Phytological composition as a hemostatic agent

Abstract

The present invention relates to a phytological composition as a hemostatic agent, for example for use in the treatment of wounds and / or bleeding lesions of the skin and / or mucous membranes. The phytological composition consists of a polysaccharide of Tremella fuciformis, an extract of leaves of Vitis vinifera, an extract of leaves of Astragalus membranaceus, an extract of Medicago sativa, an extract of Fucus vesiculosus, a powder of Spirulia platensis, an extract of root of Beta vulgaris and an extract of Polygonum cuspidatum. The present invention also relates to pharmaceutical formulations comprising said phytological composition together with suitable pharmaceutically acceptable excipients.

Description

[0001] PHYTOLOGICAL COMPOSITION AS A HEMOSTATIC AGENT

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a phytological composition as a hemostatic agent for use in the treatment of wounds and / or bleeding lesions of the skin and / or mucous membranes. The phytological composition consists of:

[0004] 10-20% (w / w) polysaccharide of Tremella fuciformis,

[0005] 5-15% (w / w) extract of leaves of Vitis vinifera,

[0006] 10-30% (w / w) extract of leaves of Astragalus membranaceus,

[0007] 8-15% (w / w) extract of Medicago sativa,

[0008] 4-15% (w / w) extract of Fucus vesiculosus,

[0009] 4-8% (w / w) powder of Spirulia platensis,

[0010] 8-15% (w / w) extract of root of Beta vulgaris and

[0011] 5-30% (w / w) extract of Polygonum cuspidatum.

[0012] BACKGROUND OF THE INVENTION

[0013] The wounds are lesions with loss of the continuity of the skin and mucous membranes and possibly of the underlying tissues. They may be of varying severity, with less or greater loss of tissue and bleeding.

[0014] A wound is defined by its nature and the period of convalescence of the patient, which may vary depending on the general health status and the onset of factors that may affect and slow down tissue repair.

[0015] Wounds and / or bleeding lesions may be acute or chronic. Acute wounds may take the form of cuts, tears, or even bites and scratches, while chronic wounds may be from compression (e.g., decubitus wounds) or consequences of a more complex disorder (e.g., diabetic foot).

[0016] They can be produced by various types of harmful agents, classified as: wounds by pointed objects, by cuts, by firearms, contused, lacerated and torn wounds.

[0017] There are also wounds that may be incidental or produced by surgery. In all cases however, in order for the wound to heal as soon as possible, it is necessary to stop the bleeding as soon as possible with a hemostatic agent, which may be a medical device or a drug.

[0018] The phytological composition of the invention comprises several natural ingredients, which may in turn comprise several phytocomplexes and has been described in the Italian patent application No. 102023000002271 and in the international patent application WO2024 / 166055. In particular, the phytological composition of the invention consists of the following ingredients, each in the concentration ranges by weight indicated in brackets (w / w, based on the total weight of the phytological composition):

[0019] Polysaccharide of Tremella fuciformis (10-20%),

[0020] Leaf extract of Vitis vinifera (5-15%),

[0021] Root extract of Astragalus membranaceus ( 10-30%),

[0022] Extract of Medicago sativa (8-15%),

[0023] Extract of Fucus vesiculosus (4- 15%),

[0024] Powder of Spirulia platensis (4-8%),

[0025] Root extract of Beta vulgaris (8-15%) and

[0026] Extract of Polygonum cuspidatum (5-30%).

[0027] Said phytological composition has been described to have a regenerative, restorative and cicatrizing effect on tissue lesions of various nature, making it suitable both as a dermatological treatment of skin lesions and in particular psoriasis, and as a cosmetic.

[0028] It has now been surprisingly found by the Applicant that the same phytological composition represents an excellent hemostatic agent for use in the treatment of wounds and / or bleeding lesions of the skin and mucous membranes.

[0029] DESCRIPTION OF THE INVENTION

[0030] The main object of the present invention is a phytological composition as a hemostatic agent, for example for use in the treatment of wounds and / or bleeding lesions of the skin and / or mucous membranes. The phytological composition of the invention consists of the following ingredients, each in the concentration ranges by weight indicated in brackets (w / w, based on the total weight of the phytological composition):

[0031] 10-20% (w / w) polysaccharide of Tremella Fuciformis,

[0032] 5-15% (w / w) extract of leaves of Vitis Vinifera,

[0033] 10-30% (w / w) extract of leaves of Astragalus Membranaceus,

[0034] 8-15% (w / w) extract of Medicago Sativa,

[0035] 4-15% (w / w) extract of Fucus Vesiculosus,

[0036] 4-8% (w / w) powder of Spirulia Platensis,

[0037] 8-15% (w / w) extract of root of Beta Vulgaris and

[0038] 5-30% (w / w) extract of Polygonum Cuspidatum.

[0039] Preferably, the ingredients of the phytological composition of the invention are in the following concentration ranges by weight (w / w):

[0040] 12-16% (w / w) polysaccharide of Tremella Fuciformis,

[0041] 8-13% (w / w) extract of leaves of Vitis Vinifera,

[0042] 15-25% (w / w) extract of leaves of Astragalus Membranaceus,

[0043] 8-13% (w / w) extract of Medicago Sativa,

[0044] 8-15% (w / w) extract of Fucus Vesiculosus,

[0045] 4-6% (w / w) powder of Spirulia Platensis,

[0046] 8-13% (w / w) extract of root of Beta Vulgaris and

[0047] 15-25% (w / w) extract of Polygonum Cuspidatum.

[0048] For the preparation of the extracts, where not indicated, the aerial parts of the plant, i.e. stem, leaves, flowers or mixtures thereof, are used.

[0049] The polysaccharide of Tremella fuciformis (CAS No. 778577-37-0) is extracted from the edible fruit bodies of the Silver Ear fungus in China. The polysaccharide comprises glucuronic acid and N-acetylglucosamine. The extracts of Tremella fuciformis can be obtained by solvent extraction from the carpophore of Tremella.

[0050] The extract of Vitis vinifera leaves (CAS No. 84929-27-1) is an extract of red grape leaves (Vitis).

[0051] The rooi exiracioi'Astragalus memhranaceus(C.\S So. 94166-93-5)is extracted from the dried roots of the medicinal herb Astragalus membranaceus. The extracts of Astragalus can be obtained through an extraction process in the following order: drying of Astragalus, grinding, screening and titration of the individual phytocomplexes.

[0052] The Medicago sativa extract (CAS No: 84082-36-0) is an extract of the enti re Medi cago sativa plant (alfalfa). The extract comprises folic acid and optionally one or more of oligosaccharides, vitamin B5 and coenzyme Q10.

[0053] The Fucus Vesiculosus extract (CAS No: 84696-13-9) is an extract of the dried thallus of the Bladderwrack, Fucus alga.

[0054] The Spirulia platensis powder (CAS No: 223751-80-2) is the powder obtained from the dried grinding preferably of the whole thallus of Arthrospira platensis, also called Spirulina platensis (spirulina).

[0055] The root extract (A Beta vulgaris (CAS No: 89957-89-1 / 89957-90-4) is an extract of the roots of sugar beet, Beta vulgaris L., obtainable by drying, extraction and titration of Beta vulgaris powders or by solvent extraction. The Polygonum cuspidatum extracts (CAS No. 501-36-0) can be obtained by drying and titration of powders or by solvent extraction.

[0056] Vitis vinifera leaf extracts and Polygonum cuspidatum extracts preferably contain resveratrol. Preferably, the phytological composition according to the present invention is formulated in a pharmaceutical formulation, more preferably for topical use. Said phytological composition is preferably present in the pharmaceutical formulation at a concentration by weight of 1-5% on the weight of the dermatological formulation; more preferably, the phytological composition is present at a concentration of 2-4%, even more preferably about 3%, on the weight of the dermatological formulation, together with suitable pharmaceutically acceptable excipients. Suitable pharmaceutically acceptable excipients include rheological additives, buffer agents, antimicrobial agents, antioxidant agents, anti-isothermal agents, antistatic agents, absorbing agents, UV absorbing agents, astringent agents, chelating agents, skin conditioning agents, preservatives, covering agents, denaturing agents, depigmenting agents, emulsifying agents, film forming agents, gelling agents, colloidal agents, hydrating agents, hydrotropic agents, binders, soothing agents, smoothing agents, opacifying agents, plasticizers, propellants, skinprotecting agents, reducing agents, refreshing agents, sebum-restoring agents, solvents, stabilizing agents, emulsifying stabilizing agents, toning agents, wetting agents, volumizing agents or combinations thereof.

[0057] Preferably, said pharmaceutically acceptable excipients comprise or consist of one or more of rheological additives, buffer agents, antimicrobial agents, antioxidant agents, emulsifying agents, hydrating agents, hydrotropic agents, smoothing agents, solvents.

[0058] The pharmaceutical formulations according to the invention are preferably aqueous formulations, more preferably comprising at least one alcohol-based solvent, at least one antimicrobial agent, at least one smoothing agent, at least one rheological additive, at least one antioxidant agent and / or at least one hydrating agent.

[0059] Particularly preferred pharmaceutically acceptable excipients which are present in the pharmaceutical formulations of the invention are: methoxymethyl butanol as an alcohol-based solvent, carbomer (or Carbopol ) as a thickening agent, propylene glycol, polyethylene glycol (PEG) compounds, such as PEG-6, PEG-32, PEG-4, including PEG-4 proline linolenate and PEG-4 proline linoleate. Preferably, the dermatological formulation of the invention further comprises one or more of: vitamins and / or provitamins, such as vitamin A, vitamin D, vitamin E and panthenol, preferably colloidal vitamins, such as colloidal vitamin D, colloidal vitamin A, inorganic elements with antimicrobial activity, such as silver, copper, zinc and other antimicrobial compounds such as phenoxyethanol, 2-bromo-2-nitropropane- 1,3 -diol.

[0060] Optionally, the pharmaceutical formulation may further comprise glycosaminoglycans, such as chondroitin, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin, heparan sulfate, hyaluronic acid and mixtures thereof.

[0061] Preferably, the pharmaceutical formulation also comprises antioxidant and / or antimicrobial agents as active agents.

[0062] The invention therefore relates to the use of the phytological composition described above as a hemostatic agent for use in the treatment of wounds and / or bleeding lesions of the skin and / or mucous membranes.

[0063] According to the present invention, wounds and / or bleeding lesions may be acute or chronic. Acute wounds may take the form of cuts, tears, or even bites and scratches, while chronic wounds may be from compression (e.g., decubitus wounds) or consequences of a more complex disorder (e.g., diabetic foot). They can be produced by various types of harmful agents, classified as: wounds by pointed objects, by cuts, by firearms, contused, lacerated and tom wounds. The wounds following surgery also benefit from the local application of the above-described phytological composition.

[0064] The bleeding lesions of the mucous membranes (oral, nasal, ear, and anus-genital area) are also quickly cured by the application of the phytological composition described above. For example, a useful application is in the case of epistaxis.

[0065] According to the present invention, we define "mucous menbranes" all areas of the skin at the orifices where the skin creates continuity therewith forming a layer without interruption.

[0066] Furthermore, the phytological composition having hemostatic activity is also suitable for veterinary use.

[0067] The formulation of said phytological composition with specific excipients further improves one or more of the aforesaid dermatological advantages of the phytological composition, so as to be able to provide formulations particularly suitable for the treatment of specific dermatological disorders or tissue lesions.

[0068] Preferred formulations include the phytological composition together with one or more of silver, iron, copper (preferably in colloidal form), phenoxyethanol, 2-bromo-2-nitropropane- 1,3-diol, vitamin A, B and D (preferably in colloidal form) and propylene glycol.

[0069] The pharmaceutical formulation comprising the phytological composition together with the following excipients is particularly suitable for the previously described use, preferably in the form of serum:

[0070] Methoxymethyl butanol

[0071] Carbomer

[0072] Propylene glycol

[0073] PEG-4 proline linolenate, PEG-4 proline linoleate

[0074] Panthenol

[0075] Tocopherol

[0076] Colloidal silver (preferably 100 ppm)

[0077] Colloidal copper (preferably 20 ppm) and

[0078] Phenoxyethanol, 2-bromo-2-nitropropane-l,3-diol.

[0079] Said pharmaceutical formulations comprising the phytological composition may be in the form of ointment, lotion, cream, emulsion, paste, gel, aqueous solution, colloid, spray, patch, serum, soaked gauze, dressing, mouthwash or a combination thereof. Particularly preferred are the formulations in the form of serum. Preferably, said pharmaceutical formulations should be administered topically, on the skin, from one to four times a day, in suitable amounts. A suitable amount is, for example, an amount that can be absorbed by massaging the formulation on the skin.

[0080] All the pharmaceutical formulation can be prepared by methods known in the pharmaceutical technique.

[0081] It should also be understood that all the combinations of preferred aspects of the phytological composition of the invention, as well as of the pharmaceutical formulation and the uses thereof, as reported above, are to be considered as described herein.

[0082] Operating examples of the present invention are given below for illustrative purposes.

[0083] EXAMPLES

[0084] Example 1

[0085] A phytological composition was prepared by mixing the following ingredients:

[0086] Example 2

[0087] The following pharmaceutical formulation was prepared comprising the phytological composition of Example 1 to be tested:

[0088] Example 3 - Evaluation of hemostatic activity in vivo

[0089] To evaluate the hemostatic activity of the pharmaceutical formulation prepared in Example 2 (also called Hemostatic Formulation hereinafter), but also to test its possible veterinary use, it was decided to carry out in vivo tests on animals and, in particular, on pigs from intensive breeding. Unfortunately, in the conditions of captivity and overcrowding of intensive breeding, these animals often present several bleeding wounds caused by bites from nearby animals, which, if not treated adequately, lead to infections, which quickly evolve into septicemia and which ultimately require the animal to be slaughtered.

[0090] The Hemostatic Formulation was administered by epilesional application on the wounds of 12 pigs of an intensive breeding, which had serious injuries due to bites on the tail, which in some cases caused their detachment.

[0091] It was noted that the first application of the Hemostatic Formulation already resulted in a stop of bleeding after about 30 seconds on all treated animals.

[0092] The treatment was repeated for 7 days (once a day) and at the end of the treatment all the animals treated had an uninfected skin and a normal skin re-epithelization in the wound area.

Claims

CLAIMS1. A phytological composition consisting of:10-20% (w / w) polysaccharide of Tremella fuciformis,5-15% (w / w) extract of leaves of Vitis vinifera,10-30% (w / w) extract of leaves of Astragalus membranaceus,8-15% (w / w) extract of Medicago sativa,4-15% (w / w) extract of Fucus vesiculosus,4-8% (w / w) powder of Spirulia platensis,8-15% (w / w) extract of root of Beta vulgaris and5-30% (w / w) extract of Polygonum cuspidatum as hemostatic agent, for example for use in the treatment of hemorrhagic wounds and / or lesions of the skin and / or mucous membranes.

2. The phytological composition of claim 1, consisting of:12-16% (w / w) polysaccharide of Tremella fuciformis,8-13% (w / w) extract of leaves of Vitis vinifera,15-25% (w / w) extract of leaves of Astragalus membranaceus,8-13% (w / w) extract of Medicago sativa,8-15% (w / w) extract of Fucus vesiculosus,4-6% (w / w) powder of Spirulia platensis,8-13% (w / w) extract of root of Beta vulgaris and15-25% (w / w) extract of Polygonum cuspidatum as hemostatic agent, for example for use in the treatment of hemorrhagic wounds and / or lesions of the skin and / or mucous membranes.

3. The composition according to claim 1 or 2, wherein the use is a veterinary use.

4. The composition according to anyone of the preceding claims, wherein the use is topical use.

5. A pharmaceutical formulation comprising the phytological composition consisting of: 10-20% (w / w) polysaccharide of Tremella fuciformis,5-15% (w / w) extract of leaves of Vitis vinifera,10-30% (w / w) extract of leaves of Astragalus membranaceus,8-15% (w / w) extract of Medicago sativa,4-15% (w / w) extract of Fucus vesiculosus,4-8% (w / w) polvere of Spirulia platensis,8-15% (w / w) extract of root of Beta vulgaris and5-30% (w / w) extract of Polygonum cuspidatum together with the following excipients: colloidal silver, colloidal copper,3 -methyl-3 -methoxybutanol, phenoxyethanol,2-bromo-2-nitro- 1 ,3 -propanediol, tocoferol,CarbomerPantenol propylene glycolPEG-4 Proline linolenate, as hemostatic agent, for example for use in the treatment of hemorrhagic wounds and / or lesions of the skin and / or mucous membranes.

6. The pharmaceutical formulation of claim 5, wherein the phytological composition is at a concentration of 1-5% in weight, on the total weight of the pharmaceutical formulation, preferably 2-4% in weight.

7. The pharmaceutical formulation of anyone of claims 5 or 6, in the form of ointment, lotion, cream, emulsion, paste, gel, aqueous solution, colloid, spray, plaster, serum, soaked gauze, dressing, mouthwash or a combination thereof, preferably in the form of serum.

8. The pharmaceutical formulation according to anyone of claims from 5 to 7, for topical epilesional use.

9. The formulation according to anyone of claims from 5 to 8, wherein the use is topical use.

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