The present invention is directed to pharmaceutical compositions comprising compounds found in Harderian gland secretions, a method of treating dry eye in a human comprising ophthalmically administering an effective amount of a compound, e.g. a lipid compound, found in Harderian gland secretions, pharmaceutical compositions comprising said lipid compounds, as identified by characteristic chemical data and mass spectra of said lipid compounds, said lipid compound in essentially pure form, and an ophthalmic vehicle comprising a therapeutic agent and a compound present in the secretions of the Harderian gland, e.g. a lipid compound, found in the secretions of the Harderian gland, e.g. a rabbit Harderian gland.

The present invention is directed to pharmaceutical compositions comprising compounds found in Harderian gland secretions, a method of treating dry eye in a human comprising ophthalmically administering an effective amount of a compound, e.g. a lipid compound, found in Harderian gland secretions, pharmaceutical compositions comprising said lipid compounds, as identified by characteristic chemical data and mass spectra of said lipid compounds, said lipid compound in essentially pure form, and an ophthalmic vehicle comprising a therapeutic agent and a compound present in the secretions of the Harderian gland, e.g. a lipid compound, found in the secretions of the Harderian gland, e.g. a rabbit Harderian gland.

Described herein is a process for the preparation of a mixture of compounds of formula ##STR00001##
having a weight ratio of the cis-diastereomers to trans-diastereoisomers higher than 1:1, where R.sub.1 represents a C.sub.1-8 alkyl group, a C.sub.2-8 alkenyl group or a C.sub.2-8 alkynyl group, each optionally substituted with one or two of a C.sub.1-4 alkyl alkoxy ether group and/or a C.sub.1-4 alkyl carboxylester group and R.sub.2 represents a C.sub.1-6 alkyl, a C.sub.2-6 alkenyl or a C.sub.2-6 alkynyl group, each optionally substituted with a C.sub.1-4 alkyl alkoxy ether group, a carboxylic acid group or a C.sub.1-4 alkyl carboxylester group and compounds suitable in the process.

Described herein is a process for the preparation of a mixture of compounds of formula ##STR00001##
having a weight ratio of the cis-diastereomers to trans-diastereoisomers higher than 1:1, where R.sub.1 represents a C.sub.1-8 alkyl group, a C.sub.2-8 alkenyl group or a C.sub.2-8 alkynyl group, each optionally substituted with one or two of a C.sub.1-4 alkyl alkoxy ether group and/or a C.sub.1-4 alkyl carboxylester group and R.sub.2 represents a C.sub.1-6 alkyl, a C.sub.2-6 alkenyl or a C.sub.2-6 alkynyl group, each optionally substituted with a C.sub.1-4 alkyl alkoxy ether group, a carboxylic acid group or a C.sub.1-4 alkyl carboxylester group and compounds suitable in the process.

The present invention provides a method for producing a hetero-type monodisperse polyethylene glycol, which includes a step (A) of carrying out a nucleophilic substitution reaction between a compound of the formula (2) and a compound of the formula (3) so as to satisfy the requirement of the expression (F1) to obtain a compound of the formula (4), a step (B) of carrying out the Michaels addition reaction of a compound of the formula (5) to the compound of the formula (4) at a temperature condition of 10° C. or lower to obtain a compound of the formula (6), a step (C) of detritylating or debenzylating the compound of the formula (6) to obtain a reaction product containing a compound of the formula (7), a step (D) of purifying the compound of formula (7) from the reaction product, a step (E) of reacting the compound of the formula (7) with phthalimide and performing dephthalimidation to obtain a compound of the formula (8), and a step (F) of subjecting the compound of formula (8) to an acid hydrolysis treatment to obtain a compound represented by the formula (1).

The present invention provides a method for producing a hetero-type monodisperse polyethylene glycol, which includes a step (A) of carrying out a nucleophilic substitution reaction between a compound of the formula (2) and a compound of the formula (3) so as to satisfy the requirement of the expression (F1) to obtain a compound of the formula (4), a step (B) of carrying out the Michaels addition reaction of a compound of the formula (5) to the compound of the formula (4) at a temperature condition of 10° C. or lower to obtain a compound of the formula (6), a step (C) of detritylating or debenzylating the compound of the formula (6) to obtain a reaction product containing a compound of the formula (7), a step (D) of purifying the compound of formula (7) from the reaction product, a step (E) of reacting the compound of the formula (7) with phthalimide and performing dephthalimidation to obtain a compound of the formula (8), and a step (F) of subjecting the compound of formula (8) to an acid hydrolysis treatment to obtain a compound represented by the formula (1).

The present invention relates to compounds of formula (I): including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of, for example, cancer.

The present invention relates to compounds of formula (I): including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of, for example, cancer.

A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.
Y1-PEG1-{R.sup.1-PEG2-{Y4}.sub.n}.sub.m  (I)
TM-{R.sup.2-PEG1-{R.sup.1-PEG2-{R.sup.3-A′-drug}.sub.n}.sub.m}.sub.l  (II)

A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.
Y1-PEG1-{R.sup.1-PEG2-{Y4}.sub.n}.sub.m  (I)
TM-{R.sup.2-PEG1-{R.sup.1-PEG2-{R.sup.3-A′-drug}.sub.n}.sub.m}.sub.l  (II)