EP4633654A1

EP4633654A1 - A synergistic composition

Info

Publication number: EP4633654A1
Application number: EP23904179.1A
Authority: EP
Inventors: Nezihe Filiz TOKER
Original assignee: Individual
Current assignee: Individual
Priority date: 2022-12-15
Filing date: 2023-12-15
Publication date: 2025-10-22
Also published as: TR2022019453A1; WO2024129048A1

Abstract

The present invention particularly relates to compositions containing St. John's Wort oil for use in the treatment and healing of external lesions such as wounds and burns. Said invention is Hypericum perforatum (St. John's Wort) extract in oil, said oil comrises a certain amount of bone marrow oil.

Description

DESCRIPTION

A SYNERGISTIC COMPOSITION

Technical Field

The invention relates to natural compositions of plant origin for use in the treatment and healing of external lesions such as wounds and bums.

The invention particularly relates to compositions containing St. John’s Wort oil for use in the treatment and healing of external lesions such as wounds and burns.

State of the Art

Species belonging to the genus Hypericum L. have been used for many years in many parts of the world for treatment in various ways due to their wound healing, bactericidal, anti-inflammatory, diuretic, and sedative effects ( irak and Kevseroglu, 2004). Among these species, Hypericum perforatum (St. John’s Wort or Klamath weed) is the most widespread. St. John’s Wort is a flowering plant that is approximately 30-100 cm in height. There are numerous studies on the history, ethnob otani cal use, chemical composition and activities of St. John’s Wort, also known in Anatolia by the names such as kiln? otu, binbirdelik otu, kan otu, koyunkiran, kuzu kiran, mayasil otu, piiren, yara otu. The English name for St. John’s Wort is St. John's wort.

St. John’s Wort oil contains hyperforin, adhyperforin and furohyperforin, which are derivatives of phloroglucinol. It is thought that from naphthodianthrones, protohypericin and pseudoprotohypericin transform into more stable hypericin and pseudohypericin (Al- tan et al., 2015). Through numerous pharmacological studies, it has been proven that these substances contained in H. perforatum exhibit anti-inflammatory and antimicrobial effects. Alongside these effects, macerated oil has been used for centuries in the treatment of wounds and burns. In addition to these effects, the plants and their extracts used in the treatment of depression also have anticancer, antioxidant, antitumoral, and antiviral effects (Schempp et al., 2002).

The oil obtained through maceration from St. John's Wort ("St. John's Wort oil" for short) is a product used for various purposes in the field of health as it contains a high concentration of beneficial ingredients. Particularly the macerate prepared with olive oil is highly popular both in our country and worldwide as a wound healing remedy. In oil maceration, the flowering tops of the H. perforatum plant are traditionally left in glass containers filled with olive oil exposed directly to sunlight for 15-45 days. The effective compounds of the obtained macerated oil, its stability, composition varying based on the method and oil used, and its characteristic ruby-red color continue to be subjects of ongoing search.

St. John's Wort oil is also effective in maintaining skin health. St. John's Wort oil supports and accelerates cell regeneration, helping to delay signs of aging, prevent wrinkles, and increase skin elasticity. It contributes to achieving the necessary moisture balance for the skin, resulting in a smoother and more vibrant appearance. Another significant effect of St. John's Wort oil on the skin is that it eliminates blemishes. Thanks to this effect, regular use of St. John’s Wort oil can reduce scars, burns, and acne marks on the face or body. In areas where the skin tone locally varies or becomes discolored due to factors such as aging, pregnancy, sun exposure, regular application of St. John's Wort oil can even out the skin tone, providing a more pleasant appearance.

In the state of the art, it is known that St. John's Wort oil is obtained through the maceration of St. John's Wort flowers in vegetable oils such as olive oil, soybean oil, wheat germ oil, and sunflower oil.

Turkish patent application no. 2022/014055 relates to an ointment that heals bedsores, first and second degree bums and rashes without leaving scars and the said ointment contains stone-milled cold-pressed olive oil, St. John's Wort oil and paraffin. Turkish patent application no. 2022/004749 describes the use of olive oil and St. John's Wort oil in skin infections.

Turkish patent application no. 2020/17736 describes a herbal analgesic cream containing olive oil with St. John's Wort for use in helping treatment in the health sector and its production method. In this document, the St. John’s Wort oil is prepared by soaking St. John’s Wort in olive oil for at least three months.

Turkish patent application no. 2019/10600 relates to a wound dressing developed for use in biomedical/health sector for treatment of chronic wounds including bedsore, diabetic food wounds. Said wound dressing comprises St. John’s Wort oil prepared by soaking St. John’s Wort flower in olive oil.

Turkish patent application no. 2011/02242 describes an ointment formulation which contains the macerate of St. John’s Wort in olive oil.

Turkish patent application no. 2015/17718 describes wound and burn cream with St. John’s Wort and sweet gum and production method of this cream. The said burn cream contains Klamath extract prepared in extra virgin olive oil.

Turkish patent application no. 2015/16956 describes a herbal skin cream that contains tetra oil, Klamath weed oil and olive oil.

Patent document no. RU2736214 describes an ointment to treat wounds.

Patent document no. EP2185168B2 describes a method to prepare an industrial-scale extract from the flowers and infructescences of H. perforatum in neem oil.

The need for compositions with natural ingredients for the treatment of wounds and burns continues. The insufficiency of existing solutions on the subject necessitates an improvement in the relevant technical field. Brief Description of the Invention

The present invention relates to compositions that meet the above-mentioned requirements and bring some additional advantages and to methods for preparing these compositions.

The primary object of the present invention is to provide a composition with natural ingredients, with improved efficacy in the treatment of external wounds and burns, sunburn, abrasions, bruises, ulcers, skin diseases and infected wounds in humans and animals.

Another object of the present invention is to provide a St. John’s Wort composition with an improved antioxidant, anti-inflammatory, anticancer and/or antimicrobial activity.

Another object of the present invention is to provide a St. John’s Wort (Hypericum perforatum) composition with an increased amount and strength of its ingredients with antioxidant, anti-inflammatory, anticancer and antimicrobial activities, such as hypericin.

A further object of the present invention is to provide a composition with an increased treatment and healing effect on wounds and burns compared to the olive oil macerate of St. John’s Wort.

To achieve the objects described above, the present invention provides Hypericum perforatum (St. John’s Wort) extract in oil, said oil comprising a certain ratio of bone marrow oil.

In a preferred embodiment of the invention, said oil further comprises a certain ratio of at least one vegetable oil selected from the group including olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil and sweet almond oil.

In another preferred embodiment of the invention, said vegetable oil is olive oil. In a further preferred embodiment of the invention, said oil comprises bone marrow oil at a ratio of at least 90% by total weight.

In a further preferred embodiment of the invention, said oil comprises olive oil at a ratio of at most 10% by total weight.

In a further preferred embodiment of the invention, said oil comprises 90% of bone marrow oil by total weight and 10% of olive oil by total weight.

To achieve the objects described above, the present invention provides use of Hypericum perforatum (St. John’s Wort) extract in oil in the preparation of a medicament for the topical treatment of external wounds, ulcers and burns in humans or animals, wherein said oil comprises a certain ratio of bone marrow oil.

To achieve the objects described above, the present invention provides Hypericum perforatum (St. John’s Wort) extract in oil for use in a method of the topical treatment of external wounds, ulcers and burns in humans or animals, wherein said oil comprises a certain ratio of bone marrow oil.

To achieve the objects described above, the present invention provides a composition comprising Hypericum perforatum extract in oil for use in the topical treatment or healing of external wounds, ulcers and burns in humans or animals, wherein said oil comprises a certain ratio of bone marrow oil.

To achieve the objects described above, the present invention provides a method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, comprising the steps of:

- mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil; and

- maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature. In a preferred embodiment of the invention, in the said method said oil further comprises a certain ratio of at least one vegetable oil selected from the group including olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil and sweet almond oil.

In another preferred embodiment of the invention, in said method, said vegetable oil is olive oil.

In a further preferred embodiment of the invention, in the said method, said oil comprises bone marrow oil at a ratio of at least 90% by total weight.

In a further preferred embodiment of the invention, in the said method, said oil comprises olive oil at a ratio of at most %10 by total weight.

In a further preferred embodiment of the invention, in the said method, said oil comprises 90% of bone marrow oil by total weight and 10% of olive oil by total weight.

In a further preferred embodiment of the invention, the maceration process is carried out at a temperature range of 18-45°C.

In a further preferred embodiment of the invention, the maceration process is carried out at a temperature range of 25-30°C. In this embodiment, the maceration process is carried out for 3 to 6 weeks, more preferably for 21 to 30 days.

In a further preferred embodiment of the invention, the maceration process is carried out in a water bath at a temperature range of 40-45°C. In this embodiment, preferably the maceration process is carried out for 1 to 5 hours.

In a further preferred embodiment of the invention, the said method comprises a step of subjecting Hypericum perforatum flowers and/or capsules to a pre-processing of drying, crushing, mincing, chopping and/or grinding. In a further preferred embodiment of the invention, the said method comprises a step of separating the obtained macerated oil through filtration.

To achieve the objects described above, the present invention provides an extract in oil obtained by a method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, said method comprising the steps of: mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil, and maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature.

To achieve the objects described above, the present invention provides use of extract in oil obtained by a method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, in the preparation of a medicament for the topical treatment of external wounds, ulcers and burns in humans or animals, said method comprising the steps of: mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil, and maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature.

To achieve the objects described above, the present invention provides an extract in oil, obtained by a method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, for use in a method of the topical treatment of external wounds, ulcers and burns in humans or animals, said method comprising the steps of mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil, and maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature.

To achieve the objects described above, the present invention provides an extract in oil obtained by a method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, for use in a topical treatment or healing of external wounds, ulcers and burns in humans or animals, said method comprising the steps of mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil, and maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature.

Detailed Description of the Invention

The subject-matter of the invention is described with references to examples in this detailed description without any restrictions but for the sole purpose of better understanding of the subject-matter.

A new composition that has a synergistic effect in the treatment and/or healing of wounds and burns has been invented by the present invention. Said composition comprises an extract of Hypericum perforatum (St. John’s Wort) plant in oil. Said oil either is bone marrow oil or comprises a certain amount of bone marrow oil. Thanks to the invention, the healing, sedative, antiseptic and antibiotic properties of H. perforatum plant extract are combined with the healing effect of bone marrow oil and it has been found that the obtained product is has a synergistically more effective healing effect on wounds and burns.

In an embodiment of the invention, the term “Hypericum perforatum extract in oil” is used in the meaning of a macerated oil obtained by maceration of St. John’ s Wort flowers, capsules (infructescence) or a mixture thereof in oil (the maceration process). In other words, this term is used in the meaning of a macerated oil (infused oil) into which the active ingredients of St. John’s Wort are extracted. According to this embodiment, St. John’s Wort maceration is carried out in the presence of bone marrow oil. In another embodiment of the invention, the bone marrow oil may be added to the macerated oil obtained through maceration, such as the macerated oil obtained by maceration in olive oil, at a later stage. Preferably, the maceration is carried out in the presence of the bone marrow oil. The macerated oil obtained this way has more healing effect. The aforementioned oil may further comprise a certain ratio of at least one vegetable oil selected from the group comprising olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil, coconut oil and sweet almond oil. In a preferred embodiment of the invention, said oil comprises at least %90 bone marrow oil by total weight. The vegetable oil is preferably olive oil. Due to the combination of bone marrow oil and olive oil, it has been observed that the beneficial effects of olive oil are also incorporated into the composition, yielding that optimal outcomes in the treatment and/or healing of wounds and burns, enhancing the healing effects of the composition. In a more preferred embodiment of the invention, said oil contains 90% bone marrow oil by total weight and %10 olive oil by total weight.

The present invention provide a novel method for preparing H. perforatum extract in oil. In the method of the invention, the flowers and/or capsules (infructescences) of H. perforatum are extracted into bone marrow oil. Preferably, the flowers and/or capsules are harvested at their most mature stage. The extraction method applied is the maceration process. It has been found that the composition of the macerated oil obtained through said method has a synergistic therapeutic and/or healing effect in recuperation of wounds and burns. Thanks to the obtained composition, it is possible to rapidly treat and/or heal wounds and burns without the need for the use of adjuvant therapeutic agents such as antibiotics, disinfectants or moisturizers.

In the method of invention, a certain amount of H. perforatum flowers and/or capsules is put into a glass container. H. perforatum flowers and/or capsules can be used as fresh, frozen or lyophilised. H. perforatum flowers and/or capsules can be subject to preprocessing of drying, crushing, mincing, chopping and/or grinding. A certain amount of an extraction solution containing bone marrow oil is also added to the same container. Said extraction solution comprises a) bone marrow oil only or b) bone marrow oil and at least a vegetable oil. The extraction solution may further comprise a pharmaceutically acceptable solvent or a solvent mixture. Among the examples of said vegetable oil are olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil and sweet almond oil. Said vegetable oil is preferably olive oil. It has been found that the effect of the macerated oil prepared with the combination of bone marrow oil and olive oil in the treatment and/or healing of wounds and burns as well as its inflammation-preventive, anti-inflammatory and cell regenerative effects are surprisingly improved compared to macerated oil prepared with only olive oil.

The extraction solution comprises at least 90% bone marrow oil by total weight. In a preferred embodiment of the invention, the extraction solution (whether macerated oil or infused oil) comprises 90% bone marrow oil based on the total weight and 10% olive oil based on the total weight.

The weight ratio of said extraction solution to flowers and/or capsules may be between 3-to-l and 15-to-l, depending on the water content of the flowers and/or capsules.

The obtained mixture is subject to maceration process for a certain period of time and at a certain temperature. As used in the present application, the maceration process means maintaining H. perforatum flowers and/or capsules in oil for a certain time at a certain temperature for extracting the active ingredients thereof into the oil. In a preferred embodiment of the invention, the maceration process is carried out for 3 to 6 weeks at a temperature of 18-35°C, more preferably at a temperature of 18-30°C. The maceration process can be carried out with or without direct sunlight. In order to accelerate the maceration process, modifications known to the person skilled person in the art can be made to the method of the invention. For instance, the digestion which serves as a faster extraction method in the context of maceration processes may be employed. This necessitates a higher temperature compared to conventional maceration. For example, the prepared mixture may undergo digestion at 45°C in a water bath for a duration of 2 hours, as a part of the digestion process. Additionally, agitation of the mixture is also possible throughout the maceration process.

As time progresses during maceration, infused oil takes on its characteristic color, transitioning from amber to orange or ruby red, depending on the solubilization of hypericin in the flowers and/or capsules in oil. Subsequently, the oil is separated from the sediment through filtration and stored in dark-colored glass containers to prevent exposure to light without contact with the air. Optionally, antioxidant, preservative and aromatic essential plant oils such as rosemary oil and basil oil may be added. Beeswax may be included as an emulsifier and hardening agent. Olive oil and other seed oils can be added to the composition.

Bone marrow oil is obtained from the bones of cattle such as calves and/or small animals like sheep, preferably from calf shinbones. The bone marrow oil obtained from calf shinbones has higher protein content. The bones are cooked in water for a certain period of time. For instance, to obtain bone marrow oil from calf shinbones, the calf shinbones are cooked in drinking water for 35 hours at a temperature below boiling, preferably at 75°C. The cooking temperature is reduced after boiling begins and maintained at this temperature. After the completion of the cooking, the mixture is allowed to rest for a certain period of time. After resting period, the layer of oil that has risen to the top is taken and separated by being passed through a strainer. Thus bone marrow oil is obtained. The obtained bone marrow oil is in a liquid-solid state at room temperature. In this form, bone marrow oil is suitable for maceration. As the temperature increases, the liquid phase of the bone marrow oil expands, making it more suitable for maceration.

The obtained bone marrow oil composition contains fatty acids such as arachidic acid, elaidic acid, gadoleic acid, heptadecenoic acid, linoleic acid, linolenic acid, margaric acid, myristic acid, myristoleic acid, oleic acid, palmitic acid, palmitoleic acid, pentadecanoic acid and stearic acid. Additionally, the bone marrow oil contains calcium, potassium, phosphorus, and magnesium. At the same time, the bone marrow oil is also rich in vitamins A and K, and Omega 3 and 6, as well as iron, zinc and selenium minerals. As it is obtained by boiling for a long duration, the bone marrow oil also contains amino acids found in bone ligaments during the boiling stage.

The composition obtained by using the method of the invention can be used in the external treatment of wounds, ulcers and burns as an anti-inflammatory drug, antiseptic, and scar reducing agent. Thanks to the synergistic effect of said composition, the therapeutic or healing effect of its natural ingredients is enhanced compared to their individual effects. EXAMPLES

Example 1 - Maceration Process Previously harvested St. John’s Wort flowers, each weighing 25 grams, were placed in 3 sealed glass bottles. One of the bottles was filled with bone marrow oil, completely covering the plants. The second bottle was filled with a mixture of olive oil and bone marrow oil in a 1/9 ratio by weight, completely covering the plants. The third bottle was filled with olive oil, completely covering the plants. The ingredients of the mixtures are pro- vided in Table 1.

Table 1

The bottles were then placed directly in a sun-exposed area and left for maceration for 45 days. At the end of the 45th day, the samples were filtered and transferred to sealed dark colored tubes, which were then stored in the refrigerator.

Claims

1. Hypericum perforatum (St. John’s Wort) extract in oil, characterized in that said oil comprises a certain ratio of bone marrow oil.

2. The extract in oil according to claim 1, characterized in that said oil comprises a certain ratio of at least one vegetable oil selected from the group including olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil and sweet almond oil.

3. The extract in oil according to claim 2, characterized in that said vegetable oil is olive oil.

4. The extract in oil according to any of preceding claims, characterized in that said oil comprises bone marrow oil at a ratio of at least 90% by total weight.

5. The extract in oil according to claim 3 or 4, characterized in that said oil comprises olive oil at a ratio of at most 10% by total weight.

6. The extract in oil according to claim 4 or 5, characterized in that said oil comprises 90% of bone marrow oil by total weight and 10% of olive oil by total weight.

7. Use of the extract in oil according to any of claims 1-6 in the preparation of a medicament for the topical treatment of external wounds, ulcers and burns in humans or animals.

8. The extract in oil according to any of claims 1-6 for use in a method of the topical treatment of external wounds, ulcers and burns in humans or animals.

9. A composition comprising Hypericum perforatum extract in oil for use in the topical treatment or healing of external wounds, ulcers and burns in humans or animals, characterized in that said oil comprises a certain ratio of bone marrow oil.

10. A method for preparing Hypericum perforatum (St. John’s Wort) extract in oil, characterized by comprising the steps of:

- mixing a certain amount of Hypericum perforatum flowers and/or capsules with a certain amount of oil, wherein said oil comprises bone marrow oil, and

- maintaining the obtained mixture to macerate for a certain period of time and at a certain temperature.

11. A method according to claim 10, characterized in that said oil further comprises a certain ratio of at least one vegetable oil selected from the group including olive oil, sunflower oil, safflower oil, walnut oil, canola oil, flax oil, sesame oil and sweet almond oil.

12. The method according to claim 11, characterized in that said vegetable oil is olive oil.

13. The method according to any of claims 10-12, characterized in that said oil comprises bone marrow oil at a ratio of at least 90% by total weight.

14. The method according to claim 12 or 13, characterized in that said oil comprises olive oil at a ratio of at most 10% by total weight.

15. The method according to claim 13 or 14, characterized in that said oil comprises 90% of bone marrow oil by total weight and 10% of olive oil by total weight.

16. The method according to any of claims 10-15, characterized in that the maceration process is carried out at a temperature range of 18-45°C.

17. The method according to claim 16, characterized in that the maceration process is carried out at a temperature range of 25-30°C.

18. The method according to claim 17, characterized in that the maceration process is carried out for 3 to 6 weeks.

19. The method according to claim 18, characterized in that the maceration process is carried out for 21 to 30 days.

20. The method according to claim 16, characterized in that the maceration process is carried out in a water bath at a temperature range of 40-45°C.

21. The method according to claim 20, characterized in that the maceration process is carried out for 1 to 5 hours.

22. The method according to any of claims 10-21, characterized by comprising a step of subjecting Hypericum perforatum flowers and/or capsules to a pre-processing step of drying, crushing, mincing, chopping, and/or grinding.

23. The method according to any of claims 12-22, characterized by comprising the step of separating the obtained macerated oil through filtration.

24. An extract in oil obtained by a method according to any of claims 10-23.

25. Use of the extract in oil according to claim 24, in the preparation of a medicament for the topical treatment of external wounds, ulcers and burns in humans or animals.

26. The extract in oil according to claim 24 for use in a method of the topical treatment of external wounds, ulcers and burns in humans or animals.

27. A composition comprising the extract in oil according to claim 24 for use in a topical treatment or healing of external wounds, ulcers and burns in humans or animals.