EP3525777A1

EP3525777A1 - Xanthohumol for use in treating haemorrhoidal disease

Info

Publication number: EP3525777A1
Application number: EP17804652.0A
Authority: EP
Inventors: Malgorzata KRUSZEWSKA-GAGOS; Mariusz GAGOS
Original assignee: Bioactive-Tech Sp Z OO
Current assignee: Bioactive-Tech Sp Z OO
Priority date: 2016-10-12
Filing date: 2017-10-12
Publication date: 2019-08-21
Also published as: WO2018069855A1; PL419082A1; PL235226B1

Abstract

The object of the invention is xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area and in the care of the skin around the anus. The invention also relates to a composition for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area, as well as in the skin care around the anus, containing the active ingredient and at least one physiologically acceptable excipient or any carrier, which as an active component comprises xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex.

Description

XANTHOHUMOL FOR USE IN TREATING HAEMORRHOIDAL DISEASE

The invention relates to the use of xanthohumol in the treatment of haemorrhoidal diseases, the prophylaxis of haemorrhoidal diseases, or the prevention of the symptoms of haemorrhoidal diseases and other diseases of the anal area and any associated conditions, as well as the care of the skin around the anus. The invention relates also to the composition containing xanthohumol for use in the treatment, prophylaxis or prevention of the symptoms of haemorrhoidal diseases and other diseases of the anal area and any associated conditions, as well as the care of the skin around the anus. Proper care and hygiene is a particularly important factor in the prophylaxis, prevention and treatment of haemorrhoidal diseases, as well as in the prophylaxis, prevention and treatment of other diseases of the anal area.

From the point of view of treating a haemorrhoidal disease, it is important to distinguish the concept of haemorrhoids and the haemorrhoidal disease. The term "haemorrhoidal diseases" refers to the conditions such as an anal fissure, a perirectal abscess, haemorrhoids and an anal fistula and other haemorrhoidal ailments arising from the enlargement of haemorrhoids. Haemorrhoids (piles) can be found in each person because they form physiological anal canal structure. They are, together with the anal sphincter muscles apparatus, necessary for a complete sealing of the rectum. Haemorrhoids (piles) are commonly called haemorrhoids only when they cause haemorrhoidal ailments. They however remain unnoticed until they are of normal size and are able to perform their precise rectal closure function (F. H. Wullink, Hemoroidy. Poradnik dla pacjentow, 1st Polish edition, ed. K. Matysiak, Wroclaw 2008, pages 10-11.)

Piles look like blood-filled little pillows and perform an extremely important function - they seal the anal canal. When a nerve impulse is felt as a push, the piles are emptied from the blood, allowing bowel emptying. The problem starts when haemorrhoids are stretched, overflowing with blood, and do not get completely empty out of it. As a result of blood retention, over time there occurs inflammation which covers both piles (enlarged venous plexi) and anal tissues. We are talking then about the development of the haemorrhoidal disease, that is anal varicose veins. Anal varicose veins can occur regardless of age. They favour a sedentary lifestyle and the lack of physical activity which causes pressure disorders in the venous system in the anal area. The cause of the disease is also an incorrect diet, including an insufficient amount of fibre.

In addition, pregnancy and associated hormonal changes create favourable conditions for anal varicose veins. The growing foetus sometimes presses against the venous system, impeding a blood flow and impairs an intestinal function. Sometimes a strong pressure during labour leads to enlargement of the piles. After delivery, haemorrhoids may reduce themselves and then they do not require any treatment.

It is estimated that about 80% of all people over the age of 30 suffer at least one episode of their life (to a greater or lesser extent of severity) from the ailments caused by the piles. However, the presence of haemorrhoids itself does not cause any ailments. Other symptoms must appear before the haemorrhoidal disease develops (R. Winkler, P. Otto, T. Schiedeck, Proktologia praktyczna, editing of 1st Polish edition A. Dziki, Wroclaw 2013, page 92.)

The symptoms of the haemorrhoidal disease occur in every fourth adult (P. K. Paszko, E. Krajewska-Kulak, J. Lewko, Ocena wiedzy pacjentow na temat profilaktyki choroby hemoroidalnej). One of the first signs of the disease is pruritus in the anal area. The enlarged piles sometimes give the impression of an incomplete bowel movement, which induces a stronger pressure. Another symptom is minor bleeding, most often during bowel movements. Pain occurs when haemorrhoids are accompanied by, for example, inflammatory and thrombotic complications (F. H. Wullink, Hemoroidy. Poradnik dla pacjentow, 1st Polish edition, ed. K. Matysiak, Wroclaw 2008, pages 9-13). It is thought that the treatment of haemorrhoids is closely related to diet and lifestyle (Lohsiriwat 2012). In advanced cases, surgery is an effective method of treating haemorrhoids, although it can be associated with perceptible complications. In the meantime, based on the known patented drugs, inoperable treatment is not fully effective, especially topical or pharmacological treatment.

Most colorectal surgeons have widely accepted the division of internal haemorrhoids proposed in 1985 by Banov and co-authors. Namely: Grade I) piles, bleeding but not prolapsing,

Grade II) piles that prolapse outside upon pressure but reduce spontaneously, with or without bleeding,

Grade III) piles that prolapse outside upon pressure and require a manual reduction, in some cases with massive oedema of the anal edge,

Grade IV) piles without the possibility of discharge, with or without thrombosis (R. Winkler, P. Otto, T. Schiedeck, Proktologia praktyczna, editing of 1st Polish edition A. Dziki, Wroclaw 2013, page 94)

Symptoms and severity are directly related to the grade of haemorrhoids:

Grade I) usually painless, slight bleeding,

Grade II) moderate discomfort, itching and feeling of fullness in the anus and bleeding, Grade III) pain, bleeding and excessive secretion of mucus with maceration, anal itching, irritation and inflammation with the possibility of getting the underwear dirty, Grade IV) pain, bleeding, the possibility of trapping and thrombosis as well as contamination.

Treatment, results and complications

The type of treatment used is clearly related to the grade in the Banov classification. In case of grade I and II haemorrhoids, conservative treatment is usually used. This includes a significant increase in dietary fibre intake (high-fibre diet) and intake of fluids.

In the available medical literature there is generally no adequate number of clinical trials on the efficacy of topical medications for the symptomatic treatment of piles, but many clinicians confirm empirically the achieved benefits and improvement, particularly with the use of preparations containing alleviating, soothing, topically anaesthetizing and anti-inflammatory agents. Among them allantoin, bismuth oxide, zinc oxide, Peruvian lotion, lignocaine, cinchocain, benzocaine and pramocaine should be mentioned. In the case of recurrent problems with grade I and II piles, apart from the conservative treatment, there is a whole arsenal of operative treatment (R. Winkler, P. Otto, T. Schiedeck, Proktologia praktyczna, editing of 1st Polish edition A. Dziki, Wroclaw 2013, pages 95-101). Their essence is a non-operative ablation by inducing vascular thrombosis, connective tissue fibrosis, shrinkage or necrosis and fixation of a mucosal part of the haemorrhoidal complex.

One of the oldest non-surgical methods is sclerotherapy. The procedure is very short and requires only an anoscope. It can be repeated every few weeks to maintain the effect. However, it is reported that up to 30% of patients after 4 years, after initially successful sclerotherapy, have recurrent symptoms of the haemorrhoidal disease.

Some use cryotherapy as a technique destructing enlarged internal haemorrhoids. The application of rubber bands (the Barron's method) consists in a tight closure of excessive mucosa, connective tissue and haemorrhoidal vessels. The resulting scar attaches the connective tissue to the rectal wall, alleviating or eliminating the prolapse - hence beyond grade I and II, the method can successfully be used in grade III of piles.

Bipolar diathermy, DC electrotherapy and infrared photocoagulation consist in turn in the closure of the vascular bundle above the anal transition zone. After the demarcation, an ulcer is formed that gets fibrous at the site of treatment.

DC electrotherapy requires time-consuming (up to 14 minutes) DC applications. Time and intensity increase with the progression of piles. Repeated applications to the same place are recorded in 30% of patients. Infrared photocoagulation focuses the infrared radiation from the halogen lamp through the polymer probe at its top. The 0.5-2 second energy pulses are delivered to the base of the vascular bundle, which penetrate about 2.5 mm into the tissue. The most effective method is rubber bands, and patients undergoing this procedure are least often treated for haemorrhoids. Unfortunately, this group of patients simultaneously reported most often pain after surgery. In conclusion it might be admitted that non-surgical methods may be considered as the initial procedures of choice in patients with grade I and II haemorrhoids and early, small piles in grade III.

The most effective of all methods is considered surgical treatment, especially for grade III and IV haemorrhoids. The present inventors have surprisingly found that the use of xanthohumol in the treatment of haemorrhoidal diseases or the prevention of haemorrhoidal diseases allows to obtain excellent therapeutic effects, including a complete elimination of any symptoms of the haemorrhoidal disease.

The object of the invention is, therefore, xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area and in the care of the skin around the anus.

According to the invention, the care action of xanthohumol includes regenerating, nourishing, antipruritic and skin care actions with respect to the anal area, removing burning sensation and soreness, resulting in a noticeable improvement and alleviation.

Xanthohumol is preferably topically applied internally, rectally in the form of an ointment or a cream or another semi-solid form, topically, internally, rectally in the form of suppositories or another solid form, topically, internally, rectally as enema or another liquid, solid or semi-solid form, or is used topically, externally to the anal area in a liquid, solid or semi- solid form.

The invention also relates to a composition for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area, as well as in the skin care around the anus, comprising the active ingredient and at least one physiologically acceptable excipient or any carrier, characterized in that as an active component it comprises xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex.

The composition of the invention is preferably in the form of a semi-solid such as an ointment or a cream, preferably comprising a petrolatum as a physiologically acceptable excipient.

The composition of the present invention is preferably in a solid form such as a suppository, powder or in a liquid form such as a spray, lotion, balsam, foam, fluid or enema or in the form of a wet wipe. The composition of the invention is preferably used topically internally or topically externally.

In a preferred embodiment, the composition comprises xanthohumol in an amount ranging from 0.001% by weight to 5.0% by weight of xanthohumol in terms of the total weight of the composition, more preferably, the composition comprises xanthohumol in an amount ranging from 0.01% by weight to 1.0% by weight of xanthohumol in terms of the total weight of the composition, most preferably, the composition comprises xanthohumol in an amount ranging from 0.1 % by weight to 0.5% by weight of xanthohumol in terms of the total weight of the composition.

In a preferred embodiment, the composition according to the invention further comprises an additional active agent and/or other additives.

Xanthohumol is a natural compound of the group of prenylated chalcones, the main source of which is the female inflorescence of Humulus Lupus. It is also found in beer, but in trace amounts (Stevens and Page 2004). This compound is composed of two benzene rings (A and B) linked together by α,β - unsaturated carbonyl system.

Fig. 1 Chemical structure of xanthohumol.

In contrast to other components contained in hop cones, xanthohumol is characterized by higher lipophilicity, which is related to the presence of a prenylated substituent in its structure (Nowakowska 2007, Vogel and Heilmann 2008). It is worth mentioning at this point that in biological systems the prenyl moieties allow numerous intracellular molecules (e.g. Ras and Rho) to anchor in the cell membrane, deciding about their proper function. Likewise, it is suggested that in the case of xanthohumol, these moieties may significantly modulate the biological activity of this compound, and further affect its physicochemical properties and subcellular arrangement (Monteghirfo, Tosetti et al. 2008).

The appearance in the medical literature of the information on the pleiotropic action of xanthohumol has increased the interest of this compound among scientists worldwide. It results from the literature data that xanthohumol has a variety of biological properties, including antibacterial, antiviral, immunomodulatory, antioxidant, antimutagenic, anti-inflammatory and anti-cancer properties (Festa, Capasso et al. 2011, Liu, Hansen et al. 2015). The neuroprotective activity and the ability to inhibit bone resorption and stimulation of osteoblastic differentiation have also been recently documented (Tobe, Muraki et al. 1997, Yen, Hsu et al. 2012). At present, there are also experimental works on the use of xanthohumol in the treatment of osteoporosis, diabetes, cardiovascular diseases, neurodegenerative and neoplastic diseases, in the pathogenesis of which inflammation plays an important role (Miranda, Stevens et al. 2000, Jeong, Han et al. 2011).

In vitro and in vivo studies show that xantohumol reduces inflammatory and oxidative processes through a variety of mechanisms. The most important of these are: removal of free oxygen radicals and their reactive forms (RTF), inhibition of cyclooxygenase activity (COX I and COX II), reduction of prostaglandin production, NO, TNFa, NF_KB and prevention of membrane peroxidation of phospholipids (Miranda, Stevens et al. 2000, Stevens and Page 2004, Nowakowska 2007, Yadav, Prasad et al. 2011). As a powerful antioxidant and modulator of pro-inflammatory factors, xanthohumol can inhibit the formation and growth of various types of cancer. The in vitro studies have revealed its cytotoxic and antiproliferative effects on neoplastic cells of breast cancer (MCF-7), colon cancer (HT-27, HCT-116), ovarian cancer (A- 2780, SCOV3), prostate cancer (DU145, PC3, LNCa, PBPH1) and cells of leukaemia and malignant glioma (Miranda, Stevens et al. 2000, Monteghirfo, Tosetti et al. 2008, Festa, Capasso et al. 2011). The wide spectrum of xanthohumol antitumour activity is probably due to the ability of this compound to bind biologically important molecules responsible for the proliferation and survival of tumour cells. The best known are the effect of xanthohumol on the synthetase of polymerase a, topoisomerase I, alkaline phosphatase, aromatase, diacylglycerol acyltransferase, MAPK signalling pathway proteins, FAK kinase, Akt kinase, and STAT or NF_KB transcription factors (Albini, Dell'Eva et al. 2005, Goto, Asai et al. 2005, Lee, Kim et al. 2007). Xanthohumol-induced decrease in the activity of these proteins induces pleiotropic cell effects resulting from proliferative disorders, a cell cycle, adhesion and migration of tumour cells (Iwashita, Kobori et al. 2000, Dorn, Weiss et al. 2010).

The studies on neoplastic cell cultures and animal models have demonstrated that xanthohumol inhibited the proliferation and migration of vascular endothelial cells, the formation of capillary structures, and also reduced the activity of proangiogenic factors. The proven biological activity and low toxicity of xanthohumol for healthy cells makes it a very promising pharmaceutical agent in the prophylaxis and treatment of many lifestyle chronic illnesses and diseases.

The term "physiologically acceptable salts" means salts which are physiologically acceptable. Particularly preferred are salts with inorganic bases such as lithium salts, sodium salts, potassium salts, calcium salts, salts with organic amines (e.g. morpholine and piperidine) and amino acids. One skilled in the art will recognize that the term "physiologically acceptable salts" includes all salts which are acceptable from the pharmaceutical, cosmetic or care point of view.

Xanthohumol also forms complexes with metals, especially with transition metals such as copper or zinc. Such xanthohumol complexes may also be used according to the invention.

One skilled in the art is aware that due to its chemical structure, xantohumol also forms molecular complexes such as supramolecular complexes or other molecular complexes with other groups of compounds such as lipids or carbohydrates such as cyclodextrins.

Xanthohumol and its physiologically acceptable salts may be present in various solvated forms. They can also be converted into hydrates from the point of view of use as pharmaceuticals or cosmetics.

The composition of the invention may be liquid, semi-solid and solid (e.g. solution, suspension, emulsion, cream, ointment, gel, foam, suppository, spray). A typical composition is prepared by mixing xanthohumol with a carrier or excipient. Suitable carries and excipients are well known to the persons skilled in the art and include materials such as carbohydrates, waxes, water soluble and/or swellable polymers, hydrophilic or hydrophobic materials, gelatine, oils, solvents, water and the like. The use of a particular carrier or excipient will depend on the intended mode of administration. Solvents are generally selected from the solvents recognized by those skilled in the art as safe to be administered to patients. The compositions may also contain one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, matting agents, lubricants, processing aids, dyes, sweeteners, perfumes, flavours and other known additives providing an elegant presentation of the drug or helping in the manufacture of a pharmaceutical or cosmetic or care product (i.e. a drug, a medicinal preparation, a medical product, a cosmetic product).

The composition for use in the treatment or prevention and prophylaxis of haemorrhoidal diseases (or a cosmetic or care composition) of the invention may be prepared by conventional methods well known in the art of pharmaceutical or cosmetic technology. In the case of the ointment, to a base (such as e.g. a hydrophilic base) there are added, if necessary, such excipients as preservatives e.g. para-oxyaminobenzoic acid esters and emulsifiers, e.g. sodium lauryl sulfate. Then xanthohumol is added to the resulting mixture and the entirety is stirred until a homogeneous mixture is obtained.

In the case of suppositories, excipients such as emulsifiers, suspending agents, preservatives, and the like are added to bases such as cocoa butter. Then xanthohumol is added to the resulting mixture and the entirety is stirred until a homogeneous composition is obtained. The suppository is made by conventional means such as, for example, melting.

The composition of the invention may be advantageously administered as an ointment or suppositories, however, other pharmaceutical or cosmetic forms such as a cream, gel or spray or dusting powder, powder or wet wipe may also be convenient for the patient or the recipient of the product.

The composition of the present invention may be applied topically, preferably in the form of ointments for lesions or susceptible sites. A composition containing xanthohumol as an active ingredient may be administered once daily or more frequently. The exact dosage regimen can be easily determined depending on the age of the patient, sex, overall health, severity of the disease treated as well as frequency and mode of administration.

The composition of the invention may additionally comprise other active agents that are useful in the treatment of haemorrhoidal diseases such as bactericides or antifungal agents, antiinflammatory agents, anaesthetics, haemostatics, peripheral circulation enhancing agents, and wound healing agents. Such compositions may also comprise analgesics such as procaine hydrochloride and dibukain hydrochloride.

Embodiment of the invention:

Preparation of the ointment:

The preparation of the ointment consists in dissolving a specific amount (in this case 50 or 100 mg) of xanthohumol of appropriate purity (in this case over 98%) dissolved in ethyl alcohol, DMSO or other acceptable organic solvents. The volume of a solvent should be as small as possible - so that xanthohumol dissolves completely. If 50 mg of xanthohumol is used, it was 1 ml of ethanol. In the case of 100 mg of xanthohumol, 2 ml of ethanol was used. 30 g of white petrolatum was heated to a semi-liquid state and the dissolved xanthohumol was added continuously while stirring. The resulting preparation is cooled to 8°C until it is solid. Other solvents and other carrier bases than white petrolatum to suspend xanthohumol in them, known in the state of the art, may also be used for the production of the ointment. It is important to create a homogeneous structure of the resulting ointment. A method known in the state of the art of preparing suppositories containing xanthohumol may also be used. Xanthohumol can also be used in enema or sprays, especially in the care of the skin around the anus. Embodiment of the invention:

Embodiment 1: Use of xanthohumol in the treatment of various stages of the haemorrhoidal disease

The petrolatum ointment, comprising 100 mg of xanthohumol in 30 g of petrolatum, was used in a person who had been subjected to treatment for several years, undergoing consecutive I-III grades of the disease. The progress of the haemorrhoidal disease brought this person to a life-threatening anaemia, which was showed by further medical examinations. Prior to the treatment with the preparation of the present invention, the Barron's method-based treatment was performed in the patient consisting in putting, by means of a special applicator, rubber bands onto the base of a varicose vein (in other words - a haemorrhoid, a pile). The effect of putting of a band is ischemia of a varicose vein, leading to its degeneration and falling away along with the band after a few days. This treatment proved to be ineffective because after one month there occurred a recurrence of the disease. Electrocoagulation (RFA, radiofrequency ablation) was used as a further treatment method. The treatment consisted in applying 60W of electrical power, which damages the tissue at the base of the pile. The electrocoagulation treatment resulted in improvement of the condition for about 6 months. After this time, a recurrence of the haemorrhoidal disease began and the patient was referred to the hospital for surgery.

The white petrolatum-based ointment containing 100 mg of xanthohumol in 30 g of white petrolatum was used for internal rectal application, and for application to lesions twice daily. It was found that already after three days of use, bleeding during defecation completely ceased. Grade III piles, that is the piles prolapsing outside upon pressure and requiring manual reduction, after two weeks of application of the ointment (twice a day) changed into grade II, that is the piles protruding outside upon pressure, but reducing spontaneously, without bleeding. After a month of applying the ointment with xanthohumol, this problem also disappeared. Within two years after the end of the therapy with the ointment according to the invention, only very light bright red spotting occurred. However, a re-use of the ointment of the invention completely eliminated the problem. This example demonstrates the very high effectiveness of the xanthohumol-containing ointment of the invention. In addition, the ointment of the invention was administered to seven individuals with varying grades of disease progression (I to III).

The doses of 50 mg or 100 mg of xanthohumol were used in 30 g of white petrolatum depending on the severity of the disease. Everyone reported a high effectiveness of the ointment.

In summary, xanthohumol used to treat haemorrhoidal diseases or prevent haemorrhoidal diseases shows an excellent therapeutic effect, leading to a gradual reversal of the symptoms of the haemorrhoidal disease until it disappears completely. Xanthohumol can also be used to relieve anal problems (such as e.g. swelling) after medical treatments. Xanthohumol supports the healing of surface inflammatory and dermatological changes associated with the haemorrhoidal disease. It also shows effects of the care of the skin in the anal area.

Embodiment 2: Use of xanthohumol in the advanced haemorrhoidal disease

The ointment containing 100 mg of xanthohumol in 30 g of white petrolatum was used for grade III haemorrhoidal disease by the internal rectal application, and also for lesions twice daily. It was found that after a few days of use, bleeding during defecation completely ceased. Grade III of the piles, after two weeks of application of the ointment (twice a day) turned into grade II. After three weeks of applying the ointment, there was a significant improvement. No deterioration or recurrence of the disease has been reported for five months. In the case of a feeling of pruritus, pain, burning sensation in the anal area, topical use of the ointment of the invention brings relief.

Thus, xanthohumol is effective and causes a gradual reversion of the symptoms of the haemorrhoidal disease to its complete disappearance even in the advanced grade of the haemorrhoidal disease.

Embodiment 3: Use of xanthohumol to prevent symptoms of the haemorrhoidal disease

After administration of the xanthohumol-containing ointment (containing 50 or 100 mg of xanthohumol) and observing its beneficial effect, in some cases it was noted several months later that recurrences of the disease such as bright red drip bleeding appeared. Another use of ointment resulted in improvement.

After the ailments ceased, the prophylactic use of the ointment containing xanthohumol prevented relapse of the disease.

Thus, xanthohumol contained in the ointment prevented the recurrent symptoms of the haemorrhoidal disease and showed a prophylactic effect.

Embodiment 4: Use of xanthohumol in the area around the anus for the skin care purposes in case of external ailments in the anal area associated with gastrointestinal disorders

The application of xanthohumol in the form of an ointment (containing 50 mg of xanthohumol in 30 g of white petrolatum) alleviated the pain, external irritation of the skin around the anus caused by diarrhoea due to an intensive slimming diet.

Therefore, xanthohumol has a regenerating, nourishing, antipruritic and care effect on the skin around the anus, eliminating burning sensation and soreness, resulting in a noticeable improvement and alleviation, especially in the case of irritation of the anus and and the anal area.

Embodiment 5: Use of xanthohumol in the anal area for the skin care purposes

Minimum xantohumol doses were also (applied in the form of the ointment, and also as a xanthohumol-moisturized wet wipe (5 mg of xanthohumol was dissolved in propylene glycol and then a wipe was soaked with it)) to the anal area of the healthy person. The use of even the minimum dose of xanthohumol shows a care effect to the anal area, refreshing, guaranteeing comfort of hygiene during the day of work.

Therefore, applying externally to the anal area of even the minimum dose of xanthohumol refreshes the skin, nourishes it (acting like a cosmetic) and prevents irritation around the anal area.

Claims

1. Xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area and in the care of the skin around the anus.

2. Xanthohumol according to claim 1, characterized in that it is topically applied in the form of an ointment, a wet wipe or a cream or another semi-solid form.

3. Xanthohumol according to claim 1, characterized in that it is topically applied in the form of suppositories, powder or another solid form.

4. Xanthohumol according to claim 1, characterized in that it is topically applied internally, rectally in the form of an ointment, enema or in another liquid, solid or semisolid form, or is topically applied externally to the anal area in the liquid, solid or semisolid form.

5. A composition for use in the treatment, prophylaxis or prevention of the haemorrhoidal disease or other diseases of the anal area, as well as in the skin care around the anus, comprising the active ingredient and at least one physiologically acceptable excipient or any carrier, characterized in that as an active component it comprises xanthohumol or its physiologically acceptable salt or a molecular complex or a metal complex.

6. The composition according to claim 5, characterized in that it is in the semi-solid form such as an ointment, a wet wipe or a cream or in another semi-solid form.

7. The composition according to claim 6, characterized in that as a physiologically acceptable excipient it comprises petrolatum.

8. The composition according to claim 5, characterized in that it is in the solid form such as a suppository, powder or dusting powder, or in another solid form.

9. The composition according to claim 5, characterized in that it is in the liquid form such as a spray, lotion, balsam, foam, fluid or enema, or in another liquid form.

10. The composition according to any one of claims 6 to 9, characterized in that it is applied internally, rectally or topically externally.

11. The composition according to any one of claims 6 to 10, characterized in that it comprises xanthohumol in an amount ranging from 0.001% by weight to 5.0% by weight of xanthohumol in terms of the total weight of the composition.

12. The composition according to claim 11, characterized in that it comprises xanthohumol in an amount ranging from 0.01% by weight to 1.0% by weight of xanthohumol in terms of the total weight of the composition.

13. The composition according to claim 12, characterized in that it comprises xanthohumol in an amount ranging from 0.1% by weight to 0.5% by weight of xanthohumol in terms of the total weight of the composition.

14. The composition according to any one of claims 5 to 13, characterized in that it comprises an additional active agent and/or other additives.