Abstract: An assembly of a tube-shaped body and a tube-shaped cap, which are open at one distal side, is provided to manufacture a capsule for enclosing a medicine. At least one recess is arranged in an outer surface of the body, wherein at least one fixating bulge is arranged in an inner surface of the cap, which is destined to be snugly received in the recess in the outer surface of the body in order to realize a fixed snap connection between the body and the cap. A smallest inner diameter of the fixating bulge of the cap is equal to or smaller than a smallest outer diameter of the recess in the body, which contributes to realizing a fixed snap connection which is firm to such an extent that the capsule is suitable for application in an inhalation apparatus comprising provisions for piercing the capsule at least one place.

Abstract: An assembly of a tube-shaped body and a tube-shaped cap, which are open at one distal side, is provided to manufacture a capsule for enclosing a medicine. At least one recess is arranged in an outer surface of the body, wherein at least one fixating bulge is arranged in an inner surface of the cap, which is destined to be snugly received in the recess in the outer surface of the body in order to realize a fixed snap connection between the body and the cap. A smallest inner diameter of the fixating bulge of the cap is equal to or smaller than a smallest outer diameter of the recess in the body, which contributes to realizing a fixed snap connection which is firm to such an extent that the capsule is suitable for application in an inhalation apparatus comprising provisions for piercing the capsule at least one place.

Abstract: The invention relates to novel esters and in particular to some novel esters of glucuronide prodrugs of anthracyclines having tunable water-solubility, their synthesis and use in tumor-selective chemotherapy. It appeared that in the final step in the synthesis of these prodrugs, i.e. the coupling of the glucuronide spacer moiety to the parent drug molecule, protection of the sugar hydroxyls is, surprisingly, no longer required. A process for the preparation of these unprotected sugar spacer moieties is also disclosed.

Abstract: For the prevention of contamination of a vial with traces of medicinal fluids, for example cytostatics and antibiotics, which may be spilt on the outside of the vial while filling, the vial is provided with a tight-fitting protective envelope, preferably made of a transparent synthetic material, as a last step in the production process. Because of this, a possible contamination which remains on the outside of the vial is encapsulated between the vial and the envelope. Hereby, a user is no longer exposed to toxic substances, because the user will not touch the vial itself, but will touch the envelope. An additional advantage of the provision of the envelope is that if breaking of the vial occurs, the envelope will keep the pieces of broken glass together and will possibly prevent the medicinal fluid from leaking away.

Abstract: This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V—(W)k—(X)l—A—Z, wherein: V is a specifier; (W)k—(X)l—A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclization elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: —when A is (Y)m: k+l+m?1, and if k+l+m=1; —when A is U: k+l?1.

Abstract: For the prevention of contamination of a vial with traces of medicinal fluids, for example cytostatics and antibiotics, which may be spilt on the outside of the vial while filling, the vial is provided with a tight-fitting protective envelope, preferably made of a transparent synthetic material, as a last step in the production process. Because of this, a possible contamination which remains on the outside of the vial is encapsulated between the vial and the envelope. Hereby, a user is no longer exposed to toxic substances, because the user will not touch the vial itself, but will touch the envelope. An additional advantage of the provision of the envelope is that if breaking of the vial occurs, the envelope will keep the pieces of broken glass together and will possibly prevent the medicinal fluid from leaking away.

Abstract: This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V—(W)k-(X)l-A-Z, wherein: V is a specifier; (W)k-(X)l-A is an elongated self-elimination spacer system; W and X are each a l,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y) m wherein: Y is a l,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that:—when A is (Y)m: k+l+m1, and if k+l+m=1;—when A is U: k+l1.

Abstract: Tin polyaalkanecarboxylates having the formula [(R1pR2qSn)rOs]t wherein R1 represents C1-C6 alkyl, branched or straight, substituted or not by one or more hydroxyl groups or halogen atoms, or a phenyl group, substituted or not by one or more hydroxyl groups or halogen atoms, R2 is carboxylic residue selected from (I), (II), (III) or (IV); and p, q, r, s and t have the following meanings: P=3, q=1, r=1, s=) and t=1, p=2, q=2, r=1, s=0, and t=1, p=2, q=1, r=2, s=1 and t=2, have anti-tumor activity.

Abstract: The invention relates to water soluble antitumor analogs of paclitaxel of formula (I) wherein R1=C(O)CH2CH(OH)COOX, R2=H, C(O)CH2CH(OH)COOX, X=H, Li, Na or any other pharmaceutically acceptable counterion, as well as to a pharmaceutical composition comprising an antineoplastically effective amount of such analogs as an active ingredient.

Abstract: The present invention relates to the inhalation of opioids, such as morphine, administered as a dry powder. Opioids administered as dry powder for inhalation are intended for local treatment in the respiratory tract, or for systemic treatment following absorption in the lungs and airways. Indications for opioids dry powder per inhalation include the treatment of dyspnoea and pain. Opioids as dry powder for inhalation may be administered with the use of an inhaler, which can be described as a multi-dose reservoir system such as the Cyclovent™, or a premetered single-dose system such as the cyclohaler™, or a premetered disposable system as the Disphaler™.

Abstract: Tin polyaalkanecarboxylates having the formula [(R1pR2qSn)rOs]t wherein R1 represents C1-C6 alkyl, branched or straight, substituted or not by one or more hydroxyl groups or halogen atoms, or a phenyl group, substituted or not by one or more hydroxyl groups or halogen atoms, R2 is carboxylic residue selected from (I), (II), (III) or (IV); and p, q, r, s and t have the following meanings: P=3, q=1, r=1, s=) and t=1, p=2, q=2, r=1, s=0, and t=1, p=2, q=1, r=2, s=1 and t=2, have anti-tumor activity.

Abstract: The invention relates to water soluble antitumor analogs of paclitaxel of formula (I) wherein R1═C(O)CH2CH(OH)COOX, R2═H, C(O)CH2CH(OH)COOX, X═H, Li, Naa or any other pharmaceutically acceptable counterion, as well as to a pharmaceutical composition comprising an antineoplastically effective amount of such analogs as an active ingredient.

Abstract: The object of the present invention is the development of new chiral auxiliaries for improved &bgr;-lactam formation that control both the diastereoselectivity of &bgr;-lactam formation and which can be removed without destruction of the sensitive azetidinone ring, providing valuable intermediates for coupling to the C-13 hydroxyl group of anti-tumor taxanes, such as paclitaxel. Further, the object of the present invention is enantiomerically pure (S)-(−)-1-(p-methoxy-phenyl)propyl-1-amine.

Abstract: 10-Deacetylbaccatin III is selectively acylated to baccatin III and derivatives thereof in high yield with anhydrides (e.g. acetic anhydride), catalysed by Lewis acids. Extremely effective catalysts in this reaction are compounds of the formula ML.sub.x wherein M is a rare earth metal and L is a anion, preferably a strong electron withdrawing counterion such as triflate.

Abstract: This invention relates to a novel method for the chemical preparation of epirubicin or acid addition salts thereof, in particular the HCl salt, from daunorubicin. This process avoids the disadvantages of the prior art. First daunorubicin is methanolized to obtain daunomycinone and daunosamine methyl ether in very high yields. Daunomycinone is converted to 14-acetoxy daunomycinone by bromination and acetoxylation, while daunosamine methyl ether is converted into an N-protected 4'-epi daunosamine. The choice of the protecting group of the amino group of the daunosamine methyl ether is important because it has to be removed after coupling the sugar with the aglycone without causing side reactions of the aglycone. Two protecting groups were selected: the trifluoroacetyl group and the allyloxycarbonyl group.

Abstract: A paclitaxel prodrug has a paclitaxel portion coupled to a cleavable N-(aliphatic or aromatic)-O-glycosyl carbamate spacer group, and can be administered orally, topically or by injection to provide an anti-tumor effect, the prodrug being activated by a hydrolizing enzyme, an endogeneous enzyme or an exogeneous enzyme.

Abstract: Anthracycline derivatives are disclosed which are coupled to an enzymatically cleavable N-phenyl-O-glycosyl carbamate spacer group, which derivatives are represented by the formula ##STR1## as well as the acid addition salts thereof. Further the synthesis of these derivatives and their use, alone or in combination with enzymes or antibody enzyme conjugates are disclosed.

Abstract: This invention provides novel Sn compounds, i.e. di-n.butyltindihydroxybenzoates, which exhibit excellent activities against varies tumors. This invention also provides pharmaceutical compositions which contain said novel Sn compounds in combination with a suitable carrier, in particular aqueous solutions which are suitable for injection.

Abstract: The invention relates to novel aromatic fluorine-containing organotin compounds of the formula {(F.sub.5 C.sub.6 RCO.sub.2 SnBu.sub.2).sub.2 O}.sub.2 and {(F.sub.5 C.sub.6 RCO.sub.2).sub.2 SnBu.sub.2 } wherein R is CH.sub.2, CH.dbd.CH or a single bond between the phenyl ring and the CO.sub.2 group, and Bu is a butyl group; as well as to anti-tumour compositions containing as an active ingredient one or more of these compounds.