt,

Ο- -O--β -D-force * Lactohi. Lanosyl)-(l → 3) -0- [(a -L-fucohi; lanosyl) -hi ^→ 4)] -N- (2,3-bis (lauroxy) fu mouth pill) -1,5- * Oxy * oxy-1,5-imino-D-crentole sodium salt,

0- (3-0-S ^ -β-D-force * lactovilanosyl)-(1 → 3) -0-[(a-L-fucopyranosyl)-(1-4)] -N- (2,3- Bis (myristixi) chlorophyll)-1,5-si, oxy-1,5-imino-D-, lucitol sodium salt,

0- (3-0-S,-/? -D-force, lactovilanosyl)-(1 → 3) -0- [(a-lefcopyranosyl)-(1 → 4)] -N- (2,3- Bis (c. Lumichixi) f. Mouth pill)-1,5-cyt *, saiki-1,5-imino-D-crent-l sodium salt,

Ο-0-O-m-β-D-lactovilanosyl)-(1 → 3) -0-[(a-lefcohi.lanosyl)-(1-4)]-N- (2,3-bis (lilyki)

Replacement form (Rule 26) Shi) Huh. Ropir)-1,5-si Y, 1,5-imino-D- ,,) YJ tol sodium salt,

0- (3-0-SΛ-β-D-force, lactovilanosyl)-(1-3) -0- [(a-lefcopyranosyl)-(1 → 4)] -N- (2,3-bisォ), 1,5-hydroxy-1,5-imino-D-, lenthol sodium salt,

0- (3-0-su;-/? -D-ca * lactovilanosyl)-(1 → 3) -0- [(Nano-fucoviranosyl)-(1 → 4)] -N- (2,3- HI, SU (Lauroy W. Kiss). Mouth pill)-1,5-S * T-oxy-1,5-imino-D-C, Lentrum sodium salt,

Ο- -O-m- β -D-force, Lactohi. Lanosyl)-(l → 3) -0-[(a-lefcopyranosyl)-(1-4)]-N- (2,3-bis (myristoy W xy) fu. 7-year-old kishi-1,5-imino-d-k, tol sodium salt,

0- (3-0-S-goods, -β-D-Γlactovilanosyl)-(1-3) -0- [(a-lefcohi.lanosyl)-(1 → 4)]-N- (2,3- Bis (c.lumitoyloxy) fu.mouth pill) -1,5-oxy-1,5-imino-D-; T-lucitol sodium salt,

0- (3- 0-s; 1-/? -D-force, lactovilanosyl)-(1-3) -0- [(na-lefcoviranosyl)-(1 → ⁴ )] -N- (2,3 -Bis (Rilni; kishi) fu. Mouth pill) -1,5-cyte * oxy-1,5-imino-D-co,> sodium sodium salt,

0- (3-0-force Λ, xymethyl-β-D-lactohi.lanosyl)-(1 → 3) -0- [(a-L-fucopyranosyl)-(1-4)]-N- (2 , 3-bis (oley; Wxy).

0- (3-0-phosphono-β-D-force * latatoviranosyl)-(1 → 3) -0- [(a-L-fucopyranosyl)-(1 —)-N- (2,3-bis Lei goods キシ。。。。.

0- (3-0-Methi sphinico-β-D-force'lactohi.lanosyl)-(1 → 3) -0-[(a-L-fucopyranosyl)-(1 → 4)]-N- (2, 3-Bis (reiki) f. Mouth pill) -1,5-si, te, oxy-1,5-imino-D-k, tol sodium salt,

0- (3-0-λ-β-D-calactohi.lanosyl)-(1-3) -0-[(a-lefcopyranosyl)-(1 → 4)]-N- (2,3-hi, , Su (Wale W "Kis) fu. Mouth pill) -1,5-sh * te * oxy-1,5-imino-D- ku, Thor) pam salt,

Ο- -O--β -D-force * lactovilanosyl)-(l → 3) -0- [(a -L-fucopyranosyl)-(1 → 4)] -N- (l, 3-bis (oley W Xy) fluoro-2-n; 1 xyca W, ell) -1,5-cyoxy-1,5-imino-D-, lucitol sodium salt,

CK3-0-S Λ-β -D-force, lactoviranosyl)-(1-3) -0- [(a -lefcopyranosyl)-(1 → 4)] -N- (l, 3-bis (oleoiki) Cis-1,2'-xyloxy'nyl) -1,5-si ', te, oxy-1,5-imino-D-co, sodium sodium salt,

0- (3-0-Slactohi.lanosyl)-(1 → 4) -0- [(α-L-fucohi.lanosyl)-(1 → 3)] -N- (2,3-bis ) フシヒ-5- 1 5-----1,5-S

0 (3-0-force kutviranosyl)-(1 ^→ 4) -0- [-Lefkohi. Lanosyl)-(1 → 3)] -N- (2,3-bis (Lauri ^ Replacement sheet (Rule 26) Shi) Huh. Mouth pill)-1,5-si, tert-oxy-1,5-imino-D-lactone, lenthol sodium salt,

0- (3-0-S; 14-β-D-force, lactovilanosyl)-(1-4) -0- [(a-lefcopyranosyl)-(1 → 3)]-N- (2,3- Bis (Sweet Leoi product) Mouth pill) 1,5-C'-te, Oxy-1,5-imino-D-k,> Sodium sodium salt,

0- (3-0-S Λ-β -D-force ', lactovilanosyl)-(1 → 4) -0- [(a -L-fucopyral)-(1 → 3)] -N- (2, 3-bis (lauroy W xy) fu. Dipyr)-1,5-si,, te, oxy-1,5-imino-D-k, tol sodium salt,

0 (3-0-,, xymethyl-β-D-force, lactobilanosyl)-(1 → 4) -0- [(a-L-fucopyranosyl)-(1 → 3)] -N- (2, 3-bis (oley Wxy). Π-pill) -1,5-si, teoxy-1,5-imino-D-co,> sodium sodium salt,

0- (3-0-phosphono-β-D-force, lactobilanosyl)-(1 → 4) -0- [(a-L-fucopyranosyl)-(1 → 3)] -N- (2,3- Bis (oley; W xy). Π-pill)-1,5-si, oxy -1,5-imino-D-crentole sodium salt,

0 (3-0-methinosphinico-β-D-force, lactosyl. Lanosyl)-(1-4) -0- [(a-L-fucohi. Lanosyl)-(1 → 3)] -N- ( 2,3-Bis (Sai Reiki) Dipir) -1,5-Te * Shi-ki 1,5-imino-D-co,>

0- -D-force 'Lactohi. Lanosyl-(l → 4) -0- [(na-refukohi; lanosyl)-(1 → 3)] -N- [3- [N-C (1,3-Hy-su (oleoyloxy). Mouth / N-2-yl) oxy or leho'nil] amino] Τπhi. -1,5-S'-te-oxy-1,5-imino-D-C'lucitol

0- (3-0-s; force, lactovilanosyl)-(1-4) -0- [(na-L-fucoviranosyl)-(1 → 3)] -N- [3- [N- ((1 , 3 -Bis (Sweet Leoi W "Kis) Fu-ro-2-n-yloxy) 力〕ミノミノミノミノ。口口. Crent-Luna Thorium salt,

O- -O- force, lactovilanosyl)-(l → 4) -0- [(a-L-fucoviranosyl)-(1 → ³ )] -N- [3- [N- [(1,3- Bis (Lauroisiki) F. Loha. Mouth pill]-1,5-cyte *, 1,5-imino-D-crent-luna sodium salt,

0- (3-0-S Λ--D-force ctopyranosyl)-(1 ^→ 4) -0- [(α-Lefcohi.lanosyl)-(1-3)] -Ν- [6- [Ν- ( (1,3-bis (oleoy; 1-xy) fu.loha.n-2-yl) oxy-force; ,, nil] amino] hexyl]-1,5-si, te 5-imino-D-alk, sodium salt,

0- (3-0-S n-/ 3-D-force * lactoviranosyl)-(1-4) -0- [(-L-fucoviranosyl)-(1-3)] -N- [8- [N -[(1,3-bis (leoxy) fu.loha.n-2-yl) oxyca ^, nil] amino] cytyl] -1,5-oxy-1,5-imino-D- Crent Luna Tribium Salt,

0- (3-0-su-/? -D-force, Lactohi. Lanosyl)-(1 → 4) -0- [(Nan-shi Fucohi. Lanosyl)-(1 → 3)] -N- [ 9- [N- [(1,3 Replacement sheet (Rule 26) -Bis. Loha. N-2-yl) oxyl force Wnil] amino] nonyl] -1,5-si, te ,, oxy-1,5-imino-D-toluene sodium salt,

.. 0- (3-0-S W- -D-force, lactovilanosyl)-(1 → 4) -0- [-Lefcoviranosyl)-(1 → 3)] -N- [12 [N- (( 1,3 -hi ,,,,,,,,,,,,,,,,,,,,,,,,,,,, (1,2 Kishi-1,5-imino-D-crent-sodium salt,

0- (3-0-methyl, sphinico- /? -0-force ', lactovilanosyl)-(l → 4) -0- [(na-lefcoviranosyl)-(1-3)] -N- [3- [N-[(1,3-bis (oleoy W "xy) fu.loha.n-2-yl) oxyl ;;, nil] amino] fluoro] -1,5-si ,,, Oxy-1,5-imino-D- ;, rentol sodium salt,

0- (3-0-Met フィ sphinico- /? -D-force, lactopyranosyl)-(l → 4) -0- [(hi-lefkohi.lanosyl)-(1-3)] -N- [3 -[N-[(1,3-bis (lauroy; xy) fu.loha.n-2-yl) oxy] amino]. Mouth pill]-1,5-te, Oxy-1,5-imino-D-co, Tol sodium salt,

CK3-0-Met) Sphinico-/? -0- Lactovilanosyl)-(1 → 4) -0- [(α-Lefcohi. Lanosyl)-(1 → 3)] -Ν- [6- [Ν-[( 1,3-Bis (Leo Ixi) F. Lo-2-N) Ability JV *, Nil] Amino] Hexyl]-1,5-Si * Ability 1,5- Imino-D-quinitol sodium salt,

0- (3-0-Met W, Sphiniko- /? -D-force, Ractopyral)-(1-4) -0- [0-Refukohi. Lanosyl)-(1-3)] -Ν- [9- [Ν-I-((1,3-bis (oleoyl-Wxy) fu.loha.n-2-yl) oxycarpho ', nil] amino] nonyl] -1,5-si ,, te ', oxy-1,5-imino-D-clentyl sodium salt,

0- (3-0-Methi sphinico- /? -0-C * lactoviranosyl)-(1-4) -0-[("-L-fucoviranosyl)-(1 → 3)]-N- [12- [ N-[(1,3-bis (oleoyloxy) fu.loha.n-2-yl) oxyl] amino] te, syl] -1,5-si, oxy-1,5-imino -D-co ,; Rentole sodium salt,

0- (3-0-phosphono-D-force, lactovilanosyl)-(l → 4) -0-[("-lefucoviranosyl)-(1 ^→ 3)]-N- [3- [N-[(1 , 3-Bis (Ole Sai W "Kishi) fu. Loha.n-2-yl) Oxika ,, Nil] Amino] Fu mouth pill]-1,5-C ', Te * oxy-1, 5-imino-d-c '> sodium-sodium salt,

0- (3-0-phosphono- ^ S-D-force, lactovilanosyl)-(1 → 4) -0-[("-fufuvilanosyl)-(1-3)]-N- [3- [N -[(1,3-Bis (lauroyoxy) fu. Lo-2-n) oxy power W, ul] aminino] fu. Pill] -1,5-si, te * oxy -1 , 5-imino-D-k, sodium monosodium salt, replacement paper (Rule 26) 0- (3-0-phosphono-/? -D-force ', lactopyranosyl)-(l → 4) -0- [(a -L-fucohi.lanosyl)-(1 → 3)] -N- [6 -[N- [(1,3-bis (oleoyl Woxy) fu.loha.n-2-yl) oxy 力 ,, nil] amino] hexyl]-1,5-si, te ', Oxy-1,5-imino-D-lentol sodium salt,

0- (3-0-phosphono-/?-D-force, lactoviranosyl)-(l → 4) -0-[(a-L-fucopyranosyl)-(1 → 3)]-Ν- [9- [ Ν-[(1,3-bis (oleoyl; 1-xy) -fu-loha.n-2-yl) oxy-force Wnyl] amino] noel] -1,5-si, oxy-1,5-imino -D-k, rentol sodium salt,

0- (3-0-phosphono-/?-D-force, lactosyllanosyl)-(1-4) -0-[(hi-lefcoviranosyl)-(1 → 3)]-Ν- [12- [ Ν- [(1,3-bis (oleoixi) fu.loha.n-2-yl) oxy-force;! ^ El] amino] to * te * sil]-1,5-shi * te * oxy- 1,5-imino-D-crent monosodium salt,

0- (3-0-force /, xymethyl- /? -D-force ', lactohi.lanosyl)-(1-4) -0-[(α-lefcoviranosyl)-(1 → 3)]-Ν- [ 3- [Ν-[(1,3-bis (oleoixi)]. Loha.n-2-yl) oxy force ¼ ,,, nil] amino]. Mouth pill] -1,5-si, Oxy-1,5-imino-D-coul * citr sodium salt,

0- (3-0-force ^, xymethyl-/ 3- -D-force, lactopyranosyl)-(1 → 4) -0- [("-lefcoviranosyl)-(1 → 3)] -N- [3 -[N-[(1,3-bis (lauroy Wxy) fu.loha.n-2-yl) oxy power W ,, 2l] amino] fu.Mouth pill] -1,5-si * te * Oxy-1,5-imino-toluene sodium salt,

0- (3-0-force W, xymethyl- -D-force, lactosyl. Lanosyl)-(1 → 4) -0- [(na-lefcoviranosyl)-(1 → 3)] -N- [6 -[N-[(1,3-bis (oleoyl Woxy) fu.loha.n-2-yl) oxy]; 14,, u] rayamino] hexyl]-1,5-si ', '' -Shiki-1,5-imino-D-crent-sodium salt,

0- (3-0-force Λ, xymethyl- -D-force, ratatopyranosyl)-(l → 4) -0- [(na-lefcopyranosyl)-(1 → 3)] -N- (9-N -[(1,3-bis (oleoyloxy) fluoro-an-2-yl) oxyl force; nil] amino] nonyl]-1,5-si, te * oxy-1,5-imino- D-k,> sodium salt,

0- (3-0-force Λ ,, xymethyl- / 3-D-force, lactohi. Lanosyl)-(1 → 4) -0- [(a-L-7 coco. Lanosyl)-(1 → 3 )) -N- [12 -N-[(1,3-bis (oleoxy) fu.loha.n-2-yl) oxycarl] amino] and te ', syl] -1,5-si Toxy-1,5-imino-D-, lucitol sodium salt,

0- (3-0-S-/? -D-) T lactovilanosyl)-(1 → 3) -0- [("-lefcoviranosyl)-(1 → 4)] -N- [3- [N- [ (1,3-bis (oleoy; W xy) 7 ° Πh-n-2-yl) oxy force; 14, nil] amino] f. Mouth pill] -1,5-si, te'oxy -1,5-Imino-D-K, Lent-Luna Replacement Sheet (Rule 26) Thorium salt,

0- (3-0-S W- / 3-D-force, lactoviranosyl)-(1 → 3) -Ο-[(α-lefcoviranosyl)-(1 → 4)]-Ν- [3- [Ν -((1,3-^ S (Lauroy Wxy) F. Loha-n-2-yl) oxy-force; 1, Nil] Amino] F. Mouth pill] -1,5-shi * te * oxy -1,5-imino-D-coke,> sodium natrium salt,

0- (3-0-methi; 1 sphinico- /? -D-force, lactobilanosyl)-(l → 3) -0- [(a-L-fucoviranosyl)-(1 → 4)] -N- [ 3- [N-[(1,3-bis (oleoyl; 1xy) loha.n-2-yl) oxyca ,, 2l] amino] 7 ° mouth pill] -1,5-si, te, , Oxy-1,5-imino-D-chlorocitr sodium salt,

0- (3-0-phosphono- / 3-D-force, lactosyl. Lanosyl)-(1-3) -0-[("-lefcoviranosyl)-(1 → 4)]-N- [3- [ N-[(1,3-bis (oleoyloxy) fu.loha.n-2-yl) oxy,, nil] amino] fu. 5-imino-0-crent-sodium salt,

0- (3-0-force, xymethyl- -D-force, lactobilanosyl)-(1 → 3) -0- [(a-L-fucoviranosyl)-(1 → 4)] -N- [3- [N-[(1,3-bis (oleoy Woxy) fluoro] .n-2-yl) oxy power ニル ,, nil] amino. Mouth pill] -1,5-oxy-1,5-imino-cyclohexyl sodium salt,

Ο-β-Ό-ij'lactopyranosyl- (1 → 4) -O-[(a-L-fucopyranosyl)-(1 → 3)]-N- (l, 3-hy's) F. Roha-n-2-yl-x-xylcaroxy-nil) -1,5-di-doxy-1,5-imino-D-c-lucitol

O-0-O-XW-β-D-force, Lactohi. Lanosyl)-(1 → 4) -0- [(a-Lefkohi. Lal)-(1 → 3)] -N- (l, 3-bis). -I-Xicarbo ', nil) -1,5-si', te, cis-1,5-imino-D-lentol sodium salt,

0- (3-0-S Λ--D- Lactopyranosyl)-(1 → 4) -0- [(α-Lefcohi.lanosyl)-(1 → 3)] -N- (l, 3-bis (lauroy Xy-2) xy-2-yl xycarbonyl * nil) -1,5-c ', te, sodium xy-1,5-imino-D-lentol sodium salt,

0- (3-0-S β-D-lactovilanosyl)-(1 → 4) -0- [(a-fufucopyranosyl)-(1 → 3)]-N- (l, 3-bis (myristoyloxy) Πh.-2-nixica ', nil) -1,5-tetraxoxy-1,5-imino-D-k, sodium sodium salt,

0- (3-0-S-β-D-force, lactovilanosyl)-(1-4) -0- [(a-lefcopyranosyl)-(1 → 3)] -N- (l, 3-bis ( C. Lumitoy; 1 Kishi) F. K-2-N W "Kishi Power; 14, Nil)-1,5-shi, te, ... Lenthol sodium salt,

0- (3-0-s β-D-force, lactosyl. Lanosyl)-(1 → 4) -0- [(a -L-fucopyranosyl)-(1 → 3)] -N- (l, 3 -H ,, S (Ril2W-x) .Han-2-yWxikalfonyl) -1,5-S ,, T-oxy-1,5-imino-D-crenthol sodium salt ,

0- (3-0-S Λ-β -D-force, lactosyl. Lanosyl)-(1-4) -0- [(a -L-fucopyranosyl)-(1 → 3)] -N- (l , 3-bis (Oreiki replacement sheet (Rule 26) Cis-fun-2-y M "xica; 1,, nil) -1,5-si, te, oxy-1,5-imin D-lenthol sodium salt,

Ο----β-D-force, lactovilanosyl)-(1 → 4) -0- [(a -lefcopyranosyl)-(1 → 3)] -N- (l, 3-bis (Rau'JW ) 7 ° π /, ° n-2-y Wx force ニル ,, nil) -1,5-Si ,, te ,, oxy-1,5-imino-D-, ,

0- (3-0-S-β-D-force ', lactovilanosyl)-(1 → 4) -0-[(a-lefcopyranosyl)-(1 → 3)]-N- (l, 3-bis ( Myristi W xy) fluoroan-2-ixicarbo, ul) -1,5-te, oxy-1,5-imino-D-c-> thanol sodium salt,

0 ⁽³ _0- scan - ^ -D- force ,, Rakutobiranoshiru) - (1 → ⁴⁾ -0- [(α -. Refukohi Ranoshiru) - (1 → ^3)] -N- (l, 3- bis (C. Lumichil) π C. 2--2-^^^) 1,, 2) 5-) -1,5-S, tert-oxy-1,5-imino-D-crenthol sodium salt,

O-0-O--β-D- force, Lactohi. Ral)-(1 → 4) -0- [(a -L-fucopyranosyl)-(1-3)] -N- (l, 3-bis (lyly; W xy) fu. -1,5-Si '), 1,5-imino-D-cyclohexyl,> sodium sodium salt,

0- (3-0-force Λ ', xymethyl-β-D-force, lactosyl. Lanosyl)-(1 ^→ 4) -0-[(a-L-fucopyranosyl)-(1 → 3)]-N -(l, 3-bis) 5-imino-D-lentol sodium salt,

0- (3-0-phosphono-β-D-force ', lactovilanosyl)-(1—-0-[(a-lefcopyranosyl)-(1-3)]-N- (l, 3-bis (Yloxy) phenyl phenyl-2-n-oxyl force; nyl) -1,5-oxy-1,5-imino-D-lentol sodium salt;

0- (3-0-Methic goods, Sphinico-β-D-lactobilanosyl)-(1-4) -0- [(a-L-fucopyranosyl)-(1 → 3)] -N- (l, 3- Bis- (l-reoxy) -l-oh-2-y-zoxyka * nil) -1,5-te, oxy-1,5-imino-D-quantol sodium salt,

Ο- -O--β-D-calactovyranosyl)-(1 → 4) -0- [(a -shifucopyranosyl)-(1 → 3)] -N- (l, 3-bis W-xy-D. D-H-2-n-I-xika;

Ο-0-Ο-ΧΛ-β-D-lactohi. Lanosyl)-(1-4) -0- [(a -L-fucopyranosyl)-(1 → 3)] -N- (2,3-bis (salt leoi W xy) fu. Α-pill) -1,5 -Teoxy-1,5-imino-D-alkane, sodium salt,

0- (3-0-su;-/? -D-force ', lactovilanosyl)-(1 → 4) -0- [(hi-fucoviranosyl)-(1-3)] -Ν- [3- [ (1,3-bis (o-leoi; 1-kis)). Ropir]-1,5-si,, te, sikiki-1,5-imino-D-crent-l-sodium salt,

0- (3-0-su; -force ', lactovilanosyl)-(l → 4) -0- [-L-fucohi. Lanosyl)-(1 → 3)] -N- [3-[(1,3-bis (lauroy Wxy) fu.loha.n-2-yl) oxy]) * nil] fu. Mouth pill) -1,5-di ', te, oxy-1,5-imino-D-lentol sodium salt

0- (3-0-s; Ι-D-force, lactovilanosyl)-(l → 4) -0- [(na-refukohi. Lanosyl)-(1 → 3)] -N- [3-[( 1,3-bis (stealoy W xy). Loha-n-2-yl) oxy power. Mouth pill] -1,5-si, Oxy-1,5-imino-D-crentitol sodium salt,

0- (3-0-s-/?-D-force, lactovilanosyl)-(1 → 4) -0- [(α-lefcoviranosyl)-(1-3)] -Ν- [3- [(1 , 3-bis (C. Replacement sheet (Rule 26) Lumi toy; Loha. -2-yl) oxyka 财, ル]. πhi. 1,5-cysteine, sodium x-1,5-imino-D-lentol sodium salt,

0- (3-0-sΛ / 3-D-force, lactosyl. Lanosyl)-(1 → 4) -0- [(a-L-fucoviranosyl)-(1 —)-Ν- [6- [ (1,3-Bis (Student Leo W "Kisyi) Ro-ha-n-2-yl) oxyl; 14 ,, nil] hexyl] -1,5-si, te ', oxy-1, 5-imino-D-knol sodium salt,

0- (3-0-S-/ 3-D-force, lactoviranosyl)-(l → 4) -0- [(a-L-fucoviranosyl)-(1-3)] -N- [6- [ (1,3-bis (la-roixoxy) -fu-lo-2-yl) oxy-force, le] hexyl]-1,5-si, te ', oxy-1,5-imino- D-Central sodium salt,

0- (3-0-force, lactovilanosyl)-(l → 4) -0- [(hi-L-fucoviranosyl)-(1 → 3)] -N- [6-[(1,3-hi ,, s (Steaalloy W xy) π /, ° n-2-yl) oxy force W hexyl] hexyl] -1,5-tetra * xy-1,5-imino-0-crent -Sodium salt,

0- (3-0-s-/?-D-force, lactovilanosyl)-(1 → 4) -0- [("-lefcoviranosyl)-(1 → 3)] -Ν- [6-[(1 , 3-hi ,, su (c. Lumitoi; 1 xy) fluor. -2-yl) oxy force; nil] hexyl] -1,5-si, te,, oxy-1,5 -Imino-0-k, sodium salt,

0- (3-0 -S,-? -D-force, lactopyranosyl)-(l → 4) -0- [("-lefcoviranosyl)-(1-3)] -N- [8- [( 1,3-bis (o-le-y-shi) -flo-ha.n-2-yl) -oxyca ', nil] octyl] -1,5-si', te-oxy-1,5-imino-D-c '' Tole sodium salt,

0- (3-0-force, lactovilanosyl)-(1 → 4) -0- [(α-lefcoviranosyl)-(1 → 3)] -Ν- [8-[(1,3-hi, S- (ラ-ゥ-キシ -yl) -oxy-force; 1 ', nil] octyl] -1,5-si ,,,,,,, Crentol sodium salt,

Ο-03-Ο-S ^-/? -D-Power, Lacto. Lanosyl)-(1 → ⁴ ) -0-[(na-L-fucoviranosyl)-(1 → 3)]-Ν- [8-[(1,3-bis (stealoyoxy). -2-yl) oxy power / 14, nil] octyl] -1,5-cyte * oxy-1,5-imino-D-crentole sodium salt,

0- (3-0-su,-/?-D-force, lactovilanosyl)-(1 → 4) -0- [(α-fufuviranosyl)-(1 → 3)] -N- [8- [(1,3-bis (ha.rumitoxy)]. Loha.n-2-yl) oxyca, nil] octyl] -1,5-si, 'te ,, oxy-1,5-imino -D-Central sodium salt,

0- (3-0-S W- /? -D-force, lactovilanosyl)-(l → 4) -0- [-lefucoviranosyl)-(1 → 3)] -N- [12- [(1, 3-bis- (1-leoxy); 。- ン -2-yl) -l-xylcarboxyl] pente, syl] -1,5-sixoxy-1,5-imino-D- > Sodium sodium salt,

0- (3-0-su,-/? -D-force, lactovilanosyl)-(1 → 4) -0- [(hi-L-fucopyranosyl)-(1 → 3)] -N- [12 -[(1,3-bis (lauroy; 1xy) fu.loha.n-2-yl) oxycarbo ,, nil] pente ,, sil] -1,5-si ', te', oxy-1, 5-imino-D-crentole sodium salt,

0- (3-0-s -force, lactovilanosyl)-(l → 4) -0- [(hi-L-fucopyranosyl)-(1-3)] -N- [12- [(1,3- Bis (Stearoy Wx) F. Loha. 2-yl) oxy force / 1,, nil] penta, syl]-1,5-si, te, oxy-1,5-imino-D -C '> tresodium salt, 0- (3-0-ose / 1-/ 3--0-ca, lactohydranosyl)-(1 → 4) -0- ((α-lefcopiral)-( 1- 3)] -N- [12- [(1,3-bis (ha.lumitoi Wki) fu.loha.n-2-yl) oxyl force W ,, nil] Pente ,, sil]- 1,5-c ', te,, cis-1,5-imino-D-co,> sodium tol, 0- (3-0-s-/ 3-D-force, lactoviranosyl)-( l → 4) -0- [(hi-L-fucopyranosyl)-(1 → 3)] -N- [4-[(1,3-bis (o Replacement paper (Rule 26) Leoi W Kiss) -2-yl) -year-old sika, ell] -3-year-old sukif ', chill] -1,5-si', te ,, seki-shi-1,5-imino-D-lenthol sodium salt, 0 -(3-0-S W- /? -D-force, lactovilanosyl)-(1 → 4) -0- [("-lefcoviranosyl)-(1 → 3)] -N- [7- [(1 , 3-bis (radio W xy). Π-han-2-yl) abilities; 1,, ell] -3,6-si, oxahefu. Tyl] -1,5- ,,,, Oxy-1,5-imino-D-lenthol sodium salt,

0- (3-0- I-/? -D-force, lactovilanosyl)-(l → 4) -0- [(a -L-fucohi.lanosyl)-(1-3)] -N- [10 -[(1,3-bis (steaalloy ktoxy) fu.loha.n-2-yl) oxyca, le] -3,6,9-trioxyl] -1,5-oxy-1,5-imino -D-k,> sodium sodium salt,

0- (3-0-S ^-/?-D-force, lactobilanosyl)-(1-4) -0- [( _a -L-fucoviranosyl)-(1 → 3)] -N- [13- [(1,3-bis (/ ,. Lumitoy; Wxy) F.loha.n-2-yl) oxylity Λ ,, Nil] -3,6,9,12-tetraxatrite, sill] -1,5-Te * oxy-1,5-imino-D-c *) Rentol sodium salt,

0- (3-0-su; 1-/? -D-force, lactovilanosyl)-(1 → 4) -0- [(hi-refukohi.lanosyl)-(1 → ³ )] -Ν- [5 -[(1,3-Bis (Ore-Sii Wki) Floha. N-2-yl) -Oxy Power W, Nil] Amino-3-Okisahefu. Chill) -1,5-soxy-1,5-imino-D-crent-sodium ioiL,

0- (3-0-S-/ 3-D-force's Lactohi. Lanosyl)-(1 → 4) -0- [("-Lefcoviranosyl)-(1-3)] -N- [8- [( 1,3-bis (radioxy) fu-lo-n-2-yl) oxyca ^ ', nil] amino-3,6-si -1,5-imino-D-crent-lunathorium salt,

0- (3-0-force, lactovilanosyl)-(1-4) -0-[(na-L-fucoviranosyl)-(1-3)]-N- [11-[(1,3-bis (Stearoyxy π.-2-Nyl) Ability M ,,, Nil] amino-3,6,9-trioxantene * sil] -1,5-Axy-1,5-imino-D -^ Lucitol sodium salt,

0- (3-0-su, -D-force, lactovilanosyl)-(1 → 4) -0- [(na-L-fucoviranosyl Hl → 3)] -N- [14- [(1, 3-bis (ha.lumitoi; 1kis) fu.loha.n-2-yl) oxyl force, nil] amino-3,6,9,12-tetraoxy torate, syl] -1,5-si ' Teoxy-1,5-imino-D-,> sodium sodium salt.

O- (3-O-sulfo- -D-force 'lactolanosyl)-(1 → 4) -O- [(α-lefcohi.lanosyl)-(1 → 3)] -1,5-si'te' Oxy-1,5-imidin Ν-oleyl-D-glucitol sodium salt

Ο- (3-Ο-sulfo-jS-D-force'lactohi. Lanosyl)-(1 → 4) -〇-[-L-fucohi. Lanosyl)-(1 → 3)] -1,5-Cytheoxy-1,5-imi N-x "xenyl-D-q '/ lecitr sodium salt Replacement paper (Rule 26) O- (3-O-sulfo- / 3-D-force "lactohylanosyl)-(1 → 4) -O- [(α-lefcolanosyl)-(1 → 3)] -1,5-si ' Te-shiki-, 5-imino-Ν-lylyl-D-glucitol sodium salt

Ο- (3-Ο-sulfo- -D-galactobilanosyl)-(1 → 4) -0- [(a -lefcolananosyl)-(1 → 3)] -1,5-di-doxy- , 5-Imino-N-arachidiel-D-k '/ resititol sodium salt

◦- (3-O-sulfo-D-force 'lactopyranosyl)-(l → 4) -O- [(a-L-fucopyranosyl)-(1 → 3)] -1,5-cy -, 5-Im. Lohi. Onylmethyl-D-C '/ recitol sodium salt

Ο- (3-Ο-Sulfo-D-force 'lactohylanosyl)-(1 → 4) -0- C (α -lefcohi.lanosyl)-(1 → 3)] -1,5-si ^, te' Toshiki-, 5-imino- Ν- (4-methoxycarbo-2 / reftyl) -D-qulucitol sodium salt

◦- (3-Ο-Sulfo-D-force'lactovilanosyl)-(1 → 4) -Ο-[(α-Lefcolanosyl)-(1 → 3)]-1,5-di-deoxy-, 5-Imi Ν- (3-methyl-off. Ropir) -D-Cullucitol sodium salt

0- (3-Ο-sulfo- / 3-D-force'lactohi. Lanosyl)-(l → 4) -O-[-refukohi. (Lanosyl)-(1 → 3)) -1,5-di'-doxy-, 5-imi Ν- (5-methylfurfuryl) -D-kullucitol-sodium salt

Ο- (3-Ο-Sulfo- / 3-D-force'lactodani.lanosyl)-(l → 4) -O-[(c∑-L-fucohilanosyl)-(1 → 3)] -1 , 5-S-doxy-, 5-imi N-^-D-C-lucitol sodium salt

O- (3-O-sulfo-D-force'lactohi.lanosyl)-(1 → 4) -0-[(a-lefcohi.lanosyl)-(1 → 3)]-1,5-di-deoxy- , 5-Imino-N- (2,3-hydroxy (hydroxyphenyl) phenyl) -D-chlorocitr sodium salt

O- (3-0-sulfo-force 'lactovilanosyl)-(l → 4) -O- [(a -lefcohi.lanosyl)-(1 → 3)] -1,5-di-deoxy-, 5 -Imino-N- (2-phenoxicetyl) -D-glucitol sodium salt

O- (3-0-Sulfo- -D-force 'Lactohi. Lanosyl)-(l → 4) -O- [-Lefkohi. Lanosyl)-(1 → 3)] -1,5-cy'the-oxy-, 5-imino-N- (3,4-cy'hydroxyphenyl) arohi. -D-da / recitol sodium salt

O- (3-O-sulfo-β-D-force'lactohi.lanosyl)-(l → 4) -0-[(a-L-fucohi.lanosyl)-(1 → 3)]-1,5- 'Te'oxy-, 5-imino-N- (4-hydroxy-3-methoxyphenyl) fu. Ropyr-D-darcitol sodium salt

O- (3-O-sulfo--D-force 'lactodani. Lanosyl)-(1 → 4) -Ο- [(α-refukohi. Lanosyl)-(1 → 3)] -1,5-si' Teoxy-, 5-imid-decyl-D-clucitol sodium salt

Ο- (3-Ο-Sulfo-D -force 'Lactohi. Lanosyl)-(1 → 4) -Ο- [(α-Lefkohi. Lanosyl)-(1 → 3)] Oxy-, 5-imino-Ν-.Ntadecyl-D-glucitol sodium salt Replacement paper (Rule 26) O- (3-O-sulfo-β-D-force'lactohi.lanosyl)-(l → 4) -O-[(a-lefcolananosyl)-(1 → 3)]-1,5-si ''' 才-キシ, 5-imino-N-eicosyl glucitol sodium salt

. · O- (3-O-sulfo force 'lactosyl. Lanosyl)-(1 → 4) -Ο- [(α-refukohi. Lanosyl)-(1 → 3)] To Kishi-, 5-imino-Ν-. Intereicosyl-D-Clulucitol Sodium Salt

Ο- (3-Ο-sulfo--D- is lactopyranosyl)-(1 → 4) -Ο- [(α-lefcohylanosyl)-(1 → 3)] -1,5-di'-doxy-, 5 -Imino- Ν-triacontyl -D- ク '/ Resirenadium salt

Ο- (3-0-Sulfo-D-force'lactohi.lanosyl)-(1 → 4) -Ο- [(α-refukohi.lanosyl)-(1 → 3)] -1,5-si To xy-, 5-imino-Ν-. Nantria Contyl -D-Clulucitol Sodium Salt

Ο- (3-0-Sulfo- / 3-D-force'lactohi. Lanosyl)-(l → 3) -O-[-Lefkohi. (Lanosyl)-(1 → 4)] -1,5-didecoxy-, 5-imino --- oleyl-D-V-lucitol sodium salt

Ο- (3-〇-Sulfo-3-D-force'lactovilanosyl)-(1 → 3) -0- [(α-Lefcohi.lanosyl)-(1 → 4)]-1,5-di-doxy- , 5-Imino-Ν-haxenyl-D-kulucitol sodium salt

Ο- (3-Ο-sulfo-β-D-force'lactolananosyl)-(l → 3) -O-[(a-L-fucohi. Lanoshi / re)-(1 → 4)]-1, 5-S-Doxy-, 5-imino-N-lylyl D-Culusitol sodium salt

O- (3-O-sulfo- -D-force'lactohi.lanosyl)-(l → 3) -O-[(a-L-fucohi.lanosyl)-(1 → 4)]-1,5-si 'Doxy-, 5-imino-N-arachito' L-D-C'lucitol sodium salt

O- (3-O-sulfo-S-D-force 'Lacto. Lanosyl)-(1 → 3) -Ο- [(α-lefcoviranosyl)-(1 → 4)] -1,5-di-doxy- , 5-Imino-p-pi-pi-nilmethyl-D-glucitol sodium salt

Ο- (3-Ο-Sulfo-D-force'lactohi.lanosyl)-(l → 3) -O-[-L-fucopyranosyl)-(1 → 4)] -1,5-cy -, 5-Imino- Ν- (4-methoxycarbo'dilf'tyl) -D-clulucitol sodium salt

Ο- (3-Ο-Sulfo-D-force'lactovilanosyl)-(1 → 3) -Ο-[(α-Lefcohi.lanosyl)-(1 → 4)] -1,5-S , 5-Imino-Ν- (3-methyl / oral) -D-Clulucitol sodium salt

Ο- (3-Ο-Sulfo-y3-D-force'lactohi.lanosyl)-(1 → 3) -Ο-[(α-lefcohi.lanosyl)-(1 → 4)]-1,5-si ' Dexyl-, 5-imidin Ν- (5-methylfurfuryl) -D-chlorocitr sodium salt

Ο- (3-Ο-sulfo--D-force 'lactovilanosyl)-(l → 3) -O- [(a -L-fucohi.lanosyl)-(1 → 4)] -1,5-cysteine 'Shi-ki-, 5-imino --- teel-D-co'lucitol sodium salt replacement sheet (Rule 26) O- (3-O-sulfo- -D-force 'lactohydranosyl)-(1 → 3) -Ο- [(α-fufucopyranosyl)-(1 → 4)] -1,5- Xy- 1,5-imid Ν- (2,3-hydroxy (hydroxyphen :: ru) arohi.-D-kulucitol sodium salt

... 0- (3-0-sulfo--D-force lactohydranosyl)-(l → 3) -O- [(a -lefcohi.lanosyl)-(1 → 4)] -1,5- 'Deoxy-1,5-imi-N- (2-phenoxicetyl) -D-ku' / resititol sodium salt

O- (3-O-sulfo--D-force 'ratatoviranosyl)-(l → 3) -O- [(a -lefcopyranosyl)-(1 → 4)] -1,5-di'-doxy-1,5 -Imi N- (3,4-dihydroxyphenyl) -D-C-lucitol sodium salt

O- (3-O-sulfo- -D-force lactohydranosyl)-(l → 3) -O- [(a -lefcohi. Lanosyl)-(1 → 4)] -1,5-dioxy -1,5-imino-N- [3- (4-hydroxy-3-methoxyphenyl) nlfl] -D-darcitol sodium salt

O- (3-0-Sulfo-3-D-force'lactovilanosyl)-(1 → 4) -Ο-[(α-lefcohi.lanosyl)-(1 → 3)]-1,5-di-doxy- 1,5-Imine Ν-te'syl-D-co'lucitol sodium salt

Ο- (3-Ο-sulfo-β-D-force'lactopyranosyl)-(l → 4) -O-[(a-lefcopyranosyl)-(1 → 3)]-1,5-cy'te'oxy- To 1,5-imino-N-. Nate'Sil -D-C'lucitol sodium salt

◦- (3-O-sulfo-D-force 'lactohi. Lanosyl)-(1 → 4) -Ο- [(α-lefcohi.lanosyl)-(1 → 3)] -1,5-si'te' 1,5-Imi エイ -eicosyl-D-C'lucitol sodium salt

Ο- (3-Ο-Sulfo- -D-force'lactohi.lanosyl)-(1 → 4) -Ο-[(α-refukohi.lanosyl)-(1 → 3)] -1,5-site 'Oxy-1,5-imi イ-. Nantaeikosyl -D-C '/ Recitol sodium salt

Ο- (3-Ο-sulfo force 'lactohi. Lanosyl)-(1 → 4) -〇- [(α-L-fucohi. Lanosyl)-(1 → 3)] -1,5-si Xy-1,5-imin N-triacontyl-D-dalcitole sodium salt

O- (3-O-sulfo- -D-force 'Lacto. Lanosyl)-(1 → 4) -Ο- [(α-lefcopyranosyl)-(1 → 3)] -1,5-si To xy-1,5-imino-Ν-. Nantria Contyl -D-kulucitol sodium salt

Preferred compounds of the present invention include, for example,

0 (3-0-S-β-D-force ', Lactohi.lanosyl)-(1 → 3) -0- [(a-L-7copyranosyl)-(1 → 4)] -N- (2, 3-bis (oleic acid), π-pill) -1,5-dimethyl * 1,5-imino-D-c

0- (3-0-s β-D-force, lactovilanosyl)-(1 → 4) -0- [(a-L-fucopyral)-(1-3)] -N- [5- (1 , 3-Bis (oleoyl-kis) Πha-n-2-yxica W, ell) hexyl] -1,5-si, te, oxy-1,5-imino-D- K, rentol sodium salt,

0 (3-0-force, lactohi.lanosyl)-(1-4) -0-[-L-fucoviranosyl)-(1 → 3)]-N- [3- [N-[(1,3 Replacement form (Rule 26) -Bis (Oreoixi) 7 ° Loha. -2-yl) oxy power),, ell] amino]. Mouth pill]-1,5-si, te, oxy-1,5-imino-D-co '

• 0 (3-0-S, l-SD-force ', lactoviranosyl)-(1-4) -0-[(a-L-fucoviranosyl)-(1 → 3)]-Ν- [6- [Ν -[(1,3-bis (oleoi Woxy) fu.loha.n-2-yl) oxyl, nil] amino] hexyl]-1,5-si, oxy-1, 5-imino-D-k '; Lenthol sodium imL,

0- (3-0-S ^-/? -D-force, Lactopyranosyl)-(1-4) -0- [-L-Fukohi. Lanosyl)-(1 → ³ )] -N- [12- [N- [(1,3-Bis (Oreji M'Kishi)]. Loha.n-2-yl) [Amino] dote * sil]-1,5-si, 1,5-imino-D-crent-lunathorium salt,

0- (3-0-S Λ--D-force, Lacto. Lanosyl)-(1 → 4) -0- [(na-L-fucoviranosyl)-(1 → 3)] -N- [8- [N- [1,3-bis (oleoy Wxii). Loha. -2-yl] oxyca,, yl] amino-3,6-si, oxasoctyl] -1,5-si, oxy-1,5-imino-D-octyl it can.

The compound according to the present invention is, for example, a method described in Japanese Patent Application No. 8-155801, Japanese Patent Publication No. 59-43459, International Publication WO95 / 13068, Japanese Patent Application Laid-Open No. 61-205455, or the like. It can be manufactured according to.

Further, the compounds according to the present invention have extremely low toxicity.

When the compound of the present invention is administered as a prophylactic / therapeutic agent for spinal cord disorders, it can be applied alone or in combination with or mixed with a drug that can be administered simultaneously.

The compound of the present invention is used as a pharmaceutical composition containing, for example, 0.01% to 99.5%, preferably 0.1% to 90%, as it is or in a pharmaceutically acceptable nontoxic and inert carrier. Can be administered.

As the carrier, one or more solid, semi-solid, or liquid diluents, fillers, and other formulation aids are used. The pharmaceutical compositions are desirably administered in unit dosage form. The pharmaceutical composition of the present invention can be administered orally, intraosseously, topically (such as transdermally), or rectally. Needless to say, it is administered in a dosage form suitable for these administration methods. For example, oral administration or intravenous administration (particularly intravenous administration) is preferred. Replacement form (Rule 26) It is desirable to adjust the dose as a therapeutic agent for spinal cord disorder in consideration of the patient's condition such as age, weight, etc., the administration route, the nature and extent of the disease, and the like. The amount of the active ingredient per day is from 10 mg to:! Og Z day Z human, preferably from 100 mg to 5 gZ day human. In some cases, lower doses may be sufficient, and conversely, higher doses may be required. It is also desirable to administer the drug divided into two or three times a day.

For oral administration, solid or liquid dosage units, such as powders, powders, fine granules, tablets, dragees, films, capsules, granules, suspensions, liquids, syrups, drops, sublingual tablets It can be done with other dosage forms.

Powders are prepared by comminuting the compound of the present invention to an appropriate degree. Powders are prepared by comminuting the compound of the present invention with a suitable finely divided material and then admixing it with a similarly comminuted pharmaceutical carrier such as an edible carbohydrate such as starch and mannitol. If necessary, flavoring agents, preservatives, dispersing agents, coloring agents, flavors and the like may be added.

Capsules are manufactured by first filling powdered powders, powders, or granules as described in the section on tablets as described above into a capsule shell such as a gelatin capsule. You. Lubricants and superplasticizers such as colloidal silica, talc, magnesium stearate, calcium stearate, and solid polyethylene dalicol are mixed with the powder and then filled. You can also. Add disintegrants and solubilizers such as carboxymethylcellulose, carboxymethylcellulose monocalcium, low-substituted hydroxypropylcellulose, croscarmellose sodium, sodium carboxymethyl starch, calcium carbonate, sodium carbonate. The effectiveness of the medicament when the capsule is taken can be improved.

Further, the fine powder of the compound according to the present invention can be suspended and dispersed in vegetable oil, polyethylene glycol, glycerin, or a surfactant, and wrapped with a gelatin sheet to form a soft capsule. Tablets are made by adding excipients to make a powder mixture, granulating or slugging, and then adding disintegrants or lubricants or by tableting the powder mixture directly. Replacement Paper (Rule 26) You. The powder mixture is prepared by mixing the appropriately powdered substance with the above-mentioned diluents and bases and, if necessary, binding agents (eg, sodium carboxymethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose, gelatin, poly). Burpyrrolidone, polyvinyl alcohol, etc.), dissolution retarders (eg, paraffin, wax, hydrogenated castor oil, etc.), resorbents (eg, quaternary salts) and adsorbents (eg, bentonite, kaolin, dicalcium phosphate, etc.) ) May be used together. The powder mixture can be first moistened with a binder such as syrup, starch paste, acacia, cellulose solution or polymer solution, stirred and mixed, dried and ground to form granules. Instead of granulating the powder in this way, it is also possible to first use a tableting machine and then crush the imperfect slag obtained into granules.

The granules thus produced can be prevented from adhering to each other by adding stearic acid, stearic acid salts, talc, mineral oil and the like as a lubricant. The lubricated mixture is then tableted.

The uncoated tablets thus produced can be coated with a film coating.

Further, the compound according to the present invention may be directly tabletted after mixing with a fluid inert carrier without going through the steps of granulating and slugging as in J ^. A transparent or translucent protective coating consisting of a shellac sealing coating, or alternatively or on top of it, a coating of sugar or a polymeric material, and a polish coating of wax can also be used.

Other oral dosage forms such as solutions, syrups, elixirs and the like can also be presented in dosage unit form so that a given quantity contains a certain amount of the compound according to the invention. Syrups are prepared by dissolving the compound of the present invention in an aqueous solution containing a suitable sweetening agent, and elixirs are prepared by using a non-toxic alcoholic carrier. Suspensions are formulated by dispersing the compound of the invention in a non-toxic carrier. Solubilizers and emulsifiers (eg, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters), preservatives, flavoring agents (eg, palmit oil, saccharin), etc. be able to. Replacement form (Rule 26) Where necessary, dosage unit formulations for oral administration can be microencapsulated. The formulation can also provide an extended period of action or sustained release by coating or embedding in polymers, waxes and the like.

Administration into tissues can be performed by using a liquid dosage unit form for subcutaneous, intramuscular or intravenous injection, for example, a solution or suspension. In these, a fixed amount of the compound of the present invention is suspended or dissolved in a non-toxic liquid carrier suitable for injection, such as an aqueous or oily medium, and the suspension or solution is sterilized. It is manufactured by Non-toxic salts or salt solutions may be added to make the injection solution isotonic. Rectal administration can be carried out by preparing the compound of the present invention as a solid soluble or insoluble in water having a low melting point and using a suppository. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described more specifically with reference to formulation examples and test examples of the preparation of the compound according to the present invention, but the present invention is not limited thereto. As the compound of the present invention, O- (3-O-sulfo-^-D-force'lactopyranosyl)-(l → 4) -O-[(α-lefucopyranosyl)-(1 → 3)]-Ν- [3- CN-[(1,3-HyIs (reoi / reoxy) fu.loha.n-2-yl) oxycarbo'nyl] amino] Τπ pill] -1,5-di'doxy-1,5 -Imino-D-C '/ resitor sodium salt was used.

Formulation Example 1

The present compound lOOmg

Lactose 25mg

Tokorodensang lOmg

Low substitution degree Dxia π. ^ Lulose 7.5mg

Hyd π Shikia D Pil π-S 2.5mg

Mac stearate nesium 5mg

After weighing and mixing at a ratio of, the tablets are manufactured using a tableting machine.

Formulation Example 2 Replacement sheet (Rule 26) The compound of the present invention is dissolved in physiological saline to make a 1 OW / V /% solution. This solution is filtered through a membrane filter, filled into 1 ml, 2 ml, 5 ml, 10 ml or 20 ml annals corresponding to the volume and sterilized in autoclave to produce injections. .

[Test Example] Effect of compound of the present invention on spinal cord injured rats

Method

1) As the compound of the present invention, 0- (3-O-sulfo- / 3-D-force'lactohi. Lanosyl)-(l → 4) -O-[-refofohi. Lanosyl)-(1 → 3)] -N- [3-CN- [(1,3-H, S (oleoyl / reoxy) aππ.n-2-yl) oxy; & ruho'nil] Amino] Alohi. 1,5-dimethyl-1,5-imi-D-co-lucitol sodium salt was used.

2) Animal model of spinal cord injury

Male Wistar rats (weight: 270-350 g) were used in the experiments. What. Under surgical anesthesia, a laminectomy of the 12th thoracic vertebra was performed using an anesthesia under anesthesia. A spinal cord compression ischemic injury model was prepared by compressing with a weight for 20 minutes.The compound of the present invention (15 mg / kg) dissolved in 5% cholesterol was injected into the vein 30 minutes before or 30 minutes after the compression injury. In the control group and leukocyte deprivation group, only 5% glucose was injected intravenously 30 minutes before the compression injury, and in the sham operation group, only laminectomy was performed.

3) Blood leukocyte destruction by nitrogen masters

Nitrogen Mustard Inject 15% Quorcose (1.75mg / kg, Sigma, st Louis, MO) solution or 5% Quorcose solution via vein 2 days before compression ischemia injury did. On the day of the wound, the white blood cell count in the group receiving knight π-gen 'mustard was reduced to about 1/6 that in the group receiving only 5% darcose.

4) Statistical analysis

The results were shown as the mean and standard deviation. Blood leukocyte counts were tested by the t-test, and motility scores were compared using the nonparametric Cranukal-Weils rank test. The results of the suspension test were tested using the modified Yates method of the two tests. Statistical analysis of the results of the inclined plate test and myeloperoxidase (hereinafter referred to as MFO) activity was performed by the methods of Variance (ANOVA) and Scheffe's post hoc test. Statistical significance was determined with p <0.05.

Test Example 1 Replacement paper (Rule 26) Effect of compounds of the present invention on MFO activity in injured spinal cord-derived tissues

The number of neutrophil infiltrates was calculated from the measurement of MFO activity. The spinal cord tissue was removed from the thoracic vertebral region 3 cm after the injury up to 1 cm above the thoracic vertebra and immersed in ice-cooled 0.9% NaCl solution within 1 hour to measure MFO activity. The tissue section was sonicated for 30 seconds in 20 mM phosphate buffer (pH 6.0) containing 9 volumes of 0.5% hexadecyltrimethylammonium (Pharmaphlomid (Sigma), and the tissue section was treated with 10% homogenate. did. The homogenate was centrifuged (10,000 rpm, 20 min), and the obtained supernatant fraction was used as an enzyme solution. The MPO enzyme reaction was started by adding 0.1 ml enzyme solution to a 0.6 ml mixture containing 0.1 M phosphate buffer (pH 6.0), 1.25 mg / ml o-dianisidine and 0.05% H ₂ O ₂ . . The activity value was determined from the change in absorbance at 460 nm for 5 minutes after the start of the reaction. Fig. 1 shows the results.

Damage from compression ischemia increased MFO activity by about 10-fold (vs. sham group) and caused neutrophil infiltration. The compound of the present invention reduced the MPO activity to 1/3 of the injured group and suppressed neutrophil infiltration 30 minutes before the injury. In addition, the number of neutrophils infiltrated in the leukocyte depleted group due to knight π-gen mustard was lower than that in the damaged group.

Evaluation of lower limb motor paralysis

The motor function of compression ischemic injury lacto was evaluated by the method of evaluation of Tar pi (Tarlov & Klinger (Arch. Neurol. Phychia try 71 (1954) 271-290)) 1977) 577-581)) and the suspension method (Kunkel-Bagden Ε ·, et al (Exp. Neurol. 119 (1993) 153-164)). Observation of lower limb paralysis was performed 24 hours after compression ischemia.

Test example 2

Effect of the compound of the present invention on the degree of motor paralysis in the spinal cord injured rats by the method of evaluating Tarf D See Figure 2. Each of the groups before and after administration of the compound of the present invention showed about twice the value of the score of the damaged group (F <0.05), and the leukocyte depleted group similarly showed about twice the score. Test example 3

Effect of the compound of the present invention on the resistance to downhilling in rats with spinal cord injury using the inclined plate method

In the inclined plate method, a rat is used as a replacement sheet (Rule 26) by using a plate on which a smooth surface of Raha'- is attached. We recorded and compared the maximum angle that we could rest on the board for 5 seconds without slipping down. Figure 3 shows the results.

The maximum angle at which the sham surgery group could rest on the ramp without slipping was about 53 degrees. In the injured group, the temperature was reduced to 42 degrees, but in the group to which the compound of the present invention was administered, the angle was recovered to a maximum angle of 45 degrees or more in both the groups before and after the injury (P <0.01). Also, the maximum angle was about 45 degrees in the leukocyte dead group.

Test example 4

Effect of the Compound of the Present Invention and Blood Leukocyte Depletion on the Suspension Climbing Rate of Spinal Cord Injured Rats In the suspension method, the number of animals successfully climbed was measured using a suspension apparatus such as Kunkel-Bagden. The results are shown in Table 1.

table 1

Number of animals Climbing rate (%)

Sham group 1 0 1 0 (1 0 0%)

Damage group 2 0 2 (1 0 *)

Leukocyte dying group 1 0 7 (70 *)

Compound of the present invention

Pre-treatment group 10 8 (80 ***)

Compound of the present invention

Post dose group 1_Q_ 17 0 * * _)

*; P <0.01 vs sham operation group: **; p <0.001 vs injury group The table shows the number and percentage of complete climbing of rats 24 hours after compression injury. In the injured group, only 2 out of 20 climbed, with a climbing rate of 10%, significantly lower than in the sham-operated group (P <0.01). The leukocyte dying group had a higher climbing rate than the damaged group, at 70%. In addition, both the pre-treatment group and the post-treatment group of the present compound had higher climbing rates than the damaged group, 80% and 70%, respectively (P 0.01).

Based on the above test results, the compound of the present invention inhibits leukocyte infiltration and has an excellent protective and ameliorating effect (preventive or therapeutic effect) on lower limb motor function paralysis due to spinal cord injury.

Replacement form (Rule 26) Is evident.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph showing the results of Test Example 1. The vertical axis represents MPO activity (U / g). The number of animals in each group was: sham operation group = 10, injured group = 10, pre-administration group of the compound of the present invention = 6, and leukocyte deprivation group = 6.

FIG. 2 is a graph showing the results of Test Example 2.

The vertical axis is tall! ] Represents the score. The score of π was evaluated according to the following criteria.

0: No voluntary movement (complete paralysis).

1: Joint movement is recognized.

2: Good joint movement is observed, but unable to stand.

3: Stand up and walkable.

4: Can jump and run.

The number of animals in each group was 20 in the damaged group, 10 in the pre-administration group of the compound of the present invention, 10 in the group after administration of the compound of the present invention, and 10 in the leukocyte killed group.

FIG. 3 is a graph showing the results of Test Example 3. The vertical axis represents the angle (°) of the inclined plate. The number of each animal was as follows: sham operation group = 10, injury group = 20, pre-administration compound of the present invention =

10, post-administration group of the compound of the present invention−10, leukocyte depletion group = 10.

Replacement form (Rule 26)

Claims

The scope of the claims

1. A preventive or therapeutic agent for spinal cord disorder comprising a Lewis-type sugar chain derivative represented by the following general formula [I] as an active ingredient.

[I]

In the formula, B represents an oxygen atom or a nitrogen atom substituted with -AR.

One A— is one (CH2) m—, one (CH2) n— NR ^e — CO— O—, — CO— O—,-(CH2) n-CO— O-, -C ₂ H ₄ (OC ₂ H ₄ ) p— OCH ₂ — CO— 0-,

-C 2H4 (OC 2H ₄ ) m— NR ^e — CO— 0— or one (CH2) n— O—

(R ^e represents a hydrogen atom or lower alkyl, m represents an integer of 0 to 12, n represents an integer of 2 to 12, p represents an integer of 0 to 3, and _Z represents an integer of 1 to 4. Represents) represents

R is

(Wherein, R ^a and R ^b are the same or different and are each a linear or branched, saturated or unsaturated aliphatic hydrocarbon group or! ^ Π or unsaturated acyl) Represents). Alternatively, A and R together represent an alkyl, an alkenyl, an alkynyl, an alkoxycarbonyl, or an aralkyl, each of which may be substituted.

One of L and E is fucosyl, and the other is sialic acid (2 → 3). Lanosyl or the hydrogen atom of the 3-position hydroxyl group

Replacement form (Rule 26) O

-SO3H, -CH ₂ COOH or one P—R °

I

R ^d

(RC and Rd are the same or different and each represents a lower alkyl, a lower alkyl group or a hydroxyl group), and is a galactopyranosyl group which may be substituted with any of the following groups, and G is a hydroxyl group or an acetamide Represents When B is an oxygen atom, M represents a hydroxyl group or ethyl ethyl 'lactopyranosit' (bonding position is 3-position). When B is a nitrogen atom substituted with -AR, M represents hydrogen.

2. B is a nitrogen atom substituted with -A-R, G is a hydroxyl group, M is hydrogen,

L and E are different from each other. On the other hand, the hydrogen atom of the hydroxyl group at the 3-position of galactopyranose is

0

-S0 ₃ H, -CH ₂ COOH or one P— R ^c

I

R ^d

(RC and Rd are the same or different and represent a lower alkyl, a lower alkenyl, or a hydroxyl group), and galactopyranosyl, and the other is fucopyranosyl,

One A— is one (CH2) m—, — (CH2) n— NR ^e —CO—O—, one CO—O—, one (CH2) n—CO—O—,-(CH2) 2- (〇— (CH2) 2) p— 0CH2—C0 — 0—, — (CH2) 2- (0— (CH ₂ ) 2) z— NR ^e — CO— 0—, or

I (CH ₂ ) n -O- (R ^e represents a hydrogen atom or lower alkyl, m represents an integer of 0 to 12, π represents an integer of 2 to 12. p represents an integer of 0 to 3. , Z represents an integer of 1 to 4)

R is

(Wherein, R ^a and R ^b are the same or different and are both linear or branched. A spinal cord disorder comprising an asia oral trisaccharide moranoline derivative or a pharmaceutically acceptable salt thereof according to claim 1, which represents a sum or unsaturated aliphatic hydrocarbon group or a saturated or unsaturated acyl group. Prophylactic or therapeutic agent.

3.-AR is a linear or branched alkyl having 1 to 30 carbons, alkenyl having 3 to 30 carbons or alkynyl having 3 to 30 carbons, 2 to carbons 30 alkoxyalkoxyalkyl having 30 to 30 carbon atoms, alkoxyalkoxyalkamide alkyl having 4 to 30 carbon atoms, or benzyl substituted with alkoxy having 1 to 20 carbon atoms. A preventive or therapeutic agent for spinal cord injury comprising the active ingredient as an active ingredient or an ash-containing trisaccharide moranoline derivative or a pharmaceutically acceptable salt thereof according to item 2.

4. B is an oxygen atom, G is an acetamide, M is a hydroxyl group or ethyl lactopyranosite (bonding position 3), L and E are different from each other, one is sialic acid (2 → 3) 2. A preventive or therapeutic agent for spinal cord disorders comprising an asia oral trisaccharide moranoline derivative or a pharmaceutically acceptable salt thereof according to claim 1, which is galactopyranosyl and the other is fucobilanosyl.

5. The Lewis-type sugar chain derivative is O- (3-O-sulfo-3-D-galactobilanosyl)-(l → 3) -O-[(aL-fucopyranosyl)-(1 → 4) 1 一 — (2,3-bis (oleyloxy) propyl) 1-1,5-dideoxy-1,5Γminnow D—glucitol or O— (3—O—sulfo D—galactobilanosyl ) 1 (l → 4) -O— [(a-L-fucopyranosyl) 1 (1 → 3)] 1Ν— [3— [Ν — [(1,3-bis (oleoyloxy) propane-1-2-yl) 3.) The preventive or therapeutic agent for spinal cord disorder according to claim 1, which is 1,5-didoxy-11,51-imimino D-glucitol or a pharmaceutically acceptable salt thereof.

6. The preventive or therapeutic agent for spinal cord injury according to claims 1 to 5, wherein the spinal cord injury is spinal cord injury or spinal cord ischemia-reperfusion injury.

Replacement form (Rule 26)