USE OF NMN FOR THE PREVENTION AND/OR TREATMENT OF A BACK PAIN AND CORRESPONDING COMPOSITIONS

Abstract

Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, are described for use thereof in the prevention and/or treatment of a back pain such as a lumbalgia (low back pain), a dorsalgia (severe back pain), or a cervicalgia (neck pain), preferably a chronic lumbalgia; as well as compositions that include the same.

Claims

1. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof via topical administration in the prevention and/or treatment of a back pain.

2. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof according to claim 1 in which the pharmaceutically acceptable derivative of NMN is dihydronicotinamide mononucleotide (NMN-H), alpha-NMN, a compound having the formula (I): ##STR00079## or one of the pharmaceutically acceptable: stereoisomers, salts, hydrates, solvates, or crystals thereof, in which: X is selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2 and C═CH.sub.2; R.sub.1 is selected from among H, azido, cyano, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) thio-alkyl, (C.sub.1-C.sub.8) heteroalkyl, and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are selected independently of one another, from among H, halogen, azido, cyano, hydroxyl, (C.sub.1-C.sub.12) alkyl, (C.sub.1-C.sub.12) thio-alkyl, (C.sub.1-C.sub.12) heteroalkyl, (C.sub.1-C.sub.12) haloalkyl, and OR; wherein R is selected from among H, (C.sub.1-C.sub.12) alkyl, C(O)(C.sub.1-C.sub.12)alkyl, C(O)NH(C.sub.1-C.sub.12)alkyl, C(O)O(C.sub.1-C.sub.12)alkyl, C(O)aryl, C(O)(C.sub.1-C.sub.12)alkyl aryl, C(O)NH(C.sub.1-C.sub.12)alkyl aryl, C(O)O(C.sub.1-C.sub.12)alkyl aryl, and C(O)CHR.sub.AANH.sub.2; wherein R.sub.AA is a side chain selected from a proteinogenic amino acid; R.sub.6 is selected from among H, azido, cyano, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) thio-alkyl, (C.sub.1-C.sub.8) heteroalkyl, and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.7 is selected from among H, P(O)R.sub.9R.sub.10, and P(S)R.sub.9R.sub.10 and ##STR00080## where n is an integer selected from 1 or 3; in which R.sub.9 and R.sub.10 are selected independently of one another, from among OH, OR.sub.11, NHR.sub.13, NR.sub.13R.sub.14, a (C.sub.1-C.sub.8) alkyl, a (C.sub.2-C.sub.8) alkenyl, a (C.sub.2-C.sub.8)alkynyl, a (C.sub.3-C.sub.10) cycloalkyl, a (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.8)alkyl aryl, (C.sub.1-C.sub.8) aryl alkyl, (C.sub.1-C.sub.8) heteroalkyl, (C.sub.1-C.sub.8) heterocycloalkyl, a heteroaryl, and NHCHR.sub.AR.sub.A′C(O)R.sub.12; in which: R.sub.11 is selected from among a group: (C.sub.1-C.sub.10) alkyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.5-C.sub.18) aryl, (C.sub.1-C.sub.10) alkylaryl, substituted (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.10) heteroalkyl, (C.sub.3-C.sub.10) heterocycloalkyl, (C.sub.1-C.sub.10) haloalkyl, a heteroaryl, —(CH.sub.2).sub.nC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)O(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nSC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl, and —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl aryl; wherein n is an integer selected from 1 to 8; P(O)(OH)OP(O)(OH).sub.2; halogen, nitro, cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, —N(R.sub.11a).sub.2, C.sub.1-C.sub.6 acylamino, —COR.sub.11b, —OCOR.sub.11b; NHSO.sub.2(C.sub.1-C.sub.6 alkyl), —SO.sub.2N(R.sub.11a).sub.2SO.sub.2; wherein each of Ria is independently selected from H and a (C.sub.1-C.sub.6) alkyl, and R.sub.11b is independently selected from OH, C.sub.1-C.sub.6 alkoxy, NH.sub.2, NH(C.sub.1-C.sub.6 alkyl) or N(C.sub.1-C.sub.6 alkyl).sub.2; R.sub.12 is selected from among H, C.sub.1-C.sub.10 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.10 haloalkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocycloalkyl, C.sub.5-C.sub.18 aryl, C.sub.1-C.sub.4 alkylaryl, and C.sub.5-C.sub.12 heteroaryl; wherein the said aryl or heteroaryl groups are optionally substituted with one or two groups selected from among halogen, trifluoromethyl, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, and cyano; and R.sub.A and R.sub.A′ are independently selected from among H, a (C.sub.1-C.sub.10) alkyl, (C.sub.2-C.sub.10) alkenyl, (C.sub.2-C.sub.10) alkynyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.1-C.sub.10) thio-alkyl, (C.sub.1-C.sub.10) hydroxylalkyl, (C.sub.1-C.sub.10) alkylaryl, and (C.sub.5-C.sub.12) aryl, (C.sub.3-C.sub.10) heterocycloalkyl, a heteroaryl, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, and a side chain selected from among a proteinogenic amino acid or a non-proteinogenic amino acid; wherein the said aryl groups are optionally substituted with a group selected from among hydroxyl, (C.sub.1-C.sub.10) alkyl, (C.sub.1-C.sub.6) alkoxy, a halogen, a nitro, and a cyano; or R.sub.9 and R.sub.10 form, together with the phosphorus atoms to which they are attached, a 6-membered ring in which —R.sub.9—R.sub.10— represents —CH.sub.2—CH.sub.2—CHR—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; or R.sub.9 and R.sub.10 form, together with the phosphorus atoms to which they are attached, a 6-membered ring in which —R.sub.9—R.sub.10— represents —O—CH.sub.2—CH.sub.2—CHR—O—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; R.sub.8 is selected from among H, OR, NHR.sub.13, NR.sub.13R.sub.14, NH—NHR.sub.13, SH, CN, N.sub.3, and halogen; wherein R.sub.13 and R.sub.14 are selected independently of one another, from among H, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) alkyl aryl, and —CR.sub.BR.sub.C—C(O)—OR.sub.D in which R.sub.B and R.sub.C are independently a hydrogen atom, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, benzyl, indolyl, or imidazolyl; where the (C.sub.1-C.sub.6) alkyl and the (C.sub.1-C.sub.6) alkoxy may be optionally and independently of one another substituted by one or more of the halogen, amino, amido, guanidyl, hydroxyl, thiol, or carboxyl groups, and the benzyl group is optionally substituted by one or more halogen or hydroxyl groups; or R.sub.B and R.sub.C form, together with the carbon atom to which they are attached, a C.sub.3-C.sub.6 cycloalkyl group optionally substituted by one or more halogens, amino, amido, guanidyl, hydroxyl, thiol, and carboxyl; and R.sub.D is a hydrogen, a (C.sub.1-C.sub.6) alkyl, a (C.sub.2-C.sub.6) alkenyl, a (C.sub.2-C.sub.6) alkynyl, or a (C.sub.3-C.sub.6) cycloalkyl; Y is selected from among CH, CH.sub.2, C(CH.sub.3).sub.2 and CCH.sub.3; represents a single or a double bond along Y; and represents the alpha or beta anomer depending on the position of R.sub.1; or a compound having the formula (Ia): ##STR00081## or one of the: stereoisomers, salts, hydrates, solvates, or crystals thereof, in which: X′.sub.1 and X′.sub.2 are independently selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2, and C═CH.sub.2; R′.sub.1 and R′.sub.13 are independently selected from among H, azido, cyano, a C.sub.1-C.sub.8 alkyl, a C.sub.1-C.sub.8 thio-alkyl, a C.sub.1-C.sub.8 heteroalkyl, and OR, wherein R is selected from H and a C.sub.1-C.sub.8 alkyl; R′.sub.2, R′.sub.3, R′.sub.4, R′.sub.5, R′.sub.9, R′.sub.10, R′.sub.11, R′.sub.12 are independently selected from among H, a halogen, an azido, a cyano, a hydroxyl, a C.sub.1-C.sub.12 alkyl, a C.sub.1-C.sub.12 thioalkyl, a C.sub.1-C.sub.12 hetero-alkyl, a C.sub.1-C.sub.12 haloalkyl, and OR; wherein R may be selected from among H, a C.sub.1-C.sub.12 alkyl, a C(O)(C.sub.1-C.sub.12) alkyl, a C(O)NH(C.sub.1-C.sub.12) alkyl, a C(O)O(C.sub.1-C.sub.12) alkyl, a C(O) aryl, a C(O)(C.sub.1-C.sub.12) aryl, a C(O)NH(C.sub.1-C.sub.12) alkyl aryl, a C(O)O(C.sub.1-C.sub.12) alkyl aryl, or a C(O)CHR.sub.AANH2 group; wherein R.sub.AA is a side chain selected from a proteinogenic amino acid; R′.sub.6 and R′.sub.8 are independently selected from among H, an azido, a cyano, a C.sub.1-C.sub.8 alkyl and OR, wherein R is selected from H and a C.sub.1-C.sub.8 alkyl; R′.sub.7 and R′.sub.14 are independently selected from among H, OR, NHR, NRR′, NH—NHR, SH, CN, N.sub.3 and a halogen; wherein R and R′ are independently selected from H and a (C.sub.1-C.sub.8) alkyl aryl; Y′1 and Y′2 are independently selected from among CH, CH.sub.2, C(CH.sub.3).sub.2, or CCH.sub.3; M′ is selected from H or a suitable counter ion; represents a single or double bond depending on Y′.sub.1 and Y′.sub.2; and represents an alpha or beta anomer depending on the position of R′.sub.1 and R′.sub.13; and combinations thereof, for use thereof via topical administration in the prevention and/or treatment of a back pain.

3. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof according to claim 2 in which the pharmaceutically acceptable derivative of NMN is selected from among: Compound I-B, Compound I-C, Compound I-D, Compound I-E, Compound I-F, Compound I-G, Compound I-H, Compound I-I, Compound I-J, preferably Compound I-B, Compound I-C, Compound I-D, Compound I-F, and combinations thereof from Table 1.

4. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof according to claim 2 is selected from among the compounds Ia-A to Ia-I, preferably from among the compound having the formula Ia-B, the compound having the formula Ia-C, the compound having the formula Ia-E, the compound having the formula Ia-F, the compound having the formula Ia-H, the compound having the formula Ia-I and the compound having the formula Ia-G of Table 2.

5. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof according to claim 1, in which the back pain is a cervicalgia, a dorsalgia, or a lumbalgia; and preferably a chronic lumbalgia.

6. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof according to claim 1 in which the back pain is due to one of the pathologies selected from among: injury to a muscle, injury to a ligament, injury to a tendon, degeneration of the intervertebral discs in the vertebrae, a herniated disc in the vertebrae, a pain that is gynecological in origin, spondylolisthesis, arthritis, osteoarthritis, osteoporosis of the vertebral column, osteoporosis-related fracture, an abdominal aortic aneurysm, a tumour, an infection, an inflammation, facet joint injuries, intervertebral disc injuries, regional or global spinal stability-related disorders, spinal deformity, muscular contraction in the vertebrae, or combinations thereof.

7. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof in combination with at least one other therapeutic agent.

8. Nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, for use thereof wherein the at least one therapeutic agent may be an analgesic, a non-steroidal anti-inflammatory drug, cortisone, a cortisone derivative, a muscle relaxant, or combinations thereof.

9. A composition comprising nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, for use thereof via topical administration, in the prevention and/or treatment of a back pain.

10. The composition according to claim 9, in which the pharmaceutically acceptable derivative is selected from among dihydronicotinamide mononucleotide (NMN-H), alpha-NMN, a compound having the formula (I): ##STR00082## or one of the pharmaceutically acceptable: stereoisomers, salts, hydrates, solvates, or crystals thereof, in which: X is selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2 and C═CH.sub.2; R.sub.1 is selected from among H, azido, cyano, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) thio-alkyl, (C.sub.1-C.sub.8) heteroalkyl, and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are selected independently of one another, from among H, halogen, azido, cyano, hydroxyl, (C.sub.1-C.sub.12) alkyl, (C.sub.1-C.sub.12) thio-alkyl, (C.sub.1-C.sub.12) heteroalkyl, (C.sub.1-C.sub.12) haloalkyl, and OR; wherein R is selected from among H, (C.sub.1-C.sub.12) alkyl, C(O)(C.sub.1-C.sub.12)alkyl, C(O)NH(C.sub.1-C.sub.12)alkyl, C(O)O(C.sub.1-C.sub.12)alkyl, C(O)aryl, C(O)(C.sub.1-C.sub.12)alkyl aryl, C(O)NH(C.sub.1-C.sub.12)alkyl aryl, C(O)O(C.sub.1-C.sub.12)alkyl aryl, and C(O)CHR.sub.AANH.sub.2; wherein R.sub.AA is a side chain selected from a proteinogenic amino acid; R.sub.6 is selected from among H, azido, cyano, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) thio-alkyl, (C.sub.1-C.sub.8) heteroalkyl, and OR; wherein R is selected from H and (C.sub.1-C.sub.8) alkyl; R.sub.7 is selected from among H, P(O)R.sub.9R.sub.10, and P(S)R.sub.9R.sub.10 and ##STR00083## where n is an integer selected from 1 or 3; in which R.sub.9 and R.sub.10 are selected independently of one another, from among OH, OR.sub.11, NHR.sub.13, NR.sub.13R.sub.14, a (C.sub.1-C.sub.8) alkyl, a (C.sub.2-C.sub.8) alkenyl, a (C.sub.2-C.sub.8)alkynyl, a (C.sub.3-C.sub.10) cycloalkyl, a (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.8)alkyl aryl, (C.sub.1-C.sub.8) aryl alkyl, (C.sub.1-C.sub.8) heteroalkyl, (C.sub.1-C.sub.8) heterocycloalkyl, a heteroaryl, and NHCHR.sub.AR.sub.A′C(O)R.sub.12; in which: R.sub.11 is selected from among a group: (C.sub.1-C.sub.10) alkyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.5-C.sub.18) aryl, (C.sub.1-C.sub.10) alkylaryl, substituted (C.sub.5-C.sub.12) aryl, (C.sub.1-C.sub.10) heteroalkyl, (C.sub.3-C.sub.10) heterocycloalkyl, (C.sub.1-C.sub.10) haloalkyl, a heteroaryl, —(CH.sub.2).sub.nC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nOC(O)O(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nSC(O)(C.sub.1-C.sub.15)alkyl, —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl, and —(CH.sub.2).sub.nC(O)O(C.sub.1-C.sub.15)alkyl aryl; wherein n is an integer selected from 1 to 8; P(O)(OH)OP(O)(OH).sub.2; halogen, nitro, cyano, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, —N(R.sub.11a).sub.2, C.sub.1-C.sub.6 acylamino, —COR.sub.11b, —OCOR.sub.11b; NHSO.sub.2(C.sub.1-C.sub.6 alkyl), —SO.sub.2N(R.sub.11a).sub.2SO.sub.2; wherein each of R.sub.11a is independently selected from H and a (C.sub.1-C.sub.6) alkyl, and R.sub.11b is independently selected from OH, C.sub.1-C.sub.6 alkoxy, NH.sub.2, NH(C.sub.1-C.sub.6 alkyl) or N(C.sub.1-C.sub.6 alkyl).sub.2; R.sub.12 is selected from among H, C.sub.1-C.sub.10 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.1-C.sub.10 haloalkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.10 heterocycloalkyl, C.sub.5-C.sub.18 aryl, C.sub.1-C.sub.4 alkylaryl, and C.sub.5-C.sub.12 heteroaryl; wherein the said aryl or heteroaryl groups are optionally substituted with one or two groups selected from among halogen, trifluoromethyl, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, and cyano; and R.sub.A and R.sub.A′ are independently selected from among H, a (C.sub.1-C.sub.10) alkyl, (C.sub.2-C.sub.10) alkenyl, (C.sub.2-C.sub.10) alkynyl, (C.sub.3-C.sub.10) cycloalkyl, (C.sub.1-C.sub.10) thio-alkyl, (C.sub.1-C.sub.10) hydroxylalkyl, (C.sub.1-C.sub.10) alkylaryl, and (C.sub.5-C.sub.12) aryl, (C.sub.3-C.sub.10) heterocycloalkyl, a heteroaryl, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, and a side chain selected from among a proteinogenic amino acid or a non-proteinogenic amino acid; wherein the said aryl groups are optionally substituted with a group selected from among hydroxyl, (C.sub.1-C.sub.10) alkyl, (C.sub.1-C.sub.6) alkoxy, a halogen, a nitro, and a cyano; or R.sub.9 and R.sub.10 form, together with the phosphorus atoms to which they are attached, a 6-membered ring in which —R.sub.9—R.sub.10— represents —CH.sub.2—CH.sub.2—CHR—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; or R.sub.9 and R.sub.10 form, together with the phosphorus atoms to which they are attached, a 6-membered ring in which —R.sub.9—R.sub.10— represents —O—CH.sub.2—CH.sub.2—CHR—O—; wherein R is selected from among H, a (C.sub.5-C.sub.6) aryl group, and (C.sub.5-C.sub.6) heteroaryl group, wherein the said aryl or heteroaryl groups are optionally substituted by a halogen, trifluoromethyl, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, and cyano; R.sub.8 is selected from among H, OR, NHR.sub.13, NR.sub.13R.sub.14, NH—NHR.sub.13, SH, CN, N.sub.3, and halogen; wherein R.sub.13 and R.sub.14 are selected independently of one another, from among H, (C.sub.1-C.sub.8) alkyl, (C.sub.1-C.sub.8) alkyl aryl, and —CR.sub.BR.sub.C—C(O)—OR.sub.D in which R.sub.B and R.sub.C are independently a hydrogen atom, a (C.sub.1-C.sub.6) alkyl, a (C.sub.1-C.sub.6) alkoxy, benzyl, indolyl, or imidazolyl; where the (C.sub.1-C.sub.6) alkyl and the (C.sub.1-C.sub.6) alkoxy may be optionally and independently of one another substituted by one or more of the halogen, amino, amido, guanidyl, hydroxyl, thiol, or carboxyl groups, and the benzyl group is optionally substituted by one or more halogen or hydroxyl groups; or R.sub.B and R.sub.C form, together with the carbon atom to which they are attached, a C.sub.3-C.sub.6 cycloalkyl group optionally substituted by one or more halogens, amino, amido, guanidyl, hydroxyl, thiol, and carboxyl; and R.sub.D is a hydrogen, a (C.sub.1-C.sub.6) alkyl, a (C.sub.2-C.sub.6) alkenyl, a (C.sub.2-C.sub.6) alkynyl, or a (C.sub.3-C.sub.6) cycloalkyl; Y is selected from among CH, CH.sub.2, C(CH.sub.3).sub.2 and CCH.sub.3; n is an integer selected from 1 to 3; represents a single or a double bond along Y; and represents the alpha or beta anomer depending on the position of R.sub.1; or a compound having the formula (Ia): ##STR00084## or one of the: stereoisomers, salts, hydrates, solvates, or crystals thereof, in which: X′.sub.1 and X′.sub.2 are independently selected from among O, CH.sub.2, S, Se, CHF, CF.sub.2, and C═CH.sub.2; R′.sub.1 and R′.sub.13 are independently selected from among H, azido, cyano, a C.sub.1-C.sub.8 alkyl, a C.sub.1-C.sub.8 thio-alkyl, a C.sub.1-C.sub.8 heteroalkyl, and OR, wherein R is selected from H and a C.sub.1-C.sub.8 alkyl; R′.sub.2, R′.sub.3, R′.sub.4, R′.sub.5, R′.sub.9, R′.sub.10, R′.sub.11, R′.sub.12 are independently selected from among H, a halogen, an azido, a cyano, a hydroxyl, a C.sub.1-C.sub.12 alkyl, a C.sub.1-C.sub.12 thioalkyl, a C.sub.1-C.sub.12 hetero-alkyl, a C.sub.1-C.sub.12 haloalkyl, and OR; wherein R may be selected from among H, a C.sub.1-C.sub.12 alkyl, a C(O)(C.sub.1-C.sub.12) alkyl, a C(O)NH(C.sub.1-C.sub.12) alkyl, a C(O)O(C.sub.1-C.sub.12) alkyl, a C(O) aryl, a C(O)(C.sub.1-C.sub.12) aryl, a C(O)NH(C.sub.1-C.sub.12) alkyl aryl, a C(O)O(C.sub.1-C.sub.12) alkyl aryl, or a C(O)CHR.sub.AANH.sub.2 group; wherein R.sub.AA is a side chain selected from a proteinogenic amino acid; R′.sub.6 and R′.sub.8 are independently selected from among H, an azido, a cyano, a C.sub.1-C.sub.8 alkyl and OR, wherein R is selected from H and a C.sub.1-C.sub.8 alkyl; R′.sub.7 and R′.sub.14 are independently selected from among H, OR, NHR, NRR′, NH—NHR, SH, CN, N.sub.3 and a halogen; wherein R and R′ are independently selected from H and a (C.sub.1-C.sub.8) alkyl aryl; Y′1 and Y′2 are independently selected from among CH, CH.sub.2, C(CH.sub.3).sub.2, or CCH.sub.3; M′ is selected from H or a suitable counter ion; represents a single or double bond depending on Y′.sub.1 and Y′.sub.2; and represents an alpha or beta anomer depending on the position of R′.sub.1 and R′.sub.13; and combinations thereof, for use thereof via topical administration in the prevention and/or treatment of a back pain.

11. The composition according to claim 9 that comprises nicotinamide mononucleotide (NMN), a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, in an amount comprised between 0.05% and 15% by weight, preferably between 1 and 10% by weight, on a more preferred basis between 3 and 5% by weight relative to the total weight of the composition.

12. The composition according to claim 9, which is in the form of a gel, a solution, a water-in-oil emulsion, an oil-in-water emulsion, an oil, a cream, an ointment, or a liniment; on a more preferred basis in the form of an oil-in-water emulsion.

13. The composition according to claim 9 further comprising at least one additional therapeutic agent.

14. The composition according to claim 10, in which the pharmaceutically acceptable derivative of NMN is selected from among: Compound I-B, Compound I-C, Compound I-D, Compound I-E, Compound I-F, Compound I-G, Compound I-H, Compound I-I, Compound I-J; preferably Compound I-B, Compound I-C, Compound I-D, Compound I-F from Table 1; Compound Ia-A, the compound having the formula Ia-B, the compound having the formula Ia-C, the compound having the formula Ia-E, the compound having the formula Ia-F, the compound having the formula Ia-H, the compound having the formula Ia-I, the compound having the formula Ia-G from Table 2, and combinations thereof.

15. The composition according to claim 13, in which the at least one therapeutic agent may be an analgesic, a non-steroidal anti-inflammatory drug, cortisone, a cortisone derivative, a muscle relaxant, or combinations thereof.

Description

FIGURES

[0308] FIG. 1 is a graph showing the evolution of intensity of the pain linked to lumbalgia (low back pain) over 10 days as measured by the visual analogue scale (VAS).

[0309] FIG. 2 is a graph showing the evolution of the WOMAC score and its different areas of assessment over 10 days.

[0310] FIG. 3 is a graph showing the evolution of the Lequesne score and its different categories over 10 days.

EXAMPLES

[0311] In the remainder of this description, the examples provided are intended byway of illustration of the present invention and are in no way intended to limit the scope thereof.

Example 1: Synthesis of the Compounds According to the Invention

[0312] Material and Methods

[0313] All the reagents were obtained from commercial suppliers and used without any further purification. Thin layer chromatography was carried out on TLC silica gel 60 F254 plastic sheets (0.2 mm layer thickness) from Merck. Purification by column chromatography was carried out on silica gel 60 (70-230 mesh ASTM, Merck). The melting points were determined either on a digital device (Electrothermal IA 8103) and are not corrected, or on a Kofler heating bench of type WME (Wagner & Munz). The .sup.1H, .sup.19F, and .sup.13C nuclear magnetic resonance (NMR) and infrared (IR) spectra confirmed the structures of all of the compounds. The IR spectra were recorded on a Perkin Elmer Spectrum 100 FT-IR spectrometer; and the NMR spectra were recorded, using CDCl.sub.3, CD.sub.3CN, D.sub.2O or DMSO-d.sub.6 as solvent, on a BRUKER AC 300 or 400 spectrometer at 300 or 400 MHz for the .sup.1H spectra, 75 or 100 MHz spectra for the .sup.13C spectra, and 282 or 377 MHz for the .sup.19F spectra. The chemical shifts (δ) were expressed in parts per million relative to the signal, indirectly (i) with CHCl.sub.3 (δ 7.27) for .sup.1H; and (ii) with CDCl.sub.3 (δ 77.2) for .sup.13C; and directly (iii) with CFCl.sub.3 (internal standard) (δ 0) for .sup.19F. The chemical shifts are provided in ppm and the peak multiplicities are denoted as follows: s, singlet; br s, broad singlet; d, doublet; dd, doublet of doublets; ddd, doublet of doublets of doublets; t, triplet; q, quartet; quint, quintet; m, multiplet. High-resolution mass spectra (HRMS) were obtained from the “Service central d'analyse de Solaize” (French National Centre for Scientific Research—Solaize) and were recorded on a Waters spectrometer using electrospray ionisation time-of-flight (ESI-TOF) mass spectrometry. Tetramethylsilane (TMS) having the formula Si(CH.sub.3).sub.4 is used as reference compound for the NMR spectra.

[0314] Protocol

[0315] Step 1—Synthesis of the Compound having the Formula X-1: The compound having the formula XIV (1.0 equiv.) is dissolved in dichloromethane. The nicotinamide having the formula XV (1.50 equiv.) and the TMSOTf (1.55 equiv.) are added at ambient temperature. The reaction mixture is heated under reflux and stirred until completion of the reaction. The mixture is cooled to ambient temperature and filtered. The filtrate is concentrated to dryness so as to give crude NR (nicotinamide riboside) tetraacetate having the formula X-1.

[0316] Step 2—Synthesis of the Compound Having the Formula X: The crude NR tetraacetate having the formula X-1 is dissolved in methanol and cooled to −10° C. This is followed by addition of 4.6 M ammonia in methanol (3.0 equivalents) at −10° C. and the mixture is stirred at this temperature until completion of the reaction. Dowex HCR (H.sup.+) is added until a pH of 6-7 is attained. The reaction mixture is heated to 0° C. and filtered. The resin is washed with a mixture of methanol and acetonitrile. The filtrate is concentrated until it becomes dry. The residue is dissolved in acetonitrile and concentrated to solid content dryness. The residue is dissolved in acetonitrile so as to give a solution of crude nicotinamide riboside triflate having the formula X.

[0317] Step 3—Synthesis of the Compound having the Formula XI: The solution of crude NR nicotinamide riboside triflate in acetonitrile is diluted with trimethyl phosphate (10.0 equivalents). The acetonitrile is distilled under vacuum and the mixture is cooled to −10° C. Phosphorus oxychloride (4.0 equiv.) is added at −10° C. and the mixture is stirred at −10° C. until completion of the reaction.

[0318] Step 4 and Step 5: Synthesis of the Compound having the Formula Ia-A: The mixture is hydrolysed by adding a 50/50 mixture of acetonitrile and water, followed by the addition of methyl tert-butyl ether (or tert-butyl methyl ether). The mixture is filtered and the solid is dissolved in water. The aqueous solution is neutralised by adding sodium bicarbonate and extracted with dichloromethane. The aqueous layer is concentrated to dryness so as to give a crude mixture of NMN (Compound I-A) and the compound having the formula Ia-A.

[0319] Isolation of the Compound having the Formula Ia-A (β,β diNMN): The NMN and the compound having the formula Ia-A are separated by purification on Dowex 50 w×8 with elution of water. The fractions containing the compound having the formula Ia-A are concentrated to solid content dryness. The residue is purified by column chromatography on silica gel (isopropanol/water gradient). The pure fractions are combined and concentrated. The residue is lyophilised so as to give the Compound I-a-A in the form of a beige solid.

[0320] .sup.31P NMR: δ (ppm, reference 85% H.sub.3PO.sub.4: 0 ppm in D.sub.2O)=−11.72; .sup.1H NMR: δ (ppm, reference TMS: 0 ppm in D.sub.2O)=4.20 (ddd, J.sub.H-H=11.9, 3.5, 2.4 Hz, 2H), 4.35 (ddd, J.sub.H-H=11.9, 3.9, 2.2 Hz, 2H), 4.43 (dd, J.sub.H-H=5.0, 2.6 Hz, 2H), 4.53 (t, J.sub.H-H=5.0 Hz, 2H), 4.59 (m, 2H), 6.16 (d, J.sub.H-H=5.4 Hz, 2H), 8.26 (dd, J.sub.H-H=8.1, 6.3 Hz, 2H), 8.93 (d, J.sub.H-H=8.1 Hz, 2H), 9.25 (d, J.sub.H-H=6.2 Hz, 2H), 9.41 (s, 2H); .sup.13C NMR: δ (ppm, reference TMS: 0 ppm in D.sub.2O)=64.84 (CH.sub.2), 70.73 (CH), 77.52 (CH), 87.11 (CH), 99.88 (CH), 128.65 (CH), 133.89 (Cq), 139.84 (CH), 142.54 (CH), 146.04 (CH), 165.64 (Cq); MS (ES+): m/z=122.8 [Mnicotinamide+H]+, 650.8 [M+H]+.

[0321] Synthesis of the Compound Having the Formula Ia-B (α,β Di-NMN)

[0322] Phosphorus oxychloride (3.0 eq.) is added to trimethylphosphate (20.0 eq.) at −5° C. β-NR chloride (1.0 eq.) is added in portions at −5° C. and the reaction mixture is stirred overnight at −5° C. Morpholine (3.0 eq.) is added dropwise at −10/0° C. and the mixture is stirred for 2-3 hrs. α-NMN (1.0 eq.) is then added in portions at −5° C. and the reaction mixture is stirred at −5° C. overnight. The hydrolysis is carried out by dropwise addition of water (5 vol.) at −10/0° C. and the mixture is stirred until complete homogenisation at 10-15° C. The reaction mixture is then extracted with dichloromethane (6*10 vol.) and the aqueous phase is neutralised by elution through the formate resin Purolite A600E (theoretical quantity to neutralise the HCl originating from POCl.sub.3). The eluate is then concentrated in vacuo at 45/50° C. in order to give the crude containing the compound having the formula Ia-B. The water elution with the H.sup.+ resin Dowex 50 w×8 100-200 mesh makes it possible to remove certain impurities. The fractions containing the Compound I-B are combined and concentrated in vacuo at 45-50° C. The crude is then purified by preparative chromatography on Luna Polar RP 10 μm stationary phase with elution with an aqueous solution of 10 mM NaH2PO4. The pure fractions are combined and eluted with water on the resin Purolite C100EH H.sup.+(quantity necessary to completely exchange Na+ by H.sup.+), then eluted on the resin Purolite A600E acetate (quantity necessary to completely exchange H.sub.2PO.sub.4— by acetate). The eluate is concentrated in vacuo and the residue is lyophilised in order to give the Compound Ia-B in the form of a white solid.

[0323] .sup.31P NMR: δ (ppm, reference 85% H.sub.3PO.sub.4: 0 ppm in D.sub.2O)=−11.87, −11.69, −11.46, −11.29; .sup.1H NMR: 6 (ppm, reference TMS: 0 ppm in D.sub.2O)=4.10 (ddd, J=11.1, 6.1, 3.1 Hz, 1H), 4.15-4.25 (m, 2H), 4.36 (ddd, J=12.2, 4.4, 2.4 Hz, 1H), 4.40 (dd, J=4.9, 2.4 Hz, 1H), 4.44 (dd, J=5.0, 2.7 Hz, 1H), 4.53 (t, J=5.0 Hz, 1H), 4.5 (m, 1H), 4.85 (m, 1H), 4.92 (t, J=5.3 Hz, 1H), 6.15 (d, J=5.5 Hz, 1H), 6.51 (d, J=5.7 Hz, 1H), 8.14 (dd, J=8.0, 6.3 Hz, 1H), 8.26 (dd, J=8.1, 6.3 Hz, 1H), 8.88 (d, J=8.1 Hz, 1H), 8.92 (d, J=8.1 Hz, 1H), 9.02 (d, J=6.3 Hz, 1H), 9.24 (s, 1H), 9.26 (d, J=6.4 Hz, 1H), 9.40 (s, 1H); .sup.13C NMR: δ (ppm, reference TMS: 0 ppm in D.sub.2O)=64.83, 64.87 (CH.sub.2), 65.30, 65.35 (CH.sub.2), 70.65 (CH), 70.74 (CH), 71.92 (CH), 77.51 (CH), 87.03, 87.10 (CH), 87.19, 87.26 (CH), 96.57 (CH), 99.83 (CH), 126.89 (CH), 128.54 (CH), 132.44 (Cq), 133.81 (Cq), 139.85 (CH), 140.92 (CH), 142.50 (CH), 143.49 (CH), 145.06 (CH), 145.97 (CH), 165.64 (Cq), 165.88 (Cq); MS (ES+): m/z=122.8 [Mnicotinamide+H]+, 650.9 [M+H]+.

[0324] Synthesis of the Compound Having the Formula Ia-C(α,α Di-NMN)

[0325] Phosphorus oxychloride (3.0 eq.) is added to trimethylphosphate (20.0 eq.) at −5° C. α-NR chloride (1.0 eq.) is added portionwise at −5° C. and the reaction mixture is stirred overnight at −5° C. Morpholine (3.0 eq.) is added dropwise at −10/0° C. and the mixture is stirred for 2-3 hrs. α-NMN (1.0 eq.) is then added in portions at −5° C. and the reaction mixture is stirred at −5° C. overnight. The hydrolysis is carried out by dropwise addition of water (5 vol.) at −10/0° C. and the mixture is stirred until complete homogenisation at 10-15° C. The reaction mixture is then extracted with dichloromethane (6*10 vol.) and the aqueous phase is neutralised by elution through the formate resin Purolite A600E (theoretical quantity to neutralise the HCl originating from POCl.sub.3). The eluate is then concentrated in vacuo at 45/50° C. to give the crude containing the compound having the formula Ia-C. The water elution with H.sup.+ resin Dowex 50 w×8 100-200 mesh makes it possible to remove certain impurities. The fractions containing the Compound I-C are combined and concentrated in vacuo at 45-50° C. The crude is then purified by preparative chromatography on Luna Polar RP 10 μm stationary phase with elution with an aqueous solution of 10 mM NaH.sub.2PO.sub.4. The pure fractions are combined and eluted with water on resin Purolite C100EH H.sup.+(quantity necessary to completely exchange Na+ by H.sup.+), then eluted on on the resin Purolite A600E acetate (quantity necessary to completely exchange H.sub.2PO.sub.4— by acetate). The eluate is concentrated in vacuo and the residue is freeze-dried in order to give the Compound Ia-C in the form of a white solid.

.sup.31P NMR: δ (ppm, reference 85% H.sub.3PO.sub.4: 0 ppm in D.sub.2O)=−11.40; .sup.1H NMR: δ (ppm, reference TMS: 0 ppm in D.sub.2O)=4.14 (ddd, J=11.4, 3.4, 2.8 Hz, 2H), 4.23 (ddd, J=11.6, 3.3, 2.8 Hz, 2H), 4.44 (dd, J=4.8, 2.3 Hz, 2H), 4.88 (m, 2H), 4.96 (t, J=5.3 Hz, 2H), 6.54 (d, J=5.7 Hz, 2H), 8.15 (dd, J=8.1, 6.2 Hz, 2H), 8.89 (d, J=8.1 Hz, 2H), 9.05 (d, J=6.3 Hz, 2H), 9.26 (s, 2H); .sup.13C NMR: δ (ppm, reference TMS: 0 ppm in D.sub.2O)=65.37 (CH.sub.2), 70.70 (CH), 71.95 (CH), 87.30 (CH), 96.62 (CH), 126.91 (CH), 132.45 (Cq), 140.94 (CH), 143.52 (CH), 145.07 (CH), 165.90 (Cq); MS (ES+): m/z=122.7 [Mnicotinamide+H]+, 650.8 [M+H]+.

Example 2: Study of the Efficacy of Compound I-A (NMN Beta)

[0326] A satisfaction study was carried out on a group of 12 volunteers, aged 42±8 years, consisting of seven female and five male subjects. The main objective of this study was to evaluate the level of satisfaction of subjects with regard to the evolution of their lumbalgia (low back pain) during the morning and/or evening application of a composition according to the invention containing 5% by weight of NMN.

[0327] The average BMI of the participants was 25.3 t 4.4, half of them were overweight (50%), 41.7% were normal weight, and the rest of the subjects were obese (8.3%). More specifically, five participants were of normal weight, six participants were overweight, and one participant was obese. None of these patients presented with a chronic pathology such as an inflammatory pathology altering their cartilage, muscles, tendons, ligaments or bones, or requiring surgery.

[0328] The duration of the existence of pains in the lumbar spine region was on average 4±3 years (ie 45 months) while the current pains of the subjects dated back to 2±3 years pre-baseline (before inclusion). These pains occurred mostly spontaneously (58.3%). More precisely, seven participants presented with a lumbalgia of spontaneous origin, one participant presented with a lumbalgia resulting from a physical or sporting activity, two participants attributed their lumbalgia to the practice of gardening, and two other participants attributed their lumbalgia to another of these causes. The participants therefore all had chronic lumbalgia.

[0329] A composition in the form of an oil-in-water emulsion comprising 5% NMN was formulated as follows, the ingredients being designated by their INCI (International Nomenclature of Cosmetic Ingredients) name: Aqua, Paraffinum liquidum, Cetyl alcohol, Glyceryl stearate, Benzyl PCA, Ceteareth-20, Ceteareth-12, Cetyl Palmitate, Cocoglycerides, Cetearyl alcohol, Sodium Hydroxide, NMN. The composition was prepared according to any method well known to the person skilled in the art.

[0330] The mass percentages are calculated by relating the mass of the ingredient to the total mass of the composition, then by multiplying by 100.

[0331] The study took place over 10 days. At baseline, ie upon inclusion (DO), the selected subjects provide their demographic characteristics (age, weight, height), indicate the period of persistence and intensity of the pain on a Visual Analogue Scale, and complete the WOMAC and Lequesne questionnaires. These different scales were used in order to assess by different means the effect of NMN on lumbalgia.

[0332] The lumbalgia at baseline was assessed at an average of 73.4±7.6 on a Visual Analogue Scale (VAS) ranging from 0 (no pain) to 100 (intolerable pain).

[0333] At baseline, the “stiffness” assessment criterion of the WOMAC questionnaire was the most significant and amounted to 64.2±21.0, the “pain” assessment criterion amounted to 59.9±13.1 and the “function” assessment criterion amounted to 57.1±15.5. The total WOMAC score was 58.3±14.8 at baseline. The higher the WOMAC score, the greater the functional pain interference.

[0334] The Lequesne algo-functional index is used for the clinical follow-up of lumbalgia in the present study. The Lequesne score on inclusion was on average 8.3±2.5, and 3 of the subjects had a score greater than or equal to 10 (16.7%), which demonstrates a very significant or indeed even intolerable impairment.

[0335] Over the subsequent 9 day period, each evening the subjects fill in the Visual Analogue Scale of pain, ensuring any discomfort or problems arising or the taking of analgesics are reported therein.

[0336] On day 10, the volunteers complete the WOMAC questionnaire, the Lequesne questionnaire, the Visual Analogue Scale (VAS) of pain, indicating the perceived improvement in lumbalgia pain relief as measured by the PGI-I index (abbreviation for “Patient Global Improvement Impression”), satisfaction with regard to evolution of the lumbalgia on a Likert scale as well as the ease of application and penetration of the composition, assessment of the texture and odour of the composition, likelihood of re-use thereof in the event of recurrence of a similar pain, and recommendation of use to third parties presenting with pain of similar nature. The PGI-I index is an index that serves as means for evaluating the response to a treatment. The Likert scale is a psychometric tool used for measuring an attitude in individuals, which consists of one or more statements for which the individual responding expresses their degree of agreement or disagreement.

[0337] During the study, product compliance was optimal with a compliance rate of 97.7%. Indeed, during the 9 days of follow-up, almost all of the subjects applied the composition twice a day, as shown in Table 1.

TABLE-US-00007 TABLE 3 Time of application D D D D D D D D D 1 2 3 4 5 6 7 8 9 Previous 10 12 11 12 12 12 11 12 12 evening and morning Previous 0 0 1 0 0 0 1 0 0 evening Morning 2 0 0 0 0 0 0 0 0 Total 12 12 12 12 12 12 12 12 12

[0338] The lumbalgia pain, as measured by the VAS, decreased steadily over the 10 days of application of the product, dropping from 73.4±7.6 at baseline to 30.8±22.6, that is to say a significant reduction of 58.7±29.2% (p<0.0001, calculated with a Student's t test). The mean time period in order to obtain an initial 50% reduction in pain relative to baseline was 5.0±2.9 days. The results expressed as mean and standard deviation, on day-by-day basis, and for all of the volunteers, are summarised in Table 2 below:

TABLE-US-00008 TABLE 4 Standard Mini- Maxi- Signif- Days Mean deviation Median mum mum p-value icance D 0 73.4 7.6 72.5 64.0 84.0 NA NA D 1 61.1 14.8 60.5 34.0 81.0 0.0163 <0.05 D 2 56.8 20.3 59.0 22.0 83.0 0.0138 <0.05 D 3 52.3 22.1 57.5 14.0 81.0 0.0031 <0.01 D 4 49.4 18.9 51.0 19.0 79.0 0.001 <0.001 D 5 45.7 19.1 45.5 17.0 76.0 0.0001 <0.001 D 6 42.4 18.5 42.5 17.0 71.0 <0.0001 <0.0001 D 7 45.2 25.2 48.0 4.0 93.0 0.0017 <0.01 D 8 35.8 24.8 38.0 4.0 96.0 0.0002 <0.001 D 9 28.3 20.2 26.0 0.0 77.0 <0.0001 <0.0001 D 10 30.8 22.6 30.0 5.0 77.0 <0.0001 <0.0001

[0339] These results are in addition represented by the graph in FIG. 1. As may be seen in FIG. 1 and in view of the results in Table 2 the pain felt by the patients decreased on average by 58.7%.

[0340] After 10 days of application of the composition according to the invention, the “pain” criterion of the WOMAC fell from 59.9±13.1 at baseline to 31.0±21.2 at the end of the study, which is a significant reduction of 50.1±31.3% (p<0.001) as may be seen in FIG. 2. The reductions for the other assessment criteria were also significant, declining from 64.2±21.0 to 31.6±25.0 for the “stiffness” criterion of the WOMAC (reduction of 52.5±32.9%, p<0.001), and from 57.1±15.5% to 30.8±21.8 for the “function” criterion of the WOMAC (reduction of 47.5±35.6%, p<0.01). The total WOMAC score also decreased significantly from 58.3±14.8 to 30.9±21.7, which is a decrease of 48.6±33.7% (p<0.001).

[0341] As may be seen in FIG. 3, the Lequesne algo-functional score decreased significantly from baseline to study endpoint, decreasing from 8.3±2.5 to 5.3±3.8 (p<0.001) which is a 38.8% reduction in the score. At the end of the study, more than three quarters of the subjects (83.4%) no longer had any impairment or had only a modest or slight impairment.

[0342] At the end of the study, 91.7% of the subjects experienced improvement, characterised as: ‘considerable’—3 subjects (25.0%); ‘a lot’—4 subjects (33.3%); and ‘slight’—4 subjects (33.3%). Only one subject showed no improvement. Almost all (91.7%) of the participants were satisfied with the evolution of their chronic lumbalgia, including 33.3% who were very satisfied.

[0343] From an organoleptic standpoint, all the patient responses confirmed that the composition: was easy to apply (66.7%—very easy); penetrated easily into the skin (58.3%—very easily); had a pleasant texture (33.3%—very pleasant); and a pleasant smell (58.3%—pleasant and 8.3%—very pleasant).

[0344] All of the patients confirmed their likelihood of: reusing the composition in the event of recurrence of a similar lumbalgia (75.0%—very certainly); and recommending it to others experiencing similar pain in the lumbar region (50.0%—very certainly).

[0345] One patient took paracetamol on D5 because of lumbar pain.

[0346] The volunteer participants experienced neither any adverse side effects following the use of the composition according to the invention nor developed any allergies.

[0347] NMN, a pharmaceutically acceptable derivative thereof, or a pharmaceutically acceptable salt thereof, as well as compositions that comprise the same are therefore effective in reducing back pain, and in particular chronic lumbalgia. Furthermore, the use of NMN and of the composition comprising NMN in accordance with the invention enabled participants to avoid having to resort to using their usual treatment to relieve their lumbar pain, or at the very least to reduce the need to use conventional therapies. Although the demonstration was carried out for the treatment of lumbalgia, the results may be transposed to the treatment of back pain. The present invention therefore provides a safe and effective alternative to conventional therapies for back pain, and in particular for lumbalgia.