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EP-4734970-A1 - COMPOSITION COMPRISING HINOKITIOL AND ZINC SALT FOR USE IN THE TREATMENT OF HERPES LABIALIS

EP4734970A1EP 4734970 A1EP4734970 A1EP 4734970A1EP-4734970-A1

Abstract

The invention relates to a composition for use in the treatment of symptoms of herpes labialis in a human subject, wherein the treatment comprises topical administration to the skin of said human subject of a composition containing hinokitiol and 0.1-3 wt.% of water-soluble zinc salt. The invention also provides a topical formulation in the form of an emulsion, said formulation comprising: 15-70 wt.% of water; 10-50 wt.% of hydrophobic carrier selected from wax, petroleum jelly, paraffin, triglycerides and combinations thereof; 0.01-1 wt.% of hinokitiol; and 0.1-3 wt.% of water-soluble zinc salt.

Inventors

  • PELLIKAAN, HUBERT CLEMENS
  • KOMMEREN, Kasper Marijn
  • VAN RIJSWIJK, JAN WILLEM

Assignees

  • AAA Investments B.V.

Dates

Publication Date
20260506
Application Date
20240628

Claims (15)

  1. 1. A composition for use in the treatment of symptoms of herpes labialis in a human subject, wherein the treatment comprises topical administration to the skin of said human subject of a composition containing hinokitiol and 0.1-3 wt.% of water-soluble zinc salt.
  2. 2. Composition for use in the treatment according to claim 1 , wherein the herpes labialis is caused by herpes simplex virus type 1.
  3. 3. Composition for use in the treatment according to claim 1 or 2, wherein the composition is topically administered onto the upper and/or lower lip of the human subject.
  4. 4. Composition for use in the treatment according to any one of the preceding claims, wherein the wherein the composition contains 0.01-1 wt.% of hinokitiol.
  5. 5. Composition for use in the treatment according to any one of the preceding claims, wherein the composition contains 0.5-2 wt.% of water-soluble zinc salt.
  6. 6. Composition for use in the treatment according to any one of the preceding claims, wherein the water-soluble zinc salt is selected from zinc sulphate, zinc chloride, zinc acetate, zinc citrate, zinc nitrate, zinc tartrate, zinc maleate, zinc lactate, zinc amino acetate, zinc aspartate, zinc glutamate, zinc propionate, zinc gluconate, zinc butyrate, zinc formate, zinc glyceride, zinc glycolate, zinc ascorbate and combinations thereof.
  7. 7. Composition for use in the treatment according to any one of the preceding claims, wherein the composition contains 10-70 wt.% water.
  8. 8. Composition for use in the treatment according to any one of the preceding claims, wherein the composition comprises 10-50 wt.% of hydrophobic carrier selected from wax, petroleum jelly, paraffin, triglycerides and combinations thereof.
  9. 9. A topical formulation in the form of an emulsion, said formulation comprising: • 15-70 wt.% of water; • 10-50 wt.% of hydrophobic carrier selected from wax, petroleum jelly, paraffin, triglycerides and combinations thereof; • 0.01-1 wt.% of hinokitiol; and • 0.1-3 wt.% of water-soluble zinc salt.
  10. 10. Topical formulation according to claim 9, wherein the water-soluble zinc salt is selected from zinc sulphate, zinc chloride, zinc acetate, zinc citrate, zinc nitrate, zinc tartrate, zinc maleate, zinc lactate, zinc amino acetate, zinc aspartate, zinc glutamate, zinc propionate, zinc gluconate, zinc butyrate, zinc formate, zinc glyceride, zinc glycolate, zinc ascorbate and combinations thereof.
  11. 11. Topical formulation according to claim 9 or 10, wherein the formulation contains 2-20 wt.% of propylene glycol.
  12. 12. Topical formulation according to any one of claims 9-11 , wherein the formulation contains 2-25 wt.% of fatty acid isopropyl ester.
  13. 13. Topical formulation according to any one of claims 9-12, wherein the formulation contains propylene glycol and fatty acid isopropyl ester.
  14. 14. Topical formulation according to any one of claims 9-13, wherein the formulation contains 0.1-5 wt.% of a tocopherol component selected from tocopherol, tocopherol ester and combinations thereof.
  15. 15. Topical formulation according to any one of claims 9-14, wherein the formulation contains 2-20 wt.% of nanoparticles of inorganic UV filter.

Description

COMPOSITION COMPRISING HINOKITIOL AND ZINC SALT FOR USE IN THE TREATMENT OF HERPES LABIALIS TECHNICAL FIELD OF THE INVENTION The present invention relates to a method of treating symptoms of herpes labialis in a human subject, the treatment comprising topical administration to the skin of said human subject of a composition containing hinokitiol and water-soluble zinc salt The invention also relates to a topical formulation in the form of an emulsion comprising hinokitiol and a water-soluble zinc salt. BACKGROUND OF THE INVENTION Herpes labialis, commonly known as cold sores, is a type of infection by the herpes simplex virus that affects primarily the lip. Symptoms typically include a burning pain followed by small blisters or sores. The first attack may also be accompanied by fever, sore throat, and enlarged lymph nodes. The rash usually heals within ten days, but the virus remains dormant in the trigeminal ganglion. The virus may periodically reactivate to create another outbreak of sores in the mouth or lip. The cause is usually herpes simplex virus type 1 (HSV-1) and occasionally herpes simplex virus type 2 (HSV-2). Attacks can be triggered by sunlight, fever, psychological stress, or a menstrual period. Once infected with herpes simplex virus, there is no cure. Antiviral medications may, however, prevent outbreaks or shorten outbreaks if they occur. The long-term use of antivirals may also decrease the risk of further spread. A zinc oxide, anesthetic, or antiviral cream can decrease the duration of symptoms of herpes simplex. Antiviral medications may also decrease the frequency of outbreaks. Hinokitiol is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. Hinokitiol is a zinc ionophore that aids zinc ions transport into cells. Ionophores are chemical compounds that reversibly bind and transport ions through biological membranes in the absence of a protein pore. Read et al. (The Role of Zinc in Antiviral Immunity, Adv Nutr 2019; 10: 696-710) provide a review that summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. According to the authors, an abundance of evidence has accumulated over the past 50 years to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings. WO 2021/184070 describes a composition for use in oral care comprising at least one water soluble zinc salt and a zinc ionophore selected from one or more of hinokitiol, quecertin, epigallocatechin, and zincophorin or a salt thereof. EP-A 3 169 433 describes a composition for the preventive treatment of fever blisters, including recurring fever blisters, wherein a composition, which comprises a physical UV filter, a zinc salt with antiviral action and an additive suitable for topical application, is preventively applied topically to parts of the face which can be affected by fever blisters. Hoang et al. (A possible application of hinokitiol as a natural zinc inophore and anti-infective agent for the prevention and treatment of CO VID-19 and viral infections, Medical Hypotheses, 145 (2020) 110333) is concerned with finding an anti-infective agent for the prevention and treatment of COVID-19 and other viral infections. US 10,463,664 relates to inhibitors of HSC nucleotidyl transferases and the use thereof in the treatment and prevention of herpesvirus diseases. Ranjbar et al. (Comparative study of serum zinc concentration in recurrent herpes labialis patients and healthy individuals, BMC Oral Health (2020) 20:296) describe a study of serum zinc concentration in recurrent herpes labialis (RHL) patients. SUMMARY OF THE INVENTION The inventors have unexpectedly discovered that symptoms of herpes labialis may be treated successfully by topical administration of a combination of hinokitiol and water-soluble zinc salt to the skin. Accordingly, one aspect of the invention relates to a composition for use in the treatment of symptoms of herpes labialis in a human subject, wherein the treatment comprises topical administration to the skin of said human subject of a composition containing hinokitiol and 0.1-3 wt.% of water-soluble zinc salt. Although the inventors do not wish to be bound by theory, it is believed that hinokitiol, when topically applied to the skin, acts as a zinc ionophore, enabling transport into epithelial cells of the zinc ions that are simultaneously provided by the same composition. Zinc is considered to have both a preventive and therapeutic effect on symptoms of herpes labialis. The invention also provides a topical formulation in the form of an emulsion, said formulation comprising: • 15-70 wt.% of water; • 10-50 wt.% of hydrophobic carrier selected from wax, petroleum jelly, paraffin, triglycerides and combinations thereof; • 0.01-1 wt.% of