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Ropivacaine, a new, long-acting local anesthetic agent, has been shown to have beneficial effects in the treatment of ulcerative colitis.Treatment with this drug results in prompt symptomatic relief.The aim of this study was to examine the effects of ropivacaine on mucosal healing and to investigate whether ropivacaine can restore the decreased colonic contractility seen in the diseased state.Colitis was induced in rats by a single intrarectal administration of trinitrobenzene sulfonic acid.Mucosal healing was assessed after 1 wk of therapy.The effects on colonic contractility were examined either after 1 wk of treatment or by application of the drugs to untreated, inflamed rat colon segments placed in organ baths.After the induction of colitis, daily intracolonic treatment with ropivacaine for 1 wk reduced morphol. damage and myeloperoxidase activity.One week of treatment also restored the contractile response to acetylcholine.By adding ropivacaine directly to untreated inflamed colonic segments in organ baths, the contractile response to acetylcholine was increased compared with controls.For comparison, the effects of budesonide and 5-aminosalicylic acid were also examinedRopivacaine improved mucosal healing and restored colonic motor activity in exptl. colitis, similar to budesonide but superior to 5-aminosalicylic acid.

01 Aug 1999·European Journal of Pharmaceutical SciencesQ2 · MEDICINE

Physical state of l-histidine after freeze-drying and long-term storage

Q2 · MEDICINE

Article

Author: Osterberg, Thomas ; Wadsten, Tommy

Liquid samples of L-histidine of varying pH values and mixed with salt, metal ions, polysorbate 80 and sucrose have been analysed by differential scanning calorimetry to evaluate the influence of these additives on the glass transition temperature and crystallisation of L-histidine during freezing and thawing. L-Histidine solutions of varying pH were freeze-dried with and without a thermal cycle and the physical state of the freeze-dried cakes, following long-term storage, were studied by powder X-ray diffraction. Amorphous L-histidine crystallised when it was exposed to moisture, and the identity of the crystalline materials is reported. The crystallisation of L-histidine during freezing and thawing is dependent on the pH of the solution and is shown to be at a minimum at pH 6, which coincides with the pK(a) of the imidazoline function. Sucrose inhibited the crystallisation of L-histidine during thawing, while sodium chloride or polysorbate 80 did not. The addition of metal ions (Ca2+ and Mg2+) up to 10% (w/w) did not depress the glass transition temperature significantly, while the addition of Zn2+ increased it. The physical state of L-histidine after freeze-drying is shown to be dependent on both the pH of the solution and the freezing cycle. The risk of crystallisation of amorphous L-histidine is low if the freeze-dried material is protected from moisture.

01 Jun 1999·Zeitschrift für Kristallographie - New Crystal Structures

Crystal structure and absolute configuration of 1'-[3-(diethylamino)-propyl]-3,4-dihydrospiro[naphthalene-1(2H),3'-pyrrolidine]-2',5'-dione hydrochloride, RAC-109 I ∙ HCl, C20H28N2O2 ∙ HCl

Author: Csöregh, I. ; SandberG, R.

The title compound is triclinic, space group P1, a 7.0746(2), b 8.8235(3), c 16.0023(8) Å, α 84.671(5), β 89.926(4), γ 85.615(6)°, Z = 2, R = 0.038, R_w = 0.043 for 1911 reflections for I > 2σ.At. coordinates are given.The tetralinspirosuccinimide moieties of the 2 independent mols. exhibit similar conformations and proved to have the same S absolute configuration, but they distinctly differ in the orientation of the attached diethylaminopropyl group.Each Cl anion is H-bonded to the protonated amine N(16) atom of the nearest mol.

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