Composition intended for oral administration in a subject, for use in the reduction and / or prevention of pain

Abstract

The present invention relates to a composition for oral administration to a subject, for use in the reduction and / or prevention of pain, particularly abdominopelvic pain, including dysmenorrhea. The composition comprises a combination of herbal preparations: yarrow powder, ginger powder, and concentrated yarrow extract.

Description

Title of the invention: Composition for oral administration in a subject, for use in the reduction and / or prevention of pain Technical field of the invention

[0001] The present invention relates to the technical field of compositions intended for oral administration in a subject, for its use in the reduction and / or prevention of pain, in particular abdominopelvic pain, in particular dysmenorrhea (also known as "painful periods"). State of the art

[0002] The reduction and / or prevention of pain, whether acute or chronic, is a fundamental objective in medicine.

[0003] Various therapeutic approaches are used to relieve pain, including analgesic drugs, anti-inflammatories, physical therapies and psychological approaches.

[0004] However, many patients continue to suffer from insufficiently controlled pain, with a significant impact on their quality of life.

[0005] The search for new effective and well-tolerated therapeutic and preventive solutions for pain management therefore remains a major public health challenge.

[0006] In this regard, abdominopelvic pain, and in particular dysmenorrhea, represents a considerable burden for a large number of women, even from adolescence.

[0007] Recent studies have highlighted the extent and impact of this problem:

[0008] - dysmenorrhea is extremely common: nearly 90% of women of age procreation is affected, and 50% to 90% of adolescent girls;

[0009] - the pain can be intense: 42% of women suffering from dysmenorrhea describe as intense;

[0010] - dysmenorrhea has a significant impact on women's lives: it is the the main cause of school absenteeism among adolescent girls and can lead to a restriction of daily activities;

[0011] - dysmenorrhea is often trivialized and undertreated: 66% of women consider menstrual pain is considered normal and 61% have never consulted a doctor for this reason.

[0012] The state of the art highlights a crucial need for new therapeutic and preventive solutions for pain management.

[0013] These solutions must be:

[0014] - effective: capable of significantly relieving pain, including pain intense;

[0015] - well tolerated: with minimal side effects, for long-term use term if necessary;

[0016] - easy to administer: to promote adherence, particularly among young people girls;

[0017] - adapted to the specific needs of women: taking into account age, the intensity of the pain and any other possible treatments. Presentation of the invention

[0018] In order to remedy the aforementioned drawback of the prior art, the present invention proposes a new composition for oral administration intended for the reduction and / or prevention of pain, in particular abdominopelvic pain, and more particularly dysmenorrhea.

[0019] This composition comprises a specific combination of plant preparations, namely:

[0020] - a powder of yarrow,

[0021] - a ginger powder, and

[0022] - a concentrated extract of yarrow.

[0023] In general, the composition according to the invention offers several advantages:

[0024] - it is effective in reducing abdominopelvic pain, in particular the dysmenorrhea;

[0025] - it is well tolerated and does not present any undesirable side effects;

[0026] - it is easy to administer orally;

[0027] - it is formulated from natural and environmentally friendly ingredients.

[0028] Without being limited by any theory, this biological action is ensured by a synergistic action on the inhibition of COX-2 and 5-LOX, two enzymes involved in inflammation and pain.

[0029] Other non-limiting and advantageous features of the product according to the invention, taken individually or in all technically possible combinations, are as follows:

[0030] - said combination of plant preparations is in powder form impregnated in which said concentrated extract of yarrow is impregnated and dried on said yarrow powder and / or said ginger powder;

[0031] - said combination of plant preparations is in powder form impregnated material having the following particle size characteristics: a size less than or equal to 50 µm representing a maximum of 25% by weight, a size less than or equal to 100 µm representing a maximum of 65% by weight, and a size less than, or equal to, 500 pm representing at least 80%, by weight; preferably, said impregnated powder has an apparent density ranging from 0.3 to 0.8 g / cm3, and a packed density ranging from 0.4 to 0.9 g / cm3;

[0032] - said concentrated extract of yarrow consists of an aqueous extract and / or hydroalcoholic ;

[0033] - said ginger powder is derived from ginger roots;

[0034] - said composition causes a decrease in COX-2 / 5-LOX activity;

[0035] - said composition is in the form of tablets.

[0036] The present invention further relates to a manufacturing process for the production of a composition according to the invention, comprising:

[0037] - an impregnation step, during which said extract of yarrow is impregnated with said ginger powder and / or said yarrow powder, and

[0038] - a drying step, during which said at least one impregnated powder is dried.

[0039] According to a particular embodiment, said manufacturing process includes a micronization step of said yarrow powder and said ginger powder, the parameters of which are adjusted to obtain an impregnated powder having, after said drying step, the following particle size characteristics:

[0040] - a size less than or equal to 50 pm representing a maximum of 25% by weight,

[0041] - a size less than or equal to 100 pm representing a maximum of 65%, by weight, And

[0042] - a size less than, or equal to, 500pm representing at least 90%, by weight.

[0043] Of course, the various features, variants, and embodiments of the invention can be combined in various ways, provided they are not incompatible or mutually exclusive. Detailed description of the invention

[0044] In addition, various other features of the invention emerge from the attached description which illustrate non-limiting forms of embodiment of the invention.

[0045] The present invention thus relates to a composition intended for oral administration in a subject, for its use in the reduction and / or prevention of pain, in particular abdominopelvic pain, in particular dysmenorrhea (also known as painful periods).

[0046] By "composition" advantageously means a mixture or combination of different constituents, in particular active ingredients derived from plant preparations, and possibly excipients, formulated for the administration of the product.

[0047] By "oral route", advantageously means a route of administration of a composition which involves the ingestion of the composition by the mouth, thus allowing its absorption by the digestive system.

[0048] By "subjects" is meant in particular a human subject suffering from pain, in particular chronic or acute pain.

[0049] Human subjects may also include healthy individuals wishing to reduce or prevent pain, including women or adolescent girls seeking to prevent or reduce abdominopelvic pain, such as dysmenorrhea.

[0050] The term "reduce pain" refers to use to reduce, relieve or eliminate pain.

[0051] The term "pain prevention" refers to use to prevent or reduce pain before it occurs.

[0052] Generally, and according to the invention, this composition comprises a combination of plant preparations:

[0053] - a powder of yarrow,

[0054] - a ginger powder, and

[0055] - a concentrated extract of yarrow.

[0056] Preferably, the present composition comprises the following preparations, expressed as a mass percentage relative to the total mass of the composition:

[0057] - an extract and / or powder of yarrow representing between 40 and 50% of the total mixture, and

[0058] - a ginger powder present at a level of 50 to 60%.

[0059] Preferably, the extraction ratio for Yarrow is at least 2.2 to 3 to 1. For Ginger, the extraction ratio is at least 0.5 to 0.8 to 1, preferably.

[0060] Generally speaking, the term "plant preparation" advantageously encompasses preparations obtained from plant raw materials, particularly by reducing them to powder and / or by processing them through extraction, distillation, expression, fractionation, purification, concentration, or fermentation. Yarrow preparation

[0061] Yarrow, scientifically known as Achillea millefolium L., is a perennial herbaceous plant belonging to the Asteraceae family.

[0062] As discussed above, the composition according to the invention comprises two different preparations of yarrow:

[0063] - a powder of yarrow,

[0064] - a concentrated extract of yarrow.

[0065] Preferably, yarrow powder and concentrated yarrow extract are derived from flowering tops.

[0066] Preferably, "flowering tops" refers to the upper parts of a plant, including the flowers and associated stems.

[0067] By "concentrated extract of yarrow", advantageously means a fraction obtained by extraction from a plant material and then by concentration of said extracted fraction.

[0068] The concentration of the compounds of interest that are present in the concentrated plant extract is greater than the concentration of the compounds of interest that are present in the original plant material.

[0069] For this purpose, the concentrated plant extract is obtained from an extraction operation from a plant material followed by a concentration operation of said plant extract.

[0070] Such extraction / concentration operations are described for example in document EP-2 080 436 or in document EP-4 159 198.

[0071] Such an extraction operation advantageously comprises the following steps:

[0072] - a contact step between the plant material of interest and a solvent,

[0073] - at least one extraction step, proper, for the extraction of at least one part of the active principles present in said plant material of interest (by migration in the solvent).

[0074] The concentration operation then advantageously consists of concentrating the active ingredients by eliminating at least part of the extraction solvent.

[0075] The concentration is advantageously by a concentration factor of at least 5, preferably by a concentration factor of 8 to 15.

[0076] Preferably, the concentrated extract of yarrow consists of an aqueous and / or hydro-alcoholic extract (preferably an aqueous extract).

[0077] More generally, different extraction processes are suitable for obtaining the concentrated extract of yarrow according to the invention.

[0078] According to one embodiment, the extraction process consists of a process for preparing a plant preparation from plant material, comprising:

[0079] - a contact step between the plant material and a solvent,

[0080] - at least one liquid-phase extraction step of the active ingredients, carried out under heating and under reduced pressure, to obtain an extraction fraction containing said active ingredients and residual plant matter, and

[0081] - a drying step of said residual plant material in the presence of said extraction fraction, in order to allow the fixation of the active ingredients on said residual plant matter.

[0082] Such a process is, for example, further described in document EP-2 080 436. Preparation of ginger

[0083] Ginger powder is advantageously derived from ginger roots.

[0084] By "ginger", we advantageously mean Zingiber officinale Roscoe, a perennial herbaceous plant of the Zingiberaceae family.

[0085] By "ginger root", advantageously means the ginger rhizome, that is to say the horizontal underground stem of the plant, which is the part used in traditional medicine and food. Impregnated powder

[0086] According to a preferred embodiment, the combination of plant preparations is in the form of an impregnated powder in which the concentrated extract of yarrow is impregnated and dried on yarrow powder and / or ginger powder.

[0087] In other words, the concentrated extract of yarrow is impregnated and dried on:

[0088] - yarrow powder, or

[0089] - ginger powder, or

[0090] - the mixture of yarrow powder and ginger powder.

[0091] More generally, the impregnated powder according to the invention advantageously comprises:

[0092] - a ginger powder,

[0093] - a preparation of yarrow, in the form of a powder and in the form of a concentrated extract.

[0094] By "impregnated and dried" advantageously means a process in which the concentrated extract of yarrow is deposited on yarrow powder and / or ginger powder so as to penetrate the porous structure of the powder, and then dried to remove the solvent and obtain a stable and homogeneous impregnated powder.

[0095] Impregnation can be achieved by various processes, such as spraying, mixing or coating.

[0096] Drying can be carried out by various means, such as hot air drying, vacuum drying or freeze-drying.

[0097] The choice of the impregnation and drying process will depend in particular on the nature of the concentrated extract, the characteristics of the powders and the desired properties for the final impregnated powder.

[0098] Generally speaking, the combination of plant preparations is advantageously in the form of an impregnated powder having the following particle size characteristics:

[0099] - a size less than or equal to 50 pm representing a maximum of 25% by weight,

[0100] - a size less than or equal to 100 pm representing a maximum of 65% by weight, And

[0101] - a size less than, or equal to, 500pm representing at least 80%, by weight.

[0102] In a conventional manner, the particle size characteristics are advantageously derived from a particle size analysis technique by sieving.

[0103] The mass percentage in question advantageously represents the part of the impregnated powder which remains on the sieve, also called "refuse" or "refuse by sieve".

[0104] Such values ​​can be measured according to a protocol described for example in the following document: European Pharmacopoeia 9.0, "2.9.38. Particle size distribution by analytical sieving" or European Pharmacopoeia 9.0, "2.9.35. Fineness of powders".

[0105] Preferably, the impregnated powder has:

[0106] - an apparent density ranging from 0.3 to 0.8 g / cm3, and

[0107] - a packed density ranging from 0.4 to 0.9 g / cm3.

[0108] The apparent density and the packed density are advantageously obtained by the process described in European Pharmacopoeia document 9.7, "2.9.34. Bulk density and density after packing".

[0109] The characteristics of an impregnated powder are described for example in document EP-4 159 198.

[0110] In general, according to the invention, the micronization step is advantageously carried out on the plant support:

[0111] - prior to the impregnation step, so as to adjust the characteristics particle size distribution of the plant support before the impregnation stage, and / or

[0112] - between the impregnation step and the drying step, so as to adjust the particle size characteristics of the impregnated, undried plant support, and / or

[0113] - after the drying stage, so as to adjust the characteristics particle size of the impregnated and dried plant support.

[0114] In general, a process for manufacturing an impregnated powder, as well as the characteristic parameters of a powder, are described for example in document EP-4 159 198.

[0115] Preferably, the dosage is 1200 to 1500 mg of the herbal preparation divided into 1 to 5 doses per day (ideally, one dose every 8 hours or so). This treatment regimen is advantageously followed for at least the first 2 to 3 days of menstruation, or during the 1 to 5 full days of menstruation, and this over a minimum period of 2 to 5 consecutive cycles.

[0116] Preferably, the daily dosage comprises 500 to 1000 mg of ginger preparation and 500 to 1000 mg of yarrow preparation, with a ratio of 4 to 6:1 for the yarrow powder / yarrow concentrate extract combination. This composition is equivalent to 2500 to 3500 mg of plant equivalent per day. Phytochemical composition

[0117] According to one embodiment, the composition according to the invention advantageously comprises the following molecules (based on an LC-MS analysis): glucose, sucrose, citric acid, chlorogenic acid, caffeic acid, luteolin-7-o-glucoside, zingiberoside C, luteolin-4-o-glucoside + apigenin-7-o-glucoside, C20H24O6, luteolin, apigenin, C23H28O8, 6-gingerdonin, 6-gingerol.

[0118] Preferably, the composition comprises the following terpenes: 6-shogaol, 10-gingerol, 8-gingerol and 6-gingerol. Decreased COX-2 / 5-LOX activity

[0119] According to a preferred embodiment, the composition causes a decrease in COX-2 / 5-LOX activity.

[0120] In general, COX-2 / 5-LOX activity can be measured using specific enzyme assay kits, such as those marketed by Cayman Chemical.

[0121] Generally, for COX-2 activity, the assay involves, for example, the conversion of arachidonic acid to PGF2, the production of which is quantified by a coupled reaction producing a measurable signal (colorimetric or fluorimetric). The addition of potential inhibitory compounds allows their effect on reducing PGF2 production to be evaluated, thus revealing their ability to inhibit the enzyme and their anti-inflammatory potential.

[0122] For 5-LOX activity, the assay preferably measures the inhibition of the 5-lipoxygenase enzyme by quantifying the production of lipid peroxides formed during the conversion of arachidonic acid to leukotrienes. This method is based on colorimetric detection, which allows for the evaluation of the effectiveness of inhibitors in reducing 5-LOX activity.

[0123] The reduction in activity is preferably at least 30%, without being limiting.

[0124] These two enzymes, cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), play a key role in the inflammatory cascade and the production of pain mediators, including prostaglandins and leukotrienes.

[0125] By inhibiting the activity of COX-2 and 5-LOX, the composition according to the invention makes it possible to reduce the production of these inflammatory mediators and of to effectively relieve pain, including abdominopelvic pain and dysmenorrhea.

[0126] As demonstrated in the examples, the combination of the different components of the composition, namely yarrow powder, ginger powder and concentrated yarrow extract, makes it possible to obtain a synergistic action on the inhibition of COX-2 and 5-LOX. Galenic

[0127] In an advantageous and non-limiting embodiment, the composition according to the invention is in the form of tablets, film-coated or not, preferably to be swallowed.

[0128] The term “tablet” advantageously means the solid pharmaceutical form obtained by compressing a powder or granule containing one or more active substances and excipients.

[0129] This pharmaceutical form offers several advantages for the administration of the composition: ease of administration, protection of the active ingredients, improved stability and controlled release.

[0130] The tablets can be obtained by standard manufacturing techniques, using excipients commonly used in the pharmaceutical or non-pharmaceutical industry, such as binding agents, diluents, lubricants and film-coating agents.

[0131] More generally, the composition according to the invention advantageously contains a combination of ingredients suitable for use in the pharmaceutical, cosmetic, food, nutrition (including food for special medical purposes - FSMP), food supplement, and animal nutrition industries.

[0132] The composition according to the invention advantageously comprises:

[0133] - a composition according to the invention, for use in human subjects, suitable for the treatment and / or prevention of pain, and

[0134] - at least one support or excipient, acceptable depending on the use for example, baobab fruit pulp and / or maltodextrin are being considered.

[0135] The composition of the present invention can be prepared in the form of a composition, which can be a formulation such as tablets, capsules, softgels, powders, granules, solutions, lozenges, jellies, cream preparations, syrups, suspensions, tinctures, aerosols and others.

[0136] The composition of the present invention can also be prepared in the form of a non-pharmaceutical composition.

[0137] Non-pharmaceutical composition includes cosmetic compositions, food compositions, nutritional compositions, and food supplements.

[0138] The non-pharmaceutical composition can be prepared by generally known preparation techniques, and acceptable additives can be added to the non-pharmaceutical composition.

[0139] For example, the non-pharmaceutical composition according to the invention advantageously consists of a food supplement.

[0140] The term “food supplement” advantageously means food supplements which are subject to all the general provisions of food law but also to the specific rules defined by Directive 2002 / 46 / EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements, transposed into French law by Decree No. 2006-352.

[0141] The term “food supplements” advantageously includes foodstuffs whose purpose is to supplement the normal diet and which constitute a concentrated source of nutrients or other substances having a nutritional or physiological effect, alone or in combination, marketed in dose form, namely presentation forms such as liquid ampoules, bottles with a dropper and other similar forms of liquid preparations.

[0142] In general, the composition may also contain probiotic strain, which in particular includes live microorganisms which, when ingested in sufficient quantities, exert positive effects on health, beyond traditional nutritional effects.

[0143] The probiotic strain suitable for the invention is physiologically acceptable. In other words, this probiotic strain can be administered safely to animals or humans.

[0144] Probiotic strains include in particular the genera lactobacilli (bacteria of the genus Lactobacillus), bifidobacteria (bacteria of the genus Bifidobacterium), streptococci (bacteria of the genus Streptococcus) or lactococci.

[0145] Again in general, specific examples of probiotic microorganisms are Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, Lactobacillus acidophilus, Lactobacillus amylovorus, Lactobacillus casei (Shirota), Lactobacillus rhamnosus (GG strain), Lactobacillus brevis, Lactobacillus crispatus, Lactobacillus delbrueckii (subsp bulgaricus, lactis), Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus gallinarum, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus alimentarius, Lactobacillus curvatus, Lactobacillus casei subsp. casei, Lactobacillus sake Lactococcus lactis, Enterococcus (faecalis, faecium), Lactococcus lactis (subspp lactis or cremoris), Leuconstoc mesenteroid.es subsp dextranicum, Pediococcus acidilactici, Sporolactobacillus inulinus, Streptococcus salvarius subsp. Thermophilus, Streptococcus thermophilus, Staphylococccus camosus, Staphylococcus xylosus, Saccharomyces (cerevisiae or boulardii), Bacillus (cereus var toyo or subtilis), Bacillus coagulons, Bacillus licheniformis, Escherichia coli strain nissle, Propionibacterium freudenreichii and their mixtures.

[0146] More specifically, these are probiotic microorganisms from the group of lactic acid bacteria, such as Lactobacillus and / or Bifidobacterium. Examples of these lactic acid bacteria include Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus casei or Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium adolescentis or Bifidobacterium pseudocatenulatum and mixtures thereof.

[0147] Generally, said at least one probiotic strain is advantageously chosen from live probiotic strains or inactivated probiotic strains.

[0148] By “living” form, we mean a form with the ability to multiply provided that it is placed in an environment conducive to the recovery of this ability.

[0149] Thus, for the purposes of the present invention, the term living covers the so-called dormant state in which microorganisms can be placed following a physicochemical treatment such as, for example, freeze-drying.

[0150] In general, the probiotic strain is advantageously implemented in a lyophilized form.

[0151] This type of formulation has the advantages of being readily available, easy to implement, and not raising any difficulties or constraints in terms of storage. Furthermore, it is compatible with the packaging of microorganisms in a dormant state.

[0152] This freeze-drying can be carried out according to conventional methods or according to a method described for example in document FR-3 103 827.

[0153] Furthermore, the term "inactivated" refers to strains that have undergone treatment intended to kill them. Such treatments may consist, by way of non-limiting example, of autoclaving, ultrasonic treatment, high-pressure homogenization, or osmotic shock.

[0154] Inactivated strains are advantageously intact.

[0155] The probiotic strain is advantageously inactivated by heat, also called the "tyndallized probiotic strain".

[0156] The composition may also contain postbiotics, corresponding to preparations of microorganisms, advantageously chosen from the aforementioned probiotic strains, inanimate and / or their components conferring a benefit to the health of the host.

[0157] The composition may still contain other types of ingredients, for example vitamins, minerals or any other nutritional ingredient.

[0158] In particular, the composition may contain nutraceutical ingredients such as vitamin C, glucosamine, chondroitin, palmitoylethanolamide or fatty acids. Non-therapeutic use

[0159] The present invention further encompasses a non-therapeutic use of a composition according to the invention, for its use in human subjects, in the treatment and / or prevention of pain.

[0160] Such non-therapeutic use thus extends to the use of this composition in human subjects outside of a therapeutic context, that is to say independently of the treatment of a pathology.

[0161] The composition according to the invention is indeed suitable for preventing the onset of pain related to various situations such as physiological events (painful periods, etc.).

[0162] Thus, the composition according to the invention can be used preventively by healthy subjects wishing to anticipate and limit the onset of pain in these situations.

[0163] For example, women prone to dysmenorrhea could take the composition before their period to alleviate any pain.

[0164] This non-therapeutic use offers a natural and preventive alternative to conventional treatments, allowing for a reduction in drug consumption and an improvement in the general well-being of individuals. Pain reduction and / or prevention

[0165] By "pain" we mean in particular abdominopelvic pain, especially dysmenorrhea.

[0166] Abdominopelvic pain is pain located in the pelvic and abdominal region, which can have various origins, including gynecological, digestive, urological or musculoskeletal.

[0167] Dysmenorrhea, on the other hand, refers to menstrual pain that occurs before or during menstruation. It is often described as cramps or spasmodic pains in the lower abdomen, and may be accompanied by other symptoms such as nausea, vomiting, headaches or fatigue.

[0168] Generally speaking, by "reduction and / or prevention of pain", the present invention includes a decrease in its intensity and / or duration.

[0169] By "intensity" of pain, we include pain measured by tools to characterize and evaluate it.

[0170] In general, questionnaires and pain scales make it possible to describe the manifestations, and to measure the intensity as well as the impact on quality of life.

[0171] For adults, the most commonly used scale is the numerical or visual analog scale, graduated from 0 for no pain, to 10 for the maximum imaginable pain.

[0172] In general, the present invention encompasses a decrease in the intensity and / or duration of pain measured in a subject receiving the composition according to the invention compared to the intensity and / or duration of pain measured in a subject not receiving the composition according to the invention.

[0173] Pain includes, in particular:

[0174] - mild pain,

[0175] - moderate pain, and

[0176] - severe pain.

[0177] Mild pain is pain of low intensity that can be easily tolerated by the subject and does not or only slightly affect their daily activity.

[0178] Moderate pain is more intense and can affect the subject's daily life, for example by limiting their movements or their ability to work.

[0179] Severe pain is the most intense pain, which can be disabling and prevent the subject from leading a normal life. Manufacturing process

[0180] The invention also relates to a manufacturing process for the composition described above.

[0181] This process comprises the following steps:

[0182] - an impregnation step

[0183] During this step, the concentrated yarrow extract is impregnated onto ginger powder and / or yarrow powder. Impregnation can be carried out by various processes, such as spraying, kneading, or coating, to obtain a homogeneous distribution of the extract on the powder. This process notably promotes the stability and bioavailability of the active ingredients in the final composition.

[0184] - a drying step

[0185] After impregnation, the impregnated powder is dried to remove the solvent (water and / or alcohol) used for extraction. Drying can be carried out by various means, such as hot air drying, vacuum drying, or freeze-drying. The drying parameters are optimized to preserve the integrity of the active ingredients and obtain a dry and stable powder.

[0186] According to a preferred embodiment, the manufacturing process includes a micronization step of said yarrow powder and said ginger powder, the parameters of which are adjusted to obtain an impregnated powder having, after said drying step, the following particle size characteristics:

[0187] - a size less than or equal to 50 pm representing a maximum of 25% by weight,

[0188] - a size less than or equal to 100 pm representing a maximum of 65%, by weight, And

[0189] - a size less than, or equal to, 500pm representing at least 80%, by weight.

[0190] By "micronization" is advantageously understood the operation having as its object the reduction of the plant support into particles having dimensions on the order of a micrometer (or micron).

[0191] The parameterization of the micronization step, which is classic in itself, depends in particular on the technology used (for example by means of a micronizer or a grinder) and on the order of the steps in the manufacturing process.

[0192] Such a micronization step is described for example in the following general document: Powder Technology Handbook, Fourth Edition, Higashitani et al. It is also possible to refer to document EP-4 159 198.

[0193] Of course, various other modifications can be made to the invention within the scope of the annexed claims. Examples

[0194] Different methods of preparing the two plants, and different ways of combining them, have been tested.

[0195] We were able to demonstrate a synergistic effect on the inhibition of COX-2 and 5-LOX enzymes with these two plants when prepared jointly. Tested preparations

[0196] - Aqueous extract of Yarrow 4:1

[0197] - Aqueous extract of dried yarrow 4:1 on ginger powder + yarrow powder

[0198] - Ginger powder

[0199] - Ginger extract (extract 3.5:1)

[0200] - Aqueous extract of yarrow 4:1 + ginger extract 3.5:1. Experimental approach

[0201] An experimental in tubo approach based on the measurement of cyclooxygenase-2 (COX-2) activity and 5-lipooxygenase (5-LOX) activity, in the absence and presence of the different test elements, has been proposed.

[0202] The COX activity of the enzyme was evaluated by measuring the level of prostaglandin PGF2a formed after incubation of the enzyme with arachidonic acid.

[0203] The LOX activity of the enzyme was evaluated by measuring the rate of hydroperoxides formed after incubation of the enzyme with linoleic acid. Results

[0204] The results are illustrated through the tables below, respectively, for the inhibition of cyclooxygenase-2 (COX-2) in Table 1 and of 5-lipooxygenase (5-LOX) in Table 2.

[0205] [Tables 1] COX-2 Inhibition % Yarrow Extract (0.649 pg / ml) 9 Ginger Powder (1.1 pg / ml) -2 Ginger Extract 3.5:1 (0.185 pg / ml) 4 Yarrow Extract (0.649 pg / ml) + Ginger Extract 3.5:1 (0.185 pg / ml) 27 Aqueous Extract of Dried Yarrow on Ginger Powder + Yarrow Powder (1.749 pg / ml) 57

[0206] [Tables2] %Inhibition 5-LOX Yarrow Extract (1298 pg / ml) 2 Ginger Powder (2200 pg / ml) 43 Ginger Extract 3.5:1 (370 pg / ml) -10 Yarrow Extract (1298 pg / ml) + Ginger Extract 3.5:1 (370 pg / ml) 8 Aqueous Extract of Dried Yarrow on Ginger Powder + Yarrow Powder (3498 pg / ml) 60

[0207] The results illustrate that, at equal quantities of yarrow extract, the association with ginger is more advantageous in the preparation of aqueous yarrow extract 4:1 dried on ginger powder + yarrow powder, to achieve interesting inhibition values ​​of COX-2 and 5-LOX activities (inhibition of at least 30%).

[0208] This method of preparation gives rise to a synergistic effect between the plant preparations. Conclusion

[0209] These data demonstrate that combining plants together makes it possible to develop a plant preparation with combined COX-2 / 5-LOX action.

[0210] The method of preparing these plants may reveal a synergistic action between the plants involved.

[0211] Such a composition, intended for oral administration in a subject, would thus be suitable for use in the reduction and / or prevention of pain, in particular abdominopelvic pain, in particular dysmenorrhea,

Claims

Demands

1. Composition intended for oral administration in a subject, for its use in the reduction and / or prevention of pain, in particular abdominopelvic pain, in particular dysmenorrhea, which composition comprises a combination of herbal preparations: - a powder of Yarrow, - a powder of ginger, and - a concentrated extract of Yarrow.

2. Composition according to claim 1, wherein said combination of plant preparations is in the form of an impregnated powder in which said concentrated extract of yarrow is impregnated and dried on said yarrow powder and / or said ginger powder.

3. Composition according to any one of claims 1 or 2, wherein said combination of plant preparations is in the form of an impregnated powder having the following particle size characteristics: - a size less than, or equal to, 50 pm representing a maximum of 25%, by weight, - a size less than, or equal to, 100 pm representing a maximum of 65%, by weight, and - a size less than, or equal to, 500 pm representing a minimum of 80%, by weight.

4. Composition according to claim 3, wherein said impregnated powder has: - an apparent density ranging from 0.3 to 0.8 g / cm3, and - a packed density ranging from 0.4 to 0.9 g / cm3.

5. Composition according to any one of claims 1 to 4, wherein said yarrow powder and said concentrated yarrow extract are derived from the flowering tops.

6. Composition according to any one of claims 1 to 5, wherein said concentrated extract of yarrow consists of an aqueous and / or hydro-alcoholic extract.

7. Composition according to any one of claims 1 to 6, wherein said ginger powder is derived from ginger roots.

8. A manufacturing process for the manufacture of a composition according to any one of claims 1 to 7, comprising: - an impregnation step, during which said yarrow extract is impregnated onto said ginger powder and / or said yarrow powder, and - a drying step, during which said at least one impregnated powder is dried.

9. A process according to claim 8, characterized in that said manufacturing process comprises a micronization step of said yarrow powder and said ginger powder, the parameters of which are adjusted to obtain an impregnated powder having, after said drying step, the following particle size characteristics: - a size less than, or equal to, 50 pm representing a maximum of 25%, by weight, - a size less than, or equal to, 100 pm representing a maximum of 65%, by weight, and - a size less than, or equal to, 500 pm representing a minimum of 80%, by weight.