Hair4U 10% Medical

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TOPICAL MINOXIDIL ANDAMINEXIL SOLUTION

HAIR4U 10%

Dr. C Sakthivel



Hair Growth Cycle





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



Androgenetic alopecia

• Miniaturization of follicles

• Decreased anagen/Increased telogen

• Increased latency to go into anagen phase

• Patterned hair loss from the scalp.

• 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



Male-pattern baldness

• Hair loss occurs on the temples and crown of the headwith 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, leading to gradual hairthinning



Progression of male pattern baldness



Progression of male pattern baldness



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, the terminal follicle is

converted to a vellus follicle

• High concentrations of DHT seen in the scalp of

patients with androgenic alopecia.



Androgenetic Alopecia

• Women also may experience AGA, often withthinning in the central and frontal scalp area butusually without frontal temporal recession

• conditions of hyperandrogenism, such as hirsutism,ovarian abnormalities, menstrual irregularities, acne,and infertility are responsible.

• Concomitant decrease in estrogens may alsocontribute to AGA.



Pathophysiology

Normally;

• On the top: Androgen-sensitive follicles

• On the sides and back of the scalp: androgen-independent

folliclesIn genetically predisposed individuals;(Under Influence of

Androgens)

• Terminal hair follicles are transformed into vellus. (terminal

and intermidiate hairs)• Shortened anagen and an increased telogen.

• Decreased growth of hair on the scalp as well as axilla





2. Foll icular miniatur ization

• Progressive diminution of hair shaft diameter and

length in response to androgens

• stepwise ↓ in size of the follicle with each successive

cycle



Diagnosis & Evaluation

• Androgenetic alopecia diagnosis

– Characteristic pattern of hair loss

– Miniaturization in thinning areas

– Family history is supportive but not necessary



EvaluationTrichoscan

• 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 impactwith hair loss

– Body image dissatisfaction

– Negative stereotype:• Older

• Weaker

• Less attractive

• Counselling patients on expectations withtreatment





Minoxidil

• Therapeutic class: Orally: Antihypertensive,Peripheral

Vasodilator

Topically: For alopecia

Indication and dose : ALOPECIA ANDROGENETICA

Dose is 1 ml of the high strength (10%) solution applied to theaffected areas of the scalp twice daily.

(maximum total daily dose is 2 ml).Hair and scalp should be dry prior to application.

Duration: till adequate clinical response.



Mechanism of minoxidil

1. increase the linear growth rate of hair

2. increase the diameter of the hair fibre

3. alter the hair cycle, either shortening telogen or prolonging anagen,

4. or act through a combination of these effects.

• Present evidence suggests that minoxidil actsmainly on the hair cycle; it may also increase hair

diameter.



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, 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.



Other mechanisms of action• Minoxidil is a potent activator of the cytoprotective isoform of

prostaglandin endoperoxide synthase-1, which is the main

isoform present in the dermal papilla

• Incorporation of cysteine into the follicle is measurablyincreased.

• There is no apparent antiandrogen effect on hair follicleepithelium.

• Increased scalp blood flow

• Prolongation of the anagen phase may result in follicularhypertrophy.

• Minoxidil appears to work only on suboptimal follicles, withno further stimulation of normal hair follicles



Minoxidil-induced hair growth mediated by adenosine

Minoxidil SulfateATPAdenosineK+

Ecto-ATPase KirSUR

Adenosine Receptors

Dermal PapillaABC transporterCells

PIP3 , cAMP KATP channel

Ca2+

c-fos

Hair growthVEGF

Release to extra-cellar

Li et al ., J Invest Dermatol , 117, 1594-, 2001

Pl i th



Place in therapy

• Topical minoxidil appears to be effective in producing moderatehair regrowth in 30% of men and 45% to 60% of women with

alopecia androgenica (Price, 1987a; DeVillez et al, 1994; Jacobs et al, 1993).

• Response is best in patients less than 35- to 40-years-old,vertex balding of less than 10 cm diameter, and more than 100

intermediate hairs within the balding area at baseline(DeVillez, 1990; Karam, 1993).

• 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, 1996).



J Dermatol. 2009 Aug;36(8):437-46.

Randomized clinical trial comparing 5% and 1% topical

minoxidil for the treatment of androgenetic alopecia inJapanese men.

• Tsuboi R , Arano O, Nishikawa T, Yamada H, Katsuoka K .

• Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

• The objective of this double blind trial was to verify thesuperiority 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% topicalminoxidil to 1% topical minoxidil in treating Japanese menwith androgenetic alopecia

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tsuboi%20R%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Arano%20O%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nishikawa%20T%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yamada%20H%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Katsuoka%20K%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Katsuoka%20K%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yamada%20H%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nishikawa%20T%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Arano%20O%22%5BAuthor%5D

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tsuboi%20R%22%5BAuthor%5D



British Journal of Dermatology

Volume 138 Issue 3, Pages 407 - 411

• Minoxidil upregulates the expression of vascular endothelialgrowth factor in human hair dermal papilla cellsLachgar, Charveron, Gall & Bonafe 0 Laboratoire de Biologie Cellulaire Cutanée, Institut de Recherche Pierre Fabre, Faculté de Médecine Rangueil, 133, route de

Narbonne, 31064 Toulouse, France

• The hair follicle dermal papilla which controls hair growth, is

characterized in the anagen phase by a highly developed vascularnetwork.

• VEGF mRNA is strongly expressed in dermal papilla cells(DPC) in the anagen phase,

• Increasing minoxidil concentrations induced a dose-dependentexpression of VEGF mRNA





• High concentration of minoxidil suppressed activity of the enzyme lysylhydroxylase thereby collagen synthesis

• Higher concentration of minoxidil produces higher scalp blood flow

Comparison of mean percentage change in interval hair weight per square centimetrefor three treatment groups: 5% minoxidil, 2% minoxidil and placebo. Vertical line at96 weeks indicates cessation of treatment.



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



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.

• High strength minoxidil gives rapid response - as quick as 2months

• Minoxidil 10% faster results than the 2% or 5% minoxidil

• Minoxidil 10% is for those who have failed to regrow hairfrom 2% or 5% Minoxidil.



Place in therapy

• Minoxidil has been tested in hundreds of clinical studies on

thousands of volunteers and has been shown to be effective inthe treatment of hair loss particularly on the vertex of the head.

• Minoxidil has been approved for use in treating male-patternhair loss for more than 15 years.

• Effects of 10% Minoxidil in treating male-pattern hair lossreport that a majority of patients found Very effective toeffective results in promoting new hair growth over the periodof treatment



Pharmacokinetics

Elimination half-life of minoxidil is 22 hours; due to the rate of

percutaneous absorption.

Topical absorption of minoxidil is increased by increasing thedose applied, increasing the frequency of dosing and

decreasing the barrier function of stratum corneum.

Minoxidil is metabolized mainly in the liver and its metabolitesare excreted in the urine.



Adverse effects

• Itching and skin irritation of the treated area of scalp

• Dryness, irritation and pruritis was noted in less than 5% of patients.

• Contact dermatitis, scaling of the scalp, and inflammation or erythema of the

scalp could also occur.

• Changes in hair pigments (reddish tint in dark hair; salt-and-pepper

appearance in dark hair; yellowish color in white hair.

• unwanted hair growth on other parts of the body, including facial hair growthin women , local erythema, scalp flaking and rarely exacerbation of hair loss.

• LEUKODERMA of the scalp, darkening of skin.

• Rarely changes in BP, Hypotension and M.I have occured

P if lli l Fib i



Perifollicular Fibrosis

• Condition that accompanies all alopecia

• Research shows - abnormal build-up of thick, rigid, collagenoften hindered new hair growth.

• Collagen around the hair root becomes rigid and tightens,

pushing the root to the surface and causing premature hair loss.

• This causes the roots to become rigid and compresses the bloodvessels that nourish and stimulate them – leads to acceleratedaging of hair roots.

• In men, stiffening of roots spreads; the roots produce hair that isincreasingly fine and has an ever shorter life span.



AMINEXIL

• Aminexil, patented research product of L'Oréal's laboratories,came on the international market on June 20, 1996.

• Aminexil has been shown to increase hair density and hair

growth by preventing perifollicular fibrosis.

• Hair thickness increased by 6%

• Many people suffer from hair loss after the summer orwintertime. Aminexil showed that such persons are no longertroubled by seasonal hair loss.



Clinical trials

• In one world-wide placebo controlled study

(1994 -1995) Aminexil was used for 42

consecutive days.

• 130 test participants; aged between 18 and 55

years, with Alopecia type II to V;



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.

• 18 male patients aged from 20 to 43 years• Evaluation from global photographs showed a moderate

decrease in 3 patients, a slight decrease in 6 patients and no

changes in the remaining 9 patients.

• Conclusion : may be helpful in preventing hair loss afterstopping finasteride treatment.



HAIR4 U

• Minoxidil: 10 %

• Aminexil: 1.5%

• Formulation : solution.

• Bioadhesive polymer technology:Hydroxypropyl cellulose (0.15% and 0.3%)

A study in 22 healthy male volunteers proved that the extent ofminoxidil absorption increases with an increase in contacttime of drug on the scalp.

(J Pharm Sciences Vol 79, Issue 6, pp 483-486, 1989)



Bioadhesive polymer

• Minoxidil must remain in contact for at least four

hours for sufficient absorption (75%).

• Addition of the bioadhesive polymer would prolongthe contact time of the drug with the scalp.

• Keep minoxidil in solution form and prolong thetime of absorption



Bioadhesive polymer

• Marketed preparation contains alcohol and propylene glycol that evaporatesresulting 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 theformulation 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, minoxidil was released over a prolonged period of24 h.



Hydroxypropyl cellulose

• derivative of cellulose

• soluble in both water and organic solvents.

• Trap water and produces a film that serves as a barrier to waterloss.

• Hydroxypropyl cellulose possesses good surface activity butdoes not gel as it forms open helical coils

• In general Hydroxypropyl cellulose is a water-solublethickener, emulsifier and film-former.



Contraindications

• individuals with a history of sensitivity

reactions to any of its components

• Pregnancy and breast feeding.



WARNINGS• Low blood pressure or are taking blood pressure lowering

medications. People with heart failure or significant coronary heartdisease

• Not be used in patients using occlusive dressings or other medicines on

the scalp, a red, inflamed, infected, irritated or painful scalp (including

psoriasis and sun burn)

• DISCONTINUE : RAPID HEART BEAT, DIZZINESS OR

SHORTNESS OF BREATH

• To prevent growth in unwanted areas: application only to the

scalp, wash hands with soap and water immediately after use.



Dosage & administration

• Applied directly to the scalp twice a day, every day, withoutskipping applications.

• 1 ml of the high strength (10%) solution applied to the affectedareas

• The hair and scalp should be dry prior to topical application ofminoxidil.

• Shake the solution well before use.

• care should be taken to apply the medicine on the scalp along

with application on hair.• Not to apply on other areas

• Wash hands after use.



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Hair4U 10% Medical