Kowa Company Limited

Nobuo Yokoo

Setsuro Fujii

Masahiko Nagakura

Kouji Ikegaya

Touru Yokoyama

Toshihito Mori

Mitsuteru Hirata

Tomio Ohta

Koichiro Watanabe

Eizou Hattori

A pharmaceutical composition is disclosed which comprises a physiologically active substance possessing peptide bonds in its structure and being inactivable by digestive enzymes, the active substances being other than insulin, and a synthetic chymotrypsin inhibitor. The composition is particularly suitable for intestinal absorption of the active substance.

Pharmaceutical composition suitable for intestinal administration

Novel benzoyl esters of the following formula (I), and acid addition salts thereof, ##STR1## in which R.sub.1 and R.sub.2 are the same or different and represent a hydrogen atom or a lower alkoxy group, A represents a single bond, a linear or branched lower alkylene group, a lower alkenylene group, R.sub.3 and R.sub.4 are the same or different and represent a hydrogen atom or a lower alkyl group, or R.sub.3 and R.sub.4 join together to form a lower alkylene group, R.sub.5 represents a group of the formula, --X--(CO).sub.n --Y in which X represents a single bond, a linear or branched lower alkylene group or an alkenylene group, n is 0 or 1, Y represents a hydrogen atom, a cycloalkyl group, an aryl group, a hydroxyl group, a lower alkoxy group and the like are prepared by reacting para-nitrobenzoic acid or its derivative with a compound of the general formula (III) or its derivative ##STR2## to obtain a compound of the general formula (IV) ##STR3## followed by reducing the compound of the formula (IX) ##STR4## and subjecting the compound (IX) to guanidylation reaction, or by reaction para-guanidinobenzoic derivative with compound (III) or its derivative. The benzoyl esters have strong anti-trypsin activity, anti-thrombin activity and anticoagulant activity with low toxicity and are useful as a medicine for treatment of pancreatitis and disseminated intravascular coagulation (DIC).

Phenyl guanidinobenzoate derivatives which have protease inhibitory

A pharmaceutical composition is disclosed which comprises a physiologically active substance possessing peptide bonds in its structure and being inactivable by digestive enzymes, the active substance being other than insulin, and a synthetic chymotrypsin inhibitor. The composition is particularly suitable for intestinal absorption of the active substance.

The specification describes an economical process for the preparation of immunoglobulin for intravenous administration. An immunoglobulin can be, in accordance with the process, purified by a combination of a fractional precipitation method and an affinity chromatography. As a precipitant, divalent or trivalent metal salts are used and a complex of human IgG and a polyhydroxy polymeric compound is employed as an adsorbent. Purified immunoglobulin contains little or no aggregated or partially denatured globulin which is believed to cause anaphylaxis when administered intravenously. Prior art techniques cannot economically provide immunoglobulin in such a purified form and only intramuscular injections were feasible. Intravenous administrations allow immunoglobulin to be dosed in a larger amount and to act much faster than intramuscular injections.

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Sayama, Japan

Nobuo Yokoo