WO2008078353A1 - A novel use of antidepressant compounds and related compositions - Google Patents
A novel use of antidepressant compounds and related compositions Download PDFInfo
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- WO2008078353A1 WO2008078353A1 PCT/IT2007/000891 IT2007000891W WO2008078353A1 WO 2008078353 A1 WO2008078353 A1 WO 2008078353A1 IT 2007000891 W IT2007000891 W IT 2007000891W WO 2008078353 A1 WO2008078353 A1 WO 2008078353A1
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- antidepressant compound
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000003135 vibrissae Anatomy 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A61K38/00—Medicinal preparations containing peptides
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- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
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- A61K31/13—Amines
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
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- A61K2800/70—Biological properties of the composition as a whole
Definitions
- the present invention relates to a novel use of antidepressant compounds.
- the invention relates to the use of an antidepressant compound, preferably belonging to the class of selective serotonin reuptake inhibitors (SSRI), in medical or cosmetic applications which require the regeneration of skin tissue and/or the stimulation of the growth of the integumentary system and of the corresponding cutaneous appendages such as body hair and head hair and/or the recovery of the original pigmentation and/or trophism of the aforesaid cutaneous appendages, including stimulation of the vitality of the hair follicles.
- SSRI selective serotonin reuptake inhibitors
- the cutaneous tissue also called skin or cuticle, is composed of three layers, namely the epidermis, the dermis and the hypodermis.
- the epidermis is the outermost layer of the skin, and is formed by numerous clearly distinguished cell layers.
- the outermost of these is called the stratum corneum; it is composed of anucleate residues which have lost most of the cellular water, and it is hardened; this is caused by the presence of keratin, a protein synthesized in large quantities by specialized tissue cells called keratinocytes.
- the surface layer is therefore composed of stratified lamellae of cell residues, which continually desquamate and must be replaced throughout the individual's life.
- the following layers can be distinguished in the epidermis: the stratum corneum (apoptotic cells which have been reduced to plates and Merkel cells with afferent nerve endings); the stratum lucidum, having a lamellar structure and also composed of anucleate residues; the stratum granulosum (keratin-rich squamous cells); the stratum spinosum (polyhedral cells in which there is a progressive accumulation of membrane proteins and lamellar granules and ramified Langerhans cells with defensive functions); and a basal layer (keratinocytes having cubic cells joined together by desmosomes, and melanocytes which produce melanin).
- stratum corneum apoptotic cells which have been reduced to plates and Merkel cells with afferent nerve endings
- stratum lucidum having a lamellar structure and also composed of anucleate residues
- stratum granulosum keratin-rich squamous cells
- the basal layer contains the numerous stem cells which give rise to new keratinocytes, enabling the tissue to be regenerated throughout a lifetime.
- the basal layer is in direct contact with the dermis through the basal membrane.
- the epidermis acts as a barrier against external physical and chemical agents (such as heat, cold, solar radiation, chemical substances present in the environment or secreted by plants or animals) and against pathogens such as bacteria, fungi and the like.
- the dermis is divided into the papillary, median and deep regions. Numerous blood and lymph vessels run into the dermis, and various nerve structures and the cutaneous appendages are present. The important appendages are the hair follicles, the sebaceous glands and the sweat glands. The cells present in the dermis are of various types, the important ones being fibrocytes, histiocytes, mast cells and melanocytes.
- the hypodermis or subcutaneous layer is composed of a loose connective tissue which delimits spaces containing numerous adipocytes.
- Wrinkles are essentially caused by facial expressions, as a result of a reflex action of the facial muscles, or by ageing, as a result of the irreversible slackening of the skin.
- Expression wrinkles also appear on the faces of young people, due to a reflex action of the facial muscles. These expression wrinkles or "creases" are different from those due to ageing, because they appear on an epidermis which has not lost its normal elasticity. Some particularly emotional persons have many creases or wrinkles on their faces, which from time to time, and often involuntarily, reflect all the emotions felt by these persons.
- wrinkles due to ageing are caused by the slackening of the skin, the reduction of the quantity of intra- and intercellular liquid and the qualitative and quantitative modification of the cellular fatty acids.
- the phenomenon begins to appear from puberty, but only becomes appreciable at around 30 years, with the appearance of the first wrinkles at the sides of the mouth, under the eyelids and on the forehead.
- the skin picture comprising wrinkles, crows' feet, and drying and slackening of the skin is the expression of the normal organic deterioration which occurs with the passage of time.
- the menopause and its characteristic endocrine disruption have a considerable effect on the development of these aesthetically displeasing phenomena. It is known that age-related lipid peroxidation processes and internal disturbances can also affect and aggravate the skin condition.
- the ageing of the epidermis leads to modifications of cell reproduction, typically in the basal layer of the skin, and a decrease in the layer of Malpighian cells which are extremely important for the epidermis.
- Some substances such as phospholipids used in the form of liposomes, have been found to be useful for maintaining the turgidity of the epidermal cells.
- the stratum corneum appears shrivelled, rough and dehydrated, and therefore it is useful to treat it with vitamin-type substances with natural moisturizing and other agents, which limit and retard the appearance of these displeasing phenomena.
- Correctly formulated skin care products therefore act as preventive and helpful agents for counteracting the appearance of wrinkles, even if they cannot rejuvenate the skin.
- the primary purpose is to maintain the moisture level, and to prevent the loss of elasticity and dehydration typical of ageing skins which tend to be lacking in water. However, they must not form a barrier which prevents the normal transpiration of the skin.
- a valid form of prevention comprises the retardation of the flattening of the papillary projections, the prevention of the slowing of the blood circulation, the avoidance of an increase in non-removed toxins, and the attempt to avoid a poor supply of nutrition to the tissues above the papillary region of the dermis.
- Correctly formulated skin care products therefore act as preventive and helpful agents for counteracting the appearance of wrinkles, although it is true that they cannot rejuvenate the skin.
- the primary purpose is to maintain the moisture level, and to prevent the loss of elasticity and dehydration typical of ageing skins which tend to be lacking in water. However, they must not form a barrier which prevents the normal transpiration of the skin.
- lopecia denotes the absence or deficiency of body or head hair in the skin areas in which it is normally present.
- alopecia covers both hypotrichosis, signifying a deficiency of body or head hair, and baldness, signifying the irreversible loss of head hair.
- defluvium is used to denote a loss of head hair which is abnormal in quantity and quality, while the term “effluvium” is used to refer to cases in which the loss is numerically very high, up to many hundreds of hairs per day, and qualitatively homogeneous.
- Alopecia has conventionally been divided into temporary forms (a transient functional inhibition of the hair papilla) and permanent forms (disappearance of the follicle and of the germinative papilla). These are to be distinguished from pseudo-alopecias, in which the hairs have been torn out or have broken up (trichoclasia) as a result of traumatic, chemical, or infective events, or due to congenital abnormalities of the shaft.
- Alopecia can arise as a result of genetic factors, ageing, or local or systemic diseases. Seborrhoeic dermatitis and psoriasis are the pathologies that most commonly affect the scalp, but they rarely lead to alopecia. Alopecia can be of the cicatricial or non-cicatricial, toxic or drug-induced, areata or pseudopelade of Brocq, iatrogenic (generally due to medicines), post-pregnancy, or post-infective, type, and it can also be caused by trichotillomania, ringworm, kerion and crusted ringworm.
- Alopecia can also be caused by lupus erythematosus (in both the systemic and the fixed discoid form), scleroderma, lichen planus, follicular mucinosis or folliculitis decalvans, and by aplasia cutis or tumours [1-4].
- Androgenic alopecia does not appear if the concentration of male hormones does not reach the levels present in adults, and therefore it never appears before puberty. In humans, baldness is not due to an excess of androgenic hormones, but to an excessive response of the integumentary system to these hormones [5].
- the sensitivity of hairs, or rather of the hair follicles, to androgenic hormones depends mainly on an enzyme, namely type 2 5-alpha-reductase, produced by the cells of the follicle [5].
- This enzyme converts testosterone, the principal male hormone, into its most powerful derivative, namely dihydrotestosterone or DHT, which is mainly responsible for androgenic alopecia.
- DHT dihydrotestosterone
- the follicles of the areas of the scalp which are subject to baldness produce large quantities of this enzyme, and therefore large quantities of DHT [5].
- Androgenic baldness in women starts at around 35 years and is typically manifested in three stages. In young women especially, thinning is frequently more evident above the forehead [4-5].
- the object of the present invention is to find a valid and efficient solution for stimulating and improving the vitality and trophism of the whole integumentary system, including the skin tissue, the scalp and the corresponding cutaneous appendages, such as body hair and head hair, thus inducing its regeneration.
- the invention is based on the observation of a specific proliferative stimulus imparted to the skin, the scalp and the corresponding cutaneous appendages (body hair and head hair) by antidepressant compounds, especially those belonging to the class of selective serotonin reuptake inhibitors (SSRI).
- SSRI selective serotonin reuptake inhibitors
- This activity of the antidepressant compounds can be usefully applied in the cosmetic and medical fields.
- an antidepressant compound in the cosmetic field, can be used for the cosmetic treatment of wrinkles, for recovering the original pigmentation of the cutaneous appendages (body hair and head hair) in mammals, including humans, and for stimulating the growth of the cutaneous appendages (body hair and head hair) in mammals.
- the antidepressant compound can be used for regenerating the skin tissue and the scalp in patients who have suffered damage to these tissues, or for treating alopecia, effluvium or defluvium.
- the antidepressant compound is a selective serotonin reuptake inhibitor (SSRI), a precursor thereof, or a natural or synthetic derivative thereof.
- SSRI selective serotonin reuptake inhibitor
- paroxetine is preferred.
- the antidepressant compound can be prepared in the form of a cosmetic composition, a pharmaceutical composition, a medical device, or a culture medium for regenerating the skin tissue in vitro or for stimulating the growth, nutrition and/or original pigmentation of the cutaneous appendages (body hair and/or head hair) in vitro.
- These preparations, comprising the antidepressant compound as the active principle can also optionally comprise one or more further synergistic active ingredients such as proteolytic enzymes and/or vitamins.
- These preparations can also optionally comprise physiologically acceptable solvents and/or diluents, as well as the usual excipients and/or additives for pharmaceutical or cosmetic compositions.
- the antidepressant compound preferred for use in the scope of the present invention is paroxetine, a well-known medicine belonging to the class of selective serotonin reuptake inhibitors (SSRI).
- SSRI selective serotonin reuptake inhibitors
- other natural or synthetic antidepressant compounds are also suitable, such as hypericum (obtained from the herb Hypericum perforatum), fluoxetine, fluvoxamine, amitriptyline, desipramine, chlorimipramine, imipramine, nortriptyline and venlafaxine.
- the antidepressant compound is used in an amount in the range from 100 mg/kg to 100 g/kg, preferably 0.05 g/kg to 20 g/kg, or even more preferably 0.5 g/kg to 10 g/kg for substantially solid compositions, and in the range from 100 mg/1 to 100 g/1, preferably 0.05 g/1 to 20 g/1, or even more preferably 0.05 g/1 to 10 g/1 for substantially liquid compositions.
- proteolytic enzymes which can optionally be used in combination with the antidepressant include, for example, protease, peptidase, papain, papain FU, collagenase (preferably type Ia, type II or type IV), serratiopeptidase, heparanase, DNase, elastase, bromelain, bradykinase, Clostridium peptidase, enzymes expressed by Lactobacillus acidophilus, enzymes expressed by the Aspergillus genus, alliinase, and f ⁇ brinolysin.
- the preferred enzymes are proteases, which are capable of activating three extremely important phenomena which can produce a synergistic effect with the activity of the antidepressant compound, namely:
- the proteolytic enzymes can be used in an amount in the range from 1 mg/kg to 1 g/kg, or preferably 10 mg/kg to 100 mg/kg, for substantially solid compositions, and in the range from 1 mg/1 to 1 g/1, or preferably 10 mg/1 to 100 mg/1, for substantially liquid compositions.
- vitamins which can be used in combination with the antidepressant compound and also with the proteolytic enzyme if necessary are retinaldehyde (retinoid), retinoic acid, and their natural or synthetic precursors and derivatives.
- Retinaldehyde is preferred since it also has a synergistic effect, being capable of inducing rapid tissue regeneration.
- the vitamin can be used in an amount in the range from 0.001 mg/kg to 10 g/kg, or preferably 0.01 mg/kg to 1 g/kg, for substantially solid compositions, and in the range from 0.001 mg/1 to 10 g/1, or preferably 0.01 mg/1 to 1 g/1, for substantially liquid compositions.
- the antidepressant compound can be formulated in solid or liquid preparations which may be anhydrous or aqueous, for example creams, ointments, pomades, powders, plasters, impregnated membranes, solutions, emulsions, suspensions, vesicular dispersions, lotions, gels or sprays.
- solid or liquid preparations which may be anhydrous or aqueous, for example creams, ointments, pomades, powders, plasters, impregnated membranes, solutions, emulsions, suspensions, vesicular dispersions, lotions, gels or sprays.
- the person skilled in the art will be able to prepare these preparations, using the appropriate additives, excipients and/or diluents or vehicles.
- a base cream is used as the diluent or vehicle of substantially solid preparations (such as creams, ointments and pomades), while a physiological solution is used as the diluent or vehicle of substantially liquid preparations.
- vitamins and vitamin factors retinoic acid, retinol, alpha-tocopherol, tocopheryl acetate, beta-carotene, ascorbic acid, pantothenic acid, D-calcium pantothenate, pyridoxine, pyridoxine HCl, folic acid, niacinamide (Nicotinamide), riboflavin, cobalamine, para-aminobenzoic acid, and biotin, and the vitamin factors para- aminobenzoic acid (PAB), inositol and myo-inositol; glucosaminoglycans: hyaluronic acid, chondroitin sulphates; saccharides: rice starch, glucose, sucrose, glucans, mannans, glucomannans, fucose, fructose, heparan sulphates, pectins, starches and their
- Ru-BASE contains paroxetine as the main active ingredient.
- the Ru-BASE composition was prepared as a cream and as an infusion. Cream, gel and infusion compositions, comprising the antidepressant alone as the active ingredient, in a physiologically acceptable medium (such as a base cream or a physiological solution), , are listed below as Ru-BASE-CREMA, Ru-BASE-GEL and Ru- BASE-INFUS, and are illustrated in Tables 1, 2 and 3 respectively.
- the subsequent Tables 4 to 18 illustrate compositions of the Ru-BASE type in which the paroxetine antidepressant compound is combined with one or more additional active ingredients.
- Tables 4, 5 and 6 illustrate, respectively, Ru-BASE compositions in a cream, gel and infusion form, comprising a combination of paroxetine and protease enzyme. These compositions are designated as Ru-BASE-CREMA-PROTEO-PLUS, Ru-BASE- GEL-PROTEO-PLUS and Ru-BASE-INFUS-PROTEO-PLUS, respectively.
- Tables 7, 8 and 9 illustrate, respectively, Ru-BASE compositions in a cream, gel and infusion form, comprising a combination of paroxetine and retinaldehyde. These compositions are designated as Ru-BASE-CREMA-RET-PLUS, Ru-BASE-GEL-RET- PLUS and Ru-BASE-INFUS-RET-PLUS, respectively.
- Tables 10, 11 and 12 illustrate, respectively, Ru-BASE compositions in a cream, gel and infusion form, comprising a combination of paroxetine and retinoic acid as an alternative to retinaldehyde. These compositions are designated as Ru-BASE-CREMA-aRET-PLUS, Ru-BASE-GEL-aRET-PLUS and Ru-BASE-INFUS-aRET-PLUS, respectively.
- Tables 13, 14 and 15 illustrate, respectively, Ru-BASE compositions in a cream, gel and infusion form, comprising a combination of paroxetine, protease enzyme and retinaldehyde. These compositions are designated as Ru-BASE-CREMA-COMBO-PLUS, Ru-BASE-GEL-COMBO-PLUS and Ru-BASE-INFUS-COMBO-PLUS, respectively.
- Tables 16, 17 and 18 illustrate, respectively, Ru-BASE compositions in a cream, gel and infusion form, comprising a combination of paroxetine, protease enzyme, and retinoic acid as an alternative to retinaldehyde. These compositions are designated as Ru-BASE- CREMA-COMBO2-PLUS, Ru-BASE-GEL-COMBO2-PLUS and Ru-BASE-INFUS- COMBO2-PLUS, respectively.
- the histological results obtained in vivo after six months of treatment with the Ru-BASE compositions illustrated below confirm the re-establishment of trophism of the wrinkles by means of a modulation of the life cycle of the fibroblast with recovery of the atrophic states and prevention of the proliferation of these.
- the re-establishment of trophism induced by the Ru-BASE compositions is morphologically comparable to the healthy in vivo state with optimal histofunctional characteristics.
- the Ru-BASE-INFUS composition was found to be capable of stimulating hair growth in vitro, improving the vitality of both atrophic and non-atrophic hair follicles. After twenty-one days of treatment in vitro, all the hairs, whether new or not, recovered their original nutrition, appeared reinvigoratedj 'with the original pigmentation, and showed an increased diameter of the shaft, which was healthy and free of desquamation.
- base in the tables showing the cream compositions denotes a base in the form of a cream or emulsion (O/A or A/0) (such as water, white vaseline, cetostearyl alcohol, liquid paraffin, Ceteth-20, sodium phosphate, p-chloro-m-cresol, and phosphoric acid).
- a cream or emulsion such as water, white vaseline, cetostearyl alcohol, liquid paraffin, Ceteth-20, sodium phosphate, p-chloro-m-cresol, and phosphoric acid.
- gel base in the tables showing the gel compositions denotes a gel base, such as carbopol or cellulose derivatives.
- Table 12 Ru-BASE-INFUS-aKET-?UJS composition
- Table 13 Ru-BASE-CREMA-COMBO-PUJS composition
- the present inventors consider that the results obtained with the Ru-BASE compositions have indicated that the state of cutaneous atrophy, and more generally integumentary atrophy, which occurs in degenerative processes is reversible. Indeed, the Ru-BASE compositions have been shown to be capable of inducing excellent growth and development of skin tissue, and of inducing the regrowth of hair in vitro with nonnal histofunctional characteristics.
- Biopsies and prototype solutions All the samples (biopsies of cartilage tissue) were washed three times with physiological solution and antibiotics (100 units/ml penicillin + 100 ⁇ g/ml streptomycin + 160 mg/L gentamicin) for 10 minutes at ambient temperature.
- antibiotics 100 units/ml penicillin + 100 ⁇ g/ml streptomycin + 160 mg/L gentamicin
- the biopsies were then divided into three parts (two controls and one sample for each patient).
- the sample was treated with a Ru-BASE solution with a final concentration of IX in 15 cm plates (Lab-Tek Chamber Slides, made by Nunc, Kamstrup, Denmark).
- control biopsy specimens were suspended in physiological solution in 15 cm plates (Lab-Tek Chamber Slides, Nunc, Kamstrup, Denmark).
- control biopsy specimens were then placed in 15 cm plates (Lab-Tek Chamber Slides, Nunc, Kamstrup, Denmark) in RPMI 1640 medium supplemented with:
- the samples were placed in a Heraeus incubator which was thermostatically maintained at a temperature of 37 0 C with an atmosphere containing 8% of constantly supplied CO 2 (v/v in air).
- the samples were subjected to phenotype analysis by the Western blot for anti-collagen type II markers (Santa Cruz Biotechnology, America, California), anti-collagen type III (Santa Cruz Biotechnology, America, California), anti-collagen type IV (Santa Cruz Biotechnology, America, California), and anti-aggrecan (Santa Cruz Biotechnology, America, California).
- the membrane were incubated with the corresponding secondary antibodies (1:1000) conjugated with horse radish peroxidase (HRP, SantaCruz Biotechnologies Inc., Santa Cruz, California, USA) for one hour at ambient temperature, as shown in Table 19 below.
- the biopsies suspended in a lysis buffer (1% SDS, 30 mM Tris pH 6.8, 5% glycerol) to which protease inhibitors were added (Protease Inhibitor Cocktail, Calbiochem, San Diego, CA), were homogenized, followed by incubation of the samples for 30 minutes at 4°C.
- the resulting lysates were centrifuged at 12,000 r.p.m. for 20 minutes at 4°C and the supernatant was collected; the protein concentration of the samples was evaluated by the Bio-Rad method (Benchmark Plus assay, Bio-Rad). Before the electrophoresis run, the samples were boiled for 5 minutes in the presence of beta-mercaptoethanol and bromophenol blue.
- the samples were subjected to electrophoresis in a 12% gel (SDS- PAGE) and transferred to a PVDF membrane (Perkin Elmer Inc.).
- the membranes were saturated with methanol at ambient temperature and then incubated with the following primary antibodies diluted in PBS with 5% skimmed milk powder: anti-cytokeratin 14 with a dilution of 1:500 (SantaCruz Biotechnologies Inc., Santa Cruz, California USA), anti- cytokeratin 18 with a dilution of 1:500 (SantaCruz Biotechnologies Inc., Santa Cruz, California USA) and anti-cytokeratin 19 with a dilution of 1:500 (SantaCruz Biotechnologies Inc., Santa Cruz, California USA) for the whole of one night at 4° C.
- the membranes were incubated with the corresponding secondary antibodies (1:1000) conjugated with horse radish peroxidase (HRP, SantaCruz Biotechnologies Inc., Santa Cruz, California, USA) for one hour at ambient temperature.
- HRP horse radish peroxidase
- the corresponding bands were displayed with chemiluminescence liquids (Super Signal Western Pico solution, Pierce Biotechnology Inc.,.Rockford, Illinois, USA) and fixed on photographic plates.
- results indicate scalp regrowth with no alopecic pathology, and with a distribution of the normal regrowth stages.
- the results relating to the expression of cytokeratin 10 and 11 and the histological dyeing of the biopsy preparations with haematoxylin-eosin (used to display follicular vitality) are shown in the table and are expressed on a quantitative scale.
- the samples were subjected to Western blot phenotype analysis for cytokeratin 14, cytokeratin 18 and cytokeratin 19 markers, as shown in Table 21 below.
- the results are highly positive for the production of cytokeratin 14, cytokeratin 18, and cytokeratin 19 in the treated samples, and particularly in the scar samples treated for six months in vitro with the Ru-BASE composition proposed by the present invention, by comparison with only a slightly positive result for the production of cytokeratin 14, cytokeratin 18, and cytokeratin 19 in the untreated control samples, as shown in Table 20.
- Cytokeratin 14, 18 and 19 are expressed in normal integumentary tissues with vital and active follicles during the stages of cell differentiation, hair follicle growth and hair formation control [8-9].
- compositions comprising hypericum (hypericum perforatum) as an alternative antidepressant to paroxetine, in combination with some preferred ancillary substances, are described below by way of a further example. These compositions proved to be effective in the regeneration and re-nutrition of the skin tissue.
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/520,503 US20100092454A1 (en) | 2006-12-22 | 2007-12-20 | novel use of antidepressant compounds and related compositions |
EP07866823A EP2120944A1 (en) | 2006-12-22 | 2007-12-20 | A novel use of antidepressant compounds and related compositions |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
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ITTO2006A000918 | 2006-12-22 | ||
ITTO20060920 ITTO20060920A1 (en) | 2006-12-22 | 2006-12-22 | COSMETIC AND PHARMACEUTICAL COMPOSITION AND MEANS OF CULTURE FOR THE REGENERATION OF CUTANEOUS FABRIC, AND RELATED USES |
ITTO20060918 ITTO20060918A1 (en) | 2006-12-22 | 2006-12-22 | COSMETIC AND PHARMACEUTICAL COMPOSITION AND MEANS OF CULTURE FOR THE REGENERATION OF CUTANEOUS FABRIC, AND RELATED USES |
ITTO2006A000920 | 2006-12-22 | ||
IT000603A ITTO20070603A1 (en) | 2007-08-20 | 2007-08-20 | NEW USE OF ANTI-PRESSURE COMPOUNDS |
ITTO2007A000603 | 2007-08-20 |
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US (1) | US20100092454A1 (en) |
EP (1) | EP2120944A1 (en) |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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ITTO20080585A1 (en) * | 2008-07-29 | 2010-01-30 | Chiara Cesano | COSMETIC COMPOSITION AND COSMETIC PROCEDURE FOR THE GROWTH OF TEGUMENTARY EQUIPMENT |
JP2015500249A (en) * | 2011-12-07 | 2015-01-05 | シャンドン ルンゼ ファーマシューティカルズ カンパニー リミテッド | Fluoxetine treatment for depigmentation disease |
WO2018011382A1 (en) * | 2016-07-15 | 2018-01-18 | Institut Pasteur | 5-hydroxytryptamine 1b receptor-stimulating agent for skin and/or hair repair |
WO2019022250A1 (en) * | 2017-07-28 | 2019-01-31 | 国立大学法人九州大学 | Percutaneous absorption composition containing controlled-release water-soluble active ingredient |
US10493046B2 (en) | 2015-07-17 | 2019-12-03 | Universite Paris Descartes | 5-hydroxytryptamine 1B receptor-stimulating agent for use as a promoter of satellite cells self-renewal and/or differentiation |
US11013830B2 (en) | 2015-11-20 | 2021-05-25 | Institut Pasteur | 5-hydroxytryptamine 1B receptor-stimulating agent for enhancing in vivo engraftment potential |
WO2021260667A3 (en) * | 2020-06-26 | 2022-04-28 | Universidade Do Minho | Composition for hair follicle modulation, methods and uses thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US9833424B2 (en) | 2011-12-07 | 2017-12-05 | Shandong Runze Pharmaceuticals Co., Ltd. | Application of fluoxetine to treatment of depigmentation diseases |
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DE19813838A1 (en) * | 1998-03-20 | 1999-09-23 | Beni Med Natuerliche Heilmitte | New skin-care composition for use in massage apparatus, for prevention of aging skin |
WO2001078674A1 (en) * | 2000-04-18 | 2001-10-25 | Ceteris Holding B.V. -Amsterdam (Olanda)- Succursale Di Lugano | A composition based on natural extracts useful in the prevention and treatment of cutaneous wrinkles |
WO2004022043A1 (en) * | 2002-09-05 | 2004-03-18 | Pantarhei Bioscience B.V. | Use of a sri and vitamin b6 for the treatment of neurological and mental disorders |
WO2007054911A2 (en) * | 2005-11-11 | 2007-05-18 | Universita' Degli Studi Di Torino | Compositions useful for recovering original trophism and pigmentation, and for stimulating growth of the integumentary apparatus, uses and products thereof . |
-
2007
- 2007-12-20 WO PCT/IT2007/000891 patent/WO2008078353A1/en active Application Filing
- 2007-12-20 US US12/520,503 patent/US20100092454A1/en not_active Abandoned
- 2007-12-20 EP EP07866823A patent/EP2120944A1/en not_active Withdrawn
Patent Citations (4)
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DE19813838A1 (en) * | 1998-03-20 | 1999-09-23 | Beni Med Natuerliche Heilmitte | New skin-care composition for use in massage apparatus, for prevention of aging skin |
WO2001078674A1 (en) * | 2000-04-18 | 2001-10-25 | Ceteris Holding B.V. -Amsterdam (Olanda)- Succursale Di Lugano | A composition based on natural extracts useful in the prevention and treatment of cutaneous wrinkles |
WO2004022043A1 (en) * | 2002-09-05 | 2004-03-18 | Pantarhei Bioscience B.V. | Use of a sri and vitamin b6 for the treatment of neurological and mental disorders |
WO2007054911A2 (en) * | 2005-11-11 | 2007-05-18 | Universita' Degli Studi Di Torino | Compositions useful for recovering original trophism and pigmentation, and for stimulating growth of the integumentary apparatus, uses and products thereof . |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ITTO20080585A1 (en) * | 2008-07-29 | 2010-01-30 | Chiara Cesano | COSMETIC COMPOSITION AND COSMETIC PROCEDURE FOR THE GROWTH OF TEGUMENTARY EQUIPMENT |
WO2010013191A2 (en) * | 2008-07-29 | 2010-02-04 | Luisa Gennero | Cosmetic composition and process for regrowth of integumentary system |
WO2010013191A3 (en) * | 2008-07-29 | 2010-04-22 | Luisa Gennero | Cosmetic composition and process for regrowth of integumentary system |
JP2015500249A (en) * | 2011-12-07 | 2015-01-05 | シャンドン ルンゼ ファーマシューティカルズ カンパニー リミテッド | Fluoxetine treatment for depigmentation disease |
EP2789333A4 (en) * | 2011-12-07 | 2015-06-03 | Shandong Runze Pharmaceuticals Co Ltd | Application of fluoxetine to treatment of depigmentation diseases |
US10493046B2 (en) | 2015-07-17 | 2019-12-03 | Universite Paris Descartes | 5-hydroxytryptamine 1B receptor-stimulating agent for use as a promoter of satellite cells self-renewal and/or differentiation |
US11344515B2 (en) | 2015-07-17 | 2022-05-31 | Institut Pasteur | 5-hydroxytryptamine 1B receptor-stimulating agent for use as a promoter of satellite cells self-renewal and/or differentiation |
US11013830B2 (en) | 2015-11-20 | 2021-05-25 | Institut Pasteur | 5-hydroxytryptamine 1B receptor-stimulating agent for enhancing in vivo engraftment potential |
WO2018011382A1 (en) * | 2016-07-15 | 2018-01-18 | Institut Pasteur | 5-hydroxytryptamine 1b receptor-stimulating agent for skin and/or hair repair |
AU2017295038B2 (en) * | 2016-07-15 | 2022-09-22 | Centre Hospitalier Sainte Anne Paris | 5-hydroxytryptamine 1B receptor-stimulating agent for skin and/or hair repair |
WO2019022250A1 (en) * | 2017-07-28 | 2019-01-31 | 国立大学法人九州大学 | Percutaneous absorption composition containing controlled-release water-soluble active ingredient |
WO2021260667A3 (en) * | 2020-06-26 | 2022-04-28 | Universidade Do Minho | Composition for hair follicle modulation, methods and uses thereof |
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US20100092454A1 (en) | 2010-04-15 |
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