TOPICAL MINOXIDIL AND AMINEXIL SOLUTION

HAIR4U 10%
Dr. C Sakthivel

Hair Growth Cycle

Hair Growth Cycle

• Stages
– Anagen = growth; Catagen = involution; Telogen = rest

Hair Growth Cycle
• Normal scalp activity
– Anagen = 90-95% – Catagen = <1% – Telogen = 5-10%

• At the end of telogen, hair is released and the next cycle is initiated • Up to 100 hairs in telogen are shed each day and about the same number of follicles enter anagen

Alopecia • Definition: – Origin: Gr. Alepekia = a disease in which the hair falls out – Loss of hair. – Absence of hair from skin areas where it is normally present Androgenetic Alopecia (AGA) • Definition – Hereditary thinning of the hair induced by androgens in genetically susceptible men and women • Also known as – Male-pattern hair loss or common baldness in men – Female-pattern hair loss in women 30% of white men by age of 30. 50% of white men by age of 50 .

• Whites 4x than black men • Average rate of hair loss of about 5% per year • Some men go completely bald in less than 5 years but most take 15-25 years .Androgenetic alopecia • Miniaturization of follicles • Decreased anagen/Increased telogen • Increased latency to go into anagen phase • Patterned hair loss from the scalp.

leading to gradual hair thinning .Male-pattern baldness • Hair loss occurs on the temples and crown of the head with sparing of the sides and back. • hair thinning in an "M"-shaped pattern pattern reflects the distribution of androgen-sensitive follicles • androgens shorten the anagen phase and promote follicular miniaturization.

Progression of male pattern baldness .

Progression of male pattern baldness .

the terminal follicle is converted to a vellus follicle • High concentrations of DHT seen in the scalp of patients with androgenic alopecia. .Role of DHT • Testosterone converted to DHT with the help of 5 reductase. • Persons with an inherited deficiency of type II 5 -reductase & castrated prepubertal boys or eunuchs do not develop androgenic alopecia • Under the influence of DHT.

such as hirsutism. • Concomitant decrease in estrogens may also contribute to AGA. menstrual irregularities. and infertility are responsible. acne. . ovarian abnormalities. often with thinning in the central and frontal scalp area but usually without frontal temporal recession • conditions of hyperandrogenism.Androgenetic Alopecia • Women also may experience AGA.

(Under Influence of Androgens) • Terminal hair follicles are transformed into vellus.Pathophysiology Normally. • Decreased growth of hair on the scalp as well as axilla . (terminal and intermidiate hairs) • Shortened anagen and an increased telogen. • On the top: Androgen-sensitive follicles • On the sides and back of the scalp: androgen-independent follicles In genetically predisposed individuals.

Increased telogen hair count: During successive passages through the hair cycle the anagen phase becomes shorter and the telogen phase elongates.increased hair shedding • latency period between telogen and anagen becomes longer .PATHOGENESIS 1. Anagen to telogen ratio : ↓ 12:1 to 5:1 Telogen hairs are more loosely anchored to the follicle The new anagen hair is shorter than its predecessor • Increased telogen count .

Follicular miniaturization • Progressive diminution of hair shaft diameter and length in response to androgens • stepwise ↓ in size of the follicle with each successive cycle .2.

Diagnosis & Evaluation • Androgenetic alopecia diagnosis – Characteristic pattern of hair loss – Miniaturization in thinning areas – Family history is supportive but not necessary .

Evaluation Trichoscan • Normal scalp – Thick terminal hair – Fine vellus hair • Miniaturization – Thick terminal hair – Fine vellus hair – Intermediate diameter hair .

Evaluation • Regions of the scalp .

Patient Evaluation • Studies reveal negative psychosocial impact with hair loss – Body image dissatisfaction – Negative stereotype: • Older • Weaker • Less attractive • Counselling patients on expectations with treatment .

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. Duration: till adequate clinical response. Peripheral Vasodilator Topically: For alopecia Indication and dose : ALOPECIA ANDROGENETICA Dose is 1 ml of the high strength (10%) solution applied to the affected areas of the scalp twice daily.Minoxidil • Therapeutic class: Orally: Antihypertensive. Hair and scalp should be dry prior to application. (maximum total daily dose is 2 ml).

4. it may also increase hair diameter. alter the hair cycle. increase the linear growth rate of hair 2. increase the diameter of the hair fibre 3. .Mechanism of minoxidil 1. either shortening telogen or prolonging anagen. • Present evidence suggests that minoxidil acts mainly on the hair cycle. or act through a combination of these effects.

. as a potassium-channel agonist or a direct stimulant • Minoxidil sulfate is active metabolite responsible for stimulating hair follicles • reverse the miniaturization process of androgenetic alopecia by normalizing the hair follicle cycle.Mechanisms of action Minoxidil may affect the androgen metabolism in the scalp by inhibiting the capacity of androgens to affect the hair follicles. • Acts at the level of the hair follicle.

• Increased scalp blood flow • Prolongation of the anagen phase may result in follicular hypertrophy. • Minoxidil appears to work only on suboptimal follicles.Other mechanisms of action • Minoxidil is a potent activator of the cytoprotective isoform of prostaglandin endoperoxide synthase-1. • There is no apparent antiandrogen effect on hair follicle epithelium. which is the main isoform present in the dermal papilla • Incorporation of cysteine into the follicle is measurably increased. with no further stimulation of normal hair follicles .

117.Minoxidil-induced hair growth mediated by adenosine Adenosine Ecto-ATPase Adenosine Receptors ABC transporter PIP3 .. J Invest Dermatol. 2001 . 1594-. cAMP ATP K+ Minoxidil Sulfate SUR Kir Dermal Papilla Cells KATP channel Ca2+ c-fos VEGF Release to extra-cellar Hair growth Li et al.

vertex balding of less than 10 cm diameter. • The American Academy of Dermatology guidelines for androgenetic alopecia list topical minoxidil solution as first-line medical treatment for both men and women (Drake et al. 1994. Jacobs et al. 1996). 1993). DeVillez et al. 1993).to 40-years-old. 1987a. Karam. 1990. and more than 100 intermediate hairs within the balding area at baseline (DeVillez. • Response is best in patients less than 35. .Place in therapy • Topical minoxidil appears to be effective in producing moderate hair regrowth in 30% of men and 45% to 60% of women with alopecia androgenica (Price.

Nishikawa T. • • Tsuboi R. Randomized clinical trial comparing 5% and 1% topical minoxidil for the treatment of androgenetic alopecia in Japanese men. • The objective of this double blind trial was to verify the superiority in clinical efficacy of 5% topical minoxidil to 1% topical minoxidil • The trial included 300 Japanese male patients aged 20 years or older with androgenetic alopecia • Conclusion: Findings confirmed the superiority of 5% topical minoxidil to 1% topical minoxidil in treating Japanese men with androgenetic alopecia . Tokyo Medical University. Katsuoka K. Tokyo. Arano O.36(8):437-46.J Dermatol. Yamada H. Japan. Department of Dermatology. 2009 Aug.

is characterized in the anagen phase by a highly developed vascular network. Faculté de Médecine Rangueil. Institut de Recherche Pierre Fabre. Gall & Bonafe 0 Laboratoire de Biologie Cellulaire Cutanée.British Journal of Dermatology Volume 138 Issue 3. France • The hair follicle dermal papilla which controls hair growth. Pages 407 . route de Narbonne. • Increasing minoxidil concentrations induced a dose-dependent expression of VEGF mRNA . 133. Charveron. 31064 Toulouse.411 • Minoxidil upregulates the expression of vascular endothelial growth factor in human hair dermal papilla cells Lachgar. • VEGF mRNA is strongly expressed in dermal papilla cells (DPC) in the anagen phase.

Review: Topically Applied Minoxidil in Baldness • ERVIN NOVAK. University of Michigan. School of Medicine.D.AND RONALD C.D. FRANZ.. M.D. Ann Arbor.. WESTER.. PH.D. Michigan. IOHN T. San Francisco. From the Upjohn Company. Kalamazoo. Seattle. M. Michigati. and School of Medicine and School of Pharmacy. University of California. Medical School. University of Washington. Washington. HEADINCTON. . THOMAS ). California • Blood Flow of the Scalp – Cumulative penetration increases with increased concentration minoxidil solutions – High strength minoxidil solution increased blood flow when compared with the other treatments. M.

2% minoxidil and placebo. . Vertical line at 96 weeks indicates cessation of treatment.• High concentration of minoxidil suppressed activity of the enzyme lysyl hydroxylase thereby collagen synthesis • Higher concentration of minoxidil produces higher scalp blood flow Comparison of mean percentage change in interval hair weight per square centimetre for three treatment groups: 5% minoxidil.

• Mean change from baseline in nonvellus hair counts (per square centimetre) in men treated with 5% minoxidil solution (TMS). 2% minoxidil and placebo. .

as quick as 2 months • Minoxidil 10% faster results than the 2% or 5% minoxidil • Minoxidil 10% is for those who have failed to regrow hair from 2% or 5% Minoxidil. • High strength minoxidil gives rapid response . .Why 10 % Minoxidil • Hair re-growth in response to minoxidil is dose dependent • Minoxidil 5% is proven to grow 45% more than the 2% formula.

• Effects of 10% Minoxidil in treating male-pattern hair loss report that a majority of patients found Very effective to effective results in promoting new hair growth over the period of treatment . • Minoxidil has been approved for use in treating male-pattern hair loss for more than 15 years.Place in therapy • Minoxidil has been tested in hundreds of clinical studies on thousands of volunteers and has been shown to be effective in the treatment of hair loss particularly on the vertex of the head.

Topical absorption of minoxidil is increased by increasing the dose applied. due to the rate of percutaneous absorption.Pharmacokinetics Elimination half-life of minoxidil is 22 hours. . increasing the frequency of dosing and decreasing the barrier function of stratum corneum. Minoxidil is metabolized mainly in the liver and its metabolites are excreted in the urine.

• Contact dermatitis. and inflammation or erythema of the scalp could also occur. • LEUKODERMA of the scalp. including facial hair growth in women . scalp flaking and rarely exacerbation of hair loss.I have occured . salt-and-pepper appearance in dark hair. irritation and pruritis was noted in less than 5% of patients. scaling of the scalp. • Rarely changes in BP. • unwanted hair growth on other parts of the body. darkening of skin. • Changes in hair pigments (reddish tint in dark hair. yellowish color in white hair. Hypotension and M. local erythema.Adverse effects • Itching and skin irritation of the treated area of scalp • Dryness.

Perifollicular Fibrosis • Condition that accompanies all alopecia • Research shows . pushing the root to the surface and causing premature hair loss. • This causes the roots to become rigid and compresses the blood vessels that nourish and stimulate them– leads to accelerated aging of hair roots. . stiffening of roots spreads.abnormal build-up of thick. • Collagen around the hair root becomes rigid and tightens. rigid. collagen often hindered new hair growth. • In men. the roots produce hair that is increasingly fine and has an ever shorter life span.

• Hair thickness increased by 6% • Many people suffer from hair loss after the summer or wintertime. • Aminexil has been shown to increase hair density and hair growth by preventing perifollicular fibrosis.AMINEXIL • Aminexil. came on the international market on June 20. Aminexil showed that such persons are no longer troubled by seasonal hair loss. . patented research product of L'Oréal's laboratories. 1996.

• 130 test participants. with Alopecia type II to V.Clinical trials • In one world-wide placebo controlled study (1994 -1995) Aminexil was used for 42 consecutive days. aged between 18 and 55 years. .

.Increase in number of hair.

Hair thickness • The hair growth thickness investigation showed that by using Aminexil hair thickness increased by 6%. .

Hair preservation Thus aminexil controls seasonal hair loss .

Clinical studies • Study was done to evaluate whether topical Aminexil lotion prevents or reduces hair loss which occurs after stoppage of oral finasteride treatment. • Conclusion : may be helpful in preventing hair loss after stopping finasteride treatment. a slight decrease in 6 patients and no changes in the remaining 9 patients. . • 18 male patients aged from 20 to 43 years • Evaluation from global photographs showed a moderate decrease in 3 patients.

• Bioadhesive polymer technology: Hydroxypropyl cellulose (0.5% • Formulation : solution. (J Pharm Sciences Vol 79.15% and 0. pp 483-486. Issue 6. 1989) .3%) A study in 22 healthy male volunteers proved that the extent of minoxidil absorption increases with an increase in contact time of drug on the scalp.HAIR4 U • Minoxidil: 10 % • Aminexil: 1.

• Addition of the bioadhesive polymer would prolong the contact time of the drug with the scalp.Bioadhesive polymer • Minoxidil must remain in contact for at least four hours for sufficient absorption (75%). • Keep minoxidil in solution form and prolong the time of absorption .

minoxidil was released over a prolonged period of 24 h.Bioadhesive polymer • Marketed preparation contains alcohol and propylene glycol that evaporates resulting in a supersaturated solution. • This leads to precipitation of minoxidil and thus abrupt absorption pattern • addition of the polymer would not allow the thermodynamic activity of the formulation to change as quickly as the plain solution. • It would keep minoxidil and aminexil in a solution form. • In a study with excised mouse skin it was found that in a formulation (gel) containing the polymer. .

• Hydroxypropyl cellulose possesses good surface activity but does not gel as it forms open helical coils • In general Hydroxypropyl cellulose is a water-soluble thickener. • Trap water and produces a film that serves as a barrier to water loss.Hydroxypropyl cellulose • derivative of cellulose • soluble in both water and organic solvents. . emulsifier and film-former.

.Contraindications • individuals with a history of sensitivity reactions to any of its components • Pregnancy and breast feeding.

People with heart failure or significant coronary heart disease • Not be used in patients using occlusive dressings or other medicines on the scalp. DIZZINESS OR SHORTNESS OF BREATH • To prevent growth in unwanted areas: application only to the scalp. a red.WARNINGS • Low blood pressure or are taking blood pressure lowering medications. inflamed. wash hands with soap and water immediately after use. . infected. irritated or painful scalp (including psoriasis and sun burn) • DISCONTINUE : RAPID HEART BEAT.

• Not to apply on other areas • Wash hands after use. • Shake the solution well before use. • care should be taken to apply the medicine on the scalp along with application on hair.Dosage & administration • Applied directly to the scalp twice a day. every day. without skipping applications. • 1 ml of the high strength (10%) solution applied to the affected areas • The hair and scalp should be dry prior to topical application of minoxidil. .

Thanks .