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Androgenetic bu,a or baldness is a physiological event that occurs in genetically predisposed individuals, leading to “hair loss”. In androgenetic alopecia occurs by accelerating the growth cycle. The hair follicles produce thinner hair, shorter and depigmented, a process called miniaturization of the wire.

There is an increase in the activity of 5a-reductase enzyme in men and in women dehydrogenases specific enzymes within the hair follicle. This enzyme is responsible for converting testosterone to dihydrotestosterone, which has high affinity for androgen receptors in dermal papilla Wiedemeyer K.

Although genes have not yet been identified, it is known that there is a genetic predisposition to the onset of alopecia, which is present in varying degrees, location and age. Non-surgical treatment of androgenetic alopecia consists mainly of three drugs: These treatments have variable effectiveness among individuals, not everyone responds avicia same way to treatments cited, moreover, the interruption of the same leads to the back of the loss.

CROSS-REFERENCE TO RELATED APPLICATIONS

Init was reported the effect of endogenous peptide angiotensin- 1 -7 Ang- 1 -7 or Asp 1 -Arg 2 -Val 3 -Tyr 4 -lle 5 -His 6 -Pro 7 and in preventing treatment of alopecia in cancer patients undergoing chemotherapy. It is worth mentioning that the administration route is subcutaneous in patients. In mice, the Ang- 1 -7 was evaluated by the subcutaneous route, as well as topical formulation of the peptide of carboxymethylcellulose. However, this study did not demonstrate the efficacy of the topical formulation, when applied to intact skin.

Finally, it has not been claimed that patent no topical formulation of Ang- 1 The beneficial effect of Ang- 1 -7 in the alopecia can be attributed to its vasodilating action in the blood vessels Santos et al.

The vasodilation of arterioles present in the dermis, improves irrigation of the hair follicles, increasing the supply of nutrients and oxygen.

Evidence That the actions of angiotensin- 1 -7 is mediated by specific angiotensin receptors Brain res Bull. Among these analogs, it highlights the Alamandina, peptide analogue of the Ang- with substitution of amino acid Ala Asp in N-terminal position of Ang- 1 This endogenous peptide has vasodilatory action similar to that of Ang- 1 -7but bind to different receptor that of Ang- 1 -7 Lautner et al Discovery and characterization of alamandine:.

A novel component of the renin- angiotensin system. This suggests possible synergistic action between the Ang- 1 -7 and Alamandina. The structure of skin is quite complex, composed of three layers: The epidermis is a stratified and avascular layer, whose outermost layer is called the stratum corneum. This consists of layers of dead vaicis thick, and is considered the main barrier to passage of substances through the skin by limiting the cutaneous absorption and percutaneous substances.

The dermis is a highly vascularized layer where the sweat glands, sebaceous glands, hair follicles and nails. The subcutaneous layer consists essentially of fat, accounting for forming a mechanical and thermal barrier Barry, ; Bouwstra et al.

The substances can pass through the skin through the appendices aviicis hair follicles, sebaceous glands and sweat secretion ducts through via transcellular or between via intercellular cells of the stratum corneum Barry. Novel Mechanisms and devices to enable successful transdermal drug delivery. European Journal of Pharmaceutical Sciences, vol. Advanced Drug Delivery Reviews, vol. AIgumas strategies have been used to increase the absorption and transport of substances through the stratum corneum: Lipid vesicles penetrate into intact skin owing to the transdermal.

Eliaz Ethosomes – novel vesicular carriers for enhanced delivery: Xvicis of Controlled Release, vol. The ultradeformable vesicles are prepared for specific combinations of phospholipids and surfactants, yielding hula deformable vesicles, which have the ability to cross bulla smaller than its own pore size. The authors claim that these avicos when applied topically under non occlusive condition, would pass through and penetrate the skin spontaneously zvicis transdermal absorption of drugs encapsulated Cevc G, D Gebauer, Stieber J, Schatzlein The Blume G.

Ultraflexible vesicles, Transfersomes, Have An extremely low pore penetration resistance and Transport therapeutic Amounts for insulin across the intact mammalian skin. Biochimica et Biophysica Acta, vol. Cevc G, Blume G. New, highly efficient bul the formulation of diclofenac topicai, transdermal administration in ultradeformable drug carriers, Transfersomes. However, there is controversy in the art if this system could be bbula to any drug Elsayed et al.

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A recent study using bulla as intermediate molecular weight hydrophilic drug model shows that ultradeformable vesicles promote a reduction of transdermal passage of the hydrophilic drug in vitro and in vivo and do not act as drug carriers across the stratum corneum Bahia et al. Therefore, the effectiveness of ultradeformable vesicles seems to bkla on the specific physical and chemical characteristics of the drug and its compatibility with the lipid composition of the vesicles ultradeformable.

This formal in the case of a hydrophilic peptide as Ang- 1 -7one can not anticipate a priori the effect of ultradeformable vesicles.

Elastic topicai liposomes for drug delivery and transdermal Curr. This property can also contribute to the enhancement of the active principle encapsulated action in the prevention or treatment of alopecia Li, L.

Topicai liposome delivery of molecules to hair follicles in mice. It notes that the present invention demonstrates for the first time that Ang- and its antagonist, D- [Ala 7] -Ang- 1 -7 or A Santos et al.

Evidence That the actions of angiotensin- 1 -7 is mediated by specific angiotensin receptors, Brain res Bull, Thus, in view of what was found in the prior art it is concluded that: Existing treatments have variable effectiveness among individuals; not all individuals respond the same way, moreover, the interruption of the same leads to the back of the hair loss.

Other limitations, these treatments frequently reported are the onset of chronic irritation after application of minoxidil or lotions. Therefore, it was not found in the art of topical formulation Ang- 1 -7 with proven efficacy in inducing hair growth and potential in the treatment and prevention of alopecia.

Contrary to alopecia, the hair growth in unwanted areas is a major problem that affects women. As an example, the hinsurtismo Hirsutism is the presence of an excess of abnormal hair growth in women in areas that are common to the growth in males only Rittmaster, R. Medical treatment of androgen-dependent hirsutism.

Insulin sensitizers for the treatment of hirsutism: Clin,93, In addition, over the years, by now considered superfluous.

The Egyptians were the first to use sandalwood extract, clay and beeswax, ingredients that give rise to waxing, which is used today. Over the years, the culture of shaving evolved before it was made only in the legs after shaving armpits became the great achievement, and from the last two decades of the twentieth century began to be made in the legsunderarms, arms and sometimes in the pubic area. It is observed, therefore, that, throughout history, women preocuparam- in removing the hair to be more attractive.

Now, men are also adhering to this fashion for the sake of hygiene and ease Available at: Thus, new depilatory methods have emerged, and now, to get rid of the growth of normal hair on certar regions of the body must resort to aggressive methods of hair removal with waxes, leisure and others more, which are time consuming, they must be made frequently and also generate high costs.

In order to solve the problem of hinsurtismo in women and also to free women and men need to resort to removal, to get rid of the, in this technology has been developed a formulation containing receptor antagonist But A, which It proved highly effective in inhibiting hair growth.

This formulation will be innovative for the market since it was not found in the prior art formulation containing receptor antagonist But for inhibition of hair growth. Thus, in the present invention topical formulations have been developed with proven efficacy in controlling growth of hair and potential for treatment and prevention of alopecia; and a formulation with efficacy in inhibiting hair growth.

Figure 1 Figure 1 shows the average length of hair Swiss mice after topical application of the formulation Ang- 1 -7formulation A and vehicle consisting of the suspension of vesicles without peptide. The data represent the hair growth of mice induced alopecia after treatment with cyclophosphamide, with or without subsequent topical treatment.

The data represent the size of hair follicles in mice, induced alopecia after treatment with cyclophosphamide, with or without subsequent topical treatment. The formulation consists of an aqueous suspension of Ang- 1 -7 or analogues thereof in the presence of lipid vesicles comprised of phospholipid and surfactant.

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The same can be easily prepared by injection of an ethanolic solution of phospholipid into an aqueous solution containing the surfactant and Ang- 1 -7 or its analogues selected from the group of the formula Y 1 -Arg 2 -Val 3 – Tyr 4 -lle 5 -His 6 -X 7 SEQ ID NO: The surfactant is added to the aqueous phase in a concentration ranging from 0. After this step, the size of the vesicles is optionally calibrated, for example, by extrusion through or nm pore diameter polycarbonate membrane, as previously proposed Mayer LD, Hope MJ, Culles PR.

Bulas de Remédios – Todas Bulas de Remédios.

Vesicles of variable sizes produced by rapid extrusion procedure. To demonstrate the ability of the formulation to promote peptide absorption into the skin and regulating hair growth, Swiss mice were shaved on the dorsal region and a specific region is selected for applying different formulations. The vehicle consisted of vesicles formed from phosphatidylcholine and avvicis cholate. The patient was treated with topically applied 4 doses at intervals of 2 days. The different groups received the formulation of Ang- 1 -7 the formulation receptor antagonist But the Ang- 1 -7 A and solvent.

Nine days after the beginning of treatment, the animal was measured avicie coat application of bkla formulations region. According to the results, the formulation of Ang- 1 -7 significantly stimulated hair growth compared to vehiclewhereas formulation A significantly inhibited growth. The data show that animal hair growth following chemotherapy-induced alopecia, was significantly higher aviciw groups that received topical formulations of Ang- 1 -7 and Alamandina daily application for 30 days compared to the group that did not receive topical treatment.

Thus, it was shown that the formulation promotes the absorption of peptides in the skin and ensures its biological effectiveness, which points to its great potential in the prevention and treatment of alopecia.

Example 1 Preparation and characterization of topical formulation of angiotensin- The formulation consists of a suspension of lipid vesicles gauged size consisting of a mixture of phospholipid and surfactant in the presence of peptide. The ethanolic solution was injected into the aqueous solution using a syringe attached to a needle, and the resulting suspension was kept under magnetic stirring at room temperature.

The aqueous solution consisted of 0. After formation of the suspension, the size of the vesicles was calibrated by repeated filtrations 5 times polycarbonate membrane with 0. The formulation was characterized with respect to size distribution of vesicles by dynamic light scattering Zetasizer, Malvern, UK.

The vesicles had a mean hydrodynamic diameter in the 80 to nm range, with a polydispersity index less than 0.

Example 2 Influence of topical formulations of Ang- and its A antagonist in hair growth in mice. The formulations of Ang- 1 -7 and its antagonist A, prepared as described in Example 1 were evaluated for their ability to modulate hair growth in mice. Evaluation of the effectiveness of the formulations was performed using Swiss mice, males, 8 weeks.

There were three groups of 4 animals avicls received the composition of the Ang- 1 -7 aviciss, formulation A or vehicle comprising the suspension of vesicles without peptide. The animals were anesthetized and their backs shaved to remove the hair. Nine buula after the beginning aviciss treatment, measurements were taken of the length of hair with the region where there caliper application of the formulations.

The results, shown in Figure 1, show that the formulation containing Ang- induced a significant increase in hair growth of the animals when compared to vehicle, whereas the formulation containing A promoted a reduction in growth when compared to the group treated with the vehicle.

This study demonstrates the effectiveness of topical formulation Ang- 1 -7 in inducing growth of hair in mice.

The fact that the formulation A inhibit hair growth suggests that the receptor but mediates the action of these peptides. This experiment demonstrates that the formulation promoting aviciw absorption of peptides on the skin and ensures its biological effectiveness, indicating the high potential of the formulation of Ang- 1 -7 the prevention and treatment of alopecia and formulation of growth inhibition in A fur.

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