Functionalization of hydrocolloids: principal component analysis applied to the study of correlations between parameters describing the consistency of hydrogels.

This work was part of a pure research project on the functionalization of three families of hydrocolloids: cellulose derivatives, carrageenates, and alginates. Principal component analysis (PCA), a powerful statistical method, was used to demonstrate the relations existing among these different parameters that describe the consistency of hydrogels and their spreadability. This approach therefore provides a basis for modeling hydrogel consistency. PCA also afforded a classification of hydrogels that demonstrated the remarkable adhesiveness of very stiff gels based on cellulose derivatives and sodium or potassium alginates. The corresponding semi-fluid gels and all the gels based on carrageenates and mixed sodium-calcium alginates, whatever their spreadability, were found to be very poorly adhesive. Generalized to all the many colloids currently marketed, this approach can be used to set up a databank for the formulation of mucoadhesive excipients.

Skin healing preparations: compared in vitro diffusion of the active ingredients.

We have developed skin healing preparations based on propolis extract:ointments, emulsions, and transparent oil-water (TOW) gels. The formulations were optimized in terms of macroscopic characteristics including spreadability and penetrability, and limpidity and isotropy for the TOW gels. We describe here the results of a study of in vitro diffusion of the active ingredients, flavonoids, and phenolic acids, from some of the preparations we developed. These results show the influence of the dosage form and the choice of excipients on the release of the active product. The least satisfactory results were obtained for hydrophobic ointments and o/w emulsions. The strongest diffusion was obtained with a TOW gel associating isopropyl palmitate, Eumulgin B3, and Cetiol HE.

Comparative texturometric analysis of hydrogels based on cellulose derivatives, carraghenates, and alginates: evaluation of adhesiveness.

This paper reports a texturometric study of hydrogels based on cellulose derivatives, carraghenates (with or without Na+ or K+), and alginates (associated or not with Ca++). The stiffness, elasticity, and cohesiveness are evaluated and the influence of the nature and the concentration of gelling agent on the adhesiveness, an indicator of bioadhesion, is discussed. The highest adhesiveness values are found among the semi-stiff gels, particularly with those based on either sodium or potassium alginate, or cellulose derivatives. The least satisfactory results are obtained with the formulations associating carraghenates and Na+ or K+.

Stabilization of Octastatin, a somatostatin analogue: comparative accelerated stability studies of two formulations for freeze-dried products.

Octastatin (vapreotide INN) is a somatostatin analogue being developed in gastro-enterologic, neuroendocrine and oncologic applications. The pharmaceutical form is a freeze-dried preparation for parental injection use. This study was intended to evaluate the stability of the freeze-dried products and to determine the optimally stable formulation. Two types of stabilizing agents (lactose and glutamic acid/sodium glutamate buffer) and three dosage forms (0.5, 1.5, 15 mg of vapreotide base) were investigated. The peptide content and chemical stability of cakes stored at 50 degrees C and 70% relative humidity were determined by HPLC and the regression analysis parameters calculated. Results indicate that the formulation with glutamate buffer is appropriate for long term storage.

Procyanidins from tormentil: antioxidant properties towards lipoperoxidation and anti-elastase activity.

Procyanidins extracted from the rhizomes of Potentilla tormentilla were fractionated according to their degree of polymerization by chromatography on Sephadex LH20. Dimers and trimers displayed the highest anti-radical activity towards lipoperoxidation. Pentamers and hexamers possessed the most marked anti-elastase properties.

Stabilization of Octastatin, a somatostatin analogue. Preparation of freeze-dried products for parenteral injection.

Octastatin (RC-160, vapreotide INN) is a somatostatin analogue being developed for use in oncological, enterologic and neuroendocrine applications. The pharmaceutical form is a freeze-dried preparation for parenteral injection use. Three dosage forms containing 0.5, 1.5 and 15 mg of vapreotide base have been investigated. Various freeze-drying conditions, stabilizing agents, membranes for sterile filtration and heating procedures have been examined. The formulation with glutamic acid-sodium glutamate buffer as a stabilizing agent, the type of membrane for filtration and the freeze-drying procedure have been found appropriate for subsequent industrial production. No evident degradation was observed either after manufacturing, or after a three-week accelerated stability study at 50 degrees C and 70% relative humidity.

Procyanidins from tormentil: fractionation and study of the anti-radical activity towards superoxide anion.

A standardised water-soluble extract was prepared from rhizomes of Potentilla tormentilla. The procyanidins in the extract were fractionated according to their degree of polymerisation by chromatography on Sephadex LH20. The anti-radical activities of the different fractions towards superoxide anion were compared when pentamers and hexamers were found to be the most active.

[Standardization of propolis extract and identification of principal constituents]. / Standardisation d'un extrait de propolis et identification des principaux constituants.

Preparation of a propolis extract was codified, conditions of pulverization, extraction and treatment of the extractive solution are specified. The wounds healing properties of this extract are related to flavonoids and phenolic acids, which were identified by TLC.

[Oral freeze-dried forms of procyanidins]. / Mise au point de lyophilisats oraux de procyanidines.

Oral freeze-dried forms based on procyanidins were prepared. Effort was focused on the choice of the binder and the determination of the optimal conditions of freeze-drying.

[Propolis extract. I. Acute toxicity and determination of acute primary cutaneous irritation index]. / Extrait de propolis: I. Etude de la toxicité aiguë et détermination de l'indice d'irritation primaire cutanée.

In first part, the aim of this work is to study the orally subacute toxicity of a propolis extract on conscious mice. LD50 is more than 7.34 g/kg propolis extract: this product is not toxic. In second part, cutaneous primary irritation of several products: excipients and propolis extract alone or in ointments, is evaluated in the rabbit. The cutaneous reactions after reiterated applications for 14 days are observed. The index of cutaneous primary irritation is calculated by evaluation of the erythematous and oedematous lesions. The propolis extract is non irritant.

[Propolis extract. II. Wound healing the the rat and rabbit]. / Extrait de propolis: II. Etude de la cicatrisation de plaies chez le lapin et chez le rat.

This work is related to wounds healing properties of a propolis extract. In first study on the Albinos Rabbit, the activity of a propolis extract is compared with these of a Peru balsam. Optimal concentrations of them in ointments are evaluated by applications on deep cutaneous scarifications. In order to go further into details, we have chosen in second part, another assay on the Rat, allowing the obtention of deeper wounds; By this way, more complete quantification of retained parameters and a better appraising of the wounds healing process evolution are possible.

Properties of a new alkaline proteinase from Aspergillus niger.

A. niger LCF 9 synthesizes a new aspergillopeptidase of potential interest in therapeutics. The properties and operating range of the enzyme were determined. It is a semi-alkaline aspergillopeptidase (EC 3.4.23.4) with one endopeptidase activity. Its pI is 4.10, its molecular weight is 21000 Da and its A1%(1 cm) at 280 nm is 9.75. It rapidly hydrolyzes casein and hemoglobin. Its optimal pH is 7.8 and optimal temperature is 45 degrees C. It is thermally labile above 40 degrees C but can be stabilized by adding calcium ions. It is inhibited by phenylmethylsulfonyl fluoride (PMSF), by ethylenediaminetetraacetic acid (EDTA) and by certain metals ions, e.g. copper, manganese and cobalt ions. It has no dipeptidase or tripeptidase activity and its esterase activity is weak. It has a high collagenase activity and is to our knowledge the only aspergillopeptidase that is active towards benzoyl-arginine p-nitroanilide (BAPNA).

Anti-ulcer activity of procyanidins preparation of water-soluble procyanidin-cimetidine complexes.

The anti-ulcer properties of water-soluble procyanidins prepared by fermentation of tannins from Fragaria vesca were studied. Complexes of procyanidins and cimetidine were prepared. The procyanidins increased the water-solubility of the cimetidine and may prevent undesirable nitrosamine formation in the stomach as they block its cyanamide function.

Tannins from Hamamelis virginiana: identification of proanthocyanidins and hamamelitannin quantification in leaf, bark, and stem extracts.

The tannins in leaf, bark, and stem extracts of HAMAMELIS VIRGINIANA were analyzed. Four proanthocyanidins were isolated by HPLC. One was a procyanidin polymer containing only one type of flavanol unit; the other three were polymers of procyanidin and prodelphinidin containing two types of flavanol units. A method of assay of hamamelitannin showed the bark extract to be 31 times richer in hamamelitannin than the leaf extract and 87 times richer than the stem extract.