Pharmachemie B.v.

Other

Syntarga Bv

Dick De Vos

Johan W Scheeren

Rudolph Willem

Marcel Gielen

Abdeslam Bouhdid

Ruben G Leenders

Hidde J Haisma

Eric Wilhelmus Damen

Stephen Martin Brown

Allan Michael Jordan

Patrick Henry Beusker

Franciscus Marinus Hendrikus De Groot

Johannes Wilhelm Scheeren

Lesly Braamer

Ralph Koekkoek

Duncan Sperling

Carsten Albrecht

Peter H G Wiegerinck

Leonardus Wilhelmus Adriaan Van Berkom

Nicholas J Lawrence

Alan Th McGown

Martine Kemmer

Hendricus B De Bont

Pieter H Houba

Guuske Frederike Busscher

Monique Biesemans

Marcel Van Der Rijst

Antoinette Eugenie Seelen

Eric W P Damen

Franciscus Marinus De Groot

Leonardus Wilhelmus Van Berkom

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.

Capsule, filled with a medicine, in particular an inhalable medicine

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.

Protected vial, and method for manufacturing same

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&#x2014;(W)&#x2014;(X)&#x2014;A&#x2014;Z, wherein: V is a specifier; (W)&#x2014;(X)&#x2014;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)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: &#x2014;when A is (Y): k+l+m&#x2267;1, and if k+l+m=1; &#x2014;when A is U: k+l&#x2267;1.

Elongated and multiple spacers in activatible prodrugs

Tin polyaalkanecarboxylates having the formula &lsqb;(R R Sn) O &rsqb; wherein R represents C -C 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, R is carboxylic residue selected from (I), (II), (III) or (IV); and p, q, r, s and t have the following meanings: P&equals;3, q&equals;1, r&equals;1, s&equals;) and t&equals;1, p&equals;2, q&equals;2, r&equals;1, s&equals;0, and t&equals;1, p&equals;2, q&equals;1, r&equals;2, s&equals;1 and t&equals;2, have anti-tumor activity.

Tin polyoxaalkanecarboxylates and compositions containing them

The invention relates to water soluble antitumor analogs of paclitaxel of formula (I) wherein R &equals;C(O)CH CH(OH)COOX, R &equals;H, C(O)CH CH(OH)COOX, X&equals;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.

Water soluble analogs and prodrugs of paclitaxel

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)-(&minus;)-1-(p-methoxy-phenyl)propyl-1-amine.

Synthesis of new &bgr;-lactams

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.

Method for the preparation of baccatin III and derivatives thereof from

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. After coupling the 14-acetoxy daunomycinone with the N-protected 4'-epi daunosamine, the obtained compound was converted to epirubicin; for the latter conversion two routes were developed, depending on the amino-protecting group.

Process for preparing epirubicin or acid addition salts thereof from

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.

Paclitaxel prodrugs, method for preparation as well as their use in

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.

Anthracycline prodrugs, method for preparation as well as their use in

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.

Dibutyltin bis(dihydroxybenzoates) and compositions containing these

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.

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Oegstgeest, Netherlands

Dick De Vos