Use of free radical scavengers for protecting and treating skin and hair damages caused by chemotherapy

Abstract

The present invention relates to the use of one or more free radical scavengers as prophylactically or therapeutically effective substances and microparticles having an average particle size ranging from 5 to 200 μm for the preparation of a topical pharmaceutical composition for the protection or treatment of skin or hair damages caused by chemotherapeutic treatment. The invention also concerns a method for the protection or treatment of skin and hair damages of a mammal caused by chemotherapy. The invention further relates to a kit for the protection or treatment of hair damages caused by chemotherapeutic treatment consisting of a topical composition comprising microparticles together with free radical scavengers and a shampoo for an effective hair cleaning and supporting the hair treatment. A kit for the protection or treatment of skin damages caused by chemotherapy consisting of a topical composition comprising microparticles together with free radical scavengers and a cleansing milk for an effective skin cleaning and supporting the skin treatment is a further object of the present invention.

1 . Use of one or more free radical scavengers as prophylactically or therapeutically effective substances together with microparticles having an average particle size ranging from 5 to 200 μm as carrier materials for the preparation of a topical pharmaceutical composition for the protection or treatment of skin and hair damages caused by chemotherapeutic treatment, wherein the microparticles are selected from the group consisting of porous materials, cyclodextrins and mixtures thereof. 
   
   
       2 . Use according to  claim 1 , wherein the radical protection factor of the composition constitutes at least 85×10 14  radicals per mg of the composition, measured by determining the number of free radicals in a solution of a test substance (S 1 ) using electron spin resonance (ESR) in comparison with the ESR measurement result of the composition according to the ratio
   RPF=( RC ×RF)/ PI      
     whereby RF=(S 1 −S 2 )/S 1 ; RC=the concentration of the test substance (radicals/ml); PI=the concentration of the active substance composition (mg/ml); S 2 =signal amplitude of the antioxidant. 
   
   
       3 . Use according to  claim 1 , wherein the radical protection factor of the composition is from 200 to 12 000×10 14  radicals per mg of the composition. 
   
   
       4 . Use according to  claim 1 , wherein the concentration of the one or more free radical scavengers in the composition ranges from 0.05 to 45% by weight relating to the total weight of the composition, preferably 1 to 40% by weight, more preferred 3 to 33% by weight, especially preferred 9 to 26% by weight. 
   
   
       5 . Use according to  claim 1 , wherein as free radical scavengers water-soluble and/or fat soluble antioxidants, enzymes or mixtures thereof are used. 
   
   
       6 . Use according to  claim 1 , wherein the free radical scavenger is selected from the group consisting of (1) an alcoholic extract mixture of green coffee beans,  Camellia sinensis, Pongamia pinnata  and  Angelica archangelica ; (2) a mixture of a) a product obtained by extraction of the bark of  Quebracho blanco  and subsequent enzymatic hydrolysis, containing at least 90% by weight of proanthocyanidine oligomers and a maximum of 10% by weight gallic acid, in microcapsules, b) an extract of silkworm obtained by extraction, containing the peptide cecropine, amino acids and a vitamin mixture, c) a non-ionic, cationic or anionic hydrogel or mixture of hydrogels, d) one or more phospholipids and e) water; (3) the product of (2) with one or more cyclodextrines selected from β- and γ-cyclodextrines and an ultrasound decomposition product of baker's or brewer's yeast containing at least 150 units/ml superoxide dismutase; and mixtures of (1) to (3). 
   
   
       7 . (canceled) 
   
   
       8 . Use according to  claim 1 , wherein the porous materials of the microparticles are selected from the group consisting of horny sponges, preferably horny sponges of types Euspongia officinalis, Spongia usitatissima, Hippospongia equina or mixtures thereof, bamboo powder, kaolin, white clay, SiO 2 , calcium carbonate, silica gel, silicates, activated carbon or mixtures thereof. 
   
   
       9 . Use according to  claim 1 , wherein as cyclodextrins β- and/or γ-cyclodextrins are used. 
   
   
       10 . Use according to  claim 1 , wherein the concentration of the microparticle(s) in the composition ranges from 0.1 to 10% by weight, relating to the total weight of the composition, preferably 0.6 to 8% by weight, more preferred 1 to 6% by weight. 
   
   
       11 . Use according to  claim 1 , wherein microparticles ranging from 5 to 100 μm, preferably from 5 to 50 μm, most preferred from 8 to 40 μm are used. 
   
   
       12 . Use according to  claim 1  for the preparation of a cream, lotion, ointment, gel or emulsion. 
   
   
       13 . Use according to  claim 1 , wherein pharmaceutically acceptable auxiliary agents are added. 
   
   
       14 . A method for the protection or treatment of skin and hair damages of a mammal caused by chemotherapeutic treatment comprising topically administering to the concerned skin and scalp areas of the mammal a prophylactically or therapeutically effective amount of one or more free radical scavengers which are administered in the form of a topical pharmaceutical composition comprising as carrier materials microparticles having an average particle size ranging from 5 to 200 μm, wherein the microparticles are selected from the group consisting of porous materials, cyclodextrins and mixtures thereof. 
   
   
       15 . The method according to  claim 14 , wherein the skin damages caused by chemotherapeutic treatment are the palmar-plantar erythrodysaesthesia syndrom (PPE), erythema and dry skin. 
   
   
       16 . The method according to  claim 14 , wherein the hair damage caused by chemotherapeutic treatment is alopecia. 
   
   
       17 . The method according to  claim 14 , wherein the concentration of the one or more radical scavengers in the topical composition ranges from 0.05 to 45% by weight, relating to the total weight of the composition. 
   
   
       18 . The method according to  claim 14 , wherein the concentration of the microparticles in the topical composition ranges from 0.1 to 10% by weight, relating to the total weight of the composition. 
   
   
       19 . The method for the protection of skin and hair damages according to  claim 14 , wherein the composition is administered to the concerned skin and/or scalp areas of the mammal prior to, during and/or subsequent to chemotherapeutic treatment with cytostatic agents, preferably 1 day prior to treatment, during the treatment and at least 6 to 7 days after the treatment. 
   
   
       20 . The method according to  claim 14 , wherein the composition is administered to the concerned skin or scalp area at least twice daily, preferably in an amount of at least 2 mg/cm 2 , especially in an amount of 2 to 10 mg/cm 2 . 
   
   
       21 . The method according to  claim 14 , wherein the topical administration of the composition to the scalp includes a massage of the scalp, preferably from 5 to 10 minutes. 
   
   
       22 . Kit for the protection or treatment of hair damages caused by chemotherapeutic treatment consisting of
 a) a topical composition comprising one or more free radical scavengers and microparticles having an average particle size ranging from 5 to 200 μm, wherein the concentration of the radical scavenger(s) in the composition ranges from 0.05 to 45% by weight, and the concentration of the microparticles in the composition ranges from 0.1 to 10% by weight and   b) a shampoo comprising a free radical scavenger up to 2% by weight of the total weight of the shampoo.   
   
   
       23 . Kit for the protection or treatment of skin damages caused by chemotherapeutic treatment consisting of
 a) a topical composition comprising one or more free radical scavengers and microparticles having an average particle size ranging from 5 to 200 μm, wherein the concentration of the radical scavenger(s) in the composition ranges from 0.05 to 45% by weight, and the concentration of the microparticles in the composition ranges from 0.1 to 10% by weight and   b) a cleansing milk comprising a free radical scavenger up to 2% by weight of the total weight of the cleansing milk.   
   
   
       24 - 25 . (canceled)