GB2212395A

GB2212395A - Treatment of baldness in humans

Info

Publication number: GB2212395A
Application number: GB8727093A
Authority: GB
Inventors: Sidney Hart
Original assignee: Individual
Current assignee: Individual
Priority date: 1987-11-19
Filing date: 1987-11-19
Publication date: 1989-07-26
Also published as: GB8727093D0

Abstract

A composition for treating baldness in humans comprises a compound having the general formula (I): <IMAGE> where either: (a) R1 is an aromatic residue (moiety); R2 is an alkylene group; and R3 and R4, which can be the same or different, are each hydrogen, a C1-6 alkyl group or other hydrocarbyl group, or R3 and R4 together with the nitrogen atom to which they are attached constitute an alicyclic or other heterocyclic ring; or, alternatively, (b) R1 is an aromatic residue (moiety); R2 together with R3 and the nitrogen atom to which they are attached constitute a heterocyclic ring; and R4 is hydrogen or a C1-6 alkyl group or other hydrocarbyl group. Preferred compounds are those where R1 is a phenyl group having one or more straight or branched chain aliphatic substituents.

Description

TREATMENT OF BALDNESS IN HUMANS This invention relates to methods and compositions for the treatment of baldness in humans, especially male pattern alopecia.

It has been discovered according to the present invention, that certain aromatic amides, especially analgesic compounds of the anilide type, are effective in the treatment of baldness, especially male pattern baldness (alopecia).

Accordingly, in a first aspect the invention provides a method of treating baldness in humans, which comprises applying to the human scalp a compound having the general formula (I):

where either (a) R1 is an aromatic residue (moiety); R2 is an alkylene group; and R3 and R , which can be the same or different, 4 are each hydrogen, a C16 alkyl group or other hydrocarbyl group, or R3 and R4 together with the nitrogen atom to which they are attached constitute an alicyclic or other h-eterocyclic ring; or, alternatively (b) R1 is an aromatic residue (moiety); R2 together with R3 and the nitrogen atom to which they are attached constitute a heterocyclic ring; and R4 is hydrogen or a C1~6 alkyl group or other hydrocarbyl group.

A preferred group of compounds for use in the method of the invention are those where R1 is a phenyl group having one or more straight or branched chain aliphatic substituents. Suitable substituents are, for example C14 alkyl, for instance methyl or ethyl. Thus, 1 can, for example, be a toluyl or xylyl moiety, which can contain one or more substituents, for example chlorine or other halogen. Such toluyl moiety is preferably attached to the adjacent carbamoyl moiety at a position ortho to the methyl group of the toluyl moiety; and such xylyl moiety is preferably attached to said carbamoyl moiety at the position ortho to both of the methyl groups of the xylyl moiety.

Where R2 is an alkylene group it can, for example, be a straight or branched chain group, for example one having 1 to 6 carbon atoms. Suitable examples are methylene, ethylene or propylene. Where R3 and/or R4 is a hydrocarbyl group it can be, for example, a C1 4 alkyl group, for instance methyl or ethyl.

Where R3 and R4 together with the nitrogen atom to which they are attached constitute an alicyclic or other heterocyclic ring; that group can be, for example, a 5- or 6-membered alicyclic ring, especially a pyrrolidine (or pyrrole ) , or other ring containing a nitrogen atom.

Where R2 together with R3 and the nitrogen atom to which they are attached constitute a heterocyclic ring, the latter can be, for example, a 5- or 6- membered alicyclic ring, especially a piperidine or other heterocyclic ring containing a nitrogen atom.

It has been found according to another aspect of the present invention that compounds of particular value in the treatment of alopecia are those having particular ion channel characteristics . Such compounds are capable of binding to sites located in the ion channels of nerves supplying vascular smooth muscle in the region of the hair follicles of the scalp. This binding causes vasodilation at certain concentrations of the compounds, due to depression of the sodium current. At other concentrations vasodilation does not occur and there is, instead, unopposed vascular tone. In this connection it has been observed that, at low concentrations, stimulation of the arrectores pilorum muscles occurs.

It has been found according to a further aspect of the present invention that compounds of particular interest are those having a suitable vasoconstrictivevasodilatory balance. Thus, by choosing two or more compounds with different vasoactivities it is possible to achieve a desired balance. Such a balance is obtained, for example, by the conjoint use of lignocaine and bupivacaine. According to the present invention I have observed that when lignocaine is used alone the patient experiences, a short time after the application to his scalp, a distinctive taste in the mouth, whereas where bupivacaine is used alone no such taste is experienced. This is consistent with lignocaine having a powerful skin vasodilatory action and bupivacaine having a skin vasoconstricting action.

Examples of compounds useful in the present invention are the following: lignocaine, mepivacaine, pyrrocaine, bupivacaine, prilocaine and butanilicaine, all of which are analgesics of the anilide type. They can all be used, for example, in the form of their hydrochloride or other acid addition salt. When they form hydrates - for example lignocaine forms a monohydrate - they may be used in such form.

Where the compound is of rapid action it may be adisable to use it in conjunction with a slow-acting more lipid-soluble congener with vasoconstricting properties at low concentration. Thus, for example lignocaine can be used in conjunction with, for example, bupivacaine.

Other compounds of the anilide type and formulations containing them are disclosed in "Anesthesia", edited by R n Miller, p.p. 563 - 565 published by Churchill Livings tone 1981 and in Local Analgesia in Dentistry by D.H. Roberts and J.H. Sowray, 2nd edition 1979, published by John Wright & Sons Limited, Bristol.

Those disclosures are incorporated herein by reference.

Some of the compounds useful in the present invention contain a chiral centre. Such compounds can be used in the form of an individual isomer or isomers or as a racemic mixture.

In a further aspect the invention provides compositions for the treatment of baldness, comprising a compound of general formula (I) as defined above and a cosmeticallyacceptable carrier or diluent. The compositions of the invention may be in a conventional cosmetic form suitable for topical administration, for example, an emulsion or an aqueous or oily solution or suspension, or a cream, ointment or gel. The composition may contain conventional cosmetic excipients, and may be manufactured by convention cosmetic techniques.

A further aspect of the invention provides the use of a compound of general formula (I) as defined above, or a composition containing said compound, for the manufacture of a medicament for the treatment of baldness in humans.

The invention is illustrated by the following Examples: EXAMPLE I A cosmetic jelly comprising a blend of the following ingredients: lignocaine hydrochloride 2 g tragacanth 2.5 g glycerin 25 ml water to 100 g EXAMPLE 2 A cosmetic jelly comprising a blend of the following ingredients: bupivacaine hydrochloride 0.5 g tragacanth 2.5 g glycerin 25 ml water to 100 g EXAMPLE 3 A cosmetic jelly comprising a blend of the following ingredients: lignocaine hydrochloride 1 g bupivacaine hydrochloride 0.25 g tragacanth 2.5 g glycerin 25 ml water to 100 g EXAMPLE 4 The cosmetic jelly of Example 1 was used in the method of the invention as follows. Application of the cosmetic jelly was to the bald scalp cf a male aged 70 who had had male pattern baldness for a continuous period of 40 years.

About 15 grams of the cosmetic jelly was applied to aboutl00 square centimetres of the bald area of his scalp and massaged into the scalp for approximately 5 minutes. This treatment was carried out twice each day, the two treatments being about 12 hours apart, for a period of 60 days. At the end of that period it was observed that vellus hair was growing on the treated area of the scalp with a few scattered terminal hairs about 0.5cm in length. Subsequently the terminal hairs grew to approximately 1 cm in length. ABout 1% of these hairs were pigmented.

EXAMPLE 5 Example 4 was repeated but using the jelly of Example 2 instead of that of Example 1. Similar results were obtained.

EXAMPLE 6 Example 4 was repeated but using the jelly of Example 3 instead of the jelly of Example 1. Similar results were obtained.

EXAMPLE 7 On continuing the treatment described in Example 4 beyond the period of 60 days it was observed that the terminal hairs continued to grow, but at a very slow rate, extending to about 1.5 cm in length over the next 60 days. In addition about 1% of the vellus hairs developed into terminal hairs. On continuing that treatment for a further period of 60 days it was observed that the rate of growth of the new terminal hairs increased until several at the periphery of the monk's cap area of the scalp, reached a length of 4cm after a further 60 days.

Claims

1. A method of treating baldness in humans, which comprises applying to the human scalp a compound having the general formula (I):

where either (a) R1 is an aromatic residue (moiety); R2 is an alkylene group; and R3 and R4, which can be the same or different, are each hydrogen, a C1 6alkyl group or other hydrocarbyl group, or R3 and R4 together with the nitrogen atom to which they are attached constitute an alicyclic or other heterocyclic ring; or, alternatively (b) R1 is an aromatic residue (moiety); R2 together with R3 and the nitrogen atom to which they are attached constitute a heterocyclic ring; and R4 is hydrogen or a C16 alkyl group or other hydrocarbyl group.

2. A method according to Claim 1, in which R is a phenyl group having one or more straight or branched chain aliphatic substituents, for example methyl, ethyl or other r ,alkyl.

3. A method according to Claim 2, in which R1 is a toluyl or xylyl moiety which can contain one or more substituents.