PHARMACEUTICAL COMPLEX AND COMPOSITION TO INHIBIT HAIR LOSS

Abstract: Complexes of allyl isothiocyanate and polyoxyalkylene glycols are useful to inhibit hair loss.

Description: PHARMACEUTICAL COMPLEX AND CCMPOSITICR TO INHIBIT HAIR LOSS This application is concerned with a pharmaceutically active complex useful to inhibit hair loss from the human scalp. More particularly, it is concerned with the complexes formed by reaction between allyl isothiocyanate and certain polyoxyalkylene glycols, with pharmaceutical compositions containing such complexes and with the use of the complexes to protect against loss of human hair. Polyoxyalkylene glycols are a well known class of surfactant polymers. They are ethers formed by the polymerization of selected • glycols. They are available in a variety of forms. Often they will carry other functional groups. The surfactant polymers useful in the practice of this invention will have a molecular weight of from 500 to 10,000, and the alkylene group will have 2 or 3 carbon atoms. Specific surfactant polymers useful in the practice of the invention may include copolymers derived from glycols with two or three carbon atoms in the alkylene groups. One class of surfactant polymers useful in the invention is available under the trademark Pluronic from BASF-Wyandotte. The class includes polyoxypropylene glycols. Another is available from ICI United States, Inc. under the trademark Tween. Tweens are polyoxyethylene glycol derivatives of fatty acid partial esters of sorbiton anhydrides. Amongst the most useful of the Tweens for the practice of this invention are polyoxyethylene glycol derivatives of sorbitan laurate, stearate, palmitate and oleate having molecular weights from 500 to 10,000. Still another useful class of polyoxyalkylene glycol derivatives is available from Union Carbide Corp. under the trademark Carbowax. It has been discovered that when the known compound allyl isothiocyanate (ITC) is reacted with polyoxyethylene glycols at a temperature of from about 20 C to 60 C for a period of from about 0.5 to 30 hours, a complex will form. The ratio of ITC to surfactant polymer will depend upon the amounts of reactants employed. For the practice of this invention, the ratio of ITC to surfactant polymer is from about 1:1 to 1:20. The preferred solvents for the reaction are water and alkanols containing up to three carbon atoms. Ethanol and isopropanol are the preferred alkanols. Mixtures of solvents can be employed. Typically, the complex wil be utilized in the solvent mixture in which it is prepared, or the solvent mixture can be combined or blended with other carriers to form creams, lotions and the like. It is also convenient to utilize the solvent mix containing the dissolved complex to form shampoos which, for the purpose of this description and claims can be regarded as pharmaceutical compositions. SUBSTITUTE SHEET The complex need not be isolated. Its presence in the solution can be readily determined by the change in the infrared pattern between the original and final mixtures. The formation of the complexes can also be established by the fact that the rate of diffusion of the ITC is different from the rate of diffusion of the complex through cellophane into the same solvent in which the complex is prepared. The diffusion constants for certain samples are as follows: -2 -1 K-ITC = 2.69 x 10 min. K-ITC-T EEN-80 ' = 8.36 x 10 "3 min. "1 The first listed diffusion constant is for ITC alone. The second is for the complex that is formed after reaction between Tween 80 and ITC. Tween 80 is polyoxyethylene sorbitan monooleate. The diffusion rates were determined by the Drobnica method [Drobnica, Kanppova: Chem. Zvesti, 27 799 (1973)]. The test material as prepared in a solvent, was placed in a cellophane dialysis cell and the cell suspended in 10 times its volume of the same solvent. Aliquots were removed at selected time intervals from the solvent outside the cell and reacted to form thioglycols as a measure of the amount diffused. The complexes can be used in any of a variety of compositions including liquids, creams, lotions, emollients or other compositions generally employed for topical application. Useful compositions will contain from about 0.01% to 10% by weight of active complex based on the total weight of the composition. The compositions may contain other ingredients such as antiseptics, germicides or anti- dandruff compounds. It has been found that compositions containing the complex when applied directly to the human scalp, for example, by washing the hair with a shampoo containing the active material or by massaging the scalp with an alcohol solution, will inhibit hair loss. In one study used to make such a determination, the preparation made according to Example 7, was tested with 30 different human subjects with a hair loss problem. As a control, the carrier of Example 7 without the complex was tested on 32 additional human subjects also suffering hair loss. The mixtures were applied by vigorous rubbing morning and evening for 30 consecutive days. Determination of the product effect was carried out by measuring the newly grown hair length, diameter and cuticle by light microscopy. The results are shown in the following table. TABLE 1 ITC TWEEN-80 COMPLEX CARRIER IMPROVED 22 7 NOT IMPROVED 8 25 30 32 SUBSTITUTE SHEET During these tests, it was observed that there was little or no allergic or photosensitization reaction. The following non-limiting examples are given by way of illustration only. EXAMPLE 1 To 100 ml. of a 1.8:1 ethanol-water solution containing 0.00897 M ITC is added a solution of 0.0045 M Carbowax-6000 and the solution is stirred for six hours. In a water bath at approximately 40 C, soften 54 g. Kanalolum, 108 g. vaseline album opthalmicum (purified white petrolatum) and 738 g. vaseline album (petrolatum). The cream base is homogenized and the solution prepared as described above is slowely dispersed into it. The warm cream is stirred continuously while cooling. The ITC:polymer ratio is 2:1. The concentration of complex in the composition is approximately 2.8 by weight. EXAMPLE 2 To 100 ml. of a 1.8:1 ethanol-water solution containing 0.00897 M ITC is added a solution of 0.0089 M Carbowax-6000 and the procedure of Example 1 is followed. The ITC:polymer ratio is 1:1. The concentration of the complex in the composition is approximately 5.3% by weight. SUBSTITUTE SHEET EXAMPLE 3 To 100 ml. of a 1.8:1. ethanol-water solution containing 0.00897 M ITC is added a solution of 0.0045 M Tween-80 and the procedure of Example 1 is followed to prepare a complex in which the molar ratio of ITC to polymer is 2:1 and the concentration of the complex in the composition is about 0.7% by weight. EXAMPLE 4 To 100 ml. of a 1.8:1 ethanol-water solution containing 0.00897 M ITC is added a solution of 0.179 Tween-80 and the procedure of Exmple 1 is followed. The mole ratio of ITC to polymer is 1:19. The concentration of the complex in the composition is about 10.7% by weight. EXAMPLE 5 To 100 ml. of a 1.8:1 ethanol-water solution containing 0.00897 M ITC is added a solution of 0.00879 M Carbowax-6000 and the resulting mixture is stirred for 15 minutes at 40 C. To the reaction mixture is added 10 g. resorcimun, 10 g. castor oil and 400 g. of isopropyl alcohol. The solution is cooled to room temperature and diluted to 1000 ml. with alcohol-water. The mole ratio of ITC to polymer is 1:1. The concentration of the complex in the composition is about 10%. SUBSTITUTE SHEET EXAMPLE 6 To 100 ml. of a 1.8:1 ethanol-water solution containing 0.00449 M ITC is added a solution of 0.0049 M Carbowax-6000 and the procedure of Example 5 is followed. The mole ratio of ITC to polymer ratio is 1:1. The concentration of the complex in the composition is about 5%. EXAMPLE 7 To 100 ml. of alcohol-water solution containing 0.00897 M ITC is added a solution of 0.0179 M Tween-80 and then the procedure described in Example 5 is followed. The ITC to polymer mole ratio is 1:1.9. The concentration of the complex in the composition is about 4.6%. - " EXAMPLE 8. Twenty-seven patients, ten male and seventeen female, ages 17-77 with hair loss were evaluated for reduction in hair loss using a 1:1.9 ITC-Tween-80 Complex in 2:1 ethanol-water at a concentration of 0.2% by weight. Procedure: A small amount was applied to scalp nightly and gently massaged. Results: Evaluations were made by the patient and examiner and related as: 0 - no change, 1+ = less hair loss, 2+ - much less hair loss and 3+ - no further hair loss. 1 ) Ten subjects (8 female, 2 male) used the mixture for one month. Of these, 6 were 0, 3 were 1+ and one was 3+. 2) Five subjects (3 female, 2 male) used the mixture for two months. Of these, 3 were 0, 3 were 1+ and one was 3+. 3) Four subjects (1 female, 3 male) used the mixture for three months. Of these, 1 was 0, 1 was 2+ and 2 were 3+. 4) One subject (female) used the mixture for four months. This patient was 2+. 5) Three subjects (1 female, 2 male) used the mixture for five months. Of these, 1_ was 2+ and 2 were 3+. 6) Four subjects (3 female, 1 male) used the mixture for six months. Of these, 1 was 0, 1 was 2+ and 2 were 3+. No adverse reactions were observed. One patient complained of "stinging". Summary: 1 ) Fifteen patients used the mixture for 1 -2 months. Of these, 9 were 0, 4 were 1+ and 2 were 3+. 2) Twelve patients used the mixture for 3-6 months. Of these, 2 had no change (0), 4 had moderate reduction in hair loss (2+) and 6 had no further hair loss (3+). SUBSTITUTE SHEET The results are summarized in the following table. TABLE FEMALE Duration of Use (Months) One Two Three Four Five Six Age Result - Age Result Age Result Age Result Age Result Age Resul 77 1+ 70 1+ 36 58 2+ 70 3+ 41 0 33 0 50 3+ 70 3+ 45 0 32 0 70 2+ 40 1+ 40 0 65 0 50 0 63 3+ MALE One Two Three Four Five Six Age Result Age Result Age Result Age Result Age Result Age Res 31 0 35 0 28 3+ 34 3+ 49 50 1+ 17 0 33 ' 2+ 25 2+ 33 3+

Claims: WHAT IS CLAIMED IS: 1. A pharmaceutical composition for the inhibition of hair loss from the human scalp which comprises complex formed by reaction between allyl isothiocyanate and a polyoxyalkylene glycol surfactant polymer having a molecular weight of from 500 to 10,000 together with a pharmaceutically acceptable carrier, the ratio of allyl isothiocyanate to polymer being from 1:1 to 1:20, the alkylene groups in the polyoxyalkylene moiety containing from 2 to 3 carbon atoms. 2. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxyethylene glycol. 3. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxyetjhylene glycol derivative of a fatty acid partial ester of sorbitol anhydride. 4. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan stearate. 5. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan laurate. 6. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan palmitate. SUBSTITUTE SHEET 7. A pharmaceutical composition of Claim 1 wnerein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan oleate. 8. A pharmaceutical composition of Claim 1 wherein the surfactant polymer is a polyoxypropylene glycol. 9. A complex which is the reaction product of allyl isothiocyanate and a polyoxyalkylene glycol surfactant polymer having a molecular weight of from 500 to 10,000, the ratio of allyl isothiocyanate to polymer being from 1:1 to 1:20, the alkylene groups in the polyoxyalkylene moiety containing from 2 to 3 carbon atoms. 10. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol. 11. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol derivative of a fatty acid partical ester of sorbitol anhydride. 12. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan stearate. 13. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan laurate. 14. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan palmitate. 15. A complex of Claim 9 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan oleate. 16. A complex of Claim 9 wherein the surfactant polymer is a polyoxypropylene glycol. 17. A method of inhibiting hair loss from the human scalp which comprises contacting the scalp with an amount which is effective to prevent hair loss of a complex which is a reaction product of allyl isothiocyanate and a polyoxyalkylene glycol surfactant polymer having a molecular weight of from 500 to 10,000, the ratio of allyl isothiocyanate to polymer being from 1:1 to 1:20, the alkylene groups in the polyoxyalkylene moiety containing 2 or 3 carbon atoms. 18. The method of Claim 17 wherein the surfactant polymer is a polyoxyethylene glycol. 19. The method of Claim 17 wherein the surfactant polymer is a polyoxyethylene glycol derivative of a fatty acid partial ester of sorbitol anhydride. 20. The method of Claim 17 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan stearate. 21. The method of Claim 17 wherein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan laurate. 22. A method of Claim 17 wherein the sirfactant polymer is a polyoxyethylene glycol derivative of sorbitan palmitate. 23.- The method of Claim 17 hwerein the surfactant polymer is a polyoxyethylene glycol derivative of sorbitan oleate.

Inventors: DARKO LASZLO L, DARKO, LASZLO, L.
Applicants: FARMACON INC, FARMACON, INC.
Application year: 1986
Main classification: A61K31
IPC codes: A61K8, A61K47, A61Q5, A61Q7