Changes
/* Structure-Activity Relationships(SARs) */
{{TOCrightEx}}
== Rationale ==
* "Medication for men plagued by hair loss has become a topic of interest in Japan since a drug company began marketing it at the end of last year." March 5th, 2006 – [http://stophair.setupmyblog.com/?p=55Source] * "An increasing number of companies are apparently turning the Chinese fear of a bald spot into big bucks with some doing so well they are branching out into other countries." February 16, 2006 – [http://stophair.setupmyblog.com/Source] * "There is something in the air, or should we say in the hair, these days. Scientific research into hair loss remedies has never been more active or more exciting." June 7, 2006 - [http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/06-07-2005/0003821470&EDATE=Source]<br><br> == Alopecia IPMap == [http://www.dolcera.com/client/ds94x0s90akq9d7xb402fm/hairloss_map.htm Dolcera IPMap for Alopecia]<br>
== Introduction ==
* Hair is a complex and delicate part of the body.
* Keeping it healthy and beautiful is a challenge.
* Hair grows everywhere on the body with the exception of the lips, eyelids, the palms of the hands and soles of the feet.
* Hair is basically a form of skin.
* Hair is made up of a protein called keratin.
* Each shaft of hair is made of two or three inter-twined layers of keratin which grow from a follicle beneath the skin.
* Hair Structure - [http://www.pg.com/science/haircare/hair_twh_12.htmSource]* Hair Cycle - [http://www.follicle.com/hair-structure-life-cycle.htmlSource] [[Image:Hairbasics.jpg|thumb|center|500px400px|Structure of Hair root and Hair bulb]]
=== What causes hair loss? ===
* Decreased Decrease in growth of the hair * Increased Increase in shedding of the hair * Breakage of hairs hair
* Conversion of thick terminal hairs to thin vellus hairs
[[Image:Facts.jpg|thumb|right|400px250px|Survey results from Japan]]Both men and women lose hair for similar reasons. Hair loss in men is often more dramatic, and follows a specific pattern of loss, one of which has been termed '''“Male Pattern Baldness"''' or '''"Androgenetic Alopecia"'''.
=== Types of alopecia=== * '''Alopecia Areata (AA):''' Used to describe hair Hair loss occurring in patches anywhere on the body.* '''Alopecia Totalis (AT):''' Total loss of the hair on the scalp.* '''Alopecia Universalis (AU):''' Total loss of all hair on the body.* '''Alopecia Barbae:''' Loss of facial hair (for a man) especially in the beard area.* '''Alopecia Mucinosa:''' A type of alopecia which results in scaley patches.* '''Androgenetic Alopecia (AGA)''': Also known as male pattern baldness. It is a thinning of the hair to an almost transparent state, in both men or women. It is thought to be a hereditary form of hair loss.* '''Traction Alopecia:''' Traction alopecia is usually due to excessive pulling or tension on hair shafts as a result of certain hair styles. It is seen more often in women, particularly those of East Indian and Afro-Caribbean origin. Hair loss depends on the way the hair is being pulled. Prolonged traction alopecia can stop new hair follicles from developing and lead leads to permanent hair loss.* '''Anagen Effluvium:''' This hair loss is generally caused by chemicals such as those used to treat cancer. Initially it causes patchy hair loss, which often then becomes leads to total hair loss. The good news is that when you stop using these chemicals the hair normally grows back (usually about 6 months later). Other drugs also can cause hair loss. Many medicines used to treat even common diseases can cause hair loss.* '''Scarring Alopecia:''' A form of alopecia which leaves scarring on the area of hair loss.* '''Telogen Effluvium:''' A form of hair loss where more than normal amounts numbers of hair fall out. There is a general 'thinning' of the hair. Unlike some other hair and scalp conditions, it is temporary and the hair growth usually recovers. ([http://www.alopeciaonline.org.uk/about/types.asp sourceSource])
=== Androgenetic alopecia ===
* Gradual Onset.onset* Transition from large, thick, pigmented terminal hairs to thinner, shorter, indeterminate hairs and finally to short, wispy, nonpigmented non-pigmented vellus hairs in the involved areas.* Characterised Characterized by a receding hairline and/or hair loss on the top of the head.
'''Main causes'''
(JICST-EPlus - Japanese Science & Technology)
== Goals ==The goal of this report is to: * Summarize IP activity over the years* Identify major players* Conduct patent analysisa) Compositionb) Naturec) Action* Technology mapping based on patent anlysis elements == IP activity over years ==
The graph indicates:
* Number of patents filed every 5 years (except for first 7 years).
== Major players ==
[[Image:players.jpg|thumb|left|400px500px|Assignees with more than 20 patents ]][[Image:players1.jpg|thumb|center|400px500px|Assignees with fewer than 20 patents ]]<br>
* '''Active assignees'''
[[Image:Active.jpg|thumb|center|500px|Active Assignees]]
== Approach and Methodalogy Taxonomy ==
== Treatment Approaches==
Composition of treatment for causes are identified and categorized as follows:
* Anti-androgens(Finasteride) [http://www.emedicine.com/DERM/topic21.htm source]* Minoxidil Vasodilators (as vasodilatorsMinoxidil)[http://www.emedicine.com/DERM/topic21.htm source]* Double action (Anti-androgen + MindoxidilVasodilator)
* Hair matrix cells activator
{|border="1" cellpadding="2", style="#008080" align="center"
|- style="font-weight:bold" valign="top"
! Cause !! Treatment approach !! Pathways affected
|- valign="top"
| Hormonal effect of androgen || Anti-androgens || Testosterone pathway
|- valign="top"
| Reduction of blood circulation around hair follicle || Vasodilators (eg. Minoxidil) || NO/cGMP Pathway
|- valign="top"
| Deactivation of hair matrix cells || Hair matrix cells activator
|
* Wnt pathway
* STAT pathway
* TGF beta/BMP Pathway
* FGF Pathway
* MAPK Pathway
* NOTCH Pathway
* Hedgehog Pathway
|}
=== Anti-androgens ===
* Anti-androgens are used in hormone therapy.
* Anti-androgens are designed to affect the hormones made in the adrenal glands. They don't stop the hormones from being made, but they stop them from having an effect leading to hair loss.
'''What causes hair loss?'''
!width="400" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220060009430%22.PGNR.&OS=DN/20060009430&RS=DN/20060009430 [US20060009430]]
BLOTECH (2004)
|bgcolor=LightCyan|Natural extracts
|bgcolor=LightCyan|Organic compound
|bgcolor=LightCyan|New class of 4-cycloalkoxy benzonitrile derivatives and salts
|bgcolor=LightCyan|Acts as androgen receptor modulators modulator and blocks formation of DHT.
|- style="height:20px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220050085467%22.PGNR.&OS=DN/20050085467&RS=DN/20050085467 US20050085467]
|bgcolor=LightCyan|Peptides/nucleic acid
|bgcolor=LightCyan|Bradykinin antagonist (peptide of plasma origin from kininogen precursor-kallikrein)
|bgcolor=LightCyan|Inhibit Inhibits synthesis of bradykinin receptors or compounds by binding to B2 receptor
|- style="height:20px"
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=EP0279010&F=0 EP0279010]
'''What causes hair loss?'''
* A thick network of tiny veins and arteries lines line the outer wall of the follicle. Blood pumps through the bulb and hair via this network.
* DHT accumulates in the hair follicles and roots, constricting the blood supply of oxygen and nutrients to the hair roots; which is also seen to possibly contribute towards hair loss.
'''How does Minoxidal Minoxidil treat hair loss?'''* Minoxidal Minoxidil is applied to the scalp topically, where it dilates blood vessels in the scalp and sustains the hair follicles for longer period of time.* Minoxidil is thought to have a direct mitogenic effect on epidermal cells, as has been observed both in vitro and in vivo. Though the mechanism of its action for causing cell proliferation is not very clear, minoxidil is thought to prevent intracellular calcium entry. Calcium normally enhances epidermal growth factors to inhibit hair growth, and Minoxidil by getting converted to minoxidil sulfate acts as a potassium channel agonist and enhances potassium ion permeability to prevent calcium ions from entering into cells.([http://www.hairtransplantadvice.com/medical-hair-restoration.php sourceSource])
* Minoxidil sulfate (MS) appears to be the active metabolite responsible for hair growth stimulation.
==== Functions of Monoxidil Vasodilators ====
[[Image:minoxidil1.jpg|thumb|center|500px|Functions of Monoxidil [http://www.nurseminerva.co.uk/diagrams.htm#Diagram%201 source]]]
==== IP Map for Minoxidil Vasodilators ====
{| border="1" cellpadding="2"
|}
=== Double action (Anti-androgen + MinoxidilVasodilator) ===* Combination of Minoxidil Vasodilator + Anti-androgen (double action) composition for effective treatment of Male-Pattern Baldness.
'''What is the problem with using only Anti-androgen therapy?'''
* Anti-androgen is not effective in addressing the issue of vasocontriction around hair follicles due to sebum oil build up.
* Anti-androgen only prevent prevents binding of DHT to androgen receptors. However, the effects of improper oxygen and nutrient supply to the brain due to vasocontriction still remains and gradually causes hair loss.
'''What is the problem with using only Minoxidal Vasodilator (or Minoxidil only) therapy?'''* Vasodilator or Minoxidil-based products are generally not effective in stopping hair loss as minoxidil does vasodilators (or Minoxidil) do not block the harmful effects of DHT in the scalp and hair follicles. * Vasodilators or Minoxidil simply dilates dilate blood vessels in the scalp. However, the harmful DHT is still being gets produced in the body and still getting into , enters the scalp and hair follicles and causing eventual hair loss.
'''How is the combination of Anti-androgens and Vasodilator (or Minoxidil ) effective?'''
* Anti-androgens target the problem of DHT binding to androgen receptors and prevents follicle miniaturization.
* Vasodilators like Minoxidil causes cause vasodilation and therefore improves improve supply of oxygen and nutrients to the hair follicle and roots.
* Combination therapy therefore proves to be much more effective than individual therapy.
==== Functions of (Anti-androgen + MinoxidilVasodilators) ==== [http://www.revivogen.com/revivogen/work.html Anti-androgen ]and [http://www.xandrox.net/articles/article01.htm Minoxidil][[Image:Doubleaction1.jpg|thumb|center|500px|Functions of (Anti-androgen + MinoxidilVasodilators)]]
==== IP Map for (Anti-androgen + MinoxidilVasodilators) ====
{| border="1" cellpadding="3"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
N/A(2000)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Testosterone blocker or vascular toner (Flutamide, cyproterone acetate, spironolactone, progesterone, or analogs or derivatives) and minoxidil mixed along with non-retinoid penetration enhance enhancer and sunscreen
|bgcolor=LightCyan|Inhibits 5.alpha.-reductase activity (block DHT) and increase blood flow on the scalp
|- style="height:100px"
* Matrix activator allows activation of hair matrix cells and therefore follicle stimulation leading to hair growth.
==== Functions of Hair matrix cell activator ==== [http://www.ijdb.ehu.es/fullaccess/fulltext.04023/ft163.pdf Hair matrix cell activator]
[[Image:Hair matrix.jpg|thumb|center|500px|Functions of Hair matrix cell activator ]]
{| border="1" cellpadding="2"
!width="120" bgcolor=DodgerBlue|'''Pat/Pub#'''
!width="75100" bgcolor=DodgerBlue|'''Nature'''!width="500200" bgcolor=DodgerBlue|'''Composition'''
!width="600" bgcolor=DodgerBlue|'''Composition action'''
|- style="height:100px50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220020052498%22.PGNR.&OS=DN/20020052498&RS=DN/20020052498 US20020052498]
SHISEIDO(1999)
|bgcolor=LightCyan|(2-substituted oxyphenyl) alkanamide derivative and its salt
|bgcolor=LightCyan|Mechanism of action has not been made clear, having excellent hair follicle activating action and regrowth promoting effect
|- style="height:100px50px"
|bgcolor=LightCyan|[http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220040071647%22.PGNR.&OS=DN/20040071647&RS=DN/20040071647 US20040071647]
L'OREAL(1998)
|bgcolor=LightCyan|Peptides
|bgcolor=LightCyan|Metalloprotease (MMP-9) inhibitor (thiol or a hydroxamate) other than chelating calcium ions
|bgcolor=LightCyan|Reducing the expression of MMPs (Metalloproteases) in the scalp - slow slows down or inhibit inhibits the degradation of the perifollicular matrix (extracellular matrix surround surrounding the hair follicle)
|}
== Technology mapping based on patents anlyzed analyzed ==
=== IPMap: Composition nature matrix ===
|bgcolor=LightCyan|....
|}
=== Focus of patents ===
{| border="1" cellpadding="17", style="#008080"
!width="600800" bgcolor=DodgerBlue|'''Focus of patents'''!width="120150" bgcolor=DodgerBlue|'''Patent no.'''!width="60100" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|2-substituted oxyphenyl alkanamide derivative having excellent hair growth effect.
=== Technology focus===
[[Image:Technologyfocus2.jpg|thumb|center|700px|Technology focus]]
=== Distribution of patents ===
==== Target species ====
[[Image:Species.jpg|thumb|center|700px|Target species]]
==== Patents by target diseases ====
{| border="1" cellpadding="16", style="#008080"
!width="600800" bgcolor=DodgerBlue|'''Target disease/ disorder'''!width="20150" bgcolor=DodgerBlue|'''Patent no.'''!width="20150" bgcolor=DodgerBlue|'''Rec. no.'''
|-
|bgcolor=LightCyan|Alopecia areata, alopecia pityrodes or alopecia seborrheica, or androgenic alopecia (i.e. male pattern baldness)
|}
== Signaling Pathway == [[List of patents]] ====== Pathways and linkages ==
=== Pathways associated with hair matric matrix cell activation===
'''Molecular mediators of hair follicle embryogenesis:''' Identification of the molecular pathways controlling differentiation and proliferation in mammalian hair follicles provides the crucial link to understanding the regulation of normal hair growth, the basis of hereditary hair loss diseases, and the origin of follicle-based tumors. Homeobox (hox), hedgehog (hh), patched (ptc), wingless (wg}/wnt, disheveled (dsh), engrailed (en), Notch 1 and armadillo/B-catenin genes are all critical for hair follicle.
* '''Wnt pathway:''' Maintains hair-inducing activity of the dermal papilla.
* '''FGF Pathway:''' Fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) potentiate the growth of dermal papilla cells. It is proposed that these proteins increase the synthesis of stromelysin (an enzyme, matrix metalloproteinase) which acts on the papilla cells and accelerates their growth.
* '''MAPK Pathway:''' Mitogen-activated protein kinase (MAPK) activation, increases keratinocyte turnover.
* '''NOTCH Pathway''': Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1, one of the three ligands is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode, and appears to promote and accelerate placode formation, while suppressing placode formation in surrounding cells. Other ligands, Serrate 1 and Serrate 2, are expressed in matrix cells destined to form the inner root sheath and hair shaft.
=== Pathways associated with Anti Androgen===
[[Image:Slide3.gif|center|720 px|Alopecia pathways]]
{| border="1" cellpadding="15", style="#008080"
!width="70150" bgcolor=DodgerBlue|'''Patent no.'''!width="20200" bgcolor=DodgerBlue|'''Key compound'''!width="70200" bgcolor=DodgerBlue|'''Players of inhibition'''
|- style="height:10px"
|bgcolor=lightyellow|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
|bgcolor=LightCyan|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO03011287&F=0 WO2003011287]
|bgcolor=LightCyan|Pyrazolon derivatives
|bgcolor=LightCyan|GSK3, βß-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6924141.PN.&OS=PN/6924141&RS=PN/6924141 US6924141]
|bgcolor=LightCyan|Lithium chloride, Wnt3/4/ 7
|bgcolor=LightCyan|βß-catenin, GSK3, Wnt
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6706685.PN.&OS=PN/6706685&RS=PN/6706685 US6706685]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|βß-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6683048.PN.&OS=PN/6683048&RS=PN/6683048 US6683048]
|bgcolor=LightCyan|Peptide sequence
|bgcolor=LightCyan|αa-catenin, βß-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6677116.PN.&OS=PN/6677116&RS=PN/6677116 US6677116]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|βß-catenin
|-
|bgcolor=LightCyan|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6303576.PN.&OS=PN/6303576&RS=PN/6303576 US6303576]
|bgcolor=LightCyan|Peptide sequence LXXLL
|bgcolor=LightCyan|βß-catenin
|}
==== Role of Pyrazole compounds in Wnt Pathway====
'''Pyrazole'''
* '''Pyrazole''' (C3H4N2) refers both to the class of simple aromatic ring organic compounds of the heterocyclic series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions and to the unsubstituted parent compound. Being so composed and having pharmacological effects on humans, they are classified as alkaloids although they are not known to occur in nature.
* Pyrazoles are produced synthetically through the reaction of αa,βß-unsaturated aldehydes with hydrazine and subsequent dehydrogenation
[[Image:pyrazole1.jpg|thumb|center|500px|Pyrazole (C3H4N2)]]
* Pyrazoles are used for their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, tranquilizing, muscle relaxing, psychoanaleptic, anticonvulsant, monoamineoxidase inhibiting, antidiabetic and antibacterial activities.
[[Image:bold3.jpg]]
{| border="1" cellpadding="2", style="#008080"
!width="100350"|[http://patft1.uspto.gov/netacgi/nph-Parser?TERM1=6989385+&Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=0&f=S&l=50 US6989385]
[[Image:US6989385.jpg]]
!width="100350"|[http://patft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=6664247.PN.&OS=PN/6664247&RS=PN/6664247 US6664247]
[[Image:US6664247.jpg]]
!width="100350"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=WO2005012256&F=0 WO2005012256]
[[Image:WO2005012256.jpg]]
|-
'''Applicant''': ''Vertex Pharmaceuticals Incorporated''
'''Title''': Pyrazole compounds useful as protein kinase inhibitors
'''Basic Structure''':
[[Image:pyrazol1.jpeg]]
'''Patent Number''': US7008948
'''Applicant''': Vertex Pharmaceuticals Incorporated
'''Title''': Fused pyrimidyl pyrazole compounds useful as protein kinase inhibitors
'''Basic Structure'''
[[Image:pyrazol2.jpeg]]
'''Patent Number''': US6977262
'''Assignee''': Mitsubishi Pharma Corporation
'''Title''': Dihydropyrazolopyridine compounds and pharmaceutical use thereof
'''Basic Structure''':
[[Image:pyrazol3.jpeg]]
----
'''Patent Number''': US6664247
'''Assignee''': Vertex Pharmaceuticals Incorporated
'''Title''': Pyrazole compounds useful as protein kinase inhibitors'''
'''Basic Structure''':
[[Image:pyrazol4.jpeg]]
----
'''Patent Number''': US2004224944
'''Assignee''': VERTEX PHARMACEUTICALS INC
'''Title''': Pyrazole compounds useful as protein kinase inhibitors
'''Basic Structure''':
[[Image:pyrazol5.jpeg]]
[[Other derivates for alopecia]]
==== GSK-3 InhibitionMechanism - Phosphorylation====* ''GSK-3 inhibition targets treatment of chemotherapy-induced alopecia'' [http://www.biomedcentral.com/1471-2199/5/15 source]
* In the canonical Wnt signaling cascade, adenomatous polyposis coli (APC), axin, and GSK3 constitute the so-called destruction complex, which controls the stability of beta-catenin. It is generally believed that four conserved Ser/Thr residues in the N terminus of beta-catenin are the pivotal targets for the constitutively active serine kinase GSK3. GSK3 covalently modifies beta-catenin by attaching phosphate groups (from ATP) to serine, and threonine residues. In so doing, the functional properties of the protein kinase’s substrate (beta-catenin) are modified.
'''Serine - pyrazole reaction'''
[[image:serine-pyrazol.jpg|600 px|center|thumb|Serine and Pyrazole reaction [http://www.genome.ad.jp/dbget-bin/www_bget?rn+R03134 source]]]
=== Pathway associated with anti-androgen ===
* Dihydrotestosterone ** Formed by peripheral conversion of testosterone by 5-alpha reductase** Binds to androgen receptor on susceptible hair follicles* Hormone-receptor complex activates genes responsible for gradual transformation of large terminal follicles to miniaturized (progressive diminution of hair shaft diameter and length in response to systemic androgens) follicles [[Image:5-alpha-reductase inhibition.jpeg|center|500 px]]
==== Structure-Activity Relationships(SARs) ====
[[Image:SAR_map.gif|center|720px]]
=== Pathway associated with Minoxidil (vasodialatorsvasodilators) ===Minoxidil is a well know drug used for the treatment of alopecia. A co-relation between Sesquiterpene lactone (Helenalin) produced from Arnica montana and Minoxidil is illustrated in the figure below. Arnica montana being , a Vasodilator act , acts on the NO/cGMP Pathway through T-cells, B-cells and epithelial cells & abrogates kappa B-driven gene expression.[[image:vasodiator-rev.jpg|800 px|center]]
== Alopecia IPMap ==
[http://www.dolcera.com/client/d8r3/hairloss_map.htm Dolcera IPMap for Alopecia]
== Patent activity in China =====Treatment approaches==={|border="2" cellspacing="0" cellpadding="4" width="100%"|align = "center"|'''Can you save me some time?Treatment approach'''* What combinations|align = "center"|'''Patent number'''|align = "center"|'''Priority year'''|align = "center"|'''Assignee/ compounds have already been triedInventor'''|-|rowspan = "7"|Vasodilators|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN200510107497.8&leixin=fmzl&title=治疗瘀血阻滞型脱发的中草药汤剂及制备方法&ipc=A61K36/804(2006.01)I CN1772105]* Is any empirical data available|2005|叶明伟|-|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=CN1772139&F=0 CN1772139]* Can you tell me the side effects|2005|王亚杰|-|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN03139861.8&leixin=fmzl&title=一种可用于治疗脱发、白发的天然中草药提取组合物及应用&ipc=A61K35/78 CN1569080]|2003|谈汝标|-|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02155404.8&leixin=fmzl&title=毛囊激活液&ipc=A61K35/78 CN1506103]|2002|赵章光|-|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN01127395.X&leixin=fmzl&title=一种止脱生发药物及其制备方法&ipc=A61K35/78 CN1403100]|2001|范希田|-|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96116925.7&leixin=fmzl&title=免洗养发生发香波&ipc=C11D3/48 CN1165181]|1996|殷国健|-|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN88103853.9&leixin=fmzl&title=一种通络生发香波&ipc=A61K7/06 CN1031022]|1988|天津市轻工业化学研究所|-|Hair matrix activator|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02111941.4&leixin=fmzl&title=一种含中西药复方的育发剂&ipc=A61K7/06 CN1463693]|2002|朱静建|-|Anti-androgen <nowiki>+</nowiki> Vasodilator|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96109964.X&leixin=fmzl&title=一种治疗脂溢性脱发的高效低副作用外用药物&ipc=A61K35/78 CN1150043]|1996|梅晓春|-|}
{|border="2" cellspacing="0" cellpadding="4" width="100%" align="left"|align = "center"|'''Any hints for research?Patent number'''* Are there any combinations |align = "center"|'''Patent title'''|align = "center"|'''Treatment approach'''|align = "center"|'''Composition nature'''|align = "center"|'''Composition'''|align = "center"|'''Composition action'''|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN200510107497.8&leixin=fmzl&title=治疗瘀血阻滞型脱发的中草药汤剂及制备方法&ipc=A61K36/804(2006.01)I could developCN1772105]<br>YE MINGWEI (CN)<br>叶明伟 (2005)|align = "justify"|Chinese herbal medicine decoction for treating blood stasis obstruction type alopecia and its prepn<br>治疗瘀血阻滞型脱发的中草药汤剂及制备方法|align = "justify"|Vasodilators|align = "justify"|Herbal extract|align = "justify"|Astragalus root, prepared rhizome of rehmannia, white peony root, angelica, peach kernel and sufflower|align = "justify"|Promote blood circulation|-|align = "justify"|[http://v3.espacenet.com/textdoc?DB=EPODOC&IDX=CN1772139&F=0 CN1772139<br>]WANG YAJIE (CN)<br>王亚杰 2005|align = "justify"|Alopecia areata treating medicine<br>一种治疗斑秃的药物|align = "justify"|Vasodilators|align = "justify"|Herbal extract|align = "justify"|Pinellia tuber, fleeceflower root, arborvitae seed, chickení s gizzard membrane, prepared rhizome of rehmannia, Poris cocos, Codonopsis pilosula, etc|align = "justify"|Promote blood circulation|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN03139861.8&leixin=fmzl&title=一种可用于治疗脱发、白发的天然中草药提取组合物及应用&ipc=A61K35/78 CN1569080]<br>TAN RUBIAO (CN)<br>谈汝标 2003|align = "justify"|Natural Chinese herb composition for treating alopecia and leucotrichia and its application<br>一种可用于治疗脱发、白发的天然中草药提取组合物及应用|align = "justify"|Vasodilators|align = "justify"|Herbal extract|align = "justify"|Ginger, Cinnamomum cassia, myrrh, clove, mace nutmeg, Loranthus mulberry mistletoe, rhizoma dioscoreae, ligustrum japonicum, drynaria, fleece-flower root, and black sesame seeds|align = "justify"|Enhances the hair growth and healthier hairs|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02111941.4&leixin=fmzl&title=一种含中西药复方的育发剂&ipc=A61K7/06 CN1463693]<br>朱静建 2002|Hair growing preparation containing compound of Chinese medicine and Western medicine<br>一种含中西药复方的育发剂|align = "justify"|Hair matrix activator|Mixture of Herbal extracts and western medicine|align = "justify"|Persimmon leaf, oriental arbor-vitae leaf, ginseng leaf, yellow qi, fruit of the glossy privet, polygonum multiflorum, Kudzu root, dry ginger; Plus：Minoxidil, Vitamins and derivative, cystine, serine, leucine.|align = "justify"|Better and faster hair growth|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN02155404.8&leixin=fmzl&title=毛囊激活液&ipc=A61K35/78 CN1506103]<br>赵章光2002|align = "justify"|Hair follice activating liquid<br>毛囊激活液|align = "justify"|Vasodilators|align = "justify"|Herbal extract|align = "justify"|Ginseng, twists the stock blue, the licorice, the Sophora flavescens and hot peppers|align = "justify"|Activates the hair-follicle and enhances the hair growth.|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN01127395.X&leixin=fmzl&title=一种止脱生发药物及其制备方法&ipc=A61K35/78 CN1403100]<br>范希田 2001|align = "justify"|Trichogen and its prepn<br>一种止脱生发药物及其制备方法|align = "justify"|Vasodilators|align = "justify"|Herbal extract|align = "justify"|Ginseng, ganoderma lucidum, Chinese rhubarb, polygonum multiflorum, Chinese prickly ash, ginger, grass seed|align = "justify"|Promote blood circulation and enhance hair growth|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96116925.7&leixin=fmzl&title=免洗养发生发香波&ipc=C11D3/48 CN1165181]<br>殷国健 1996|Washing free shampoo for nourishing and growing hair<br>免洗养发生发香波|align = "justify"|Vasodilator|Vitamin composition|align = "justify"|Vitamin P (Bioflavonoids), Vitamin B15, Vitamin B2, nicotinic acid, bromo—geramineum|align = "justify"|Stimulate hair growth|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN96109964.X&leixin=fmzl&title=一种治疗脂溢性脱发的高效低副作用外用药物&ipc=A61K35/78 CN1150043]<br>梅晓春 1996|Efficient low-side effect external use medicine for curing seborrheic baldness<br>一种治疗脂溢性脱发的高效低副作用外用药物|align = "justify"|Anti-androgen <nowiki>+</nowiki> Vasodilator|Mixture of Herbal extracts and organic compounds|align = "justify"|Polygonum multiflorum, Ligustrum lucidum, Morus alba, Rehmannia glutinosa, Eclipta prostrata, Saliva miltiorrhiza, Carthamus tinctorius, Cnidium monnieri, Sophora flavescens, Dictamnus dasycarpus, Kochia scoparia, and antioxidants|align = "justify"|Inhibit the excess secretion of the sebaceous glands, increase the blood circulation on scalp and enhance the hair growth|-|align = "justify"|[http://search.sipo.gov.cn/sipo/zljs/hyjs-yx-new.jsp?recid=CN88103853.9&leixin=fmzl&title=一种通络生发香波&ipc=A61K7/06 CN1031022]<br>天津市轻工业化学研究所 1988|Channel-stimulating and hair-growing hair shampoo<br>一种通络生发香波|align = "justify"|Vasodilators|Herbal extract <nowiki>+</nowiki> detergent|align = "justify"|<font color="#454545">Herbal extracts, Penetration media, Detergents.</font>|align = "justify"|Increases the blood circulation under the scalp, reduces the hair los|-|}<br clear="all">
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