composition

Abstract

To provide a composition capable of realizing sustained release of a suitable functional substance, easily producible and improved in stability.SOLUTION: The composition 10 includes a functional substance 11 which is a substance having a predetermined function, and a holding material 12 configured to hold the functional substance 11 and transported together with the functional substance 11 to a place where the function is exhibited in a state where the functional substance 11 is held. The holding material 12 contains a polysaccharide derived from a gelatinous material AG obtained from an aloe plant as a skeleton 121.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a composition comprising a functional substance and a holding material configured to be able to hold the functional substance. [Background technology]

[0002] Conventionally, compositions comprising a functional substance and a retention material configured to retain the functional substance have been known. The compositions are used, for example, in drug delivery systems. In this case, a drug as the functional substance is retained in the retention material. The retention material, while retaining the drug, is transported together with the drug to a location where the drug's function is to be expressed.

[0003] Patent Document 1 discloses a sustained-release composition. This composition uses liposomes as a retention material. The liposomes retain a therapeutic agent, and sustained release of the therapeutic agent is expected. This is achieved by adjusting the ratio of the therapeutic agent to the total lipids. The ratio may be, for example, 0.0001 mol / mol to 0.15 mol / mol.

[0004] Patent Document 1 also discloses that the pharmaceutically effective amount of the therapeutic agent, the concentration of the phospholipid, etc. may be adjusted. In this case, the pharmaceutically effective amount of the therapeutic agent may be, for example, 0.0001 mg / mL to 10 mg / mL. The concentration of the phospholipid may be, for example, 0.01 mM to 100 mM.

[0005] Patent Document 1 also discloses that various therapeutic agents can be used. The therapeutic agents are selected from the group consisting of, for example, antitumor agents, analgesics, anesthetics, and immunomodulators.

[0006] [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Taiwan Patent Application Publication No. 202106287 Summary of the Invention [Problem to be solved by the invention]

[0008] The composition of Patent Document 1 has sustained release properties. However, special techniques and devices are required to retain the therapeutic agent in the liposomes. Furthermore, liposomes are easily trapped in tissues (e.g., liver, spleen, etc.) and are poorly stable in the blood.

[0009] In view of the above, an object of the present invention is to provide a composition having sustained release properties, which can be easily produced and is stable. [Means for solving the problem]

[0010] The technical means of the present invention for solving this technical problem is characterized as follows: The composition of the present invention comprises a functional substance, which is a substance having a predetermined function, and a retention material configured to retain the functional substance and transported together with the functional substance to a location where the function is to be expressed while retaining the functional substance. The retention material contains, as a skeleton, a polysaccharide derived from a gel-like substance obtained from an aloe plant.

[0011] In the compositions of the present invention, the retention material comprises a hydrophobic structure having a chemical structure that, when incorporated into the scaffold, increases the hydrophobicity of the retention material.

[0012] In the composition of the present invention, the polysaccharide in the backbone has a chemical structure corresponding to acemannan or an oxide of acemannan. The hydrophobic structure corresponds to one or more components selected from the group consisting of hydrocarbon chains, aromatic rings, fluorine compounds, alkyl groups, sterically hindered structures, nonpolar functional groups, long carbon chains, compounds having both a methyl group and a primary amine, compounds having both a benzene ring and a primary amine, amino acids having a benzyl structure or modified amino acids having a benzene derivative, sulfur-modified amino acids having a benzene derivative, ester-modified amino acids having a benzene derivative, and compounds having an amino acid benzyl ester. The compound having both a methyl group and a primary amine is methylamine, ethylamine, or isopropylamine. The compound having both a benzene ring and a primary amine is aniline, benzylamine, or toluidine. The amino acid having a benzyl structure or the modified amino acid having a benzene derivative is any one of phenylalanine, tyrosine, tryptophan, phenylglycine, para-aminophenylalanine, histidine, 3,4-dihydroxyphenylalanine, phosphotyrosine, N-methylphenylalanine, 4-hydroxyphenylglycine, O-benzyltyrosine, benzoyl-lysine, L4-benzoylphenylalanine, N1m-benzyl-L-histidine, and N-epsilon-benzoyl-lysine. The sulfur-modified amino acid having a benzene derivative is any one of S-benzylcysteine, S-benzylhomocysteine, S-phenylcysteine, and S-phenylmethionine ester. The ester-modified amino acid having a benzene derivative is any one of phenylalanine methyl ester, tyrosine methyl ester, phenylalanine ethyl ester, tyrosine ethyl ester, and tyrosine benzyl ester. The compound having an amino acid benzyl ester is any one of phenylalanine benzyl ester, tyrosine benzyl ester, leucine benzyl ester, alanine benzyl ester, and valine benzyl ester.

[0013] In the composition of the present invention, the retention material exhibits a zeta potential in the range of 0.312 mV to 36.0 mV when dispersed in pure water.

[0014] In the composition of the present invention, the retention material exhibits a particle size in the range of 28.41 nm to 2238 nm when dispersed in pure water.

[0015] In the composition of the present invention, the functional substance is any one of a medicine, a nutrient, a food supplement, and a cosmetic.

[0016] In the composition of the present invention, when the functional substance is a pharmaceutical, the pharmaceutical is any one of selexipag, sildenafil, colistin, doxorubicin, organ drugs, small RNA drugs, vaccines, anticancer drugs, drugs for lung-related diseases, antitumor drugs, analgesics, anesthetics, immunomodulators, small molecule drugs, therapeutic proteins, nucleic acids, polymer drugs, peptide drugs, proapoptotic proteins, antibodies, siRNA, miRNA, shRNA, glatiramer acetate, and insulin. The pharmaceutical is administered by inhalation, intravenous injection, oral administration, topical application to the skin, or intramuscular administration.

[0017] In the composition of the present invention, when the functional substance is a nutrient, the nutrient is any one of fish oil, red yeast rice, glucosamine, chondroitin, anthocyanin, vitamin C, vitamin D, vitamin E, punicalagin, omega-3 fatty acid, glucosinolate, organic sulfur compound, lignan, α-linolenic acid, curcumin, polyphenol, β-carotene, flavonoid, anthocyanin, resveratrol, lycopene, arbutin, tranexamic acid, astaxanthin, calcium, phosphorus, potassium, sodium, chlorine, magnesium as major minerals, and iron, zinc, copper, manganese, iodine, selenium, and fluoride as trace elements.

[0018] In the composition of the present invention, the retention material is obtained by introducing the hydrophobic structure toward the oxygen atom site obtained by oxidizing the hydroxyl groups of the polysaccharide. The oxidizing agent used to oxidize the hydroxyl groups exposes aldehyde groups in the polysaccharide. The oxidizing agent may be any of peroxides, strong oxidizing agents, free radical initiators, halogenating agents, cleavage reagents, strong acids, mineral acids, hydrogen peroxide, organic peroxides, benzoyl peroxide, dicumyl peroxide, tert-butyl hydroperoxide, ozone, chromium trioxide, atmospheric oxygen, chlorine, bromine, sodium periodate, enzymes, periodate lyase, sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, and perchloric acid. The functional substance is encapsulated and retained by the retention material. The encapsulation process may include any of water-in-oil or oil-in-water emulsification, self-assembly, rotational evaporation, film rehydration, solvent displacement, double emulsion, and nanoprecipitation.

[0019] In the composition of the present invention, the purity of the polysaccharide derived from the gel-like substance obtained from the aloe plant is 80% or more. [Effects of the Invention]

[0020] According to the present invention, it is possible to realize the sustained release of an appropriate functional substance. Since the retention material contains the above-mentioned polysaccharide as a backbone, the composition of the present invention can be easily produced and the stability of the composition can be improved. [Brief explanation of the drawings]

[0021] [Figure 1] 1 is a schematic diagram of a composition according to an embodiment of the present invention. [Figure 2] FIG. 2 is a diagram showing the process in which the composition shown in FIG. 1 is transported toward an affected area in the body and the functional substance diffuses. [Figure 3] FIG. 2 is a diagram showing an example of a gel-like substance from an aloe plant, which is the origin of the holding material for the composition shown in FIG. 1. [Figure 4] FIG. 2 is a structural diagram of a retaining material included in the composition shown in FIG. 1. [Figure 5]2 is a chemical structural formula showing an example of the skeleton of a polysaccharide constituting the retention material included in the composition shown in FIG. 1. [Figure 6] 2 is a chemical structural formula showing an example of the skeleton of a polysaccharide constituting the retention material included in the composition shown in FIG. 1. [Figure 7] 2 is a chemical structural formula showing an example of a hydrophobic structure constituting a retention material included in the composition shown in FIG. 1. [Figure 8] 2 is a chemical structural formula showing an example of a retaining material included in the composition shown in FIG. 1. [Figure 9] 9 is a 1H-NMR spectrum of the support material shown in FIG. 8. [Figure 10] 2 is a chemical structural formula showing an example of a retaining material included in the composition shown in FIG. 1. [Figure 11] 11 is a 1H-NMR spectrum of the support material shown in FIG. 10. [Figure 12] 2 is a chemical structural formula showing an example of a retaining material included in the composition shown in FIG. 1. [Figure 13] 13 is a 1H-NMR spectrum of the support material shown in FIG. 12. [Figure 14] 2 is a chemical structural formula showing an example of a retaining material included in the composition shown in FIG. 1. [Figure 15] 16 is a 1H-NMR spectrum of the support material shown in FIG. 15. [Figure 16] 1H-NMR spectrum of the polysaccharide backbone shown in FIG. 5. [Figure 17] 1H-NMR spectrum of the polysaccharide backbone shown in FIG. 6. [Figure 18] 2 is a TEM image showing an example of the shape of a retaining material included in the composition shown in FIG. 1. [Figure 19] 2 is a table showing an example of particle size and zeta potential of the retention material included in the composition shown in FIG. 1. [Figure 20] 2 is a table showing an example of particle size and zeta potential of the retention material included in the composition shown in FIG. 1. DETAILED DESCRIPTION OF THE INVENTION

[0022] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0023] As shown in FIG. 1, a composition 10 according to an embodiment of the present invention comprises a functional substance 11 and a supporting material 12 .

[0024] The functional substance 11 is a substance having a predetermined function. The functional substance 11 is held in the holding material 12. The holding mode may be, for example, the functional substance 11 being enclosed in the holding material 12 or the functional substance 11 being encapsulated in the holding material 12. More specifically, when the holding material 12 has, for example, a polymeric skeleton 121, the functional substance 11 may be held so that it is entangled in the skeleton 121. In this case, in the composition 10, the functional substance 11 may be dispersed in the holding material 12 (skeleton 121).

[0025] When the functional substance 11 is encapsulated by the holding material 12, any process may be employed as long as the functional substance 11 is contained within the holding material 12. More specifically, the encapsulation process may include, for example, any of water-in-oil or oil-in-water emulsification, self-assembly, spin-coating, film rehydration, solvent displacement, double emulsion, and nanoprecipitation.

[0026] The retention material 12 is configured to be able to retain the functional substance 11. The retention material 12 is transported together with the functional substance 11 while retaining the functional substance 11. That is, the functional substance 11 is transported together with the retention material 12 while being retained by the retention material 12. The functional substance 11 and the retention material 12 are transported toward a location where the function of the functional substance 11 is to be expressed.

[0027] The function of the functional substance 11 is, for example, a chemical, pharmaceutical, or physical function. The location where the function is to be exerted is, for example, an affected area in the body or a part in the body where the effect of the function is expected. The functional substance 11 and the retention material 12 may be transported, for example, by a fluid (liquid or gas) separate from the composition 11. The transport of the composition 10 is achieved by flow or permeation.

[0028] As shown in FIG. 2, for example, composition 10 may be administered from outside the human body HB into the body via the respiratory tract RT. Composition 10 is transported by the above-mentioned fluid flow and reaches the vicinity of the affected area AP within the body. In this example, the affected area AP is located in the lungs within the body. Functional substance 11, retained by retention material 12, penetrates through the cell wall of the affected area AP toward its interior. During this process, the retention material 12 dissolves, and the functional substance 11 diffuses. The rate of this diffusion gradually increases as the retention material 12 dissolves. The diffused functional substance 11 then exhibits its function.

[0029] The functional substance 11 is a substance having a predetermined function and may be any substance as long as it can be held by the holding material 12. The functional substance 11 may be, for example, any of medicines, nutrients, food supplements, and cosmetics.

[0030] When the functional substance 11 is a drug, the drug may be, for example, selexipag, sildenafil, colistin, doxorubicin, organ drugs, small RNA drugs, vaccines, anticancer drugs, drugs for lung-related diseases, antitumor drugs, analgesics, anesthetics, immunomodulators, small molecule drugs, therapeutic proteins, nucleic acids, polymer drugs, peptide drugs, proapoptotic proteins, antibodies, siRNA, miRNA, shRNA, glatiramer acetate, or insulin. When the functional substance 11 is a drug, the drug may be administered by inhalation, intravenous injection, oral administration, application to the skin, or intramuscular administration.

[0031] When the functional substance 11 is a nutrient, the nutrient may be, for example, any of fish oil, red yeast rice, glucosamine, chondroitin, anthocyanin, vitamin C, vitamin D, vitamin E, punicalagin, omega-3 fatty acid, glucosinolate, organic sulfur compound, lignan, α-linolenic acid, curcumin, polyphenol, β-carotene, flavonoid, anthocyanin, resveratrol, lycopene, arbutin, tranexamic acid, astaxanthin, calcium, phosphorus, potassium, sodium, chlorine, magnesium as major minerals, iron, zinc, copper, manganese, iodine, selenium, and fluoride as trace elements.

[0032] The retention material 12 includes a polysaccharide backbone derived from a gel-like substance obtained from the aloe plant, which may be, for example, Aloe Vera, Aloe arborescens, Aloe Barbadense, or Aloe Ferox.

[0033] As shown in Figure 3, for example, assume that the aloe plant AV is Aloe Vera. The aloe plant AV comprises the epidermis OR / endodermis IR and the gel-like substance AG. The gel-like substance AG is covered by the epidermis OR / endodermis IR. After removing the epidermis OR / endodermis IR from the aloe plant AV, polysaccharides are produced from the remaining gel-like substance AG.

[0034] Polysaccharides may be extracted from the gel-like substance AG, for example. The extraction method is not limited, but may be, for example, extraction using a supercritical fluid or the extraction method described in Taiwan Patent Publication No. 10130748. The purity of polysaccharides derived from the gel-like substance AG is preferably, for example, 80% or higher. For example, when polysaccharides are obtained from the gel-like substance AG, impurities can be reduced by purification. The purity is adjusted depending on the degree of purification. The range of purity of the polysaccharides may be, for example, 80% to 85%, 85% to 90%, 90% to 95%, or 95% to 100%.

[0035] As shown in Fig. 4, the retention material 12 includes a polysaccharide skeleton 121 derived from the gel-like substance AG and a hydrophobic structure 122. The polysaccharide that forms the skeleton 121 may have any chemical structure or molecular weight as long as it has a sugar chain based on a sugar skeleton such as glucose, mannose, or galactose. One sugar chain of the polysaccharide contains at least -OH (hydroxyl group), -COCH3 (acetyl group), etc.

[0036] More specifically, -OH may be contained in each of the glucose backbone and the mannose backbone constituting the sugar chain. -COCH3 may be contained in the mannose backbone constituting the sugar chain. In one sugar chain of a polysaccharide, the number of -COCH3 may be less than the number of -OH. For example, in one sugar chain, one, two, or three of the -OH of the mannose backbone may be replaced with -COCH3, while the -OH of the glucose backbone is maintained, so that the number of -COCH3 is less than the number of -OH.

[0037] The polysaccharide may have, for example, a chemical structure corresponding to Acemannan AC, as shown in Figure 5. Acemannan AC may have at least a β(1,4)-mannose backbone and a β(1,4)-glucose backbone.

[0038] As shown in Figure 6, the polysaccharide may have a chemical structure corresponding to, for example, the oxide of acemannan AC, ACCHO. Using an oxidizing agent, the -OH (hydroxyl group 121a) of acemannan AC is oxidized to expose the -CHO (aldehyde group 121b), yielding the oxide of acemannan AC. When the oxide of acemannan ACHO is used as the retention material 12, the efficiency of encapsulating a hydrophobic functional substance 11 (e.g., a drug) can be improved by approximately 70% compared to when no oxidation is performed.

[0039] The oxidizing agent is not limited as long as it oxidizes —OH (hydroxyl group 121a) and exposes —CHO (aldehyde group 121b). The oxidizing agent may be, for example, any of peroxides, strong oxidizing agents, free radical initiators, halogenating agents, cleavage reagents, strong acids, mineral acids, hydrogen peroxide, organic peroxides, benzoyl peroxide, dicumyl peroxide, tert-butyl hydroperoxide, ozone, chromium trioxide, oxygen in the air, chlorine, bromine, sodium periodate, enzymes, periodate lyase, sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, and perchloric acid.

[0040] 4, the hydrophobic structure 122 is configured to be able to be introduced into the backbone 121. The hydrophobic structure 122 has a chemical structure that, when introduced into the backbone 121, increases the hydrophobicity of the retention material 12 compared to when the hydrophobic structure 122 is not introduced. The hydrophobic structure 122 may be a structure corresponding to one or more components selected from, for example, a hydrocarbon chain, an aromatic ring, a fluorine compound, an alkyl group, a steric hindrance structure, a nonpolar functional group, a long carbon chain, a compound having both a methyl group and a primary amine, a compound having both a benzene ring and a primary amine, an amino acid having a benzyl structure or a modified amino acid having a benzene derivative, a sulfur-modified amino acid having a benzene derivative, an ester-modified amino acid having a benzene derivative, and a compound having an amino acid benzyl ester.

[0041] The compound having both a methyl group and a primary amine may be, for example, methylamine, ethylamine, or isopropylamine. The compound having both a benzene ring and a primary amine may be, for example, aniline, benzylamine, or toluidine.

[0042] The amino acid having a benzyl structure or the modified amino acid having a benzene derivative described above may be, for example, any of phenylalanine, tyrosine, tryptophan, phenylglycine, para-aminophenylalanine, histidine, 3,4-dihydroxyphenylalanine, phosphotyrosine, N-methylphenylalanine, 4-hydroxyphenylglycine, O-benzyltyrosine, benzoyl-lysine, L4-benzoylphenylalanine, N im-benzyl-L-histidine, and N epsilon-benzoyl-lysine.

[0043] The sulfur-modified amino acid having a benzene derivative may be, for example, any one of S-benzylcysteine, S-benzylhomocysteine, S-phenylcysteine, and S-phenylmethionine ester. The ester-modified amino acid having a benzene derivative may be, for example, any one of phenylalanine methyl ester, tyrosine methyl ester, phenylalanine ethyl ester, tyrosine ethyl ester, and tyrosine benzyl ester. The compound having an amino acid benzyl ester may be, for example, any one of phenylalanine benzyl ester, tyrosine benzyl ester, leucine benzyl ester, alanine benzyl ester, and valine benzyl ester.

[0044] 6, the hydrophobic structure 122 is introduced toward the site of the oxygen atom 121c obtained by oxidizing the hydroxyl group 121a of the polysaccharide, thereby obtaining the retention material 12. The oxygen atom 121c is located at the end of the aldehyde group 121b.

[0045] As shown in FIG. 7, the hydrophobic structure 122 is, for example, O-benzyl-L-tyrosine OBLY, L-phenylalanine methyl ester PHEH, S-benzyl-L-cysteine ​​SBLC, or L-tyrosine ethyl ester TYRH.

[0046] As shown in Figure 8, the case where O-benzyl-L-tyrosine OBLY is introduced into the oxide ACCHO of acemannan AC will be described. In this case, the oxygen atom 121c of the oxide ACCHO faces the -NH2 (amino group 122a) of O-benzyl-L-tyrosine OBLY. A dehydration reaction then occurs between the oxygen atom 121c and the -NH2 (amino group 122a). As a result, the carbon atom of the aldehyde group and the nitrogen atom of the amino group 122a are bonded via a double bond. This results in a retention material 12 into which O-benzyl-L-tyrosine OBLY has been introduced.

[0047] FIG. 9 shows the results after introducing O-benzyl-L-tyrosine (OBLY) into the oxide of acemannan AC. 1 9 shows the H-NMR spectrum. The peaks a, b, c, d, e, f, g, h, i, j, and k in the spectrum in FIG. 9 correspond to the positions of hydrogen atoms a, b, c, d, e, f, g, h, i, j, and k in the structural formula of the retention material 12. In this way, it can be confirmed that O-benzyl-L-tyrosine OBLY has been introduced into the retention material 12.

[0048] As shown in Figure 10, the case where L-phenylalanine methyl ester PHEH is introduced into the oxide ACCHO of acemannan AC will be described. In this case, the oxygen atom 121c of the oxide ACCHO faces the -NH2 (amino group 122a) of L-phenylalanine methyl ester PHEH. A dehydration reaction then occurs between the oxygen atom 121c and the -NH2 (amino group 122a). As a result, the carbon atom of the aldehyde group and the nitrogen atom of the amino group 122a are bonded via a double bond. This results in a retention material 12 into which L-phenylalanine methyl ester PHEH has been introduced.

[0049] FIG. 11 shows the results after introducing L-phenylalanine methyl ester PHEH into the oxide of acemannan AC, ACCHO. 111 shows the H-NMR spectrum. The peaks a, b, c, d, e, f, g, h, i, and j in the spectrum correspond to the positions a, b, c, d, e, f, g, h, i, and j of the hydrogen atoms in the structural formula of the retention material 12. In this way, it can be confirmed that L-phenylalanine methyl ester PHEH has been introduced into the retention material 12.

[0050] As shown in Figure 12, the case where S-benzyl-L-cysteine ​​SBLC is introduced into the oxide ACCHO of acemannan AC will be described. In this case, the oxygen atom 121c of the oxide ACCHO faces the -NH2 (amino group 122a) of S-benzyl-L-cysteine ​​SBLC. A dehydration reaction then occurs between the oxygen atom 121c and the -NH2 (amino group 122a). As a result, the carbon atom of the aldehyde group and the nitrogen atom of the amino group 122a are bonded via a double bond. This results in a retention material 12 into which S-benzyl-L-cysteine ​​SBLC has been introduced.

[0051] FIG. 13 shows the results after introducing S-benzyl-L-cysteine ​​SBLC into the oxide of acemannan AC, ACCHO. 1 13 shows the H-NMR spectrum. The peaks a, b, c, d, e, f, g, h, i, j, and k in the spectrum correspond to the positions of hydrogen atoms a, b, c, d, e, f, g, h, i, j, and k in the structural formula of retention material 12. In this way, it can be confirmed that S-benzyl-L-cysteine ​​SBLC has been introduced into retention material 12.

[0052] As shown in FIG. 14, the case where L-tyrosine ethyl ester TYRH is introduced into the oxide ACCHO of acemannan AC will be described. In this case, the oxygen atom 121c of the oxide ACCHO faces the -NH2 (amino group 122a) of L-tyrosine ethyl ester TYRH. A dehydration reaction then occurs between the oxygen atom 121c and the -NH2 (amino group 122a). As a result, the carbon atom of the aldehyde group and the nitrogen atom of the amino group 122a are bonded via a double bond. This results in a retention material 12 into which L-tyrosine ethyl ester TYRH has been introduced.

[0053] FIG. 15 shows the results of the reaction of L-tyrosine ethyl ester TYRH with accemannan AC oxide ACCHO. 1 15 shows the H-NMR spectrum. The peaks a, b, c, d, e, f, g, h, i, and j in the spectrum correspond to the positions a, b, c, d, e, f, g, h, i, and j of the hydrogen atoms in the structural formula of the retention material 12. In this way, it can be confirmed that L-tyrosine ethyl ester TYRH has been introduced into the retention material 12.

[0054] FIG. 16 shows the results of the analysis of acemannan AC. 1 16 shows the H-NMR spectrum. Peaks a, b, c, d, and e in the spectrum in Fig. 16 correspond to the positions of hydrogen atoms a, b, c, d, and e in the structural formula of acemannan AC. Fig. 17 shows the H-NMR spectrum of ACCHO, an oxide of acemannan AC. 1 17 shows the H-NMR spectrum. The peaks a, b, c, d, e, e', and f in the spectrum of FIG. 17 correspond to the positions of hydrogen atoms a, b, c, d, e, e', and f in the structural formula of ACCHO, the oxide of acemannan AC. These 1 The H-NMR spectrum confirms that acemannan AC is oxidized to give the oxide ACCHO.

[0055] Furthermore, by comparing the spectrum in Figure 17 with the spectra in Figures 9, 11, 13, and 15, it can be confirmed that a hydrophobic structure 122 is introduced into ACCHO, an oxide of acemannan AC, a polysaccharide, to obtain a retention material 12.

[0056] FIG. 18 is an example of a TEM image of a retention material 12 dispersed in pure water. In the TEM image marked with the letters "AC," the retention material 12 is acemannan AC. In the TEM image marked with the letters "AC-CHO," the retention material 12 is ACCHO, an oxide of acemannan AC. In the TEM image marked with the letters "OBLY," the retention material 12 is ACCHO, an oxide of acemannan AC, to which O-benzyl-L-tyrosine OBLY has been introduced. In the TEM image marked with the letters "SBLC," the retention material 12 is ACCHO, an oxide of acemannan AC, to which S-benzyl-L-cysteine ​​SBLC has been introduced. The particle size is approximately 20 nm to 100 nm, i.e., the retention material 12 and the composition 10 comprising the retention material 12 exhibit nano-sized particles.

[0057] The retention material 12 and the composition 10 including the retention material 12 are prepared to have various particle sizes. The retention material 12 may exhibit a small particle size of, for example, 28.76±0.346 nm when dispersed in pure water. The retention material 12 may also exhibit a large particle size of, for example, 2208±29.7 nm when dispersed in pure water. The retention material 12 may also exhibit an intermediate particle size between these. That is, the retention material 12 may exhibit a particle size in the range of 28.41 nm to 2238 nm when dispersed in pure water.

[0058] The retention material 12 and the composition 10 comprising the retention material 12 can be adjusted to exhibit various zeta potentials. For example, the retention material 12 may exhibit a zeta potential in the range of 0.312 mV to 36.0 mV when dispersed in pure water.

[0059] FIG. 19 shows an example of the particle size and zeta potential of a retention material 12 dispersed in pure water. The retention material 12 labeled "Acemannan (AC)" is acemannan AC. When the particle size of acemannan AC is 65.28±1.268 nm, the PDI is 0.546±0.062 and the zeta potential is 20.9±1.21 mV. The retention material 12 labeled "Acemannan-CHO" is ACCHO, an oxide of acemannan AC. When the particle size of ACCHO, an oxide of acemannan AC, is 80.23±3.837 nm, the PDI is 0.456±0.022 and the zeta potential is 20.2±0.97 mV.

[0060] Figure 20 shows an example of the particle size and zeta potential of retention material 12 dispersed in Dulbecco's modified Eagle's medium. The retention material 12 labeled "Acemannan (AC)" is acemannan AC. When the particle size of acemannan AC is 49.37 + / - 1.881 nm, the PDI is 0.386 + / - 0.062 and the zeta potential is -18 + / - 5.66 mV. The retention material 12 labeled "Acemannan-CHO" is ACCHO, an oxide of acemannan AC. When the particle size of ACCHO, an oxide of acemannan AC, is 94.81 + / - 14.42 nm, the PDI is 0.699 + / - 0.426 and the zeta potential is -2.63 + / - 1.68 mV.

[0061] The support material 12, labeled "SBLC / AC-CHO," is an oxide of acemannan AC (ACCHO) with S-benzyl-L-cysteine ​​(SBLC). When the particle size of SBLC / AC-CHO was 28.43±4.384 nm·305.5±65.34 nm, the PDI was 0.580±0.132·0.338±0.100, and the zeta potential was -17.7±1.13 mV·-36.9±7.64 mV.

[0062] The support material 12, labeled "OBLY / AC-CHO," is an oxide of acemannan AC (ACCHO) with O-benzyl-L-tyrosine (OBLY). When the particle size of OBLY / AC-CHO was 310.9±28.43 nm·299.9±12.94 nm, the PDI was 0.324±0.035·0.509±0.196, and the zeta potential was -7.95±5.16 mV·-6.79±0.693 mV.

[0063] The retention material 12, labeled "PheH / AC-CHO," is an oxide of acemannan AC (ACCHO) with L-phenylalanine methyl ester (PHEH). When the particle size of PheH / AC-CHO was 346.2±11.47 nm·88.39±18.82 nm, the PDI was 0.273±0.075·0.283±0.098, and the zeta potential was -11.9±2.26 mV·-24.6±6.36 mV.

[0064] The support material 12, labeled "Tyr / AC-CHO," is an oxide of acemannan AC (ACCHO) doped with L-tyrosine ethyl ester (TYRH). When the particle size of Tyr / AC-CHO was 201.7±9.962 nm·135.1±12.52 nm, the PDI was 0.480±0.155·0.279±0.051, and the zeta potential was -2.79±1.77 mV·-31.2±0.529 mV.

[0065] [Effects of the embodiment] As described above, the composition 10 according to an embodiment of the present invention comprises a functional substance 11, which is a substance having a predetermined function, and a retention material 12 configured to be able to retain the functional substance and transported together with the functional substance 11 to a location where the function is to be expressed while retaining the functional substance. The retention material 12 includes, as a skeleton 121, a polysaccharide derived from a gel-like substance AG obtained from an aloe plant AV [Claim 1].

[0066] This allows for the sustained release of an appropriate functional substance. Since the retention material contains the above-mentioned polysaccharide as a backbone, the composition of the present invention can be easily produced and the stability of the composition can be improved.

[0067] The retention material 12 includes a hydrophobic structure 122 having a chemical structure that, when introduced into the backbone 121, increases the hydrophobicity of the retention material 12 [Claim 2].

[0068] This increases the hydrophobicity of the retention material 12. This improves the interaction between the functional substance 11, such as a medicine, and the retention material 12, which serves as its carrier. This increases the retention force of the retention material 12.

[0069] The polysaccharide in the skeleton 121 has a chemical structure corresponding to acemannan AC or the oxide of acemannan AC, ACCHO, and the hydrophobic structure 122 has a structure corresponding to one or more components selected from the group consisting of hydrocarbon chains, aromatic rings, fluorine compounds, alkyl groups, steric hindrance structures, non-polar functional groups, long carbon chains, compounds having both a methyl group and a primary amine, compounds having both a benzene ring and a primary amine, amino acids having a benzyl structure or modified amino acids having a benzene derivative, sulfur-modified amino acids having a benzene derivative, ester-modified amino acids having a benzene derivative, and compounds having an amino acid benzyl ester [Claim 3].

[0070] This allows the hydrophobic structure 122 to be introduced into the polysaccharide through chemical bonding, thereby reliably increasing the hydrophobicity of the retention material 12.

[0071] The retention material 12 exhibits a zeta potential in the range of 0.312 mV to 36.0 mV when dispersed in pure water [Claim 4].

[0072] This allows the retention material 12 to have an appropriate degree of dispersion during transportation.

[0073] The retention material 12 exhibits a particle size in the range of 28.41 nm to 2238 nm when dispersed in pure water [Claim 5].

[0074] This allows the retention material 12 to have an appropriate particle size during transportation.

[0075] The functional substance 11 is any one of a medicine, a nutrient, a food supplement, and a cosmetic [Claim 6].

[0076] This allows the functional substance 11 to have various functions.

[0077] When the functional substance 11 is the medicine, the medicine is any one of selexipag, sildenafil, colistin, doxorubicin, organ medicine, small molecule RNA medicine, vaccine, anticancer drug, lung-related disease drug, antitumor drug, analgesic, anesthetic, immunomodulator, small molecule medicine, therapeutic protein, nucleic acid, polymer medicine, peptide medicine, apoptosis-promoting protein, antibody, siRNA, miRNA, shRNA, glatiramer acetate, and insulin, and the route of administration of the medicine is any one of inhalation, intravenous injection, oral administration, application to the skin, and intramuscular administration [Claim 7].

[0078] This makes the composition 10 suitable for use in a drug delivery system, in which various drugs can be used.

[0079] When the functional substance 11 is a nutrient, the nutrient is any one of fish oil, red koji rice, glucosamine, chondroitin, anthocyanin, vitamin C, vitamin D, vitamin E, punicalagin, omega-3 fatty acid, glucosinolate, organic sulfur compound, lignan, α-linolenic acid, curcumin, polyphenol, β-carotene, flavonoid, anthocyanin, resveratrol, lycopene, arbutin, tranexamic acid, astaxanthin, calcium, phosphorus, potassium, sodium, chlorine, magnesium as major minerals, iron, zinc, copper, manganese, iodine, selenium, fluoride as trace elements [Claim 8].

[0080] This makes the composition 10 suitable for use in a drug delivery system. A variety of nutrients can be used in the drug delivery system.

[0081] The retention material 12 is obtained by introducing the hydrophobic structure 122 toward the oxygen atom site obtained by oxidizing the hydroxyl group of the polysaccharide. The hydroxyl group is oxidized using an oxidizing agent that exposes aldehyde groups in the polysaccharide. The oxidizing agent may be any of peroxides, strong oxidizing agents, free radical initiators, halogenating agents, cleavage reagents, strong acids, mineral acids, hydrogen peroxide, organic peroxides, benzoyl peroxide, dicumyl peroxide, tert-butyl hydroperoxide, ozone, chromium trioxide, atmospheric oxygen, chlorine, bromine, sodium periodate, enzymes, periodate lyase, sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, and perchloric acid. The functional substance 11 is encapsulated and thereby retained by the retention material 12. The encapsulation process includes any of water-in-oil or oil-in-water emulsification, self-assembly, spin-concentration, film rehydration, solvent displacement, double emulsion, and nanoprecipitation [Claim 9].

[0082] According to this method, by oxidizing the hydroxyl groups of the polysaccharide, it is possible to easily obtain binding points for introducing the hydrophobic structure 122. Furthermore, the oxidation of the hydroxyl groups does not destroy the polysaccharide skeleton. Therefore, the hydrophobic structure 122 can be reliably and easily introduced while maintaining the polysaccharide skeleton. Furthermore, various oxidizing agents can be used for introducing the hydrophobic structure 122.

[0083] The purity of the polysaccharide derived from the gel-like substance AG obtained from the aloe plant is 80% or more [Claim 10].

[0084] According to this, polysaccharides obtained by extraction or the like from the gel-like substance AG can be used for the retention material 12. Therefore, the retention material 12 can be easily produced.

[0085] The above-described embodiments disclosed herein are to be considered as illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0086] 10...composition 11...Functional substances 12...retaining material 121...Skeleton 122...Hydrophobic structure

Claims

1. a functional substance that is a substance having a predetermined function; a retaining material configured to be able to retain the functional substance and transported together with the functional substance to a location where the function is to be exhibited while retaining the functional substance; In a composition comprising: The retaining material is Contains polysaccharides as a backbone derived from the gel-like substance obtained from the aloe plant composition.

2. 10. The composition of claim 1 , The retaining material is and a hydrophobic structure having a chemical structure that, when incorporated into the scaffold, increases the hydrophobicity of the support material. composition.

3. 3. The composition of claim 2, The polysaccharide in the backbone is It has a chemical structure corresponding to acemannan or an oxide of acemannan, The hydrophobic structure is a structure corresponding to one or more components selected from the group consisting of a hydrocarbon chain, an aromatic ring, a fluorine compound, an alkyl group, a sterically hindered structure, a non-polar functional group, a long carbon chain, a compound having both a methyl group and a primary amine, a compound having both a benzene ring and a primary amine, an amino acid having a benzyl structure or a modified amino acid having a benzene derivative, a sulfur-modified amino acid having a benzene derivative, an ester-modified amino acid having a benzene derivative, and a compound having an amino acid benzyl ester; The compound having both a methyl group and a primary amine is methylamine, ethylamine, or isopropylamine; The compound having both a benzene ring and a primary amine is It is either aniline, benzylamine, or toluidine, The amino acid having a benzyl structure or the modified amino acid having a benzene derivative is phenylalanine, tyrosine, tryptophan, phenylglycine, para-aminophenylalanine, histidine, 3,4-dihydroxyphenylalanine, phosphotyrosine, N-methylphenylalanine, 4-hydroxyphenylglycine, O-benzyltyrosine, benzoyl-lysine, L4-benzoylphenylalanine, N im-benzyl-L-histidine, or N epsilon-benzoyl-lysine; The sulfur-modified amino acid having a benzene derivative is S-benzylcysteine, S-benzylhomocysteine, S-phenylcysteine, or S-phenylmethionine ester, The ester-modified amino acid having a benzene derivative is phenylalanine methyl ester, tyrosine methyl ester, phenylalanine ethyl ester, tyrosine ethyl ester, or tyrosine benzyl ester; The compound having an amino acid benzyl ester is It is either phenylalanine benzyl ester, tyrosine benzyl ester, leucine benzyl ester, alanine benzyl ester, or valine benzyl ester. composition.

4. 4. The composition of claim 3, The retaining material is When dispersed in pure water, it exhibits a zeta potential in the range of 0.312 mV to 36.0 mV. composition.

5. 4. The composition of claim 3, The retaining material is When dispersed in pure water, it exhibits particle sizes in the range of 28.41 nm to 2238 nm. composition.

6. The composition according to any one of claims 1 to 5, The functional substance is It is either a medicine, nutrient, food supplement, or cosmetic product composition.

7. 7. The composition of claim 6, When the functional substance is the medicine, The medicine is The drug is any one of selexipag, sildenafil, colistin, doxorubicin, organ drugs, small molecular weight RNA drugs, vaccines, anticancer drugs, drugs for lung-related diseases, antitumor drugs, analgesics, anesthetics, immunomodulators, small molecule drugs, therapeutic proteins, nucleic acids, polymer drugs, peptide drugs, proapoptotic proteins, antibodies, siRNA, miRNA, shRNA, glatiramer acetate, and insulin, The route of administration of the medicament is It can be inhaled, injected intravenously, orally, applied to the skin, or administered intramuscularly. composition.

8. 7. The composition of claim 6, When the functional substance is a nutrient, The nutrients are Fish oil, red yeast rice, glucosamine, chondroitin, anthocyanin, vitamin C, vitamin D, vitamin E, punicalagin, omega-3 fatty acids, glucosinolates, organic sulfur compounds, lignans, alpha-linolenic acid, curcumin, polyphenols, beta-carotene, flavonoids, anthocyanin, resveratrol, lycopene, arbutin, tranexamic acid, astaxanthin, calcium, phosphorus, potassium, sodium, chlorine, magnesium as major minerals, iron, zinc, copper, manganese, iodine, selenium, fluoride as trace elements composition.

9. The composition according to any one of claims 2 to 5, The retaining material is the hydrophobic structure is introduced toward the site of an oxygen atom obtained by oxidizing a hydroxyl group of the polysaccharide, The oxidation of the hydroxyl groups is carried out using an oxidizing agent that exposes aldehyde groups in the polysaccharide; The oxidizing agent is peroxides, strong oxidizing agents, free radical initiators, halogenating agents, cleaving reagents, strong acids, mineral acids, hydrogen peroxide, organic peroxides, benzoyl peroxide, dicumyl peroxide, tert-butyl hydroperoxide, ozone, chromium trioxide, atmospheric oxygen, chlorine, bromine, sodium periodate, enzymes, periodate lyase, sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, or perchloric acid; The functional substance is By being encapsulated, it is held by the holding material, The encapsulation process comprises: Includes water-in-oil or oil-in-water emulsification, self-assembly, spin-concentration, film rehydration, solvent displacement, double emulsion, and nanoprecipitation composition.

10. 10. The composition of claim 9, The composition contains polysaccharides derived from the gel-like substance obtained from the aloe plant, the purity of which is 80% or more.

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