Mangostin solid forms

Abstract

The present invention refers to new mangostin solid form prepared from mangostin and a coformer for their use in therapeutic and non-therapeutic applications.

Description

[0001] MANGOSTIN SOLID FORMS

[0002] TECHNICAL FIELD OF THE INVENTION

[0003] The present invention refers to new mangostin solid forms, their preparation and their use in therapeutic or non-therapeutic applications, such as medical prevention and treatment applications, cosmetic applications, dietary supplements, animal nutrition, functional food and others.

[0004] BACKGROUND

[0005] Mangostin is a natural compound found in various parts of the mangosteen tree (Garcinia mangostana) and has a prenylated xanthone structure. Mangostin may occur in the form of different derivatives, such as alpha-mangostin (aMG), beta-mangostin (bMG) or gamma- mangostin (gMG). Even glucoside derivatives thereof are known.

[0006] Among those, the alpha-mangostin is the major derivative found in the fruit hull of mangosteen. Alpha-mangostin, as well as its derivatives, may be obtained from the plant source by extraction.

[0007] Mangostin shows interesting pharmacological activities that might be useful in either non- therapeutical cosmetic applications or in therapeutic medical applications. For example, it has been reported that mangostin has antioxidant, anti-bacterial, anti-inflammatory or anticancer activities. However, mangostin is a hydrophobic molecule and thus almost insoluble in water, making any applications in aqueous systems or for oral administration complicated. Further, the poor solubility in water also affects the bioavailability of mangostin, which is detrimental to therapeutic applications.

[0008] The prior art has been tried to overcome those problems, for example, by encapsulating mangostin in poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles (Verma et al. in “a- Mangostin-encapsulated PLGA nanoparticles inhibit pancreatic carcinogenesis by targeting cancer stem cells in human, and transgenic (KrasG12D, and KrasG12D / tp53R270H) mice”, Sci Rep. 2016 Sep 14;6:32743), dispersing mangostin in vegetable oil in soft capsules (Zhao et al. in “A Method of Effectively Improved a-Mangostin Bioavailability”, Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):605-13), or by providing new mangostin derivatives modifying chemical groups in mangostin or introducing new chemical groups (Chi et al. in “Design, synthesis and structure-activity relationships of mangostin analogs as cytotoxic agents”, RSC Adv. 2018 Dec 12;8(72):41377-41388). However, these are complicated approaches that require either complex technology or further chemical transformations. Hence, there is a need to provide a simple form of improving mangostin’s water-solubility and making thus mangostin suitable for exploiting the full potential of the cosmetic or therapeutic applications.

[0009] SUMMARY OF THE INVENTION

[0010] The present invention overcomes the prior art limitations by providing new mangostin solid forms that are simple to obtain, while at the same time showing enhanced solubility in water. Moreover, these new mangostin solid forms can be readily used in therapeutic as well as in non-therapeutic applications.

[0011] In one aspect of the invention, a new mangostin solid form is provided comprising mangostin and a coformer, preferably wherein the coformer is an organic base, such as an amine.

[0012] In a preferred embodiment, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4-diazabicyclo[2.2.2]octane, 1 -octylamine, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13-tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, 1-hexylamine, or caffeine. In a more preferred embodiment, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4-diazabicyclo[2.2.2]octane, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13-tridecanediamine, cyclopentylamine, 3- dimethylamine-1-propylamine, or 1-hexylamine. In a still more preferred embodiment, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, or piperidine. And in an even more preferred embodiment, the amine is selected from the group of ethylenediamine, or pyrrolidine.

[0013] In an alternative embodiment, the molar ratio of mangostin:amine is from 1 :0.3 to 1 :5, preferably from 1 :1 to 1 :5.

[0014] In another preferred embodiment, the mangostin solid form is a crystalline solid form or an amorphous solid form. Preferably, the mangostin solid form is a crystalline solid form.

[0015] In another preferred embodiment, the mangostin is selected from the group consisting of alpha-mangostin, beta-mangostin or gamma-mangostin. In a more preferred embodiment, the mangostin is alpha-mangostin.

[0016] In another preferred embodiment, the mangostin solid form is a crystalline alpha-mangostin ethylenediamine showing an X-ray powder diffraction pattern, measured using a CuKa radiation, that comprises at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 7.6°, 8.5°, 9.7°, 10.3°, 12.8°, 19.9°, 20.5°, 21.8°, 22.9°, or 26.1°. In a preferred embodiment, said crystalline alpha-mangostin ethylenediamine solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.1°, 8.5°, 8.9°, 9.7°, 10.3°, 15.8°, 16.1°, 18.3°, 19.6°, 19.9°, 20.5°, 21.0°, 21.5°, 22.8°, 22.9°, 25.8°, and 26.8°

[0017] In another preferred embodiment, the mangostin solid form is a crystalline alpha-mangostin pyrrolidine solid form showing an X-ray powder diffraction pattern, measured using a CuKa radiation, that comprises at least 5 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.0°, 15.3, 18.3°, 20.2°, 20.7°, 22.2°, 23.2°, or 24.6°. In a preferred embodiment, said crystalline alpha-mangostin pyrrolidine solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.9°, 11.0°, 11.9°, 13.1°, 13.6°, 14.4°, 15.3, 16.1°, 17.4°, 18.3°, 20.2°, 20.7°, 21.6°, 22.2°, 23.2°, 24.6 and 26.6°

[0018] In another aspect of the invention, a composition comprising a mangostin solid form as described above is provided. Preferably, the composition is selected form the group consisting of pharmaceutical compositions, non-therapeutic compositions, cosmetic compositions, dietary supplement compositions, functional food compositions, animal nutrition compositions, or medical food compositions. In a preferred embodiment, these compositions are in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, gummies, nutritional bars, aerosol, spray, topical solutions, transdermal patch, biscuits, snacks, powder for reconstitution, paste or ointment.

[0019] In another aspect of the invention, a process for the manufacture of a mangostin solid form as described above is provided, the process comprising the steps of:

[0020] (i) providing a mixture of mangostin and a coformer, wherein the coformer is an organic base;

[0021] (ii) crystallising the mangostin solid form; and

[0022] (iii) isolating the mangostin solid form.

[0023] In still another aspect of the invention, the mangostin solid form, preferably comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine is for the use as a medicament. In a preferred embodiment, said mangostin solid forms comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine are for use as an antimicrobial agent, an antiviral agent, an antiparasitic agent, an antimycotic agent, an anti-inflammatory agent or an anticancer agent, in a subject selected form the group consisting of humans or animals.

[0024] In a more preferred embodiment, the mangostin solid forms comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine are for use in the prevention or the treatment of periodontal or skin diseases; or for use in the treatment of microbial infections, optionally in combination with an antibiotic compound.

[0025] In still another aspect of the invention, the mangostin solid form comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine is for use in non-therapeutic applications. In a preferred embodiment, the mangostin solid form comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine is for use in a cosmetic antioxidant product, in a cosmetic antiaging product, in a cosmetic antiseptic product, or in a cosmetic antiallergic product.

[0026] In still another aspect of the invention, the mangostin solid form comprising ethylenediamine, pyrrolidine, trimethylamine or piperidine is for use in functional food, medical food, dietary supplements or animal nutrition.

[0027] FIGURES

[0028] Fig. 1 illustrates the standard line for determining the molar extinction coefficient of alpha- mangostin, necessary to determine the solubility of different mangostin solid forms.

[0029] Fig. 2 illustrates the solubility of different mangostin amine solid forms, compared to alpha- mangostin alone.

[0030] Fig. 3 illustrates the cytotoxic effect of alpha-mangostin ethylenediamine solid form aMG-XXV- 1 compared to alpha-mangostin dissolved in DMSO. Results are expressed as % compared to the C- set to 0 % cytotoxicity and C+ set as 100% of cell death. Data represent the mean ± SEM (n=9). Results were statistically compared by Student t-test: *p<0.05 Treatment vs. C+; $ p<0.05 Treatment vs. C-.

[0031] Fig. 4 shows the RXPD patterns for new solid forms aMG-XXXVII-1 , aMG-XXXVII-2, aMG- XXXV-1 , and aMG-XXXV-2 in a stacked representation.

[0032] Fig. 5 shows the RXPD patterns for new solid forms aMG-XXV-1 , aMG-XXV-2, aMG-XXV-3, aMG-XXV-4, aMG-XXV-5, and aMG-XXV-5.1 in a stacked representation.

[0033] Fig. 6 shows the RXPD patterns for new solid forms aMG-XXXIX-1 , aMG-XLII-2, aMG-LXI-1 , and aMG-LXI-3 in a stacked representation.

[0034] Fig. 7 shows the XRPD pattern of an alpha-mangostin triethylamine solid form having a stoichiometric ratio of aMG:triethylamine in the crystal structure of 1 :1.

[0035] Fig. 8 shows the XRPD pattern of an alpha-mangostin triethylamine solid form having a stoichiometric ratio of aMG:triethylamine in the crystal structure of 1 :1. Fig. 9 shows a XRPD pattern of an alpha-mangostin 4,7,10-Trioxa-1 ,13-tridecanediamine solid form having a stoichiometric ratio in the crystal structure of 1 :1.

[0036] Fig. 10 shows a XRPD pattern of an alpha-mangostin 3-dimethylamine-1 -propylamine solid form having a stoichiometric ratio in the crystal structure of 1 :1.

[0037] Fig. 11 shows a XRPD pattern of an alpha-mangostin hexylamine solid form having a stoichiometric ratio in the crystal structure of 1 :1 .

[0038] Fig. 12 shows a XRPD pattern of an alpha-mangostin cyclopentylamine solid form having a stoichiometric ratio of aMG:cyclopentylamine in the crystal structure of 1 :1 .

[0039] Fig. 13 shows a XRPD pattern of an alpha-mangostin diethylentriamine solid form having a stoichiometric ratio in the crystal structure of 3:2.

[0040] Fig. 14 shows a XRPD pattern of a gamma-mangostin pyrrolidine solid form having a stoichiometric ratio in the crystal structure of 1 :2.

[0041] Fig. 15 shows a XRPD pattern of a gamma-mangostin triethylenamine solid form having a stoichiometric ratio in the crystal structure of 1 :1 .

[0042] DETAILED DESCRIPTION OF THE INVENTION

[0043] As used herein, the singular forms “a”, “an”, and “the” include plural references unless the context clearly indicates otherwise. Further, unless otherwise indicated, the term “at least” preceding a series of elements is to be understood to refer to every element in the series.

[0044] The term “about” when referring to a given amount, quantity or value indicates that a number can vary between ± 20% around its indicated value. Preferably, “about” means ± 10% around its indicated value, more preferably "about" means ± 10, 8, 6, 5, 4, 3, 2 % around its value, or even "about" means ± 1 % around its value, in that order of preference. In the case of the XRPD peaks, every peak, independently if one or two decimals are indicated, may vary by ± 0.2° as indicated throughout the specification.

[0045] As used herein, the conjunctive term "and / or" between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by "and / or", a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term "and / or" as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term "and / or."

[0046] Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step. When used herein, the term "comprising" can be substituted with the term "containing" or "including" or sometimes when used herein with the term "having". Any of the aforementioned terms (comprising, containing, including, having), whenever used herein in the context of an aspect or embodiment of the present invention may be substituted with the term "consisting of", though less preferred.

[0047] When used herein, "consisting of" excludes any element, step, or ingredient not specified in the claim element. When used herein, "consisting essentially of” does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claim.

[0048] Throughout the description, the term "mangostin” is used herein to refer to those substances found in various parts of the mangosteen tree (Garcinia mangostana) and having a prenylated xanthone structure. In particular, “mangostin” refers to alpha-mangostin (aMG), beta- mangostin (bMG) or gamma-mangostin (gMG) and derivatives thereof, including glucoside derivatives thereof. The different mangostin derivatives present in mangosteen have a common xanthone skeleton with two isoprenyls and four hydroxyls, which may or may not be methylated, resulting in 2 (beta), 3 (alpha) or 4 (gamma) free hydroxyl groups.

[0049] Without being bound by any theory, it is believed that these mangostin compounds described above share the combined ability to form cocrystals with coformers of interest, in particular organic bases, such as amines as defined herein, because the free hydroxyl groups may form hydrogen bonds with the coformers, especially with receptor atoms present in organic bases, such as amines, while still being therapeutically active.

[0050] When used herein, the term “coformer” represents a compound or mixtures of compounds that are able to form a new solid form, preferably a new crystalline solid form, with a molecule of interest. In the present case, the molecule of interest is mangostin. The coformer may be solid or liquid, it may be a small molecule or a polymer (artificial or natural), and it may be ionizable or non-ionizable. The use of a coformer in the present invention may lead to the formation of new solid forms that may be either salts or co-crystals. Preferably, the coformer is an organic base. More preferably, the organic base may be an amine. As used herein, the term “amine” means any molecule having an amine function, such as a primary, secondary, tertiary amine or other basic nitrogen-containing compounds, such as purines. “Amine” is meant to be equivalent to “organic amine”. Amines may have any structure, for example linear or branched or cyclic, including any type of heterocycles.

[0051] When used herein, the term “alkyl” means any short, medium or long carbon hydrogen chain, either linear, branched or cyclic. The alkyl may be unsubstituted or carry further substitutions in form of halogen, hydroxy, amine, carboxylic acid, or thiol group(s).

[0052] One object of the invention is the provision of a mangostin having improved water solubility to allow its use in therapeutical and non-therapeutical applications that require good water solubility and / or oral administration. Another object of the invention is the provision of a mangostin with enhanced water-solubility that at the same time also shows an enhanced bioavailability.

[0053] By converting an active ingredient, such as a drug substance, into its salt form, the ionic interactions in the drug's structure can be modified, which may lead to increased dissolution rates in aqueous environments, and thus in a better water-solubility. This process often involves the combination with a suitable counterion in order to obtain the salt form. The resulting salt form may be more soluble, and the enhanced water-solubility then can also improve other physicochemical properties such as stability, permeability, and / or taste.

[0054] Another possibility is the formation of cocrystals. Cocrystals are a newer class of crystalline structures where the active ingredient is combined with a molecule, sometimes also called coformer, that is pharmaceutically acceptable and able to interact with the active ingredient mostly by non-ionic interactions. Hence, non-ionizable molecules may be used as coformers, forming non-covalent interactions like hydrogen bonding, van der Waals forces, or TT-TT interactions. Notwithstanding, also ionizable coformers may be used for forming cocrystals. The resulting cocrystal maintains the active ingredient’s integrity while significantly altering its physicochemical properties, particularly solubility. This can then lead to improved absorption rates and better pharmacokinetic profiles.

[0055] Both salt and cocrystal forms offer thus means to improve solubility of an active ingredient, such as a drug substance, and so enhance drug absorption, reduce variability in drug response, and potentially lower the required dose, leading to fewer side effects. All this is possible without altering chemical nature of the active ingredient.

[0056] However, it is impossible to foresee which type of salts or cocrystals may form and which of those may then even be working in the sense of providing a better solubility in water. The inventors of the present invention have now surprisingly found that specific substances interact with mangostin to provide new solid forms of mangostin. Preferably, these new mangostin solid forms are either salts or co-crystals. More preferably, these new mangostin solid forms comprise mangostin and an organic base, preferably an amine.

[0057] The inventors of the present invention have tested different types of molecules to obtain salts or cocrystals. However, most coformers tested only provided physical mixtures without forming any salt or cocrystal. For example, molecules such as L-proline, 2,5-dihydroxybenzoic acid, ascorbic acid or quercetin did not work and did not form salts or cocrystals. However, when mangostin was combined with organic bases, preferably with amines, new salt and cocrystal forms were obtained.

[0058] Preferably, the amines are primary, secondary, tertiary alkyl amines or purines. The amine may include one amine group, two amine groups, three amine groups or four amine groups, each of which may be a primary, secondary, or tertiary alkyl amine. The alkyl residue or residues of the amine, depending on whether the amine is a primary, secondary, or tertiary alkyl amine, may be an acyclic, cyclic, bicyclic, or tricyclic alkyl residue. When the alkyl residue is a cyclic, bicyclic, or tricyclic alkyl residue, the nitrogen atom of the amine group may be bound to the cyclic structure or may be incorporated into the cyclic structure. When there is more than one amine group, either all amine groups are bound to the cyclic structure, or all amine groups are incorporated into the cyclic structure, or there may be even at least one amine group bound to the cyclic structure and at least one amine group incorporated into the cyclic structure.

[0059] In one embodiment, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4-diazabicyclo[2.2.2]octane, 1- octylamine, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13-tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, 1-hexylamine, or caffeine. These amines form readily new solid forms with mangostin and improve the solubility thereof in water. Preferably, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4-diazabicyclo[2.2.2]octane, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13-tridecanediamine, cyclopentylamine, 3- dimethylamine-1 -propylamine, or 1-hexylamine. More preferably, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, or 1 ,4-diazabicyclo[2.2.2]octane. Even more preferably, the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, or piperidine. Still more preferably, the amine is selected from the group of ethylenediamine, or pyrrolidine. In one preferred embodiment, the new mangostin solid form is a mangostin ethylenediamine solid form. In another preferred embodiment, the new mangostin solid form is a mangostin pyrrolidine solid form. In particular these two new mangostin solid forms have shown excellent water-solubility and shown the best improvement compared to mangostin alone.

[0060] The new mangostin solid forms may have any stochiometric ratio between mangostin and the amine. Preferably, the molar ratio of mangostimamine is from 1 :0.3 to 1:8, preferably from 1 :1 to 1 :5, more preferably from 1 :1 to 1:3. Within these molar ratios, the new mangostin solid forms show the best water solubilities.

[0061] Mangostin may be any mangostin derivative based on a xanthone structure with at least two prenyl groups thereon and at least one OH group that may interact with an amine. Preferably, the mangostin is selected from the group consisting of alpha-mangostin, beta-mangostin or gamma-mangostin. More preferably, the mangostin is alpha-mangostin.

[0062] The new mangostin solid forms may be either amorphous or crystalline. In one embodiment, the new mangostin solid forms may be amorphous mangostin solid forms. In another embodiment, the new mangostin solid forms may be crystalline mangostin solid forms. Preferably, the crystalline mangostin solid forms are polymorphs, salts or cocrystals.

[0063] In the following, preferred mangostin solid forms are described.

[0064] Mangostin ethylenediamine

[0065] In one preferred embodiment, the mangostin solid form is mangostin ethylenediamine.

[0066] More preferably, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 7.6°, 8.5°, 9.7°, 10.3°, 12.8°, 19.9°, 20.5°, 21.8, 22.9°, or 26.1°

[0067] Even more preferably, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.1°, 8.5°, 8.9°, 9.7°, 10.3°, 15.8°, 16.1°, 18.3°, 19.6°, 19.9°, 20.5°, 21.0°, 21.5°, 22.8°, 22.9°, 25.8°, and 26.8°

[0068] Alternatively, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.8°, 8.7°, 9.9°, 10.4°, 10.8°, 11.7°, 15.6°, 19.9°, 20.5°, 22.0°, and 23.1° Alternatively, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.5°, 9.9°, 10.3°, 11.3°, 12.0°, 16.9°, and 19.7°

[0069] Alternatively, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 9.0°, 11.4°, 12.8°, 14.6°, 16.7°, 21.8°, 23.0°, 24.7°, 26.1°, and 27.3°

[0070] Alternatively, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.7°, 8.5°, 8.8°, 9.7°, 10.3°, 10.7°, 11.7°, 15.5°, 20.0°, 20.8°, 22.1°, 22.4°, 23.5°, and 26.2°

[0071] Alternatively, the mangostin solid form is alpha-mangostin ethylenediamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 8.6°, 10.0°, 10.4°, 11.2°, 12.6°, 15.6°, 15.8°, 16.9°, 20.9°, 21.7°, 22.9°, 24.8°, 25.1°, 26.5°, and 32.4°

[0072] More preferably, the mangostin ethylenediamine solid form can be isolated either as solid form aMG-XXV-1 , aMG-XXV-2, aMG-XXV-3, aMG-XXV-4, aMG-XXV-5, or aMG-XXV-5.1 , depending on the manufacturing process, and shows the corresponding XRPD patterns illustrated in Table 1 and Table 2, respectively.

[0073] Table 1 below shows the detailed peak lists for the solid forms aMG-XXV-1 , aMG-XXV-2 and aMG-XXV-3, wherein “Pos.” stands for position, measured at °20, and “Rel. Int.” stands for relative intensity and is measured in %:

[0074] Table 1

[0075] Table 2 below shows the detailed peak lists for the solid forms aMG-XXV-4, aMG-XXV-5 and aMG-XXV-5.1 , wherein “Pos.” stands for position, measured at °20, and “Rel. Int.” stands for relative intensity and is measured in %: Table 2 Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here ethylenediamine. This allows to deduce an approximate molar relationship between the two compounds. In Table 3, the TGA of new alpha-mangostin ethylenediamine form aMG-XXV-1 and aMG-XXV- 2 is shown.

[0076] Table 3

[0077] As can be seen from Table 3 for aMG-XXV-1 , there is a first mass loss showing the ethylenediamine calcination and a second mass loss being the calcination of aMG. The diagram allows to calculate the molar ratios between ethylenediamine and aMG, which is 2.68 molecules of ethylenediamine for each molecule of aMG.

[0078] As can be seen from Table 3 for aMG-XXV-2, there is a first mass loss belonging to the ethylenediamine calcination and a second one belonging to the calcination of aMG. The weight variation observed from the beginning of the test indicates that the compound is not stable, since part of the ethylenediamine starts to be eliminated when it comes into contact with air.

[0079] Likewise, the molar relationship of crystalline forms aMG-XXV-3, aMG-XXV-4, aMG-XXV-5, and aMG-XXV-5.1 has been determined. It was thus observed that form aMG-XXV-3 has a 1 :1 molar relationship (aMG:ethylenediamine); form aMG-XXV-4 has a 1 :2 molar relationship (aMG:ethylenediamine); form aMG-XXV-5 has a 2:1 molar relationship (aMG:ethylenediamine) with additional water molecules retained in the structure; and form aMG-XXV-5.1 has a 2:1 molar relationship (aMG:ethylenediamine) with additional MeOH molecules retained in the structure.

[0080] The solid form aMG-XXV-1 has been further analysed by NMR analysis and by elemental analysis. Proton NMR analysis revealed that the proton on the C-5 carbon of alpha-mangostin was shifted upfield from 6.793 ppm (alpha-mangostin alone) to 6.118 ppm, which is indicative for a proton transfer from alpha-mangostin to ethylenediamine and, hence, for the presence of an alpha-mangostin ethylenediamine salt. Likewise, elemental analysis confirms the molar ratio found by TGA and indicates a molar ratio of alpha-mangostin to ethylenediamine of about 1 :2.5.

[0081] Mangostin pyrrolidine In another preferred embodiment, the mangostin solid form is mangostin pyrrolidine.

[0082] More preferably, the mangostin solid form is alpha-mangostin pyrrolidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.0°, 15.3, 18.3°, 20.2°, 20.7°, 22.2°, 23.2°, or 24.6°

[0083] Even more preferably, the mangostin solid form is alpha-mangostin pyrrolidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.9°, 11.0°, 11.9°, 13.1°, 13.6°, 14.4°, 15.3, 16.1°, 17.4°, 18.3°, 20.2°, 20.7°, 21.6°, 22.2°, 23.2°, 24.6 and 26.6°

[0084] Alternatively, the mangostin solid form is alpha-mangostin pyrrolidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 8.1°, 10.1°, 11.2°, 11.6°, 18.4°, 20.2°, 20.9°, and 22.4°

[0085] More preferably, the mangostin pyrrolidine solid form can be isolated either as solid form aMG- XXXVI 1-1 or aMG-XXXVII-2, depending on the manufacturing process, and shows the corresponding XRPD patterns illustrated in Table 4.

[0086] Table 4 below shows the detailed peak lists for both solid forms aMG-XXXVII-1 and aMG- XXXVII-2, wherein “Pos.” stands for position, measured at °20, and “Rel. Int.” stands for relative intensity and is measured in %:

[0087] Table 4

[0088] Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here pyrrolidine. This allowed to deduce an approximate molar relationship between the two compounds. In Table 5, the TGA of new alpha-mangostin pyrrolidine form aMG-XXXVII-1 and aMG-XXXVII-2 are shown.

[0089] Table 5

[0090] As can be seen from Table 5 for aMG-XXXVII-1 , there was a first mass loss showing the pyrrolidine calcination and a second mass loss being the calcination of aMG. The diagram allowed to calculate the molar ratios between pyrrolidine and aMG, which was 2 molecules of pyrrolidine for each molecule of aMG.

[0091] As can be seen from Table 5 for aMG-XXXVII-2, there was a first mass loss belonging to the pyrrolidine calcination and a second one belonging to the calcination of aMG. The diagram allowed to calculate the molar ratios between pyrrolidine and aMG, which was 1 molecule of pyrrolidine for each molecule of aMG.

[0092] The solid forms aMG-XXXVII-1 and aMG-XXXVII-2 were further analysed by NMR analysis and by elemental analysis. Proton NMR analysis revealed in both cases that the proton on the C-5 carbon of alpha-mangostin was shifted upfield, in the case of aMG-XXXVII-1 from 6.793 ppm (alpha-mangostin alone) to 6.156 ppm, and in the case of aG-XXXVII-2 from 6.793 ppm (alpha-mangostin alone) to 6.195 ppm, which was indicative for a proton transfer from alpha- mangostin to pyrrolidine and, hence, for the presence of an alpha-mangostin pyrrolidine salt. Likewise, elemental analysis confirmed the molar ratio found by TGA and indicated a molar ratio of alpha-mangostin to pyrrolidine of about 1 :2 in the case of solid form aMG-XXXVII-1 , and a molar ratio of alpha-mangostin to pyrrolidine of about 1 :1 in the case of solid form aMG- XXXVII-2. Manqostin piperidine

[0093] In another preferred embodiment, the mangostin solid form is mangostin piperidine.

[0094] More preferably, the mangostin solid form is alpha-mangostin piperidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.1°, 12.1°, 14.5°, 15.2°, 16.2°, 18.4°, or 25.1°

[0095] Even more preferably, the mangostin solid form is alpha-mangostin piperidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.1°, 11.7°, 12.1°, 14.5°, 15.2°, 15.8°, 16.2°, 17.5°, 17.6°, 17.9°, 18.4°, 19.8°, 20.4°, 21.3°, 21.5°, 22.3°, 22.7°, 22.9°, 25.1°, 25.3°, 26.5°, 27.0°, 27.3°, and 28.4°

[0096] Alternatively, the mangostin solid form is alpha-mangostin piperidine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.4°, 10.4°, 10.9°, 12.0°, 15.2°, 18.5°, 19.5°, and 23.6°

[0097] More preferably, the mangostin piperidine solid form can be isolated either as solid form aMG- XLII-1 or aMG-XLII-2, depending on the manufacturing process, and shows the corresponding XRPD patterns illustrated in Table 6, respectively. The XRPD pattern for aMG-XLII-1 contains also traces of alpha-mangostin, while the pattern for aMG-XLII-2 is of the pure solid.

[0098] Table 6 below shows the detailed peak lists for both solid forms aMG-XLII-1 and aMG-XLII-2, wherein “Pos.” stands for position, measured at °20, and “Rel. I nt.” stands for relative intensity and is measured in %:

[0099] Table 6

[0100] Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here piperidine. This allowed to deduce an approximate molar relationship between the two compounds. In Table 7, the TGA of new alpha-mangostin piperidine form aMG-XLII-2 is shown, new form aMG-XLII-

[0101] 1 was not further analysed due to the traces of alpha-mangostin therein.

[0102] Table 7

[0103] As can be seen from Table 7, there was a first mass loss showing the piperidine calcination and a second mass loss being the calcination of aMG. The diagram allowed to calculate the molar ratios between piperidine and aMG, which was 1 molecule of piperidine for each molecule of aMG.

[0104] The solid form aMG-XLII-2 was further analysed by NMR analysis and by elemental analysis. Proton NMR analysis revealed that the proton on the C-5 carbon of alpha-mangostin was shifted upfield from 6.793 ppm (alpha-mangostin alone) to 6.206 ppm, which was indicative for a proton transfer from alpha-mangostin to piperidine and, hence, for the presence of an alpha- mangostin piperidine salt. Likewise, elemental analysis confirmed the molar ratio found by TGA and indicated a molecular ratio of alpha-mangostin to piperidine of about 1 :1.

[0105] Mangostin trimethylamine In another preferred embodiment, the mangostin solid form is mangostin trimethylamine.

[0106] More preferably, the mangostin solid form is alpha-mangostin trimethylamine and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.2°, 11.8°, 11.9°, 12.2°, 15.5°, 17.5°, or 22.6° Even more preferably, the mangostin solid form is alpha-mangostin trimethylamine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.2°, 11.8°, 11.9°, 12.2°, 15.5°, 17.5°, 17.7°, 17.9°, 18.4°, 18.6°, 19.2°, 21.1°, 21.9°, 22.6°, 25.8°, or 29.0°

[0107] More preferably, the mangostin trimethylamine solid form can be isolated as solid form aMG- XXXIX-1 and shows the corresponding XRPD pattern illustrated in Table 8.

[0108] Table 8 below shows the detailed peak lists for solid form aMG-XXXIX-1 , wherein “Pos.” stands for position, measured at °20, and “Rel. I nt.” stands for relative intensity and is measured in %:

[0109] Table 8

[0110] Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here trimethylamine. This allowed to deduce an approximate molar relationship between the two compounds. In Table 9, the TGA of new alpha-mangostin trimethylamine form aMG-XXXIX-1 is shown.

[0111] Table 9

[0112] As can be seen from Table 9, there was a first mass loss showing the trimethylamine calcination and a second mass loss being the calcination of aMG. The diagram allowed to calculate the molar ratios between trimethylamine and aMG, which was 1 molecule of trimethylamine for each molecule of aMG.

[0113] The solid form aMG-XXXIX-1 was further analysed by NMR analysis and by elemental analysis. Proton NMR analysis revealed that the proton on the C-5 carbon of alpha-mangostin did not shift very much and compared to 6.793 ppm of alpha-mangostin alone in the new solid form the 05 proton was found at 6.687 ppm, which was indicative for the presence of an alpha- mangostin trimethylamine cocrystal. Hence, there was no proton transfer in the 05 vicinity. Likewise, elemental analysis confirmed the molar ratio found by TGA and indicated a molecular ratio of alpha-mangostin to trimethylamine of about 1 :1.

[0114] Mangostin 1 ,4-diazabicyclo[2.2.21octane (DABCO)

[0115] In another preferred embodiment, the mangostin solid form is mangostin DABCO.

[0116] More preferably, the mangostin solid form is alpha-mangostin DABCO and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 8.7°, 9.5°, 10.2°, 12.0°, 12.6°, 14.4°, or 20.3°

[0117] Even more preferably, the mangostin solid form is alpha-mangostin DABCO and shows an X- ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 4.5°, 8.7°, 9.1°, 9.5°, 10.2°, 12.0°, 12.6°, 13.0°, 13.9°, 14.4°, 15.1°, 16.1°, 16.6°, 16.8°, 17.1°, 17.5°, 17.8°, 18.0, 18.4, 18.8, 18.9, 20.3, 20.9, 22.6, or 27.8°

[0118] Alternatively, the mangostin solid form is alpha-mangostin DABCO and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 8.7°, 9.4°, 10.0°, 10.6°, 10.8°,

[0119] 12.0°, 12.5°, 13.6°, 14.5°, 15.4°, 16.3°, 16.7°, 17.2°, 17.7°, 18.2°, 18.9, 20.4, 20.9, 21.5, 22.0, 22.6, 23.4, 24.0°, 26.1°, or 26.5°

[0120] More preferably, the mangostin DABCO solid form can be isolated either as solid form aMG- LXI-1 or aMG-LXI-3, depending on the manufacturing process, and shows the corresponding XRPD patterns illustrated in Table 10.

[0121] Table 10 below shows the detailed peak lists for both solid forms aMG-LXI-1 and aMG-LXI-3, wherein “Pos.” stands for position, measured at °20, and “Rel. I nt.” stands for relative intensity and is measured in %:

[0122] Table 10

[0123] Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here DABCO. This allowed to deduce an approximate molar relationship between the two compounds. In Table 11 , the TGA of the new alpha-mangostin DABCO form aMG-LXI-1 and aMG-LXI-3 are shown.

[0124] Table 11

[0125] As can be seen from Table 11 for aMG-LXI-1 , there was a first mass loss showing the DABCO calcination and a second mass loss being the calcination of aMG. The diagram allowed to calculate the molar ratios between DABCO and aMG, which was 7.28 molecules of DABCO for each molecule of aMG.

[0126] As can be seen from Table 11 for aMG-LXI-3, there was a first mass loss belonging to the DABCO calcination and a second one belonging to the calcination of aMG. The diagram allowed to calculate the molar ratios between DABCO and aMG, which was 0.5 molecule of DABCO for each molecule of aMG.

[0127] Mangostin 1 ,4-dimethylpiperazine

[0128] In another preferred embodiment, the mangostin solid form is mangostin 1 ,4- dimethylpiperazine.

[0129] More preferably, the mangostin solid form is alpha-mangostin 1 ,4-dimethylpiperazine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 10.5°, 10.8°, 15.6°, 17.1°, 17.8°, 18.5°, or 21.6°

[0130] Even more preferably, the mangostin solid form is alpha-mangostin 1 ,4-dimethylpiperazine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 3.9°, 7.2°, 8.2°, 10.5°, 10.8°, 11.7°, 13.5°, 14.3°, 15.6°, 16.1°, 17.1°, 17.8°, 18.5°, 19.7°, 20.4°, 21.0°, 21.6°, 22.2°, 23.5°, or 23.9° Alternatively, the mangostin solid form is alpha-mangostin 1 ,4-dimethylpiperazine and shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.9°, 8.8°, 10.5°, 10.8°, 11.1°, 11.4°, 12.3°, 13.1°, 13.2°, 14.0°, 14.9°, 15.2°, 16.5°, 17.5°, 17.8°, 18.6°, 18.9°, 19.3°, 19.5°, 19.7°, 20.6°, 21.3°, 21.5°, 21.7°, 22.2°, 22.5°, 23.2°, 24.1°, 24.3°, 25.3°, 26.0°, 27.2°,

[0131] 28.0°, or 28.2°

[0132] More preferably, the mangostin 1 ,4-dimethylpiperazine solid form can be isolated either as solid form aMG-XXXV-1 or aMG-XXXV-2, depending on the manufacturing process, and shows the corresponding XRPD patterns illustrated in Table 12, respectively. Table 12 below shows the detailed peak lists for solid forms aMG-XXXV-1 and aMG-XXXV-2, wherein “Pos.” stands for position, measured at °20, and “Rel. I nt.” stands for relative intensity and is measured in %:

[0133] Table 12

[0134] Thermogravimetric analysis (TGA) was performed to determine approximately the amount of alpha-mangostin present in the sample and the amount of the amine, here 1 ,4- dimethylpiperazine. This allowed to deduce an approximate molar relationship between the two compounds. In Table 13, the TGA of new alpha-mangostin 1 ,4-dimethylpiperazine form aMG-XXXV-1 is shown.

[0135] Table 13

[0136] As can be seen from Table 13, there was a first mass loss showing the 1 ,4-dimethylpiperazine calcination and a second mass loss being the calcination of aMG. The diagram allowed to calculate the molar ratios between 1 ,4-dimethylpiperazine and aMG, which was 1 molecule of 1 ,4-dimethylpiperazine for each molecule of aMG.

[0137] Mangostin solid form preparation

[0138] The new mangostin solid forms may be prepared using any method that allows obtaining a solid form of mangostin and an organic base, preferably an amine. Preferably, the process for the manufacture of the mangostin solid forms described herein comprises the steps of:

[0139] (i) providing a mixture of mangostin and a coformer, wherein the coformer is an organic base;

[0140] (ii) crystallising the mangostin solid form; and (iii) isolating the mangostin solid form.

[0141] Step (i) of providing a mixture of mangostin and an organic base coformer, preferably an amine may be done in any suitable way. Preferably, the mixture may be a solution or a suspension or slurry. Where needed, additional solvent(s), like cosolvents, may be added or used to provide for a solution or suspension. The mixture may be heated, if this is necessary for obtaining a solution and the formation of the new mangostin solid form.

[0142] Step (ii) of crystallising the mangostin solid form may include steps of cooling to room temperature, cooling to temperatures below 10°C, adding an anti-solvent, concentrating of the solution or suspension under elevated temperatures and / or in vacuum, adding seed crystals, and / or combinations thereof.

[0143] Preferably, step (ii) is a type known as reaction crystallisation or a type known as slurry crystallisation, and, optionally, may include the use of one or more different solvents and / or cosolvents.

[0144] In the case of the reaction crystallization (RC), a saturated solution of the most soluble component (aMG or the amine) in different solvents is prepared in a sealed vial under stirring. Preferably, the molar ratio of mangostin:amine is from 5:1 to 1 :50, preferably from 3:1 to 1 :40, and more preferably from 2:1 to 1 :30. A small quantity of the less soluble component is added until it did not dissolve anymore. The suspension is kept under stirring for several days and the resulting solids are then filtered and analysed by XRPD.

[0145] In the case of slurries (SY), a suspension of mangostin and the amine in different molar ratios in selected solvents is prepared. Preferably, the molar ratio of mangostimamine is from 5:1 to 1 :30, preferably from 3:1 to 1 :20, and more preferably from 2:1 to 1 :10. The sealed vials were kept under stirring for one day and the resulting solids were filtered and analysed by XRPD.

[0146] Possible solvents and / or cosolvents that may be used in the process for manufacturing the mangostin solid forms may be methanol, ethanol, ethyl acetate, acetonitrile, benzyl alcohol, acetone, 2-propanol, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether (MTBE), dichloromethane, or chloroform. Preferably, the solvent and / or cosolvent is selected form the group consisting of methanol, ethyl acetate, 2-methyltetrahydrofuran, methyl tert-butyl ether (MTBE), or acetonitrile.

[0147] In some embodiments, no solvent is used, and the manufacture of the new solid form is carried out using the amine as reagent and as solvent. In other embodiments, the manufacture of the new solid form is carried out using the amine as reagent and as solvent, with the addition of an amount of cosolvent sufficient to help in the formation of the new solid form.

[0148] Step (iii) of isolating the mangostin solid form may include the steps of solvent removal and / or filtration and / or any suitable work-up, like washing the isolated solid form or drying the isolated solid form. Solvent removal may be carried out by standard distillation, removal using vacuum at room temperature or at elevated temperatures, or slow evaporation. The solvent may be removed entirely or only partially, followed then by filtering the solid material to separate the solid form from the remaining solvent. If necessary, the isolated solid form may then be washed with a washing solvent to remove any impurity still present. To obtain the solid form, it may then be further dried, under vacuum and / or at elevated temperatures.

[0149] Mangostin solid form compositions and applications

[0150] The mangostin solid forms described herein may be used to prepare compositions comprising said mangostin solid forms. The composition may be selected from the group consisting of pharmaceutical composition, non-therapeutic compositions, cosmetic compositions, functional food compositions, animal nutrition compositions, dietary supplement compositions, or medical food compositions. Preferably, the compositions are selected from the group consisting of pharmaceutical composition, non-therapeutic compositions, or cosmetic compositions.

[0151] Any composition of the present invention may be in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, gummies, nutritional bars, aerosol, spray, topical solution, transdermal patch, biscuits, snacks, powder for reconstitution, paste or ointment.

[0152] In one embodiment of the present invention, the mangostin solid forms described herein may be used to provide compositions for therapeutic applications. The compositions may comprise the mangostin solid form and at least one pharmaceutically acceptable excipient. The compositions may be present in solid, semi-solid or liquid form. Preferably, the composition is a pharmaceutical composition. More preferably, the pharmaceutical composition may be in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, aerosol, spray, topical solution, transdermal patch, powder for reconstitution, paste or ointment. Optionally, the composition may comprise additionally other additives, such as colorants, stabilisers, preservatives, fillers, antioxidants, or flavours.

[0153] Preferably, the mangostin solid forms of the present invention are for use as a medicament. More preferably, the mangostin solid forms of the present invention are for use as an antimicrobial agent, an antiviral agent, an antiparasitic agent, an antimycotic agent, an anti- inflammatory agent, or an anticancer agent, in a subject selected form the group consisting of humans or animals. Alternatively or additionally, the mangostin solid forms of the present invention are used in methods for treating microbial conditions, viral conditions, parasitic conditions, mycotic conditions, inflammatory conditions or cancer conditions in a subject selected form the group consisting of humans or animals.

[0154] In one preferred embodiment, the mangostin solid forms of the present invention are for use in the prevention or the treatment of periodontal or skin diseases. Alternatively or additionally, the mangostin solid forms of the present invention are used in methods for preventing or treating periodontal or skin diseases.

[0155] In another preferred embodiment, the mangostin solid forms of the present invention are for use in the treatment of microbial infections, optionally in combination with an antibiotic compound. Alternatively or additionally, the mangostin solid forms of the present invention are used in methods for treating microbial infections, optionally in combination with an antibiotic compound.

[0156] The use in a treatment of periodontal or skin diseases or microbial infections, or the methods for preventing or treating periodontal or skin diseases or the methods for treating microbial infections, may include treating periodontal or skin disorders, conditions and diseases, or treating infections, such as treating dental plaque, dental biofilm, dental caries, bacteremia, nosocomial bacteremia, mucosal disorders and conditions, acne, infections associated with implants or prosthetic devices, throat infections, pharyngitis, group A streptococcal infections, and similar.

[0157] In any of the above therapeutic uses or method of treatments, the mangostin solid form is administered to the subject in need thereof in a therapeutically effective amount.

[0158] In any of the above therapeutic uses or method of treatments, the mangostin solid form may be combined and administered together, either before, at the same time or after, with one or more antibacterial agents, one or more chemotherapeutic agents, one or more immunomodulatory agents, one or more cancer hormone therapeutic agent, one or more targeted cancer therapeutic agent, one or more anti-inflammatory agents, one or more antiviral agents, one or more antiparasitic agents, one or more antimicrobial agents, one or more antidiabetic agents, one or more lipid-lowering agents, one or more antiarthritic agents, one or more dementia treatment agents, one or more antiatherosclerotic agents, one or more antiobesity agents, one or more antiosteoporotic agents, one or more age related disease treatment agents, and one or more antifungic agents. 1

[0159] In another embodiment of the present invention, the mangostin solid forms described herein may be used in compositions for non-therapeutic applications, such as cosmetic applications. The compositions may comprise the mangostin solid form and at least one cosmetically acceptable excipient. The compositions may be present in solid, semi-solid or liquid form. Preferably, the composition is a cosmetic composition. More preferably, the non-therapeutic or cosmetic composition may be in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, aerosol, spray, topical solution, transdermal patch, powder for reconstitution, paste or ointment. Optionally, the composition may comprise additionally other additives, such as colorants, stabilisers, preservatives, fillers, antioxidants, or flavours.

[0160] Preferably, the mangostin solid forms of the present invention are for use in non-therapeutic applications. More preferably, said non-therapeutic applications are cosmetic applications. Even more preferably, the mangostin solid forms of the present invention are for use in a cosmetic antioxidant product, in a cosmetic anti-aging product, in a cosmetic antiseptic product, or in a cosmetic antiallergic product. Alternatively or additionally, the mangostin solid forms of the present invention are used in non-therapeutic method of treatments. More preferably, said non-therapeutic method of treatments are methods of cosmetic treatments. Even more preferably, the mangostin solid forms of the present invention are used in methods of cosmetic antioxidant treatments, of cosmetic anti-aging treatments, of cosmetic antiseptic treatments, or of cosmetic antiallergic treatments.

[0161] In any of the above non-therapeutic uses or method of treatments, the mangostin solid form is administered to the subject in need thereof in an amount that is effective to obtain the desired cosmetic effect.

[0162] In any of the above cosmetic uses or method of treatments, the mangostin solid form may be combined and administered together, either before, at the same time or after, with one or more antiseptic agents, one or more anti-aging agents, one or more antioxidants, and one or more antiallergic agents.

[0163] In another embodiment of the present invention, the mangostin solid forms described herein may be used in compositions for other non-therapeutic applications, such as functional food applications, medical food applications, dietary supplement applications, or animal nutrition applications. The compositions may comprise the mangostin solid form and at least one human food grade or animal food grade excipient. The compositions may be present in solid, semisolid or liquid form. In case of functional food applications, medical food applications, or dietary supplement applications, the composition may be in the form of tablet, capsule, powder, granulate, solution, suspension, gummies, nutritional bars, biscuits, snacks, powder for reconstitution, paste or ointment. Optionally, the composition may comprise additionally other food grade additives, such as colorants, stabilisers, preservatives, fillers, antioxidants, or flavours.

[0164] Functional food as used herein is a food or beverage that has an additional ingredient providing a therapeutic or non-therapeutic benefit and / or prevention of condition. Functional food may appear similar to conventional food and be part of a regular diet. Functional food is not considered being a medicament.

[0165] Medical food as used herein is a food or beverage that is specially formulated and intended for the dietary management of a disease that has distinctive nutritional needs that cannot be met by normal diet alone. Medical food may be defined also as a food for special medical purposes, and is distinct from food for special dietary use, functional food, or dietary supplements.

[0166] Dietary supplements are products intended to supplement a person’s diet, but that is not used as conventional food or as a sole item of a meal or of the diet. Dietary supplements used herein may further comprise one or more active ingredients selected form the group consisting of L- carnitine, xylitol, vitamin or mixtures of vitamins, carotenoids, omega-3 fatty acids, flavonoids, coenzyme Q10, natural products inhibiting 5-LOX, harpagoside (Devil’s Claw), copper, zinc, and / or manganese.

[0167] In case of animal nutrition applications, the composition may be designed for livestock or for pet animals. The composition may be in the form of tablet, capsule, powder, granulate, solution, suspension, injection, suppository, gummies, nutritional bars, biscuits, snacks, powder for reconstitution, or ointment. Optionally, the composition may comprise additionally other food grade additives, such as colorants, stabilisers, preservatives, fillers, antioxidants, or flavours.

[0168] In any of the above non-therapeutic uses or method of treatments, the mangostin solid form is administered to the subject in need thereof in an amount that is effective to obtain the desired cosmetic effect.

[0169] EXAMPLES

[0170] Methods and

[0171] XRPD method X-ray powder diffraction (XRPD) was used to identify a new solid form by comparison with reference patterns of pure a-mangostin (aMG, CCDC structure refcode: QAYQA3) and every polymorph and solvate reported for the amines, with the following instrumentation and analysis conditions.

[0172] X-ray Powder Diffraction (XRPD):

[0173] • Bruker D2 Phaser 3 / 3 powder diffractomer of 141.5 mm measurement radius, in a Bragg-Brentano reflection geometry with a Si-Einkr Probenhalter sample holder with 15 rpm rotation.

[0174] • Cu Ka radiation (A = 1.5418 A)

[0175] • Work power: 30 kV - 10 mA

[0176] • Incident divergence beam slit defining a beam height of 0.2 mm

[0177] • Incident and diffracted beam 0.04 radians Soller slits

[0178] • 1 D-Detector (SSD160_2) detector: Active length = 3.007° -

[0179] • 20 / 0 scans from 2 to 30° 20 with a step size of 0.016° 20 and a measuring time of 1 second per step

[0180] - TGA method

[0181] TGA was carried out on a TA Instruments model SDT Q600 with simultaneous thermogravity and differential thermal analysis equipment. Thermogravimetric analysis was carried out in nitrogen atmosphere, and with a temperature ramp from room temperature to 800°C with a temperature increase of 10 °C / min.

[0182] NMR method

[0183] NMR analysis was carried out with a Bruker Avance 300 MHz nuclear magnetic resonance spectrometer. The1H-NMR method used DMSO-d6 to dissolve the mangostin solid forms for analysis.

[0184] - Elemental analysis method

[0185] Elemental analysis was carried out on a Thermo Scientific Elemental Microanalyser (A7) model Flash 2000. The modified Pregl-Dumas method (dynamic flash combustion) was performed, using helium as carrier gas. Standards of known composition according to the Standard Operating Procedures were used to calibrate the equipment.

[0186] Examples

[0187] Example 1 : Alpha-mangostin ethylenediamine aMG-XXV-1 was obtained by slurry in ethylenediamine. 100 mg of alpha-mangostin were mixed with ethylenediamine (0.1 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 3 days. The XRPD result is pure new form aMG-XXV-1 (Fig.5).

[0188] Example 2:

[0189] Alpha-mangostin ethylenediamine aMG-XXV-2 was obtained from slow evaporation of an equimolar suspension of alpha-mangostin and ethylenediamine in methanol. 151.7 mg of a- mangostin and 22.3 mg of ethylenediamine were mixed with methanol (about 7 mL) to produce a suspension. As such amount of alpha-mangostin was theoretically expected to solubilize in about 0.5 mL of methanol, it is very likely that a new solid, way less soluble, formed through reaction crystallization. This suspension was stirred homogeneously for 14 days, while being left for slow evaporation from small holes pierced in a parafilm cover. A dry powder was obtained. The corresponding XRPD is pure new form aMG-XXV-2 (Fig. 5).

[0190] Example 3:

[0191] Alpha-mangostin ethylenediamine aMG-XXV-3 was obtained by the crystallisation method. For this purpose, 20 mg alpha-mangostin was dissolved in 0.5 mL of methanol and then the corresponding amount of ethylenediamine was added in a 1 :8 molar ratio of alpha- mangostimethylenediamine. It was left to evaporate for 3 days. The crystals obtained were analysed by single crystal XRD. The corresponding XRPD is pure new form aMG-XXV-3 (Fig. 5).

[0192] Example 4:

[0193] Alpha-mangostin ethylenediamine aMG-XXV-4 was obtained by the crystallisation method. For this purpose, 20 mg alpha-mangostin was dissolved in 0.5 mL of methanol and then the corresponding amount of ethylenediamine was added in a molar ratio ranging from 1 :12 to 1 :40. It was left to evaporate for 3 days. The crystals obtained were then analysed by single crystal XRD (Fig. 5). The resulting XRPD corresponds to the new pure form aMG-XXV-4 for all molar ratios tested. This means that this crystalline form can be obtained with a wide range of molar ratios between 1 :12 to 1 :40. The list of peaks is shown above in Table 2.

[0194] Example 5:

[0195] Alpha-mangostin ethylenediamine forms aMG-XXV-5 and XXV-5.1 were obtained by the crystallisation method. For this purpose, 20 mg alpha-mangostin was dissolved in 0.5 mL of methanol and then the corresponding amount of ethylenediamine was added in a molar ratio ranging from 1 :0.5 to 1 :2. It was left to evaporate for 3 days. The crystals obtained were then analysed by single crystal XRD (Fig.5). The XRPD identified new pure forms aMG-XXV-5 and aMG-XXV-5.1. These crystalline forms contained traces of solvent encapsulated within the crystalline structure. The corresponding lists of peaks are shown above in Table 2.

[0196] Example 6:

[0197] Alpha-mangostin ethylenediamine aMG-XXXVII-2 was obtained by slurry in pyrrolidine. 100 mg of alpha-mangostin were mixed with pyrrolidine (0.2 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 3 days. The XRPD result is pure new form aMG-XXXVII-2 (Fig.4).

[0198] Example 7:

[0199] Alpha-mangostin pyrrolidine aMG-XXXVII-2 was obtained from slow evaporation of an equimolar suspension of alpha-mangostin and pyrrolidine in methanol. 159.9 mg of alpha- mangostin and 27.8 mg of pyrrolidine were mixed with methanol (about 7 mL) to produce a suspension. As such amount of alpha-mangostin was theoretically expected to solubilize in about 0.5 mL of methanol, it is very likely that a new solid, way less soluble, formed through reaction crystallization. This suspension was stirred homogeneously for 14 days, while being left for slow evaporation from small holes pierced in a parafilm cover. A dry powder was obtained. The corresponding XRPD is pure new form aMG-XXXVII-2 (Fig.4).

[0200] Example 8:

[0201] Alpha-mangostin piperidine aMG-XLII-1 was obtained by slurry in piperidine. 100 mg of alpha- mangostin were mixed with piperidine (0.1 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 1 night. The corresponding XRPD is a new form aMG-XLII-1 with traces of alpha-mangostin. Because of the high threshold used for peak listing, this pattern could be used to produce the peak list reference of form aMG-XLII- 1 by ignoring the traces of alpha-mangostin.

[0202] Example 9:

[0203] Alpha-mangostin piperidine aMG-XLII-2 was obtained by dissolving 20-50 mg of an equimolar mixture of alpha-mangostin and piperidine in 1 mL of methanol at room temperature. The solution was kept tightly sealed at room temperature until precipitation of a solid. A singlecrystal of pure new form aMG-XLII-2 was obtained, and its structure solved by means of SC- XRD, whose GIF file was later used to simulate its XRPD pattern. The corresponding peak list is shown above in table 6. A XRPD measurement of sample aMG-XLII-2 confirms the sample is pure aMG-XLII-2, and shows slight peak shifts compared to its simulated pattern because it was measured at room temperature while the cocrystal structure was solved at 100K (Fig. 6).

[0204] Example 10a: Alpha-mangostin trimethylamine aMG-XXXIX-1 was obtained by slurry in trimethylamine. 100 mg of alpha-mangostin were mixed with trimethylamine (0.1 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 1 night. The corresponding XRPD is pure new form aMG-XXXIX-1 (Fig. 6).

[0205] Example 10b:

[0206] Alpha-mangostin trimethylamine aMG-XXXIX-1 was obtained by slurry in trimethylamine. 100 mg of alpha-mangostin were mixed with trimethylamine (0.1 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 3 days. The corresponding XRPD is pure new form aMG-XXXIX-1 (Fig. 6).

[0207] Example 11 :

[0208] Alpha-mangostin DABCO aMG-LXI-1 was obtained by reaction cocrystallization in ethyl acetate. A saturated solution of alpha-mangostin in ethyl acetate was prepared in a sealed vial under stirring. A small quantity of DABCO was added until it did not dissolve any more. The resulting suspension was kept under stirring for 2 to 7 days and the resulting solid was filtered and analysed by XRPD. The corresponding XRPD is pure new form aMG-LXI-1 (Fig. 6).

[0209] Example 12:

[0210] Alpha-mangostin DABCO aMG-LXI-3 was obtained from slow evaporation of an equimolar suspension of alpha-mangostin and DABCO in methanol. 154.9 mg of alpha-mangostin and 42.3 mg of DABCO were mixed with methanol (about 7 mL) to produce a suspension. This suspension was stirred homogeneously for 14 days, while being left for slow evaporation from small holes pierced in a parafilm cover. A dry powder was obtained. The corresponding XRPD is pure new form aMG-LXI-3 (Fig. 6).

[0211] Example 13:

[0212] Alpha-mangostin 1 ,4-dimethylpiperazine aMG-XXXV-1 was obtained by slurry in 1 ,4- dimethylpiperazine. 100 mg of alpha-mangostin were mixed with 1 ,4-dimethylpiperazine (0.1 mL) and the mixture was stirred overnight at room temperature. The next day, it was dried under vacuum for 1 night. The corresponding XRPD is pure new form aMG-XXXV-1 (Fig .4).

[0213] Example 14:

[0214] Alpha-mangostin 1 ,4-dimethylpiperazine aMG-XXXV-2 was obtained by dissolving 20-50 mg of an equimolar mixture of alpha-mangostin and 1 ,4-dimethylpiperazine in 1 mL of acetonitrile at 50°C. The solution was slowly cooled down to room temperature inside the heating block. The solution was kept tightly sealed at room temperature until precipitation of some solid. A single-crystal of pure new form aMG-XXXV-2 was obtained, and its structure solved by means of SC-XRD, whose CIF file was later used to simulate its XRPD pattern. The corresponding peak list is shown above in table 12. An XRPD measurement of sample aMG-XXXV-2 confirms the sample is pure aMG-XXXV-2 and shows slight peak shifts compared to its simulated pattern because it was measured at room temperature while the cocrystal structure was solved at 100K (Fig .4).

[0215] Example 15:

[0216] 20 mg of aMG were dissolved in 0.5mL of IPA and triethylamine was added in a stoichiometric ratio of 1 :1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 7. The resolution of the monocrystal structure displayed a structure of aMG:triethylamine with a stoichiometric ratio of 1 :1 with an IPA inclusion of 1 equivalent (meaning a stoichiometric ratio of aMG:triethylamine:IPA = 1 :1 :1). The most relevant peaks of its XRPD pattern are shown below in Table 14.

[0217] Table 14

[0218] Example 16:

[0219] 20 mg of aMG were dissolved in 0.5mL of IPA and triethylamine was added in a stoichiometric ratio of 2:1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 8. The resolution of the monocrystal structure displayed a structure of aMG:triethylamine with a stoichiometric ratio of 1 :1 with an IPA inclusions of 0.5 equivalent (meaning a stoichiometric ratio of aMG:triethylamine:IPA = 1 :1 :0.5 or 2:2:1). The most relevant peaks of its XRPD pattern are shown below in Table 15. Table 15

[0220] Example 17:

[0221] 20 mg of aMG were dissolved in 0.5mL of MeOH and 4,7,10-Trioxa-1 ,13-tridecanediamine was added in a stoichiometric ratio of 20:1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 9. The resolution of the monocrystal structure displayed a structure of aMG:4,7,10-Trioxa-1 ,13- tridecanediamine having a stoichiometric ratio of 1 :1. The most relevant peaks of its XRPD pattern are shown below in Table 16.

[0222] Table 16 Example 18:

[0223] 20 mg of aMG were dissolved in 0.5mL of MeOH and 3-dimethylamine-1 -propylamine was added in a stoichiometric ratio of 5:1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 10. The resolution of the monocrystal structure displayed a structure of aMG:3-dimethylamine-1 -propylamine having a stoichiometric ratio of 1 :1. The most relevant peaks of its XRPD pattern are shown below in Table 17.

[0224] Table 17

[0225] Example 19:

[0226] 20 mg of aMG were dissolved in 0.5mL of MeOH and 1 -Hexylamine was added in a stoichiometric ratio of 5:1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 11. The resolution of the monocrystal structure displayed a structure of aMG: 1 -Hexylamine having a stoichiometric ratio of 1 :1 . The most relevant peaks of its XRPD pattern are shown below in Table 18.

[0227] Table 18

[0228] Example 20:

[0229] 20 mg of aMG were dissolved in 0.5mL of MeOH and Cyclopentylamine was added in a stoichiometric ratio of 5:1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 12. The resolution of the monocrystal structure displayed a structure of aMG:Cyclopentylamine having a stoichiometric ratio of 1:1 with MeOH inclusion of 1 equivalent (meaning a stoichiometric ratio of aMG:cyclopentylamine:MeOH = 1:1 :1). The most relevant peaks of its XRPD pattern are shown below in Table 19.

[0230] Table 19

[0231] Example 21 :

[0232] 20 mg of aMG were dissolved in 0.5mL of IPA and Diethylenetriamine was added in a stoichiometric ratio of 1 :1 with respect to aMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 13. The resolution of the monocrystal structure displayed a structure of aMG: Diethylenetriamine having a stoichiometric ratio of 3:2. The most relevant peaks of its XRPD pattern are shown below in Table 20.

[0233] Table 20

[0234] Example 22:

[0235] 50 mg of aMG were placed in a glass vial with the corresponding amount of caffeine in a 1 :2 stoichiometry. Next, 150 L of a MeOH / H2O mixture (2:1 v / v) was added and left to stir overnight. The resulting crystals were dried under vacuum and then analysed using XRPD.

[0236] The most relevant peaks of its XRPD pattern are shown below in Table 21.

[0237] Table 21

[0238] Example 23: 5 mg of gamma-mangostin (gMG) were dissolved in 0.5mL of EtOH and pyrrolidine was added in a stoichiometric ratio of 1:5 with respect to gMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 14. The resolution of the monocrystal structure displayed a structure of gMG:pyrrolidine having a stoichiometric ratio of 1 :2. The most relevant peaks of its XRPD pattern are shown below in Table 22. Table 22

[0239] Example 24:

[0240] 5 mg of gamma-mangostin (gMG) were dissolved in 0.5mL of EtOH and triethylenamine was added in a stoichiometric ratio of 1 :5 with respect to gMG. The resulting crystals obtained were analysed by using single crystal X-ray diffraction and is shown in Fig. 15. The resolution of the monocrystal structure displayed a structure of gMG:triethylenamine having a stoichiometric ratio of 1 :1. The most relevant peaks of its XRPD pattern are shown below in Table 23. Table 23

[0241] Reference example

[0242] Experiments were performed to evaluate whether alpha-mangostin could crystallize with Na or K ions as coformer. For this purpose, the crystallization method was used. 1 M KOH or NaOH solutions in methanol were prepared. Different amounts (mg) of alpha-mangostin were dissolved in 0.5mL of said KOH or NaOH solutions. The molar ratios used in these experiments for each solution were 1 :1 , 1 :2 and 1 :4 (aMG:coformer). Crystallization of alpha-mangostin with NH3 was also tested. 20 mg of alpha-mangostin was dissolved in 0.5 mL of methanol and different amounts (mL) of NH3 were added. The molar ratios used were 1 :1 , 1 :2 and 1 :4 (a MG: coform er).

[0243] In all the experiments, aMG crystals without presence of coformer were obtained. This indicates that Na, K and NH3 single ions were not included in the crystal structure for the molar ratios tested and thus did not result in any new mangostin solid form, in particular not in any salt or co-crystal of mangostin.

[0244] - TGA results

[0245] Thermogravimetric analysis was performed for all the pure phases obtained in the previous examples. Thermogravimetric analysis allows to observe mass losses in % as the temperature increases. This allows to know approximately the amount of alpha-mangostin present in the sample and the amount of the amine, allowing to deduce an approximate molar relationship between the two compounds (Table 25).

[0246] Table 25

[0247] - NMR analysis results

[0248] With the displacement data obtained for carbons 4 and 5, compared to the data for alpha- mangostin, a significant displacement of the protons can be observed, especially in carbon number 5, in most cases. This displacement is due to a proton transfer from the mangostin to the amine, revealing whether the crystal structures in which this displacement is observed correspond to salts or cocrystals (Table 26). Table 26 Comparison of observed shifts in the different mangostin solid forms

[0249] C4 C5 Crystalline structure aMG 6.338 6.793 aMG-XXV-1 6.118 6.118 Salt aMG-XXXVII-2 6.333 6.195 Salt aMG-XLII-2 6.206 6.206 Salt aMG-XXXIX-1 6.299 6.686 Cocrystal aMG-XXXVII-1 6.177 6.156 Salt

[0250] Elemental analysis results

[0251] The elemental analysis allows to confirm the theoretical structure determined with the TGA analysis. The % of carbon, nitrogen and hydrogen in the elemental analysis corresponds with the % obtained in the theoretical representation (Table 27).

[0252] Table 27. Data obtained from elemental analysis.

[0253] - Solubility experiments

[0254] Determination of molar extinction coefficient for alpha-mangostin

[0255] Solutions of different concentrations of alpha-mangostin were prepared with a MeOH / PBS solution (2:1 v / v), wherein PBS is phosphate buffer saline. The 372 nm LIV-VIS absorbance of each concentration was measured. The concentrations (in pM) used for the calibration curve were: 0, 5, 10, 15, 20, 25, 30, 35, 40, 45 pM. From the Lambert-Beer equation, the molar extinction coefficient for alpha-mangostin was determined.

[0256] A = s ■ b ■ C As a result of the absorption measurements at 372 nm, a standard line was obtained from which the molar spreading coefficient for alpha-mangostin in a MeOH / PBS solution (2:1 v / v) with 40 pL of NaOH 5M is 0,037 L mol'1cm'1. This is illustrated in Fig. 1.

[0257] Determination of new mangostin solid form solubility Samples of the different new solid mangostin forms obtained above were incubated in 2mL of milliQ water for one hour at 37°C and then filtered with 0.2pm filters. 700 pL of the filtered solution were diluted in 1400 pL of MeOH and 20 pL of concentrated NaOH. Then, different dilutions were prepared using a MeOH / water solution (2:1 v / v), depending on the observed aMG concentration in order to not saturate the equipment. Eventually, the concentration of the samples was determined from the absorbance at 372 nm. The results are shown below in Table 28 and in Fig. 2.

[0258] Table 28 Solubility of different mangostin solid forms in water after a 1h incubation.

[0259] As can be seen from Table 28 or Fig. 2, the amines used herein in the new mangostin solid forms provide an improved solubility to mangostin, and so the new mangostin solid forms of the present invention provide higher mangostin concentrations in therapeutic and non- therapeutic applications, which may help in increasing bioavailability and / or reducing the therapeutic amount of the active ingredient.

[0260] - Biologic activity

[0261] Evaluation of different concentrations of salts / cocrystals of aMG on fibroblast viability

[0262] Four different concentrations (100, 50, 20, 10, 1 pM) of alpha-mangostin and alpha-mangostin ethylenediamine (aMG-XXV-1) were used for studies with gingival fibroblasts and bacteria. Treated cells without any of mangostin or mangostin ethylenediamine served as negative control (C-) and Triton X-100 at 1 % served as positive control (C+).

[0263] Test with immortalized human gingival fibroblasts (iHGF)

[0264] Immortalized Human Gingival Fibroblasts-hTERT (iHGF) (Applied Biological Materials Inc., Richmond, BC, Canada) were grown at 37°C in an atmosphere of 5% CO2 using fibroblast medium that consists of Dulbecco's modified Eagle's medium (DM EM) low glucose (Biowest, Nuaille, France) / Ham's F12 (3 / 1) (Biowest), supplemented with 10%(v / v) fetal bovine serum embryonic stem cells tested (FBS) (Biowest) and 100 pg / mL penicillin, and 100 pg / mL streptomycin (Biowest). The culture medium was renewed twice per week. Cells were seeded in 96-well plates at a density of 5x103cells / well. At confluence, these cells were used for the biocompatibility assays. Forty-eight hours after seeding iHGF in 96 well plates, the cells were treated with different concentrations (1 pM, 10pM, 20 pM, 50 pM, 100pM) of alpha-mangostin and alpha-mangostin ethylenediamine (aMG-XXV-1) in fibroblast medium for 24 hours. Fibroblast medium without xanthones served as the negative control. The assays were carried out in triplicate (n=3).

[0265] Cell Cytotoxicity

[0266] To estimate the cytotoxicity of the different concentrations of alpha-mangostin and alpha- mangostin ethylenediamine (aMG-XXV-1), the presence of lactate dehydrogenase (LDH) in culture media 24h after the treatment with the alpha-mangostin and alpha-mangostin ethylenediamine (aMG-XXV-1) was used as an index of cell death. Following the manufacturer’s instructions (Cytotoxicity Detection kit, Roche Diagnostics, Mannheim, Germany), LDH activity was determined spectrophotometrically after 30 min of incubation at room temperature (RT) of 50 pL of culture media and 50 pL of the reaction mixture, by measuring the oxidation of nicotinamide adenine dinucleotide (NADH) at 490 nm in the presence of pyruvate. The results were presented relative to the LDH activity of the media of cells seeded on tissue culture plastic (TCP) without treatment (negative control, 0% of cell death) and on cells grown on TCP treated with 1% Triton X-100 (positive control, 100% of death), using the following equation: Cytotoxicity (%) = [(expected value - negative control) / (positive control- negative control)] x100. The assays were carried out in triplicate (n=3).

[0267] Total metabolic activity was evaluated after 24h of treatment for iHGF. Presto Blue reagent (Life Technologies, Carlsbad, CA) was used at 1 h of reagent incubation time following the manufacturer’s protocol. Not-treated cells were set as 100 %. The assays were carried out in triplicate (n=3).

[0268] As illustrated in Fig. 3, the new solid form of alpha-mangostin ethylenediamine (aMG-XXV-1) has a similar range of cytotoxicity than alpha-mangostin alone dissolved in DMSO.

[0269] Evaluation of antimicrobial activity on different bacterial strains

[0270] P. gingivalis culture and proliferation assay

[0271] P. gingivalis is a Gram-negative, anaerobic bacterium considered a key pathogen in periodontitis and plays an essential role in the initiation and progression of disease. P. gingivalis (ATCC 33277TM, Manassas, VA) was grown on Brain Heart Infusion (BHI) (Scharlab, Barcelona, Spain), supplemented with 0.5 g / l L-Cysteine hydrochloride (Thermo Fisher Scientific), 5.0 mg / l hemin (Thermo Fisher Scientific) and 1.0 mg / l Vitamin K (Thermo Fisher Scientific) under anaerobic conditions (10% H2, 10% CO2, and 80% N2) achieved with an Oxoid Anaerogen™ sachet (Thermo Fisher Scientific) at 37 °C for 24-72 h.

[0272] The bacteria were grown from frozen stocks in BHI broth medium. After overnight incubation, 100|JL bacterial suspensions were incubated with different concentrations of aMG and aMG ethylenediamine cocrystal aMG XXV-1 (200, 100, 50, 25,12.5, 6.25, 3.13, 1.56, 0.78 and 0.3 pM) for 48h under anaerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The minimum inhibitory concentration (MIC) was determined by observing bacterial growth in the different wells. Subsequently, a colony count may be performed after 72h incubation, and the CFU / mL obtained for each concentration tested can be calculated.

[0273] S. mutans culture and proliferation assay

[0274] S. mutans CECT 479 (obtained from The Spanish Type Culture Collection (CECT), University of Valencia) was grown from frozen stocks in BHI broth (Scharlab), at 37 °C under aerobic conditions. After overnight incubation, 100pL bacterial suspensions were incubated with different concentrations of aMG and aMG cocrystals XXV-1 (ethylenediamine) (200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 pM) and XXXVI 1-1 (pyrrolidine) (300, 150, 75, 37.5, 18.75, 9.38, 4.69, 2.34, 1.17, 0.59 pM) for24h under aerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The MIC was determined by observing bacterial growth in the different wells. Subsequently, a colony count was performed after 48h incubation, and the CFU / mL obtained for each concentration tested was calculated.

[0275] S. aureus culture and proliferation assay

[0276] S. aureus ATCC 29213 was grown from frozen stocks in Luria-Bertani (LB) broth (Scharlab), at 37 °C under aerobic conditions. After overnight incubation, 100pL bacterial suspensions were incubated with different concentrations of aMG and aMG cocrystals XXV-1 (ethylenediamine) (200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 pM) and XXXVII-1 (pyrrolidine) (300, 150, 75, 37.5, 18.75, 9.38, 4.69, 2.34, 1.17, 0.59 pM) for 18h under aerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The MIC was determined by observing bacterial growth in the different wells. Subsequently, a colony count may be performed after 24h incubation and the CFU / mL obtained for each concentration tested can be calculated.

[0277] S. epidermidis culture and proliferation assay

[0278] S.epidermidis CECT 4184 (obtained from The Spanish Type Culture Collection (CECT), University of Valencia) was grown from frozen stocks in Lysogeny broth (LB) (Scharlab), at 37 °C under aerobic conditions. After overnight incubation, 100pL bacterial suspensions were incubated with different concentrations of aMG and aMG cocrystals XXV-1 (ethylenediamine) (200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 pM) and XXXVII-1 (pyrrolidine) (300, 150, 75, 37.5, 18.75, 9.38, 4.69, 2.34, 1.17, 0.59 pM) for 24h under aerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The MIC was determined by observing bacterial growth in the different wells.

[0279] C. acnes culture and proliferation assay

[0280] C. acnes CECT 5684 (obtained from The Spanish Type Culture Collection (CECT), University of Valencia) was grown from frozen stocks in Tryptic Soy broth (TSB) (Condalab), at 37 °C under aerobic conditions. After overnight incubation, 100pL bacterial suspensions were incubated with different concentrations of aMG and aMG cocrystals XXV-1 (ethylenediamine) (200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 pM) and XXXVII-1 (pyrrolidine) (300, 150, 75, 37.5, 18.75, 9.38, 4.69, 2.34, 1.17, 0.59 pM) for 24h under aerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The MIC was determined by observing bacterial growth in the different wells.

[0281] S. pyogenes culture and proliferation assay

[0282] S. pyogenes D3 HUSE (obtained from Universitary Hospital Son Espases (HUSE)), Balearic Islands) was grown from frozen stocks in Tryptic Soy broth (TSB) (Condalab), at 37 °C under aerobic conditions. After overnight incubation, 100pL bacterial suspensions were incubated with different concentrations of aMG and aMG cocrystals XXV-1 (ethylenediamine) (200, 100, 50, 25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39 pM) and XXXVII-1 (pyrrolidine) (300, 150, 75, 37.5, 18.75, 9.38, 4.69, 2.34, 1.17, 0.59 pM) for 24h under aerobic conditions at 37 °C. Bacterial suspension without treatment served as negative control. The MIC was determined by observing bacterial growth in the different wells.

[0283] RESULTS:

[0284] P. gingivalis is a microorganism of the human oral cavity, forming part of dental plaque or dental biofilm. It is associated with the onset and development of periodontal diseases.

[0285] S. mutans is a microorganism of the human oral cavity, forming part of dental plaque or dental biofilm. It is associated with the onset and development of dental caries and is the one that has the most influence on the development of the disease.

[0286] Staphylococcus aureus is a Gram-positive bacterium characterized by being the main cause of nosocomial bacteremia in different places of the world, due to the high virulence and pathogenicity factors. Staphylococcus epidermidis is a gram-positive bacterium, part of the normal skin and mucosal microbiota. It is usually harmless but can become an opportunistic pathogen. It forms biofilms that enable strong surface adhesion and increase its resistance to antibiotics.

[0287] Cutibacterium acnes is a gram-positive anaerobic bacterium that is part of the normal skin microbiota. It is usually harmless but can contribute to acne and occasionally cause infections associated with implants or prosthetic devices.

[0288] Streptococcus pyogenes is a gram-positive, beta-hemolytic bacterium that colonizes the throat and skin. It commonly causes pharyngitis and skin infections, and can occasionally lead to severe invasive disease.

[0289] In this example (Table 29 and 30) we can observe the different MIC values obtained for both bacteria after incubation. The MIC for the different bacteria are in the same range of concentration for aMG (dissolved in DMSO) and the new solid forms aMG-XXV-1 and aMG- XXXVII-1 (dissolved in water), especially for aMG-XXV-1.

[0290] In conclusion, the use of the amine solid form of aMG provides a significant advantage over the pure compound alone, which lacks solubility. By crystallizing the new solid forms, a better solubility in aqueous environments is ensured, such as those encountered in biological systems, without compromising antibacterial efficacy of mangostin. As demonstrated by the MIC values, both the new solid form and the original compound (when dissolved in DMSO) exhibit comparable antibacterial effects. This highlights that improving the solubility of the compound through solid form formation does not diminish its potency, while offering enhanced practicality for applications where water solubility is critical.

[0291] Table 29 MIC data obtained for P. gingivalis.S. mutans bacteria and S. aureus. S. mutans

[0292] Sample Analyzed MIC CFU / mL aMG 6.25-3.13 pM 6-101-1.23-108aMG-XXV-1 6.25-3.13 pM 3.95' 102-1.3T 108aMG-XXXVII-1 150-75 pM 1.54- 105-1.85-10® P. gingivalis

[0293] Sample Analyzed MIC aMG 3.12 - 1.56 pM aMG-XXV-1 6.25 - 3.12 pM

[0294] The first results obtained with aMG-XXXVII-1 were somehow inconsistent in the case of S. mutans. Hence, these experiments were repeated in triplicate and additionally other bacteria were included. The results obtained from said repetition in triplicate are shown in table 30.

[0295] Table 30

[0296] For reasons of completeness, various aspects of the invention are set out in the following numbered clauses:

[0297] 1. A mangostin solid form comprising mangostin and a coformer. 2. The mangostin solid form according to clause 1 , wherein the coformer is an amine.

[0298] 3. The mangostin solid form according to clause 2, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1,4-dimethylpiperazine, or 1 ,4-diazabicyclo[2.2.2]octane.

[0299] 4. The mangostin solid form according to clause 3, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, or piperidine.

[0300] 5. The mangostin solid form according to clause 4, wherein the amine is selected from the group of ethylenediamine, or pyrrolidine.

[0301] 6. The mangostin solid form according to any of clauses 1 to 5, wherein the molar ratio of mangostimamine is from 1 :0.3 to 1:5, preferably from 1:1 to 1 :5. 7. The mangostin solid form according to any of clauses 1 to 6, wherein the mangostin solid form is a crystalline solid form or an amorphous solid form.

[0302] 8. The mangostin solid form according to clause 7, wherein the mangostin solid form is a crystalline solid form.

[0303] 9. The mangostin solid form according to any of clauses 1 to 8, wherein the amine is ethylenediamine.

[0304] 10. The mangostin solid form according to any of clauses 1 to 8, wherein the amine is pyrrolidine.

[0305] 11. The mangostin solid form according to any of clauses 1 to 10, wherein the mangostin is selected from the group consisting of alpha-mangostin, beta-mangostin or gamma-mangostin.

[0306] 12. The mangostin solid form according to clause 11 , wherein the mangostin is alpha- mangostin.

[0307] 13. The mangostin solid form according to clause 8, wherein the mangostin is alpha- mangostin; the amine is ethylenediamine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 7.6°, 8.5°, 9.7°, 10.3°, 12.8°, 19.9°, 20.5°, 21.8°, 22.9°, or 26°

[0308] 14. The mangostin solid form according to clause 13, wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.1°, 8.5°, 8.9°, 9.7°, 10.3°, 15.8°, 16.1°, 18.3°, 19.6°, 19.9°, 20.5°, 21.0°, 21.5°, 22.8°, 22.9°, 25.8°, and 26.8°

[0309] 15. The mangostin solid form according to clause 8, wherein the mangostin is alpha- mangostin; the amine is pyrrolidine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.0°, 15.3, 18.3°, 20.2°, 20.7°, 22.2°, 23.2°, or 24.6°

[0310] 16. The mangostin solid form according to clause 15, wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.9°, 11.0°, 11.9°, 13.1°, 13.6°, 14.4°, 15.3, 16.1°, 17.4°, 18.3°, 20.2°, 20.7°, 21.6°, 22.2°, 23.2°, 24.6 and 26.6°. 17. A composition comprising the mangostin solid form according to any of clauses 1 to 16.

[0311] 18. The composition according to clause 17, wherein the composition is selected from the group consisting of pharmaceutical compositions, non-therapeutic compositions, cosmetic compositions, dietary supplement compositions, functional food compositions, animal nutrition compositions, or medical food compositions.

[0312] 19. The composition according to clause 18, wherein the composition is in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, gummies, nutritional bars, aerosol, spray, topical solution, transdermal patch, biscuits, snacks, powder for reconstitution, paste or ointment.

[0313] 20. A process for the manufacture of the mangostin solid form according to any of clauses 1 to 16, comprising the steps of:

[0314] (i) providing a mixture of mangostin and a coformer, preferably an amine;

[0315] (ii) crystallising the mangostin solid form; and

[0316] (iii) isolating the mangostin solid form.

[0317] 21. The mangostin solid form according to any of clauses 1-16 for use as a medicament.

[0318] 22. The mangostin solid form according to clause 21 for use as an antimicrobial agent, an antiviral agent, an antiparasitic agent, an antimycotic agent, an anti-inflammatory agent, or an anticancer agent, in a subject selected form the group consisting of humans or animals.

[0319] 23. The mangostin solid form according to clause 22 for use in the prevention or the treatment of periodontal or skin diseases.

[0320] 24. The mangostin solid form according to clause 22 for use in the treatment of microbial infections, optionally in combination with an antibiotic compound.

[0321] 25. The mangostin solid form according to any of clauses 1-16 for use in non-therapeutic applications.

[0322] 26. The mangostin solid form according to clause 25 for use in a cosmetic antioxidant product, in a cosmetic anti-aging product, in a cosmetic antiseptic product, or in a cosmetic antiallergic product.

[0323] 27. The mangostin solid form according to any of clauses 1-16 for use in functional food, medical food, dietary supplements, or animal nutrition. 28. A mangostin solid form comprising mangostin and a coformer, wherein the coformer is an organic base.

[0324] 29. The mangostin solid form according to clause 28, wherein the organic base is an amine.

[0325] 30. The mangostin solid form according to clause 29, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4- diazabicyclo[2.2.2]octane, 1 -octylamine, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13- tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, 1 -hexylamine, or caffeine.

[0326] 31. The mangostin solid form according to clause 30, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4- diazabicyclo[2.2.2]octane, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13- tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, or 1 -hexylamine.

[0327] 32. The mangostin solid form according to clause 31 , wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, or piperidine; preferably wherein the amine is selected from the group of ethylenediamine, or pyrrolidine.

[0328] 33. The mangostin solid form according to any of clauses 28 to 32, wherein the mangostin solid form is a crystalline solid form or an amorphous solid form; preferably wherein the mangostin solid form is a crystalline solid form.

[0329] 34. The mangostin solid form according to any of clauses 28 to 33, wherein the mangostin is selected from the group consisting of alpha-mangostin, beta-mangostin or gamma-mangostin; preferably wherein the mangostin is alpha-mangostin.

[0330] 35. The mangostin solid form according to clause 33, wherein the mangostin is alpha- mangostin; the amine is ethylenediamine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 7.6°, 8.5°, 9.7°, 10.3°, 12.8°, 19.9°, 20.5°, 21.8°, 22.9°, or 26°; preferably wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.1°, 8.5°, 8.9°, 9.7°, 10.3°, 15.8°, 16.1°, 18.3°, 19.6°, 19.9°, 20.5°, 21.0°, 21.5°, 22.8°, 22.9°, 25.8°, and 26.8°

[0331] 36. The mangostin solid form according to clause 33, wherein the mangostin is alpha- mangostin; the amine is pyrrolidine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.0°, 15.3, 18.3°, 20.2°, 20.7°, 22.2°, 23.2°, or 24.6°; preferably wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.9°, 11.0°, 11.9°, 13.1°, 13.6°, 14.4°, 15.3, 16.1°, 17.4°, 18.3°, 20.2°, 20.7°, 21.6°, 22.2°, 23.2°, 24.6 and 26.6°.

[0332] 37. A composition comprising the mangostin solid form according to any of clauses 28 to 36; preferably wherein the composition is selected from the group consisting of pharmaceutical compositions, non-therapeutic compositions, cosmetic compositions, dietary supplement compositions, functional food compositions, animal nutrition compositions, or medical food compositions; and wherein the composition is in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, gummies, nutritional bars, aerosol, spray, topical solution, transdermal patch, biscuits, snacks, powder for reconstitution, paste or ointment.

[0333] 38. A process for the manufacture of the mangostin solid form according to any of clauses 28 to 36, comprising the steps of:

[0334] (i) providing a mixture of mangostin and a coformer, preferably an amine;

[0335] (ii) crystallising the mangostin solid form; and

[0336] (iii) isolating the mangostin solid form.

[0337] 39. The mangostin solid form according to clauses 28 to 36 for use as a medicament.

[0338] 40. The mangostin solid form according to clause 39 for use as an antimicrobial agent, an antiviral agent, an antiparasitic agent, an antimycotic agent, an anti-inflammatory agent or an anticancer agent, in a subject selected form the group consisting of humans or animals; preferably for use in the prevention or the treatment of periodontal or skin diseases; or for use in the treatment of microbial infections, optionally in combination with an antibiotic compound.

[0339] 41. The mangostin solid form according to clauses 28 to 36 for use in non-therapeutic applications.

[0340] 42. The mangostin solid form according to clause 41 for use in a cosmetic antioxidant product, in a cosmetic anti-aging product, in a cosmetic antiseptic product, or in a cosmetic antiallergic product.

[0341] 43. The mangostin solid form according to clauses 28 to 36 for use in functional food, medical food, dietary supplements, or animal nutrition.

Claims

CLAIMS1. A mangostin solid form comprising mangostin and a coformer, wherein the coformer is an organic base.

2. The mangostin solid form according to claim 1 , wherein the organic base is an amine.

3. The mangostin solid form according to claim 2, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4- diazabicyclo[2.2.2]octane, 1 -octylamine, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13- tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, 1 -hexylamine, or caffeine.

4. The mangostin solid form according to claim 3, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, piperidine, 1 ,4-dimethylpiperazine, 1 ,4- diazabicyclo[2.2.2]octane, diethylentriamine, triethylamine, 4,7,10-trioxa-1 ,13- tridecanediamine, cyclopentylamine, 3-dimethylamine-1 -propylamine, or 1 -hexylamine.

5. The mangostin solid form according to claim 4, wherein the amine is selected from the group of ethylenediamine, pyrrolidine, trimethylamine, or piperidine; preferably wherein the amine is selected from the group of ethylenediamine, or pyrrolidine.

6. The mangostin solid form according to any of claims 1 to 5, wherein the mangostin solid form is a crystalline solid form or an amorphous solid form; preferably wherein the mangostin solid form is a crystalline solid form.

7. The mangostin solid form according to any of claims 1 to 6, wherein the mangostin is selected from the group consisting of alpha-mangostin, beta-mangostin or gamma-mangostin; preferably wherein the mangostin is alpha-mangostin.

8. The mangostin solid form according to claim 6, wherein the mangostin is alpha-mangostin; the amine is ethylenediamine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 5.7°, 7.6°, 8.5°, 9.7°, 10.3°, 12.8°, 19.9°, 20.5°, 21.8°, 22.9°, or 26°; preferably wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.1°, 8.5°, 8.9°, 9.7°, 10.3°, 15.8°, 16.1°, 18.3°, 19.6°, 19.9°, 20.5°, 21.0°, 21.5°, 22.8°, 22.9°, 25.8°, and 26.8°9. The mangostin solid form according to claim 6, wherein the mangostin is alpha-mangostin; the amine is pyrrolidine; and the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising at least 4 of the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 11.0°, 15.3, 18.3°, 20.2°, 20.7°, 22.2°, 23.2°, or 24.6°; preferably wherein the crystalline mangostin solid form shows an X-ray powder diffraction pattern, measured using a CuKa radiation, comprising the following degrees 2 theta (± 0.2°) peaks selected from the group consisting of 7.6°, 8.9°, 11.0°, 11.9°, 13.1°, 13.6°, 14.4°, 15.3, 16.1°, 17.4°, 18.3°, 20.2°, 20.7°, 21.6°, 22.2°, 23.2°, 24.6 and 26.6°10. A composition comprising the mangostin solid form according to any of claims 1 to 9; preferably wherein the composition is selected from the group consisting of pharmaceutical compositions, non-therapeutic compositions, cosmetic compositions, dietary supplement compositions, functional food compositions, animal nutrition compositions, or medical food compositions; and wherein the composition is in the form of tablet, capsule, powder, granulate, solution, suspension, injection, gel, hydrogel, cream, suppository, foam, gummies, nutritional bars, aerosol, spray, topical solution, transdermal patch, biscuits, snacks, powder for reconstitution, paste or ointment.11 . A process for the manufacture of the mangostin solid form according to any of claims 1 to 9, comprising the steps of:(i) providing a mixture of mangostin and a coformer, preferably an amine;(ii) crystallising the mangostin solid form; and(iii) isolating the mangostin solid form.

12. The mangostin solid form according to claims 1 to 9 for use as a medicament.

13. The mangostin solid form according to claim 12 for use as an antimicrobial agent, an antiviral agent, an antiparasitic agent, an antimycotic agent, an anti-inflammatory agent or an anticancer agent, in a subject selected form the group consisting of humans or animals; preferably for use in the prevention or the treatment of periodontal or skin diseases; or for use in the treatment of microbial infections, optionally in combination with an antibiotic compound.

14. The mangostin solid form according to claims 1 to 9 for use in non-therapeutic applications.

15. The mangostin solid form according to claim 14 for use in a cosmetic antioxidant product, in a cosmetic anti-aging product, in a cosmetic antiseptic product, or in a cosmetic antiallergic product.

16. The mangostin solid form according to claims 1 to 9 for use in functional food, medical food, dietary supplements, or animal nutrition.

Images