Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-08-24
2001-04-03
Moezie, F. T. (Department: 1653)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S017400, C514S016700, C514S015800, C530S328000, C530S329000, C530S330000, C530S331000
Reexamination Certificate
active
06211155
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to novel synthetic derivatives of two thymic hormones, i.e. thymulin and thymosin, and to their uses as a medicament or in the field of cosmetology.
The large number of studies which have been carried out on the functioning of the immune system have demonstrated the cardinal role played by the thymus and the thymic hormones in stimulating the immune defences of the organism.
The thymic hormones, in particular thymulin, “J. F. Bach et al.”, thymopoietin “Grandstein” and thymosin “Dayne” have been identified as being of a polypeptide or peptide nature.
These hormones, principally thymulin and thymopoietin, possess the property of inducing maturation of the T lymphocytes and of stimulating the immune response of the organism.
It has been scientifically demonstrated that a close relationship exists between the decrease in thymic functions with age and cutaneous ageing under normal physiological circumstances.
At a pathological level, the loss of thymic activity, i.e. “involution”, finds expression in the appearance of physiological disorders: “autoimmune diseases, alopecias (abnormal hair loss), etc.”.
It has also been shown that a relationship exists between the physiological properties of the thymus and certain cells of the epidermis.
Thus, a structural similarity exists between certain cells of the thymus and keratinocytes. It has also been shown that, under certain conditions, the keratinocytes also secrete a hormone of the thymopoietin type which is identical to that secreted by the thymus and are able to induce post-thymic lymphocyte maturation and in this way to take over from the thymus.
This relationship between the physiological activities of the cells of the thymus and the keratinocytes has recently been confirmed by demonstrating that keratin and keratohyalin, which have identical structures to those of the keratin and keratohyalin which are secreted by the epidermal keratinocytes, are present in the cells of the thymus.
Furthermore, the scientific demonstration that keratinocytes which are in the differentiation phase secrete a substance, i.e. ETAF, which activates thymocyte growth, confirms the physiological relationships which exist between the thymus and the keratinocytes. (ETAF: epidermal thymocyte activating factor).
A parallel exists between the “involution” of the thymus and the decrease in the synthesis of ETAF by the keratinocytes as a function of age, with, however, a functional time-lag in favour of the keratinocytes (post-thymic lymphocyte maturation).
The thymic hormones, in particular thymulin and thymopoietin, have been used therapeutically in a large number of pharmacological and clinical studies with the aim in view of stimulating and regulating the immune defenses of the organism.
When used in the form of extracts or of molecules obtained by chemical synthesis, these products have yielded variable and disappointing results as a result of their lack of stability and a ubiquitous effect linked to the absence of dose-effect relationships.
SUMMARY OF THE INVENTION
The present invention relates to using chemical synthesis to obtain peptide derivatives of the thymic hormones, the structure of which derivatives has been adjusted so as to provide the derivatives with a high degree of physicochemical stability and a precisely defined pharmacological activity.
Using all the knowledge which our research groups have recently acquired and developed concerning the essential role of the epidermis in immune defense and its relationships with the thymus (International Society of Development and Comparative Immunology), the present invention relates to the creation of synthetic peptide derivatives whose physiological and therapeutic activity is directed toward stimulating and modulating the immune defenses of the corium and the epidermis in preference to any systemic action.
In one aspect, the invention preferably relates to using chemical synthesis to create metallopeptides whose physiological properties are specifically directed toward activating the cutaneous immune system and stimulating the germinative functions of the basal cells of the epidermis to the exclusion of any secondary effect on systemic (general) immunity.
The present invention relates to the creation of peptide molecules which are homologs or derivatives of the active peptide sequences of the principal thymic hormones, i.e. thymulin and thymopoietin.
The large number of clinical tests which have been carried out using these hormonal mediators have failed to demonstrate that these mediators have any therapeutic relevance.
Thus, when these hormones have been used in the form of injectable preparations for treating immune deficiencies and autoimmune disorders, the results obtained have all been negative because of the ubiquitous activity of the hormones in terms of the doses administered.
It appears that these ubiquitous effects are linked to the structure of these compounds which results from synthesis and which does not enable them to bind normally to globulins and cell receptors, taking into account the fact that they are administered parenterally.
For this reason, one aspect of the invention relates to creating compounds in the form of metallopeptides which are obtained by synthesis and whose physiological activities are directed toward modulating the immune system and activating the germinative cells of the epidermis, by means of local topical applications in accordance with the pharmacological principle of “structure-activity relationships” (Hänch's principle).
More specifically, the present invention relates to a pharmaceutical or cosmetological composition which contains at least one peptide conjugate which comprises a sequence of at least three amino acids which are derived from the total sequence of thymulin or of thymopoietin, with it being possible for the amino acids to be in the D, L or DL form, the said sequence being conjugated chemically or physically with at least one compound which is selected from:
monocarboxylic acids of the general formula
HOOC—R (I)
in which R represents a straight-chain or branched, optionally substituted C
1
-C
20
aliphatic radical which can contain one or more unsaturations, as well as the alcohol or aldehyde or amide derivatives of the acids of the formula I;
dicarboxylic acids of the general formula
HOOC—R
1
—COOH (II)
in which R
1
represents a straight-chain or branched divalent aliphatic radical which comprises at least 3 carbon atoms, preferably from 3 to 10 carbon atoms, in particular an alkyl, alkylene, alkenylene or alkynylene radical, and which can contain one or more unsaturations and can optionally be substituted, in particular by one or more amino, hydroxyl or oxo groups or by a C
1
-C
3
alkyl radical, with it also being possible for R
1
to form a cycle with one of the acid functions.
The conjugates according to the invention are low-molecular-weight derivatives which are obtained, in particular, in the form of salts, esters or amides of the compounds of the formula I or II.
The compounds of the formula I which are particularly preferred are carboxylic acids which have a metabolic activity which is essential for the Krebs tricarboxylic cycle and which act in the mitochondria as coenzymes of oxidative decarboxylation, and whose properties are to bind, preferably covalently, to the &egr; amino functions of certain peptides, in the form of lipoamides, thereby facilitating presentation of the peptide conjugates, which are obtained in accordance with the invention, to the G class &bgr; receptor of the epidermal cells.
In the case of these acids, and of others which are suitable for implementing the invention, R can represent a substituted or unsubstituted, straight-chain or branched C
1
-C
20
, in particular C
1
-C
4
, aliphatic radical, in particular an alkyl, alkenyl or alkynyl radical, which can contain one or more unsaturations and which can be substituted by one or more radicals which are selected from the group comprising: NH
2
, OH, oxo or thiol or a non
Dussourd Lucien
Pinel Anne-Marie
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Institut European de Biologie Cellulaire
Moezie F. T.
LandOfFree
Peptide conjugates derived from thymic hormones, their use... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peptide conjugates derived from thymic hormones, their use..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptide conjugates derived from thymic hormones, their use... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2484572