Muscle atrophy

Abstract

This disclosure relates to L-lactic acid and / or polymers thereof for the treatment of muscle injuries and / or diseases, conditions and / or disorders characterized by muscle atrophy. Compositions comprising L-lactic acid and / or polymers thereof for said uses are also disclosed.

Description

Technical Field

[0001] This disclosure relates to L-lactic acid and / or polymers thereof for the treatment of muscle injuries and / or diseases, conditions and / or disorders characterized by muscle atrophy. Compositions comprising L-lactic acid and / or polymers thereof for said uses are also disclosed. Background Technology

[0002] Muscle atrophy and muscle loss in the human body can be caused by: injury; conditions such as disuse, aging, and lack of exercise; and diseases and / or conditions that lead to adverse consequences such as muscle imbalance, weakness, falls, and even death. Research into pharmacological and therapeutic solutions for addressing muscle atrophy or muscle loss is of great significance for improving people's quality of life and health. However, to date, apart from exercise programs and nutritional supplements, there are no effective treatment options for preventing or treating muscle injuries, diseases, conditions, and / or disorders characterized by muscle atrophy and / or muscle loss / weakness. Exercise programs can be quite complex and time-consuming, and do not always yield the desired results. While nutritional supplements can be helpful to some extent, their effectiveness is limited.

[0003] Skeletal muscular atrophy (SMA) is a debilitating consequence of many chronic diseases and disorders involving starvation. It reduces treatment options and positive clinical outcomes, impairs quality of life, and increases morbidity and mortality. Despite considerable research to identify drug targets and the molecular mechanisms by which SMA improves, no drugs have been approved for the treatment of skeletal or other muscle atrophy. Current drug treatments used in clinical practice for muscle injuries, diseases, conditions, and disorders characterized by muscle atrophy and / or muscle loss / weakness do not directly promote muscle tissue regeneration and are therefore unsatisfactory.

[0004] Muscle injury refers to a condition in which muscle tissue is damaged or injured. It can involve partial damage to muscle tissue, or a complete tear or rupture. Some muscle injuries can lead to loss of muscle function and require appropriate treatment and rehabilitation to promote muscle repair and recovery.

[0005] Traditional views suggest that polylactic acid (PLA) used for these purposes, while gradually generating collagen, may induce an inflammatory response, thus possessing limited repair capabilities. However, during this limited repair process, inflammation and / or excessive fibrosis can occur, leading to scar tissue formation, which may impair mobility and tissue function. Therefore, PLA is not recommended for treating the aforementioned muscle injuries, conditions, and disorders characterized by muscle atrophy and / or muscle loss / weakness. Despite numerous attempts in this field, providing an effective solution for treating muscle injuries, conditions, and disorders characterized by muscle atrophy remains a challenge. Summary of the Invention

[0006] One object of this disclosure is to provide a pharmaceutical agent and / or composition capable of reducing or at least partially overcoming the difficulties in the prior art related to the treatment of muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy.

[0007] One objective is to provide a pharmaceutical agent and / or composition for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. Another objective is to provide a pharmaceutical agent and / or composition for the preventative treatment of muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. A third objective is to provide a pharmaceutical agent and / or composition for the therapeutic treatment of muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. Specifically, one objective of the present invention is to provide a manner for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy, wherein said treatment does not induce a significant inflammatory response.

[0008] The inventors of this case unexpectedly discovered that L-lactic acid and / or its polymers and compositions thereof have unexpected therapeutic potential in the treatment of muscle injuries and / or diseases, conditions and / or disorders characterized by muscle atrophy. Furthermore, the inventors of this case also discovered that the L-lactic acid and / or its polymers and compositions thereof disclosed herein, for use according to this disclosure, do not cause excessive inflammation and / or fibrosis. Therefore, one or more of the aforementioned objectives, as well as other objectives that are obvious to those skilled in the art from reading the complete disclosure, are satisfied by the various aspects disclosed herein.

[0009] L-lactic acid and / or its polymers

[0010] Therefore, in a first aspect of this disclosure, L-lactic acid and / or its polymers are provided for treating muscle injuries and / or diseases, conditions and / or disorders characterized by muscle atrophy.

[0011] Based on the in vitro experimental models presented in the appended embodiments, the inventors have discovered that L-lactic acid and / or its polymers unexpectedly prove beneficial in the treatment of muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. As demonstrated by the inventors, for example in Example 3, L-lactic acid and its polymers achieve the disclosed therapeutic effects. Therefore, in one embodiment, L-lactic acid is provided for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy.

[0012] As illustrated below, polymers of L-lactic acid can be particularly beneficial in the treatment of muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. For example, the inventors have found that this benefit lies in the fact that polymers of L-lactic acid degrade more slowly than L-lactic acid when administered to a subject in need. As demonstrated in the examples, this beneficial characteristic of polymers of L-lactic acid allows the therapeutic effects disclosed herein to be achieved when the polymer of L-lactic acid is administered to a subject in need at least once. Therefore, in one embodiment, a polymer of L-lactic acid is provided for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. The inventors envision that any polymer containing L-lactic acid would be beneficial in said treatment. Therefore, in one embodiment, the polymer is selected from the group consisting of poly-L-lactic acid, poly-D,L-lactic acid, and any copolymer containing L-lactic acid but not D-lactic acid.

[0013] The inventors of this invention have shown, for example, in Examples 1 and 2, that poly-L-lactic acid and poly-D,L-lactic acid, as a copolymer of L-lactic acid and D-lactic acid, are advantageous in the treatment. Therefore, in one embodiment, the polymer may be selected from the group consisting of poly-L-lactic acid and poly-D,L-lactic acid.

[0014] Not bound by theory, the inventors envision that the concentration of L-lactic acid in the poly-D,L-lactic acid can vary and may be lower than the concentration of D-lactic acid in the poly-D,L-lactic acid. In these cases, not bound by theory, the inventors envision that treatment conditions, such as the frequency and / or dosage of administration, can be adjusted to achieve the disclosed therapeutic effect. Thus, in some embodiments, the concentration of L-lactic acid in the poly-D,L-lactic acid is at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%. In another embodiment, the ratio of L-lactic acid to D-lactic acid in the poly-D,L-lactic acid is at least about 1:5, such as where the ratio is about 1:1. In one particular embodiment, the concentration of L-lactic acid in the poly-D,L-lactic acid is at least about 50%, such as about 50%. Therefore, in one particular embodiment, the ratio of L-lactic acid to D-lactic acid in the poly-D,L-lactic acid is about 1:1. It should be understood that the percentage corresponds to the concentration as a weight-to-volume ratio (weight / weight; w / w).

[0015] In another embodiment, the polymer is selected from the group consisting of poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid. The inventors have demonstrated that, in some embodiments, poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid can be advantageous for the treatment, since D-lactic acid and its polymers without L-lactic acid have been shown to be ineffective in the treatment. Indeed, as shown in the embodiments of the present invention, D-lactic acid and its polymers without L-lactic acid induce an inflammatory response and have no beneficial therapeutic effect, for example, in terms of the cross-section of muscle fibers (see...). Figure 3 and Figure 4 (and Table 3). Without being bound by theory, the inventors envision that the concentration of L-lactic acid in the copolymer containing L-lactic acid but not D-lactic acid can vary and can be lower than the concentration of one or more other components in the copolymer. In these cases, without being bound by theory, the inventors envision that therapeutic conditions, such as the frequency and / or dosage of administration, can be adjusted to achieve the disclosed therapeutic effect. Therefore, in one embodiment, the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%. In one particular embodiment, the concentration of L-lactic acid in the copolymer containing L-lactic acid but not D-lactic acid is at least about 20%, such as about 20%. It should be understood that the % corresponds to the concentration in weight-to-volume ratio (weight / weight; w / w).

[0016] The inventors have discovered that any copolymer containing L-lactic acid but not D-lactic acid is advantageous for the treatment due to the presence of L-lactic acid in the copolymer. Therefore, one or more other components in the copolymer do not need to have any therapeutic effect. In one embodiment, therefore, the copolymer does not contain glycolic acid. In some embodiments, the polymer is selected from the group consisting of: poly-L-lactic acid; any copolymer containing L-lactic acid and ethylene glycol; any copolymer containing L-lactic acid, ethylene glycol, and glycolic acid; any copolymer containing L-lactic acid and taurine; any copolymer containing L-lactic acid and chitosan; and any copolymer containing L-lactic acid and ε-caprolactone; such as those selected from the group consisting of poly-L-lactic acid and any copolymer consisting of L-lactic acid and ethylene glycol. In one embodiment, the polymer is a copolymer consisting of L-lactic acid and ethylene glycol. As shown in Example 4, copolymers consisting of L-lactic acid and ethylene glycol are beneficial in the treatments disclosed herein. In some embodiments, the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%. In one particular embodiment, the concentration is at least about 30%, such as about 30%. As shown in Example 4, in one embodiment, the concentration of L-lactic acid in the copolymer is at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 86%. In one particular embodiment, the concentration of L-lactic acid in the copolymer is about 86%. It should be understood that the percentage corresponds to the concentration expressed as a weight-to-volume ratio (weight / weight; w / w).

[0017] In one particular embodiment, the polymer is poly-L-lactic acid. As shown by the inventors in the embodiments, poly-L-lactic acid is particularly beneficial in the treatment. It should be understood that poly-L-lactic acid is a homopolymer of L-lactic acid, i.e., the concentration of L-lactic acid in the polymer is 100%. The inventors have concluded that the higher the concentration of L-lactic acid in the polymer, the better the therapeutic effect.

[0018] In some embodiments, the polymer has a molecular weight of at least about 400 kDa, such as at least about 500 kDa, such as at least about 1 kDa, such as at least about 2 kDa, such as at least about 5 kDa, such as at least about 10 kDa, such as at least about 20 kDa, such as at least about 30 kDa, such as at least about 40 kDa, such as at least about 50 kDa, such as at least about 100 kDa, such as at least about 150 kDa, such as at least about 200 kDa, such as at least about 250 kDa, such as at least about 300 kDa. In some embodiments, the polymer has a molecular weight of no more than about 300 kDa, such as no more than about 275 kDa, such as no more than about 250 kDa, such as no more than about 225 kDa, such as no more than about 200 kDa, such as no more than about 175 kDa, such as no more than about 150 kDa, such as no more than about 125 kDa, such as no more than about 100 kDa. The inventors have discovered that polymers within a certain molecular weight range can be advantageous because polymers with a molecular weight less than 400 kDa may degrade too quickly, while polymers with a molecular weight greater than 300 kDa may be difficult to degrade. Therefore, in one embodiment, the molecular weight of the polymer is from about 400 Da to about 300 kDa, such as from about 500 Da to about 300 kDa, such as from about 1000 Da to about 300 kDa, such as from about 1500 Da to about 275 kDa, such as from about 2000 Da to about 250 kDa, such as from about 2500 Da to about 225 kDa, such as from about 3000 Da to about 200 kDa, such as from about 3500 Da to about 175 kDa, such as from about 4000 Da to about 150 kDa, such as from about 4500 Da to about 125 kDa, such as from about 5000 Da to about 100 kDa. In a particular embodiment, the molecular weight of the polymer is from about 5000 Da to about 100 kDa. In one embodiment, the polymer has a molecular weight of about 1 kDa to about 100 kDa, such as about 5 kDa to about 90 kDa, such as about 10 kDa to about 80 kDa, such as about 15 kDa to about 70 kDa, such as about 20 kDa to about 60 kDa, such as about 25 kDa to about 50 kDa, such as about 30 kDa to about 40 kDa. As shown in the accompanying examples, in one embodiment, the polymer has a molecular weight of about 34 kDa.In one embodiment, the molecular weight of the PLLA homopolymer is from about 1 kDa to about 100 kDa, such as from about 5 kDa to about 90 kDa, such as from about 10 kDa to about 80 kDa, such as from about 15 kDa to about 70 kDa, such as from about 20 kDa to about 60 kDa, such as from about 25 kDa to about 50 kDa, such as from about 30 kDa to about 40 kDa. As shown in the accompanying examples, in one embodiment, the molecular weight of the PLLA homopolymer is about 34 kDa. In one embodiment, the molecular weight of the polymer is from about 1 kDa to about 100 kDa, such as from about 5 kDa to about 90 kDa, such as from about 10 kDa to about 80 kDa, such as from about 10 kDa to about 70 kDa, such as from about 10 kDa to about 60 kDa, such as from about 10 kDa to about 50 kDa, such as from about 10 kDa to about 40 kDa, such as from about 15 kDa to about 40 kDa, such as from about 15 kDa to about 35 kDa, such as from about 16 kDa to about 34 kDa. In one embodiment, the molecular weight of the PLLA copolymer is from about 1 kDa to about 100 kDa, such as from about 5 kDa to about 90 kDa, such as from about 10 kDa to about 80 kDa, such as from about 10 kDa to about 70 kDa, such as from about 10 kDa to about 60 kDa, such as from about 10 kDa to about 50 kDa, such as from about 10 kDa to about 40 kDa, such as from about 10 kDa to about 30 kDa, such as from about 10 kDa to about 20 kDa, such as from about 15 kDa to about 20 kDa, such as from about 16 kDa. In a particular embodiment, the PLLA copolymer is a PLLA-PEG copolymer.

[0019] Composition

[0020] In a second aspect of this disclosure, there is provided a composition for treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy, the composition comprising L-lactic acid and / or a polymer thereof, wherein the L-lactic acid and / or the polymer thereof is as defined in any of the foregoing embodiments relating to the first aspect of this disclosure; and wherein the composition comprises at least one pharmaceutically acceptable carrier and / or excipient.

[0021] The inventors have discovered that, as demonstrated in the embodiments, the compositions comprising L-lactic acid and / or its polymers discussed above are advantageous for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. For clarity and to avoid any doubt, each embodiment discussed in relation to the first aspect of this disclosure is equally relevant to and applicable to the second aspect disclosed herein. For the sake of brevity, these embodiments will not be repeated or will only be briefly mentioned in the second aspect.

[0022] The inventors have demonstrated that the composition is effective in the treatments disclosed herein because it contains L-lactic acid and / or its polymers. Therefore, in some embodiments, the composition contains at least about 1%, such as at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 1%. The composition comprises 00% of the L-lactic acid; and / or at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of the L-lactic acid polymer. In one embodiment, the composition comprises at least about 5% of the L-lactic acid, such as about 5% of the L-lactic acid; and / or at least about 10% of the L-lactic acid polymer, such as about 10% of the L-lactic acid polymer. In a particular embodiment, the composition comprises at least about 5% of the L-lactic acid, such as about 5% of the L-lactic acid. In another embodiment, the composition comprises at least about 10% of the L-lactic acid polymer, such as about 10% of the L-lactic acid polymer. It should be understood that the percentage corresponds to the concentration expressed as a weight-to-volume ratio (weight / volume; w / v).

[0023] As presented in the appended embodiments, the inventors have tested several compositions disclosed herein comprising L-lactic acid and / or its polymers, wherein the compositions are formulated in different ways and wherein the compositions have proven effective in the disclosed treatments. Therefore, in one embodiment, the composition is formulated as a solution, suspension, gel, and / or implant. In one embodiment, the composition is formulated as a solution, suspension, and / or implant. For example, an implant may be formulated to provide sustained release of L-lactic acid and / or polymers into muscle tissue. In another embodiment, the composition is formulated as a solution and / or suspension. In yet another embodiment, the composition is formulated as a solution, such as an injectable solution. The solution may be an L-lactic acid solution. In a particular embodiment, the composition is formulated as a suspension, such as an injectable suspension. The suspension may be a suspension of an L-lactic acid polymer.

[0024] In one embodiment, the composition comprises particles of the L-lactic acid and / or its polymer. In a particular embodiment, the composition comprises particles of the L-lactic acid polymer. Those skilled in the art will recognize that different types of particles can be formulated in a composition. Without being bound by theory, the inventors envision several types of particles that can be used in the compositions disclosed herein. Thus, in some embodiments, the particles are selected from the group consisting of microcells, nanoparticles, and microspheres. In other embodiments, the particles are selected from the group consisting of nanoparticles and microspheres. In a particular embodiment, the particles are microspheres. The inventors have shown in the appended examples that compositions comprising microspheres of the L-lactic acid polymer are particularly beneficial in the treatments disclosed herein. It is envisioned that the particles of the L-lactic acid polymer can provide a sustained release of the active agent over time, and therefore require a lower frequency of application to achieve the desired therapeutic effect compared to, for example, a solution thereof. The invention relies on the pharmaceutical properties of L-lactic acid and / or its polymers themselves; therefore, it should be understood that L-lactic acid and / or its polymers exert the therapeutic effects described herein.

[0025] The inventors have demonstrated in the appended embodiments a range of particle sizes that can be used in the treatments disclosed herein, namely, a particle size of about 30 to about 60 µm. Without being bound by theory, the inventors envision that particle sizes outside this range can also be used in the treatments disclosed herein. Therefore, in some embodiments, the particles have a particle size of at least about 10 µm, such as at least about 15 µm, such as at least about 20 µm, such as at least about 25 µm, such as at least about 30 µm, such as at least about 35 µm, such as at least about 40 µm, such as at least about 45 µm, such as at least about 50 µm, such as at least about 55 µm, such as at least about 60 µm; and / or a particle size of about 1 to about 100 µm, such as about 2 to about 90 µm, such as about 5 to about 85 µm, such as about 10 to about 80 µm, such as about 15 to about 75 µm, such as about 20 to about 70 µm, such as about 25 to about 65 µm, such as about 30 to about 60 µm; and / or a particle size of about 45 µm ± 15 µm, such as a particle size of about 45 µm. In one particular embodiment, the particles comprising the PLLA polymer have a particle size of at least about 10 µm, such as at least about 15 µm, such as at least about 20 µm, such as at least about 25 µm, such as at least about 30 µm, such as at least about 35 µm, such as at least about 40 µm, such as at least about 45 µm, such as at least about 50 µm, such as at least about 55 µm, such as at least about 60 µm; and / or a particle size of about 1 to about 100 µm, such as about 2 to about 90 µm, such as about 5 to about 85 µm, such as about 10 to about 80 µm, such as about 15 to about 75 µm, such as about 20 to about 70 µm, such as about 25 to about 65 µm, such as about 30 to about 60 µm; and / or a particle size of about 45 µm ± 15 µm, such as a particle size of about 45 µm. In one embodiment, the particle size is at least about 20 µm, such as about 20 µm. In one particular embodiment, the particle size is about 30 to about 60 µm. In another embodiment, the particle size is about 10 to about 100 µm, such as about 15 to about 90 µm, such as about 20 to about 80 µm, such as about 25 to about 70 µm, such as about 30 to about 65 µm, such as about 40 to about 65 µm. As shown in the accompanying examples, in some embodiments, the particle size is about 30 to about 65 µm. As shown in Example 4, in one particular embodiment, the particles comprising the PLLA-PEG polymer have a particle size of about 10 to about 100 µm, such as about 15 to about 90 µm, such as about 20 to about 80 µm, such as about 25 to about 70 µm, such as about 30 to about 65 µm, such as about 40 to about 65 µm. It should be understood that the particle size in the composition may be the same.On the other hand, the particles in the composition may have any particle size within a specified particle size range exhibiting any distribution pattern. Alternatively, the particles may exhibit a normal distribution within a specified particle size range in the composition. Thus, in a particular embodiment, the particles in the composition exhibit a normal distribution with a particle size of about 30 to about 60 µm. For clarity and to avoid any doubt, it should be understood that in embodiments where the particles are microspheres, the particle size corresponds to the size of the microspheres.

[0026] The inventors have demonstrated in the appended embodiments that microspheres with smooth surfaces can be used in the treatments disclosed herein. Without being bound by theory, the inventors envision that microspheres with smooth surfaces could be particularly advantageous in the treatments disclosed herein. Therefore, in one particular embodiment, the microspheres have smooth surfaces. As used herein, the term "smooth surface" means that on the surface of 10 microspheres, there are no more than 50 protrusions with a height measurement of 1-3 μm and no protrusions with a height exceeding 5 μm. Therefore, in one embodiment, the composition comprises microspheres of the L-lactic acid and / or its polymers, wherein on the surface of at least 10 microspheres, there are no more than 50 protrusions with a height measurement of 1-3 μm extending beyond the microspheres. In one embodiment, the composition comprises microspheres of the L-lactic acid and / or its polymers, wherein on the surface of at least 10 microspheres, no protrusions with a height exceeding 5 μm extend beyond the microspheres. In one particular embodiment, the composition comprises microspheres of the L-lactic acid and / or its polymer, wherein no more than 50 protrusions with a height measurement of 1-3 μm are present on the surface of at least 10 microspheres, and no protrusions with a height exceeding 5 μm protrude beyond the microspheres. In this embodiment, it should be understood that the characteristics “no more than 50 protrusions with a height measurement of 1-3 μm” and “no protrusions with a height exceeding 5 μm” are measured on the same surface of at least 10 microspheres.

[0027] Unbound by theory, the inventors of this case envision that, compared to particles with more uneven and rougher structures, the smooth surface of microspheres, or the smooth surface of the particles disclosed herein, is associated with less inflammatory response in the treated patients.

[0028] Consistent with the embodiments discussed in relation to the first aspect of this disclosure, the inventors have demonstrated that, in certain embodiments, compositions comprising L-lactic acid and / or polymers comprising L-lactic acid but not D-lactic acid can be advantageous for the treatment, since compositions comprising D-lactic acid and polymers not comprising L-lactic acid have been shown to be ineffective in the treatment disclosed herein. Therefore, in one embodiment, the composition does not comprise D-lactic acid and / or its polymers.

[0029] As discussed above, the inventors have unexpectedly discovered that the compositions comprising L-lactic acid and / or its polymers, as described above, are unexpectedly beneficial in the treatment of muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy. For example, the inventors demonstrate that this unexpected effect is achieved using compositions that do not contain any other active ingredients besides L-lactic acid and / or its polymers, as described in the appended examples. Therefore, the inventors propose that the effective treatment disclosed herein is attributable to the presence of the L-lactic acid and / or its polymers in the compositions. Thus, in one particular embodiment, the L-lactic acid and / or its polymers are the sole active ingredients. Therefore, as disclosed herein, the presence of any other (one or more) active ingredients in the compositions is not required to achieve the therapeutic effect. Thus, in one embodiment, the compositions do not contain glycolic acid. As explained above, the inventors have found that L-lactic acid and / or its polymers are inherently beneficial for the treatment. However, in some cases, it may be advantageous to administer additional therapeutic active ingredients or supporting agents (e.g., structural agents) with the same composition. Therefore, in one embodiment, the composition comprises one or more additional active ingredients. Techniques for formulating compositions comprising at least one pharmaceutically acceptable carrier and / or excipient are well known in the art. It should be understood that the compositions disclosed herein are formulated to be suitable for human therapeutic use. Therefore, the compositions may be pharmaceutical compositions. As used herein, the term "pharmaceuticalally acceptable carrier and / or excipient" encompasses adjuvants, carriers, diluents, and mediators. The appropriate selection of adjuvants, carriers, diluents, and mediators is within the knowledge of those skilled in the art. Those skilled in the art will understand that the compositions can be adapted to a chosen route of administration and the desired dosage. Furthermore, the inventors of this application contemplate that the selected pharmaceutically acceptable carrier and / or excipient may, for example, stabilize the L-lactic acid and / or its polymers in the compositions disclosed herein. In one embodiment, the pharmaceutically acceptable carrier and / or excipient is selected from the group consisting of physiological saline solutions, surfactants, and stabilizers. In one particular implementation, the pharmaceutically acceptable carrier and / or excipient is a physiological saline solution.

[0030] Application and dosage

[0031] As discussed above, the L-lactic acid and / or its polymers, or the compositions disclosed herein, can be adapted to a desired route of administration. It should be understood that the route of administration may, for example, depend on the type of muscle to be treated, and / or its location in the body of the subject to be treated. Additionally, it may depend on other factors associated with the injury, disease, condition, and / or ailment, and also on the individual circumstances of the subject requiring the treatment. Therefore, in some embodiments, the L-lactic acid and / or its polymers, or the compositions, are formulated for oral, nasal, transdermal, ocular, intramuscular, and / or subcutaneous administration. In one embodiment, the L-lactic acid and / or its polymers, or the compositions, are formulated for intramuscular and / or subcutaneous administration. In a particular embodiment, the L-lactic acid and / or its polymers, or the compositions, are formulated for intramuscular administration. In another particular embodiment, the L-lactic acid and / or its polymers, or the compositions, are formulated for subcutaneous administration. As previously mentioned, those skilled in the art will understand the techniques and principles for formulating compositions according to the routes of administration discussed above. Therefore, some non-invasive routes of administration include oral administration, transdermal patches, nasal sprays, oral sprays, and eye drops. These methods, for example, allow the delivery of the L-lactic acid and / or its polymers, or the compositions disclosed herein, to specific sites in the muscles through the mouth, skin, nose, and eye. Intramuscular injection is a method of directly applying a drug to muscle tissue.

[0032] In one embodiment, the uses disclosed herein include administering the L-lactic acid and / or its polymers, or the composition, to a subject in need at least once. In some embodiments, the at least once administration is intramuscular and / or subcutaneous administration. In a particular embodiment, the at least once administration is intramuscular administration, such as the at least once administration described herein being an intramuscular injection.

[0033] In any of these or other routes of administration, the composition may be adapted or modified according to general pharmacological procedures, comprising an effective dose of the L-lactic acid and / or its polymers suitable for the chosen route, and suitable excipients commonly used and well known to those skilled in the art, such as adjuvants, carriers, diluents and mediators.

[0034] In one embodiment, the at least one application does not induce a significant inflammatory response in the subject. As used herein, the term "significant inflammatory response" refers to a marked and persistent inflammatory response caused by the application. This may include inflammatory symptoms such as local redness, swelling, pain, a feeling of heat, local congestion, and tissue swelling. Such a response may be triggered by activation of the immune system and the release of inflammatory mediators. As shown in the appended examples, such as Example 1, the inventors have demonstrated that the significant inflammatory response can be assessed using standard laboratory methods, such as hematoxylin-eosin staining of muscle tissue to analyze the infiltration of inflammatory cells into the application site and / or analysis of inflammatory markers in the blood.

[0035] In one embodiment, the at least one application does not induce a significant fibrotic response and / or scar tissue formation in the subject. As used herein, the term "significant fibrotic response and / or scar tissue formation" refers to the abnormal proliferation of fibrous tissue in the treated area and / or during wound healing, resulting in the formation of scars or fibrous scars. Such a response is often accompanied by structural and functional impairment of the original tissue and can lead to swelling, stiffness, pain, and undesirable cosmetic outcomes. The inventors here contemplate that the L-lactic acid and / or its polymers, or the compositions disclosed herein, will not induce a significant fibrotic response and / or scar tissue formation in the subject.

[0036] Those skilled in the art will understand that the appropriate dosage will generally depend on the administration modality, the specific condition to be treated or the desired effect, the patient's sex, age, weight and health status, and other possible factors, and will vary based on the evaluation of the treating physician. Specifically, the appropriate dosage may depend on the size and / or weight of the muscle to be treated. In one embodiment of this disclosure, a dose of the L-lactic acid is administered during the at least one administration, wherein the dose is about 2.25 to about 1152 mg / kg; and / or a dose of the L-lactic acid polymer is administered during the at least one administration, wherein the dose is about 22.5 to about 57600 mg / kg. In one embodiment of this disclosure, a dose of the L-lactic acid is administered during the at least one administration, wherein the dose is about 112.5 to about 576 mg / kg; and / or a dose of the L-lactic acid polymer is administered during the at least one administration, wherein the dose is about 1125 to about 28800 mg / kg. In one particular embodiment, the dose of L-lactic acid is administered during the at least one administration, wherein the dose is about 2.25 to about 1152 mg / kg, such as about 112.5 to about 576 mg / kg. In one embodiment, the dose of L-lactic acid is about 2.25 to 1152 mg / kg, such as about 5 to about 1000 mg / kg, such as about 10 to about 900 mg / kg, such as about 25 to about 800 mg / kg, such as about 50 to about 700 mg / kg, such as about 75 to about 600 mg / kg, such as about 100 to about 600 mg / kg, such as about 110 to about 580 mg / kg, such as about 112.5 to about 576 mg / kg. In one embodiment, the dose is about 115 to about 575 mg / kg, such as about 150 to about 550 mg / kg, such as about 200 to about 525 mg / kg, such as about 250 to about 500 mg / kg, such as about 300 to about 500 mg / kg, such as about 350 to about 500 mg / kg, such as about 375 to about 500 mg / kg. As shown in the appended examples, in one particular embodiment, the dose of the L-lactic acid is about 375 to about 500 mg / kg. In another particular embodiment, the dose of the L-lactic acid polymer is administered during the at least one administration, wherein the dose is about 22.5 to about 57,600 mg / kg, such as about 1,125 to about 28,800 mg / kg.In one embodiment, the dosage of the L-lactic acid polymer is about 22.5 to about 57,600 mg / kg, such as about 25 to about 57,500 mg / kg, such as about 50 to about 57,000 mg / kg, such as about 100 to about 55,000 mg / kg, such as about 150 to about 52,500 mg / kg, such as about 200 to about 50,000 mg / kg, such as about 300 to about 47,500 mg / kg, such as about 400 to about 45,000 mg / kg, such as about 500 to about 42,500 mg / kg, such as about 600 to about 40,000 mg / kg, such as about 700 to about 37,500 mg / kg, such as about 800 to about 35,000 mg / kg, such as about 900 to about 32,500 mg / kg, such as about 1,000 to about 30,000 mg / kg, such as about 1,100 to about 29,000 mg / kg. mg / kg, such as about 1125 to about 28800 mg / kg. In one embodiment, the dose is about 1150 to about 25000 mg / kg, such as about 1200 to about 20000 mg / kg, such as about 1250 to about 15000 mg / kg, such as about 1250 to about 10000 mg / kg, such as about 1250 to about 5000 mg / kg, such as about 1250 to about 2500 mg / kg, such as about 1250 to about 2000 mg / kg, such as about 1250 to about 1750 mg / kg, such as about 1250 to about 1700 mg / kg, such as about 1250 to about 1670 mg / kg, such as about 1250 to about 1667 mg / kg. As shown in the appended examples, in a particular embodiment, the dose of the L-lactic acid polymer is about 1250 to about 1667 mg / kg. Not bound by theory, the inventors envision that the dosage can be adjusted according to the route of administration and / or selected based on, for example, the degree and / or type of the injury, disease, condition, and / or ailment. Furthermore, it can also be adjusted according to the muscle to be treated and / or the subject. It can also be adjusted for the type of muscle atrophy. Therefore, not bound by theory, the inventors envision that, for example, a higher dosage can be used in the case of chronic muscle atrophy, while a lower dosage may be effective in the treatment of acute muscle atrophy.

[0037] In one embodiment, the at least one administration is a single administration, such as the administration of said L-lactic acid and / or said polymer thereof to a subject in need of a single dose. Therefore, a single administration of said L-lactic acid and / or said polymer thereof can be effective in the treatments disclosed herein. As shown in the appended examples, a single administration of said L-lactic acid and / or said polymer thereof to a subject in need of a single dose is effective in the treatments disclosed herein. Specifically, the inventors demonstrate that a single administration of a composition comprising an L-lactic acid polymer to a subject in need of a single dose is effective in the treatments disclosed herein. Therefore, in one embodiment, the at least one administration is a single administration.

[0038] In another embodiment, the at least one administration is repeated administration, such as the dose of said L-lactic acid and / or said polymer thereof being repeatedly administered to a subject in need. Therefore, the repeated administration of said L-lactic acid and / or said polymer thereof can be effective in the treatments disclosed herein. As shown in the appended examples, repeated administration of said dose of said L-lactic acid and / or said polymer thereof to a subject in need is effective in the treatments disclosed herein. Specifically, the inventors of this invention demonstrate that repeated administration of said dose of said L-lactic acid to a subject in need is effective in the treatments disclosed herein. Therefore, in one embodiment, the at least one administration is repeated administration.

[0039] The inventors have demonstrated that single and repeated applications of the L-lactic acid and / or its polymers, or compositions disclosed herein, are effective in the treatments disclosed herein. The inventors also anticipate that the number and / or frequency of applications can be selected and adjusted based on various factors, such as the dosage; the extent of muscle injury, disease, condition, and / or disorder characterized by muscle atrophy; and / or the type of muscle atrophy, such as chronic or acute muscle atrophy. For example, in the case of, for instance, chronic muscle atrophy, a higher number of applications and / or a higher frequency of applications may be used, while a lower number of applications and / or a lower frequency of applications may be effective in the treatment of acute muscle atrophy. Thus, in one embodiment, the application is given once daily to the patient in need for at least 2 days, such as at least 3 days, such as at least 4 days, such as at least 5 days, such as at least 6 days, such as at least 7 days, such as at least 8 days, such as at least 9 days, such as at least 10 days, such as at least 11 days, such as at least 12 days, such as at least 13 days, such as at least 14 days. In another embodiment, the administration is at least once daily, such as at least twice daily, such as at least three times daily, to the subject in need of the L-lactic acid. In another embodiment, the administration is once daily to the subject in need of the L-lactic acid. In another embodiment, the administration is twice daily to the subject in need of the L-lactic acid. In another embodiment, the administration is three times daily to the subject in need of the L-lactic acid. In one embodiment, the administration is at least once every two days, such as once every three days, to the subject in need of the L-lactic acid. In one embodiment, the administration is once every two days to the subject in need of the L-lactic acid. In another embodiment, the administration is once every three days to the subject in need of the L-lactic acid. The frequency of administration of the L-lactic acid described above can continue until the desired therapeutic effect is achieved, such as for at least one week, for at least two weeks, for at least three weeks, for at least one month, for at least two months, for at least three months, for at least four months, for at least five months, for at least six months, for at least seven months, for at least eight months, for at least nine months, for at least ten months, for at least eleven months, or for at least twelve months. In one embodiment, the administration is the repeated application of the L-lactic acid polymer to a subject in need, such as at least every ten days.The frequency of application of the L-lactic acid polymer may continue until the desired therapeutic effect is achieved, such as for at least 1 month, such as for at least 2 months, such as for at least 3 months, such as for at least 4 months, such as for at least 5 months, such as for at least 6 months, such as for at least 7 months, such as for at least 8 months, such as for at least 9 months, such as for at least 10 months, such as for at least 11 months, such as for at least 12 months. In one embodiment, the application of the L-lactic acid polymer is at least every ten days for a period of one year.

[0040] For clarity and to avoid any doubt, the above-described implementations relating to application and dosage should be understood to be equally applicable to all implementations discussed in relation to the first and second aspects of this disclosure.

[0041] Muscle atrophy

[0042] As those skilled in the art will know, muscle atrophy is the loss or thinning of muscle mass. Symptoms of muscle atrophy may include reduced muscle mass, one limb being smaller than the other, numbness, weakness, and / or tingling in the limbs. As discussed below, muscle atrophy may, for example, be characterized by different injuries, conditions, diseases, and / or disorders, depending on its cause.

[0043] Those skilled in the art will recognize that muscle injury can lead to limb immobilization, requiring bed rest and / or making movement difficult or impossible. This lack of mobility can cause muscle wasting. Therefore, in one embodiment of this disclosure, the muscle injury is characterized by muscle atrophy.

[0044] In some embodiments, the treatment is preventative and / or therapeutic treatment for the injury, disease, condition, and / or disorder characterized by muscle atrophy. In one embodiment, the treatment is preventative and / or therapeutic treatment for the injury characterized by muscle atrophy. In another embodiment, the treatment is preventative and / or therapeutic treatment for the disease, condition, and / or disorder characterized by muscle atrophy. The therapeutic treatment may be curative treatment and / or treatment to relieve, reduce, and / or eliminate the symptoms of the injury, disease, condition, and / or disorder characterized by muscle atrophy. The muscle atrophy may be acute muscle atrophy and / or chronic muscle atrophy. The term "acute muscle atrophy" herein refers to an acute, short-term condition characterized by muscle tissue loss and / or thinning. The term "chronic muscle atrophy" herein refers to a chronic, long-term condition characterized by muscle tissue loss and / or thinning; and a condition where muscle tissue loss and / or thinning recurs.

[0045] Muscle atrophy can be mild or severe. The inventors of this application anticipate that the L-lactic acid and / or its polymers, or the compositions thereof, can be used for the treatment of various types of muscle atrophy disclosed herein. The inventors envision that, based on the type of muscle atrophy, as discussed above, treatment conditions, such as the route of administration and / or dosage, can be adjusted to effectively treat the injury, condition, disease, and / or disorder characterized by said muscle atrophy.

[0046] As presented in the in vivo model of muscle atrophy used in Example 1 of the appended document, the inventors have found that, as disclosed herein, the L-lactic acid and / or its polymers, or the composition thereof, are beneficial in preventing the development of muscle atrophy. Therefore, in one embodiment, the treatment is a preventative treatment for the injury, disease, condition, and / or disorder characterized by muscle atrophy. In another embodiment, the treatment is a preventative treatment for the disease, condition, and / or disorder characterized by muscle atrophy. As demonstrated by the inventors in Example 1, the preventative treatment disclosed herein is beneficial in preventing muscle loss, upregulation of molecular markers of muscle atrophy, and muscle tissue degeneration induced by limb immobilization in one limb. Therefore, in one embodiment, the preventative treatment prevents muscle tissue degeneration; muscle loss; muscle wastage and / or thinning; and / or decreased muscle strength.

[0047] As presented in the in vivo models of muscle atrophy used in the appended Examples 2 and 3, the inventors have found that, as disclosed herein, the L-lactic acid and / or its polymers, or the compositions thereof, are beneficial in the therapeutic treatment of muscle atrophy. Therefore, in one embodiment, the treatment is a therapeutic treatment for the injury, disease, condition, and / or disorder characterized by muscle atrophy. In another embodiment, the treatment is a therapeutic treatment for the disease, condition, and / or disorder characterized by muscle atrophy. As demonstrated by the inventors in Examples 2 and 3, the therapeutic treatment disclosed herein is beneficial in increasing muscle mass in limb muscles where muscle atrophy is induced by limb immobilization. Furthermore, the inventors anticipate that the therapeutic treatment disclosed herein is beneficial in inducing the downregulation of molecular markers of muscle atrophy and inducing muscle tissue regeneration in said muscles where muscle atrophy is induced by limb immobilization. Therefore, the treatment disclosed herein is expected to produce therapeutically significant results in terms of muscle tissue and muscle mass regeneration. Therefore, in one embodiment, the therapeutic treatment induces muscle tissue regeneration.

[0048] In some embodiments, the injury, disease, symptom, or disorder is characterized by a decrease in muscle mass, wasting and / or thinning, and / or a reduction in muscle strength. In one embodiment, the injury is characterized by a decrease in muscle mass, wasting and / or thinning, and / or a reduction in muscle strength. In another embodiment, the disease, symptom, or disorder is characterized by a decrease in muscle mass, wasting and / or thinning, and / or a reduction in muscle strength.

[0049] For clarity and to avoid any doubt, the above-discussed embodiments relating to muscle atrophy should be understood to refer to all embodiments relating to the muscle atrophy discussed in connection with the first and second aspects of this disclosure.

[0050] Diseases, conditions and / or disorders characterized by muscle atrophy

[0051] In one implementation, the treatment is the treatment of a disease, condition, and / or disorder characterized by muscle atrophy.

[0052] As is known in the art, muscle atrophy can be a characteristic of various diseases, conditions, and disorders. For example, disuse atrophy (i.e., physiological atrophy) can be caused by sedentary lifestyles, bed rest due to injury, and / or lack of exercise. Muscle atrophy can also occur due to aging and / or may be a result of malnutrition. Neurological disorders, such as damage or disease affecting the nerves connected to the muscles, can also induce muscle atrophy, commonly referred to as neurogenic atrophy. Diseases that may affect these nerves include, for example, amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome, carpal tunnel syndrome, poliomyelitis, spinal cord injury, and multiple sclerosis. Myopathy, known as a disease of skeletal muscles, is also characterized by muscle atrophy. Therefore, in one embodiment, the disease, condition, or disorder is selected from the group consisting of: disuse atrophy, age-related atrophy, malnutrition-induced atrophy, muscle disorders, and neurogenic disorders.

[0053] In one implementation, the disease, symptom, or ailment is disuse atrophy.

[0054] In one implementation, the disease, symptom, or disorder is myopathy. As discussed above, myopathy is known to be a skeletal muscle disease. It affects muscle fibers and induces muscle weakness.

[0055] Generally, myopathy can be classified into two categories based on its cause. Therefore, in some embodiments, the myopathy is hereditary myopathy and / or acquired myopathy. In one embodiment, the myopathy is hereditary. In another embodiment, the myopathy is acquired. Hereditary myopathy is caused by abnormal gene mutations inherited from parents that cause the disease. In one embodiment, the hereditary myopathy is selected from the group consisting of: congenital myopathy, mitochondrial myopathy, metabolic myopathy, and muscular dystrophy. Acquired myopathy develops later in life and may be caused by medical conditions, infections, exposure to certain drugs, or electrolyte imbalances. In one embodiment, the acquired myopathy is selected from the group consisting of: autoimmune / inflammatory myopathy, toxic myopathy, endocrine myopathy, infectious myopathy, myopathy associated with electrolyte imbalance, and critical illness myopathy.

[0056] Conditions, diseases, and / or disorders characterized by muscle atrophy are typically characterized by muscle atrophy in one or more skeletal muscles. Therefore, in one particular embodiment, the muscle atrophy is skeletal muscle atrophy.

[0057] Conditions, diseases, and / or disorders characterized by muscle atrophy commonly affect humans and may also affect animals. Therefore, as disclosed herein, the L-lactic acid and / or its polymers, or the compositions thereof, can be used in the treatments disclosed herein in animals and humans. Thus, in one embodiment, the subject is a person and / or an animal. In a particular embodiment, the subject is a human.

[0058] For clarity and to avoid any doubt, the embodiments discussed above relating to diseases, conditions and / or disorders characterized by muscular atrophy should be understood to refer to all embodiments relating to the first and second aspects of this disclosure that involve the diseases, conditions and / or disorders characterized by muscular atrophy.

[0059] Muscle injury

[0060] As used herein, the term "muscle injury" refers to a condition in which muscle tissue is damaged and / or injured. A muscle injury may involve partial damage to muscle tissue or complete tearing or rupture of muscle tissue. Symptoms of a muscle injury may include pain, swelling, muscle weakness, muscle stiffness, chafing, or limited muscle function. As shown in the accompanying examples, and as disclosed herein, the L-lactic acid and / or its polymers, or the composition, can be used to treat conditions characterized by muscle loss, muscle weakness, and / or limited muscle function. The inventors have discovered that, as disclosed herein, the L-lactic acid and / or its polymers, or the composition, are unexpectedly advantageous for treating muscle injuries. Therefore, in one embodiment, the treatment is a treatment for muscle injuries, such as preventative and / or therapeutic treatments for muscle injuries. The therapeutic treatment may be a curative treatment and / or a treatment to relieve, reduce, and / or eliminate the symptoms of the injury, disease, condition, and / or disorder characterized by muscle atrophy. Unbound by theory, the inventors of this case envision that the treatment disclosed herein may have a beneficial effect on the healing of muscle injuries, such as shortening the time required for healing or improving the degree of healing, such as restoring muscle tissue to partial or complete health and / or its original state.

[0061] In one embodiment, the treatment is a preventative treatment for muscle injury. In one embodiment, the preventative treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or decreased muscle strength.

[0062] In one embodiment, the treatment is a therapeutic treatment for muscle injury. In another embodiment, the therapeutic treatment induces muscle tissue regeneration. Those skilled in the art will recognize that muscle injury can occur acutely, caused by a single traumatic event, such as severe muscle strain during strenuous physical activity.

[0063] Therefore, acute muscle injury can be a single muscle injury event, such as a muscle injury occurring during physical activity. On the other hand, muscle injury can be long-term, gradually progressing due to prolonged repetitive or overuse of the muscle (such as overtraining in athletes). Chronic muscle injury can also develop due to muscle injuries that are difficult to heal. Therefore, in some embodiments, the muscle injury is selected from the group consisting of acute muscle injury or chronic muscle injury. In one embodiment, the muscle injury is an acute muscle injury. In one embodiment, the muscle injury is a chronic muscle injury.

[0064] The inventors of this invention envision that, as disclosed herein, the L-lactic acid and / or its polymers, or the composition thereof, can be used to treat different types of muscle injuries. Therefore, in one embodiment, the muscle injury is selected from the group consisting of abrasions, sprains, tears, spasms, and lacerations. In one embodiment, the muscle injury is selected from the group consisting of sprains, tears, and spasms. In one embodiment, the muscle injury is selected from the group consisting of sprains, tears, and lacerations. The term "muscle sprain" herein refers to a partial tear of a muscle fiber. The term "muscle tear" herein refers to a complete or partial tear of a muscle fiber. The term "muscle spasm" herein refers to a sudden and sustained muscle contraction. The term "laceration" or "cut" herein refers to the result of a sharp instrument injury that penetrates the skin and fascia to reach the muscle. In one embodiment, the muscle injury is a sprain. In one embodiment, the muscle injury is a tear. In one embodiment, the muscle injury is a spasm. In one embodiment, the muscle injury is a laceration. The muscle injury can be mild, moderate, or severe. The muscle injury can therefore be a grade I, II, or III injury. Grade I injuries, such as minor tears, spasms, lacerations, sprains, and / or abrasions, are known to affect only a portion of muscle fibers. Grade II injuries, such as moderate tears, spasms, lacerations, sprains, and / or abrasions, exhibit greater muscle damage, accompanied by significant loss of function. Grade III injuries, such as severe tears, spasms, lacerations, sprains, and / or abrasions, extend to the entire cross-section of the muscle, primarily causing complete loss of muscle function. Based on this, the inventors of this invention anticipate that, as disclosed herein, the L-lactic acid and / or its polymers, or the compositions thereof, can be used to treat muscle injuries of all severity.

[0065] Muscle injuries typically occur in skeletal muscles. In one particular embodiment, the muscle injury is a skeletal muscle injury.

[0066] For clarity and to avoid any doubt, the above-discussed embodiments relating to muscle injury should be understood to refer to all embodiments relating to the muscle injury discussed in connection with the first and second aspects of this disclosure.

[0067] In a third aspect of the invention, the use of L-lactic acid and / or its polymers for manufacturing an agent for treating muscle injuries and / or diseases, conditions, and / or ailments characterized by muscle atrophy is provided. Embodiments of said use may be described above with respect to the first aspect of this disclosure, and for the sake of brevity, will not be repeated here.

[0068] In a fourth aspect of the invention, there is provided the use of a composition comprising L-lactic acid and / or its polymers for manufacturing a medicament for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy, wherein the L-lactic acid and / or its polymers are as defined in any of the embodiments discussed with respect to the third aspect of this disclosure; and wherein the composition comprises at least one pharmaceutically acceptable carrier and / or excipient. Embodiments of the use may be discussed above with respect to the second aspect of this disclosure and will not be repeated here for the sake of brevity.

[0069] In a fifth aspect of this disclosure, a method is provided for treating muscle injuries and / or diseases, conditions, and / or disorders characterized by muscle atrophy using L-lactic acid and / or its polymers. The embodiments described herein may be as discussed above with respect to the first aspect of this disclosure, and for the sake of brevity, will not be repeated here.

[0070] In a sixth aspect of this disclosure, a method is provided for treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy using a composition comprising L-lactic acid and / or its polymers, wherein the L-lactic acid and / or its polymers are as defined in any of the embodiments discussed with respect to the fifth aspect of this disclosure; and wherein the composition comprises at least one pharmaceutically acceptable carrier and / or excipient. The embodiments described herein may be as discussed above with respect to the second aspect of this disclosure, and for the sake of brevity, will not be repeated here.

[0071] For clarity and to avoid any ambiguity, the terms "polymer of L-lactic acid" and "L-lactic acid polymer" are used interchangeably herein. Similarly, the terms "polymer of D-lactic acid" and "D-lactic acid polymer" are used interchangeably herein, and the terms "copolymer of L-lactic acid and D-lactic acid" and "D,L-lactic acid copolymer" are used interchangeably herein.

[0072] It should be noted that, as used in this specification and the appended claims, the singular forms “a”, “an”, and “the” also include the plural forms, unless the context clearly specifies otherwise.

[0073] As used herein, when the terms “about” or “approximately” are used with numerical values, they should be interpreted as ±10%, such as ±9%, such as ±8%, such as ±7%, such as ±6%, such as ±5%, such as ±4%, such as ±50%, such as ±3%, such as ±2%, such as ±1%. For example, when indicating that the value is about 10, this means that the value is actually in the range of 9 to 11, such as in the range of 9.9 to 10.9, such as in the range of 9.8 to 10.8, such as in the range of 9.7 to 10.7, such as in the range of 9.6 to 10.6, such as in the range of 9.5 to 10.5, such as in the range of 9.4 to 10.4, such as in the range of 9.3 to 10.3, such as in the range of 9.2 to 10.2, such as in the range of 9.1 to 10.1.

[0074] Those skilled in the art will know that numerical values ​​related to measurements are affected by measurement errors, thereby limiting their accuracy. Therefore, the general conventions found in the following scientific and technical literature apply: the last decimal place of a numerical value indicates its degree of accuracy. In the absence of other error ranges, the maximum range is determined by applying rounding conventions to the last decimal place; for example, for a measurement of 3.5 cm, the error range is 3.45–3.54. Those skilled in the art will base their interpretation of the ranges of values ​​in this specification on this principle.

[0075] Although the invention has been described with reference to various exemplary aspects and embodiments, those skilled in the art will understand that various changes may be made without departing from the scope of the invention, and equivalents may be substituted for its elements. Therefore, the invention is intended to be limited to any particular embodiment covered, and will include all embodiments within the scope of the appended claims. The invention will be further illustrated by the following non-limiting examples. Brief description of the attached diagram

[0076] Figure 1 The gastrocnemius and brachialis muscles (1: gastrocnemius (fixed), 2: gastrocnemius (unfixed), 3: brachialis (fixed), 4: brachialis (unfixed)) of the right hind limb (unfixed) and left hind limb (fixed) from control mice (Group A) tested according to Example 1 are shown.

[0077] Figure 2 Comparative data of muscle atrophy indices of the fixed gastrocnemius (A) and brachialis (B) muscles in the test experimental groups as described in Example 1 are shown on the x-axis (preventive treatment model; Group A: control group; Group B: PLLA; Group C: PDLA; and Group D: PDLLA, p*<0.05 and p**<0.01).

[0078] Figure 3 Representative images of the brachialis muscle as described in Example 1 are shown, with representative muscle fibers indicated by black arrows (A); and their quantification (B), where (preventive treatment model; Group A: control group; Group B: PLLA; Group C: PDLA; and Group D: PDLLA, shown on the x-axis; while the mean cross-sectional area (mean ± SD) is shown on the y-axis, p** < 0.01).

[0079] Figure 4 Representative images of H&E staining of the brachialis muscle as described in Example 1 are shown, with representative inflammatory cells indicated by black arrows and representative muscle fibers indicated by white arrows (A); and their quantification (B) (preventive treatment model; Group A: control group; Group B: PLLA; Group C: PDLA; and Group D: PDLLA, shown on the x-axis; and the mean number of inflammatory cells (mean ± SD) is shown on the y-axis, p** < 0.01 and p*** < 0.001).

[0080] Figure 5 The results of RT-PCR analysis of the expression levels of myostatin (A), MuRF-1 (B), and atrogin-1 (C) mRNA in the fixed rat brachial muscle tissue according to the test experimental group of Example 1 are presented (preventive treatment model; Group A: control group; Group B: PLLA; Group C: PDLA; and Group D: PDLLA, p**<0.01 and p***<0.001).

[0081] Figure 6 Comparative data of muscle atrophy indices of the fixed gastrocnemius (A) and brachialis (B) muscles in the test experimental groups as described in Example 2 are shown (therapeutic treatment model; A1 group: control group; B1 group: PLLA; C1 group: PDLA; and D1 group: PDLLA, shown on the x-axis; while muscle atrophy indices (mean ± SD) are shown on the y-axis, p*<0.05, p**<0.01 and p***<0.001).

[0082] Figure 7 The comparison data of muscle atrophy index of the fixed gastrocnemius (A) and brachialis (B) muscles in the test experimental groups as described in Example 3 are shown on the x-axis; while the muscle atrophy index (mean ± SD) is shown on the y-axis, p*<0.05, p**<0.01 and p**<0.001).

[0083] Figure 8 The comparison data of muscle atrophy index of the fixed gastrocnemius (A) and brachialis (B) in the test experimental groups as described in Example 4 are shown (therapeutic treatment model; A3 group: control group; B3 group: PLLA-PEG, shown on the x-axis; while muscle atrophy index (mean ± SD) is shown on the y-axis, p*<0.05 and p**<0.01). Detailed Implementation

[0084] Example

[0085] The following examples use animal models of muscle atrophy to demonstrate the effectiveness of compositions according to the invention for the prevention and treatment of muscle atrophy. Experimental results indicate that L-lactic acid and its polymers disclosed herein, as well as compositions comprising L-lactic acid and / or its polymers, are effective in preventing muscle mass loss and inducing muscle tissue regeneration and / or recovery without inducing inflammation. Overall, the presented examples demonstrate the effectiveness of using L-lactic acid and its polymers disclosed herein, as well as compositions comprising L-lactic acid and / or its polymers, in vivo for the treatment of muscle atrophy. These results, described below, show that compositions comprising L-LA or PLLA are effective in the therapeutic treatment and prevention of muscle atrophy, and the inventors conclude that such compositions are expected to be effective in the therapeutic treatment and / or prevention of various disorders, diseases, and / or conditions and / or muscle injuries (such as muscle injuries characterized by muscle atrophy). Example 1

[0086] Preventive treatment of muscle atrophy using compositions containing microspheres of L-lactic acid polymer.

[0087] This embodiment describes an in vivo experiment in which a composition comprising microspheres of L-lactic acid homopolymer (poly-L-lactic acid, PLLA), D-lactic acid homopolymer (poly-D-lactic acid, PDLA), or copolymers of L-lactic acid (L-LA) and D-lactic acid (D-LA) (poly-D,L-lactic acid, PDLLA) was tested in a rat model of muscle atrophy. The above composition was administered to animals in a single dose prior to inducing muscle atrophy, and the muscle atrophy index was measured as the primary indicator of muscle atrophy. Changes in molecular markers of muscle tissue regeneration, muscle atrophy, and / or inflammation were analyzed using histochemical and standard biochemical and molecular biological methods.

[0088] Materials and Methods

[0089] Preparation of the composition:

[0090] 1. A composition comprising poly-L-lactic acid (PLLA) microspheres

[0091] Nine g of poly-L-lactic acid (molecular weight 34,000 g / mol, i.e., 34 kDa) was dissolved in 135 mL of dichloromethane. This solution was then added to 1800 mL of a 0.5% aqueous solution of polyvinyl alcohol. The mixture was emulsified at 2000 rpm / min for 10 minutes. The mixture was then stirred continuously at 300 rpm / min for 3 hours to remove the dichloromethane, thereby obtaining poly-L-lactic acid microspheres.

[0092] 2. A composition comprising poly-L-lactic acid (PDLA) microspheres

[0093] Nine g of poly(D-lactic acid) (molecular weight 34,000 g / mol, i.e., 34 kDa) was dissolved in 135 mL of dichloromethane. This solution was then added to 1800 mL of a 0.5% aqueous solution of polyvinyl alcohol. The mixture was emulsified at 2000 rpm / min for 10 minutes. The mixture was then stirred continuously at 300 rpm / min for 3 hours to remove the dichloromethane, thereby obtaining poly(D-lactic acid) microspheres.

[0094] 3. A composition comprising poly-L-lactic acid (PDLLA) microspheres

[0095] 9 g of poly(DL-lactic acid) (molecular weight 34,000 g / mol, i.e., 34 kDa) was dissolved in 135 mL of dichloromethane. This solution was then added to 1800 mL of a 0.5% aqueous solution of polyvinyl alcohol. The mixture was emulsified at 2000 rpm / min for 10 minutes. The mixture was then stirred continuously at 300 rpm / min for 3 hours to remove the dichloromethane, thereby obtaining poly(DL-lactic acid) microspheres.

[0096] Microsphere suspension injection method:

[0097] The microspheres were dispersed in a saline solution at a concentration of 50 mg / ml to produce a microsphere suspension. The microsphere suspension was shaken and thoroughly mixed before injection, followed by rapid aspiration and injection using a 1 ml syringe. 0.1 ml (equivalent to 5 mg) was injected into the gastrocnemius muscle of the left hind limb, and another 0.1 ml (equivalent to 5 mg) was injected into the biceps brachii muscle of the left hind limb, as described below.

[0098] Experimental model:

[0099] Eight-week-old Sprague-Dawley rats were kept in a temperature-controlled chamber (22±2℃) with a 12-hour dark-light cycle for 7 days to acclimatize. On day 8, the animals were divided into four groups and each animal received a single intramuscular injection of the composition into the gastrocnemius and brachialis muscles of the left hind limb, according to Table 1.

[0100] Table 1. Experimental groups in Example 1

[0101]

[0102] * All microspheres in all groups were dispersed in physiological saline solution. Control group animals (Group A) received intramuscular administration of physiological saline solution, with an administration volume equal to that of the compositions administered in Groups B through D.

[0103] ** All microspheres in all groups had smooth surfaces and a roughly normally distributed particle size of 30–60 µm.

[0104] *** PDLLA was prepared with a 1:1 ratio of D-LA to L-LA.

[0105] Following intramuscular administration of the composition, the animal's left hind limb was immobilized with a plaster cast to maintain the muscles in a relaxed state, thereby inducing muscle atrophy. This physical immobilization of the left hind limb was maintained until day 14, at which point the rat was euthanized, and the gastrocnemius and brachialis muscles (biceps brachii) were dissected from both the right and left hind limbs and samples were taken for further analysis. Blood samples were collected from the eyes under anesthesia prior to euthanasia.

[0106] Muscle atrophy index:

[0107] Muscle mass of the gastrocnemius and brachialis muscles from the right and left hind limbs was measured. To calculate the muscle atrophy index, the mass of individual muscles on each side (right: internal control side; left: physically fixed side) was normalized using the animal's total body weight (measured on day 14), and the resulting values ​​were divided to obtain the muscle atrophy rate (e.g., normalized M). 腓肠肌 (Left side) / Normalized M 腓肠肌 (Right side) The muscle atrophy index can be used to determine muscle loss and / or muscle weakness, and to indicate muscle tissue regeneration / degeneration.

[0108] Muscle tissue sections and histochemistry (Masson staining and H&E staining):

[0109] Biceps brachii muscle tissue was fixed with fresh 4% paraffin solution and then embedded in paraffin. The paraffin-embedded tissue was cut into 4–8 μm thick sections and mounted on glass slides for staining. Hematoxylin and eosin (H&E) staining or Masson's staining was performed according to standard protocols.

[0110] In short, for Masson's staining, tissue sections are dewaxed and rehydrated. They are then stained with Masson's trichrome stain, which involves sequentially applying Acid Fuchs Red, Aniline Blue, and Orange G. After staining, the sections are rinsed, dehydrated, and covered with coverslips for microscopic examination. The principle of Masson's staining is related to the size of the anionic dye molecules and their tissue permeability. Molecular size is indicated by their molecular weight. Small molecular weight dyes easily penetrate dense, less permeable tissues, while large molecular weight dyes can only penetrate loose, highly permeable tissues. Light green and Aniline Blue dyes have larger molecular weights, therefore Masson's staining allows the observation of blue or green collagen fibers and red muscle fibers, while unstained areas remain white. In this paper, images are presented in grayscale, and representative muscle fibers are indicated by arrows. This staining method is primarily used to differentiate collagen fibers from muscle fibers.

[0111] For H&E staining, tissue sections were dewaxed and rehydrated. Next, sections were stained with hematoxylin to observe cell nuclei, and after acid washing, eosin was used to stain the sections to highlight cytoplasmic structures. The stained sections were then rinsed, dehydrated, and covered with coverslips for microscopic examination. During H&E staining, the basic Sudan III staining solution primarily stained the chromatin within the cell nucleus and ribosomes in the cytoplasm purple-blue. Eosin, on the other hand, is an acidic dye that primarily stained components in the cytoplasm and the extracellular matrix red. Therefore, during H&E staining, inflammatory cells were stained blue-purple, while muscle fibers appeared red / pink. In this paper, images are presented in grayscale, with representative muscle fibers indicated by white arrows and inflammatory cells by black arrows. The stained inflammatory cells included neutrophils, eosinophils, monocytes / macrophages, lymphocytes, and plasma cells. Hematoxylin and eosin (HE) staining is primarily used to observe the morphological structure and color changes of tissue cells, providing detailed information about tissue structure and cell morphology. H&E staining can observe local inflammatory responses caused by inflammatory cell infiltration and assess the biocompatibility of test compositions.

[0112] Following staining, tissue sections were examined under a microscope to analyze and evaluate the stained structures. Masson's staining results were presented as the average cross-sectional area of ​​the muscle fibers of the biceps brachii muscle from the fixed left hind leg, normalized for the average cross-sectional area of ​​the muscle fibers of the unfixed right hind leg muscle in each animal. H&E staining results were presented as cell counts of inflammatory cells, calculated using... Figure 4 The process takes place within the equivalent field of view in A and is not normalized.

[0113] Muscle tissue preparation, RNA extraction, and RT-PCR:

[0114] Gastrocnemius and brachialis muscle samples were collected from the right and left hind limbs and immediately flash-frozen in liquid nitrogen, then stored at -80°C for further analysis. The frozen muscle tissue was homogenized using a tissue homogenizer prior to RNA extraction.

[0115] Total RNA was extracted from homogenized muscle tissue using a commercially available RNA extraction kit (RNAeasy™ Animal RNA Isolation Kit, purchased from Beyotime Biotechnology (China)) following the manufacturer's instructions. The quality and quantity of the extracted RNA were assessed using a spectrophotometer.

[0116] The extracted RNA was reverse transcribed using a complementary DNA (cDNA) synthesis kit (purchased from Beyotime Biotechnology (China)) according to the manufacturer's instructions. The extracted RNA was reverse transcribed into cDNA using reverse transcriptase and oligomeric (dT) primers.

[0117] The expression levels of myosin, MuRF-1, and dystrophin-1 mRNA were measured using RT-PCR according to standard laboratory protocols. PCR amplification was performed using specific primer sequences targeting the genes of interest. The primer sequences used for amplification are as follows:

[0118] - Myosin: Forward primer: 5'-ACCTGGCTTCAACCTGATG-3' (SEQ ID NO:1), Reverse primer: 5'-TGCATCTGCTGTCCACCTT-3' (SEQ ID NO:2);

[0119] - MuRF-1: Forward primer: 5'-AGATGTACCCAGAGCGAGG-3' (SEQ ID NO:3), Reverse primer: 5'-CGGATGAAGGCTTTGGTGT-3' (SEQ ID NO:4);

[0120] - Dystrophin-1: Forward primer: 5'-AGTCAACCTGGCTCCTGAG-3' (SEQ ID NO:5), Reverse primer: 5'-CCGTCTGCATCCACCTTTC-3' (SEQ ID NO:6);

[0121] - GAPDH (reference gene): forward primer: 5'-GGAGCGAGATCCCTCCAAAAT-3' (SEQ ID NO:7), reverse primer: 5'-GGCTGTTGTCATACTTCTCATGG-3' (SEQ ID NO:8).

[0122] PCR was performed using a cDNA template and corresponding primer set. PCR products were separated by agarose gel electrophoresis and observed under ultraviolet (UV) light. Band intensity was analyzed using gel imaging software, and the mRNA expression levels of the target genes were normalized to the expression levels of a reference gene (GAPDH) to obtain relative expression levels. Upregulation of these genes suggests muscle loss and atrophy, as the proteins encoded by these genes negatively regulate muscle growth and promote protein degradation. Therefore, myosin, a secreted growth differentiation factor and member of the TGF-β family, acts on muscle cells and inhibits muscle growth by inhibiting Akt kinase-induced protein synthesis and stimulating ubiquitin-regulated protein degradation. MuRF-1 is an E3 ubiquitin ligase that induces proteasome-mediated myosin heavy chain degradation and is a major component of sarcomeres. It plays a crucial role in skeletal muscle breakdown under atrophic conditions. Dystrophin-1 is also an E3 ubiquitin ligase and a key regulator of ubiquitin-mediated skeletal muscle protein degradation.

[0123] Blood sampling and ELISA:

[0124] On day 14, blood samples were collected from each animal. The levels of inflammatory cytokines TNF-α and IL-6 were measured using a commercially available ELISA kit (Anoric Bio-technology Co., Ltd., Tianjin, China) according to the manufacturer’s instructions.

[0125] result

[0126] like Figure 1 As shown in Table 2 using samples obtained from control rats (Group A), physical fixation of the left hind leg resulted in a decrease in the muscle mass of the gastrocnemius and brachialis muscles of the left hind leg compared to the muscle mass of the unfixed (i.e., freely movable during the experiment) right hind leg.

[0127] Table 2. Muscle mass of the gastrocnemius and brachialis muscles in the left hind limb (fixed) and right hind limb (unfixed) of control rats (Group A)

[0128]

[0129] Figure 2 As shown in Figure A, the calculated muscle atrophy index (mean ± SD, evaluated by unpaired t-test) of the gastrocnemius muscle in group C (PDLA group) was similar to that in the control group (Group A). ​​Conversely, the muscle atrophy indices in groups B (PLLA group) and D (PDLLA group) were significantly lower compared to groups A (control group) and C (PDLA group). Group B (PLLA group) had the lowest mean muscle atrophy index.

[0130] Figure 2 As shown in Figure B, the calculated brachialis muscle atrophy index (mean ± SD, evaluated by unpaired t-test) in group C (PDLA group) was similar to that in the control group (Group A). ​​Conversely, the muscle atrophy indices in groups B (PLLA group) and D (PDLLA group) were significantly lower compared to groups A (control group) and C (PDLA group). The mean muscle atrophy index was lowest in group B (PLLA group).

[0131] Figure 2 The results presented together indicate that, compared with groups A and C (control and PDLA groups, respectively), the reduction in skeletal muscle mass induced by immobilization of the left hind leg of rats was significantly prevented in groups B and D (PLLA and PDLLA groups). The presented data show that, among the experimental groups compared, group B (PLLA group) experienced the least reduction in muscle mass.

[0132] like Figure 3 As shown in Figure A, compared with the control group (Group A), the mean cross-sectional area of ​​the biceps brachii muscle fibers in Group B (PLLA group) with the left hind leg fixed was significantly larger in Masson's staining indication. Figure 3 B, mean ± SD, evaluated by unpaired t-test. It was also observed that the mean cross-sectional area of ​​the muscles described in group D (PDLLA group) was larger compared to the control group (group A). ​​However, the mean cross-sectional area of ​​the muscles described in group C (PDLA group) was similar to that in group A (PDLA group and control group, respectively).

[0133] like Figure 4 As shown in Figure A, H&E staining revealed the average number of inflammatory cells infiltrating the biceps brachii muscle of the fixed left hind leg, indicated by the arrows in group C (PDLA group). Figure 4 Group B (mean ± SD, evaluated by unpaired t-test) showed a significantly higher mean number of inflammatory cells than the control group (Group A). ​​The mean number of inflammatory cells in Group D (PDLLA group) was also increased, but significantly lower than the mean number in Group C (PDLA group). In Group B (PLLA group), the mean number of inflammatory cells was comparable to that in the control group (Group A). ​​These results together indicate that a single dose of the composition containing PDLA homopolymer microspheres induces inflammatory cell infiltration into the muscle to which the composition was applied. The results also revealed that the use of the composition containing PDLLA polymer microspheres only partially induced this infiltration, while no infiltration was observed when the composition containing PLLA polymer microspheres was used.

[0134] Furthermore, no significant histopathological or inflammatory responses were observed in any of the experimental groups. The inventors conjecture that this could be explained by the relatively short duration of the experiment, and that in cases where the experiment duration was longer than those presented herein, significant histopathological or inflammatory responses, such as significant fibrosis and / or scar tissue formation, were observed in group C (PDLA group), to a lesser extent in group D (PDLLA group), but not in group B (PLLA group), in relation to the results related to inflammatory cell infiltration presented herein.

[0135] Figure 5 This image shows myostatin in a brachialis muscle tissue sample from the left hind leg of a rat that had been fixed to induce muscle atrophy. Figure 5 A) MuRF-1 ( Figure 5 B) and dystrophin-1 ( Figure 5 C) RT-PCR analysis of relative mRNA expression levels (mean ± SD, evaluated by unpaired t-test). The results showed that, compared with groups D (PDLLA group) and B (PLLA group), the expression levels of all tested mRNAs were significantly higher in groups A (control group) and C (PDLA group). Group B (PLLA group) had the lowest expression level of tested mRNAs.

[0136] Overall, these data indicate that the expression of molecular markers of muscle atrophy is induced in the control group (Group A) and Group C (PDLA group). The expression levels of these molecular markers of muscle atrophy were decreased in Group B (PLLA group) and Group D (PDLLA group), specifically, the decrease was more pronounced in Group B (PLLA group). These data indicate a preventative therapeutic effect on muscle atrophy in animals of Groups B and D, and are associated with lower muscle atrophy indices, such as... Figure 2 As shown in the image.

[0137] Table 3. Blood analysis results of TNF-α and IL-6 inflammatory markers (mean ± SD)

[0138]

[0139] Table 3 shows the results of blood analysis of TNF-α and IL-6 inflammatory markers. The results indicate that, compared with the control group (group A) and group B (PLLA group), the blood TNF-α levels in groups C and D (PDLA and PDLLA groups, respectively) were significantly increased. The blood TNF-α levels in group B (PLLA group) rats were similar to those in the control group (group A).

[0140] Similar trends were observed in the IL-6 levels in the blood of each experimental group.

[0141] In summary, the data revealed that, compared to the control group, the levels of inflammatory markers in the blood of animals in group C (PDLA group) were elevated, while the levels of inflammatory markers in group D (PDLLA group) were elevated to a lesser extent. No increase in inflammatory marker levels was observed in the blood of animals in group B (PLLA group). The inventors anticipated that a mild inflammatory response would be observed after any intramuscular application; however, this response diminished in blood samples 14 days after application, as was the case in this embodiment. Therefore, it is concluded that intramuscular application of the composition containing D-LA polymer microspheres (PDLA group) induced a significant inflammatory response (PDLLA group induced a lesser level of inflammatory response). On the other hand, the composition containing L-LA homopolymer microspheres did not induce any significant inflammatory response.

[0142] in conclusion

[0143] As demonstrated by comparing the muscle mass of the fixed and unfixed hind legs of control group animals ( Figure 1 (See Table 2) The physical fixation method induced a reduction in muscle mass in the gastrocnemius and brachialis muscles of the fixed limbs in rats. Therefore, this method is an effective model for evaluating the in vivo therapeutic effect on muscle atrophy.

[0144] like Figure 2 The results presented indicate that animals not treated with compositions containing L-LA polymers (such as compositions containing microspheres of a homopolymer (PLLA) composed of L-LA or microspheres containing microspheres of a copolymer (PDLLA) composed of L-LA and D-LA) developed significantly more muscle atrophy than animals treated with a single dose of compositions containing L-LA polymers (such as compositions containing microspheres of a homopolymer of PLLA or microspheres containing microspheres of a PDLLA copolymer). Therefore, a single dose of compositions containing L-LA polymers (such as compositions containing microspheres of a homopolymer of PLLA or microspheres containing microspheres of a PDLLA copolymer) is effective in preventing muscle atrophy in vivo. In the experimental groups tested in this study, the best results in preventing muscle atrophy were achieved with the composition containing microspheres of a homopolymer of PLLA. The data also indicate that a single dose of compositions not containing L-LA polymers (such as compositions containing microspheres of a homopolymer (PDLA) composed of D-LA) is not effective in preventing muscle atrophy in vivo. Therefore, these data indicate that compositions including polymers containing only D-LA are not effective in preventing muscle atrophy in vivo.

[0145] like Figure 3As shown, Masson's staining revealed that a single application of a composition comprising a polymer containing D-LA but not L-LA (such as a composition containing microspheres of PDLA homopolymer) did not prevent a reduction in the average cross-sectional area of ​​muscle fibers in the fixed left hind leg biceps brachii muscle, which had been induced to atrophy. Consistent with these results, the muscle tissue was characterized by a high muscle atrophy index (e.g., Figure 2 (as shown in B).

[0146] In fact, the average cross-sectional area of ​​the biceps brachii muscle fibers in the fixed left hind leg in this experimental group (Group C) was similar to the average cross-sectional area of ​​the biceps brachii muscle fibers measured in the control group (Group A). ​​Therefore, a single application of a composition containing polymers with D-LA but not L-LA is not an effective preventative treatment for muscle atrophy.

[0147] Conversely, a single application of a composition containing an L-LA polymer significantly prevented the reduction of the average cross-sectional area of ​​the muscle fibers and also effectively prevented the development of muscle atrophy. Figure 2 Compositions including polymers containing both L-LA and D-LA also prevent a reduction in the average cross-sectional area of ​​the muscle fibers, although to a lesser extent than compositions including polymers containing L-LA but not D-LA.

[0148] Overall, these data indicate that a single application of a composition containing an L-LA polymer effectively prevents the reduction in the mean cross-sectional area of ​​muscle fibers in the biceps brachii muscle, which has been induced to atrophy. Figure 3 It also effectively prevents the development of muscle atrophy. Figure 2 Therefore, the compositions of the present invention disclosed herein are advantageous in the preventive treatment of muscle atrophy.

[0149] like Figure 4 As shown in the study, H&E staining revealed that a single application of a composition comprising a polymer containing D-LA but not L-LA (such as a composition comprising microspheres containing PDLA homopolymers) induced an increase in the average number of inflammatory cells in the biceps brachii muscle of the immobilized left hind leg, in which muscle atrophy had been induced and the composition had been applied. Therefore, the application of the composition comprising a polymer containing D-LA but not L-LA (such as a composition comprising microspheres containing PDLA homopolymers) induced a significant inflammatory response.

[0150] Conversely, a single application of a composition containing an L-LA polymer (such as a composition containing microspheres of PLLA homopolymer) did not induce an increase in the mean number of inflammatory cells in the biceps brachii muscle of the immobilized left hind leg. Therefore, application of a composition containing an L-LA polymer did not induce a significant inflammatory response. A single application of a composition comprising polymers containing both L-LA and D-LA (such as a composition containing microspheres of PDLLA copolymer) induced an increase in the mean number of inflammatory cells in the biceps brachii muscle of the immobilized left hind leg, although the increase was less than that induced by a single application of a composition comprising a polymer containing D-LA but not L-LA.

[0151] Overall, these results indicate that application of compositions comprising polymers containing D-LA induces a significant inflammatory response. The inventors believe that the extent of this inflammatory response depends on the concentration and / or amount of D-LA in the polymer, as compositions comprising polymers containing both L-LA and D-LA induce a lower inflammatory response. Compositions containing L-LA polymers but not D-LA do not induce a significant inflammatory response. This indicates good biocompatibility of the compositions.

[0152] The results presented in this article relate to the preventive effect of compositions containing L-LA polymers in the development of muscle atrophy (e.g. Figure 2 (as shown in B).

[0153] like Figure 5 As shown, a single application of a composition comprising a polymer containing D-LA but not L-LA (such as a composition containing microspheres of PDLA homopolymer) did not prevent an increase in the expression levels of molecular markers of muscle atrophy (such as myosin, MuRF-1, and dystrophin-1) in the test brachial muscle tissue that had induced muscle atrophy. Consistent with these results, the muscle tissue was characterized by a high muscle atrophy index (e.g., Figure 2 (As shown in B). In fact, the expression levels of these mRNAs in this experimental group (Group C) were similar to those measured in the control group (Group A). ​​Therefore, a single application of a composition comprising a polymer containing only D-LA (such as a composition containing microspheres of PDLA homopolymer) is not effective in preventing muscle atrophy.

[0154] Conversely, a single application of a composition containing an L-LA polymer (such as a composition containing microspheres of PLLA homopolymer) prevents the upregulation of molecular markers associated with muscle atrophy. This is related to the preventive effect of said composition in the development of muscle atrophy (e.g. Figure 2(As shown in B). Compositions including polymers containing L-LA and D-LA, such as compositions containing microspheres of PDLLA copolymers, also prevented upregulation of molecular marker expression levels, but to a lesser extent. However, these higher expression levels were also significantly lower than those measured in control groups and in tissues of animals that had been treated with compositions containing D-LA but not L-LA polymers.

[0155] Overall, the data indicate that a single application of a composition containing an L-LA polymer (e.g., a composition containing microspheres of PLLA homopolymer) effectively prevents the upregulation of genes associated with worsening muscle atrophy. Figure 5 It also effectively prevents the development of muscle atrophy. Figure 2 Therefore, the compositions of the present invention disclosed herein are advantageous in the preventive treatment of muscle atrophy because they prevent the upregulation of genes associated with the worsening of muscle atrophy.

[0156] As shown in Table 3, a single administration of a composition comprising a polymer containing D-LA but not L-LA (such as a composition containing microspheres of PDLA homopolymer) induced a significant inflammatory response in animals. Conversely, a single administration of a composition containing only an L-LA polymer (such as a composition containing microspheres of PLLA homopolymer) did not induce a significant inflammatory response. This is related to the preventative effect of these compositions in the development of muscle atrophy (e.g., Figure 2 (As shown in B). Compositions including polymers containing both L-LA and D-LA also induce inflammatory responses, but the degree of induced inflammation is less than that induced by compositions including polymers containing only D-LA. Therefore, the compositions of the present invention disclosed herein are advantageous in the preventive treatment of muscle atrophy because they do not induce significant inflammatory responses. Example 2

[0157] Therapeutic treatment of muscle atrophy using compositions containing microspheres of L-lactic acid polymer.

[0158] This embodiment describes an in vivo experiment in which a composition comprising microspheres of L-lactic acid homopolymer (poly-L-lactic acid, PLLA), D-lactic acid homopolymer (poly-D-lactic acid, PDLA), or copolymers of L-lactic acid (L-LA) and D-lactic acid (D-LA) (poly-D,L-lactic acid, PDLLA) was tested in a rat model of muscle atrophy. This experiment was performed essentially as described in Example 1; however, a single dose of the above composition was administered to the animals after inducing muscle atrophy. The muscle atrophy index was measured as the primary indicator of muscle atrophy. Changes in molecular markers of muscle tissue regeneration, muscle atrophy, and / or inflammation were analyzed using histochemical and standard biochemical and molecular biological methods.

[0159] Materials and Methods

[0160] Preparation of the composition:

[0161] As described in Example 1, a composition comprising poly-L-lactic acid (PLLA), poly-D-lactic acid (PLDA), and / or poly-D,L-lactic acid (PDLLA) microspheres was prepared.

[0162] Experimental model:

[0163] Eight-week-old Sprague-Dawley rats were acclimatized for 7 days in a temperature-controlled chamber (22±2°C) with a 12-hour dark-light cycle. After 7 days of acclimatization, on day 8, the left hind limb of each animal was immobilized with a plaster cast to maintain relaxation of the muscles, thereby inducing muscle atrophy. After 18 days of this physical immobilization, immobilization was discontinued, the plaster cast was removed, and a single intramuscular injection of the composition according to Table 4 was administered into the gastrocnemius and brachialis muscles of the left hind limb of each animal.

[0164] Table 4. Experimental groups in Example 2

[0165]

[0166] * All microspheres in all groups were dispersed in physiological saline solution. Control group animals (Group A1) received only intramuscular administration of physiological saline solution, with an administration volume equal to that of the compositions administered in Groups B1 through D1.

[0167] ** All microspheres in all groups had smooth surfaces and a roughly normally distributed particle size of 30–60 µm.

[0168] *** PDLLA was prepared with a 1:1 ratio of D-LA to L-LA.

[0169] Fourteen days after a single intramuscular administration of the composition, rats were euthanized, and the gastrocnemius and brachialis muscles (biceps brachii) were dissected from the right and left hind limbs and samples were taken for further analysis. Blood samples were collected from the eyes under anesthesia prior to euthanasia of the animals.

[0170] The measurement and calculation of the muscle atrophy index, muscle tissue sections and histochemistry, muscle tissue preparation and RT-PCR, as well as blood sampling and ELISA were performed as described in Example 1.

[0171] result

[0172] Figure 6As shown in Figure A, the calculated muscle atrophy index (mean ± SD, evaluated by unpaired t-test) of the gastrocnemius muscle in group C1 (PDLA group) was similar to that in the control group (A1 group). Conversely, the muscle atrophy indices in groups B1 (PLLA group) and C1 (PDLLA group) were significantly lower compared to groups A1 (control group) and C1 (PDLA group). The mean muscle atrophy index was lowest in group B1 (PLLA group).

[0173] Figure 6 As shown in Figure B, the calculated brachialis muscle atrophy index (mean ± SD, evaluated by unpaired t-test) in group C1 (PDLA group) was similar to that in the control group (A1 group). Conversely, the muscle atrophy index in groups B1 (PLLA group) and C1 (PDLLA group) was significantly lower compared to groups A1 (control group) and C1 (PDLA group). The mean muscle atrophy index was lowest in group B1 (PLLA group).

[0174] Figure 6 The results presented together indicate that, compared with groups A1 and C1 (control and PDLA groups, respectively), skeletal muscle mass was effectively regenerated in groups B1 and D1 (PLLA and PDLLA groups) after inducing muscle loss by immobilizing the left hind leg of rats. The presented data show that the level of muscle mass regeneration was highest in group B1 (PLLA group) among the experimental groups compared.

[0175] in conclusion

[0176] like Figure 6 The study presented that a single application of compositions containing L-LA polymers (such as compositions containing microspheres of PLLA homopolymers or microspheres of PDLLA copolymers) induces effective muscle tissue regeneration in skeletal muscle, wherein muscle atrophy has been induced by physical fixation prior to treatment. Therefore, a single application of compositions containing L-LA polymers is effective in treating muscle atrophy in vivo. In the experimental group tested in this study, the application of compositions using microspheres containing PLLA homopolymers achieved the best results in treating muscle atrophy. The data also indicate that a single application of compositions not containing L-LA polymers (such as compositions containing microspheres of PDLA homopolymers) is not effective in treating muscle atrophy in vivo. Therefore, these data indicate that compositions including polymers containing only D-LA are not effective in treating muscle atrophy in vivo.

[0177] The results and conclusions related to changes in molecular markers for muscle tissue regeneration and muscle atrophy and / or inflammation, analyzed by histochemical and standard biochemical and molecular biological methods, are expected to provide substantially the same results as presented in Example 1 in the therapeutic model described herein, as described in Example 1. For the sake of brevity, these descriptions will not be repeated in this example.

[0178] The results of these analyses are expected to support the trends and conclusions obtained from the experimental data on the muscle atrophy index presented in Example 2 above, and possess the characteristics shown in Example 1. It is anticipated that most desired results will be obtained using compositions comprising L-LA or L-LA polymers, such as compositions comprising polymers containing L-LA but not D-LA and / or compositions comprising microspheres of PLLA homopolymers. Example 3

[0179] Therapeutic treatment of muscle atrophy using compositions containing L-lactic acid or L-lactic acid polymers.

[0180] This embodiment describes an in vivo experiment in which compositions comprising microspheres containing L-lactic acid homopolymer (poly-L-lactic acid, PLLA), scaffolds containing poly-L-lactic acid (PLLA), compositions containing L-lactic acid (L-LA), and compositions containing D-lactic acid (D-LA) were tested in a rat model of muscle atrophy. This experiment was conducted essentially as described in Example 2, i.e., the above compositions were administered to animals after inducing muscle atrophy. However, the compositions containing PLLA microspheres and the cuboid scaffolds containing PLLA were administered as a single dose, while the compositions containing L-LA or D-LA were administered repeatedly (daily for 14 days). The muscle atrophy index was measured as the primary indicator of muscle atrophy. Changes in molecular markers of muscle tissue regeneration, muscle atrophy, and / or inflammation were analyzed using histochemical and standard biochemical and molecular biological methods.

[0181] Materials and Methods

[0182] Preparation of the composition:

[0183] As described in Example 1, a composition comprising poly-L-lactic acid (PLLA) microspheres was prepared and injected.

[0184] PLLA stent preparation and implantation methods:

[0185] PLLA was fabricated into a solid block using 3D printing. The solid block was then cut into several smaller pieces, each weighing 10 mg. Each 10 mg PLLA block was subcutaneously implanted near a muscle region.

[0186] Preparation and administration of the composition containing L-LA (i.e., L-LA solution): The L-LA solution was diluted with saline solution to a concentration of 15 mg / ml. 0.1 mL was injected once daily into the gastrocnemius and biceps brachii muscles of rats, as described below.

[0187] Preparation and application of compositions containing D-LA (i.e., D-LA solutions): The methods for preparing and applying D-LA are the same as those for preparing and applying L-LA.

[0188] Experimental model:

[0189] Eight-week-old Sprague-Dawley rats were acclimatized for 7 days in a temperature-controlled chamber (22±2°C) with a 12-hour dark-light cycle. After 7 days of acclimatization, on day 8, the animals' left hind limbs were immobilized with plaster casts to maintain relaxation of the left hind limb muscles, thereby inducing muscle atrophy. Immobilization was discontinued and the plaster casts removed 18 days later (day 25). Following removal of the plaster casts, each animal received treatment of the left hind limb gastrocnemius and brachialis muscles as indicated in Table 5. Thus, group A2 received a single intramuscular injection of a single dose of saline solution, with an injection volume equal to the single-dose composition in groups B2, D2, and E2. Group B2 received a single intramuscular injection of a composition containing microspheres of PLLA homopolymer, while group C2 received a subcutaneous implantation of a scaffold (cubic prism) containing PLLA homopolymer. Single-dose administration and scaffold implantation were performed after removal of physical immobilization (day 25). Groups D2 and E2 received repeated intramuscular injections of either the composition containing L-LA (Group D2) or the composition containing D-LA (Group E2), i.e., a 3 mg dose once daily for 14 days.

[0190] After a 14-day treatment period as described above (including single or repeated administrations of the composition described above), the rats were euthanized, and the gastrocnemius and brachialis muscles (biceps brachii) were dissected from the right and left hind limbs and samples were taken for further analysis. Blood samples were collected from the eyes under anesthesia prior to euthanasia of the animals.

[0191] Table 5. Experimental groups in Example 3

[0192]

[0193] * The microspheres in group B2 were dispersed in physiological saline solution, and the L-LA / D-LA in groups D2 / E2 were prepared in physiological saline solution respectively. The control group animals (group A2) received only intramuscular administration of physiological saline solution, with an administration volume equal to that of the compositions administered in groups B2, D2, and E2.

[0194] The microspheres have a smooth surface and a particle size of 30-60 µm that is approximately normally distributed.

[0195] *** Dosage / injection (i.e., repeated injection of the specified dose).

[0196] The measurement and calculation of the muscle atrophy index, muscle tissue sections and histochemistry, muscle tissue preparation and RT-PCR, and blood sampling and ELISA were performed as described in Example 1.

[0197] result

[0198] Figure 7 As shown in Figure A, the calculated muscle atrophy index (mean ± SD, evaluated by unpaired t-test) of the gastrocnemius muscle in group E2 (D-LA) was similar to that in the control group (A2). Conversely, the muscle atrophy indices of groups B2 (PLLA) and D2 (L-LA) were significantly lower than those of groups A2 (control) and E2 (D-LA). The mean muscle atrophy index of group C2 (PLLA-S) was slightly lower than that of groups A2 (control) and E2 (D-LA), but this difference was not statistically significant. The mean muscle atrophy index of group B2 (PLLA) was the lowest.

[0199] Figure 7 As shown in Figure B, the calculated brachialis muscle atrophy index (mean ± SD, evaluated by unpaired t-test) in group E2 (D-LA) was similar to that in the control group (A2). Conversely, compared with groups A2 (control) and E2 (D-LA), the muscle atrophy indices in groups B2 (PLLA), D2 (L-LA), and C2 (PLLA-S) were significantly lower. Group B2 (PLLA) had the lowest mean muscle atrophy index.

[0200] Figure 7 The results presented indicate that, compared with groups A2 and C2 (control and D-LA groups, respectively), skeletal muscle mass regenerated effectively in groups B2 and D2 (PLLA and L-LA groups) after inducing muscle mass reduction by immobilizing the left hind leg of rats. Effective skeletal muscle mass regeneration was also observed in the brachialis muscle of group C2 (PLLA-S group). The presented data show that the highest level of muscle mass regeneration was observed in group B (PLLA group) among the compared experimental groups.

[0201] in conclusion

[0202] like Figure 7As presented, a single application of a composition containing an L-LA polymer (such as a composition containing microspheres of PLLA homopolymer) induces effective muscle tissue regeneration in skeletal muscle, where muscle atrophy has been induced by physical fixation. Furthermore, repeated application of the L-LA-containing composition also induces effective muscle tissue regeneration in skeletal muscle. Therefore, both single application of a composition containing an L-LA polymer (such as a composition containing microspheres of PLLA homopolymer) and repeated application of the L-LA-containing composition are effective treatments for muscle atrophy in vivo. Additionally, subcutaneous application of an implant (i.e., a scaffold) containing an L-LA polymer (such as PLLA homopolymer) also induces effective muscle tissue regeneration in skeletal muscle. Therefore, such implants are also considered effective in treating disorders, diseases, and / or conditions characterized by muscle atrophy in vivo.

[0203] Among these compositions demonstrating effective treatment for muscle atrophy, compositions containing L-LA or L-LA polymers, such as microspheres containing PLLA homopolymers, yield the best results. Because compositions containing L-LA polymers ensure sustained release of L-LA into muscle tissue, a single application is sufficient to achieve a therapeutic effect. On the other hand, for effective treatment of muscle atrophy using compositions containing L-LA, repeated applications of the composition are necessary. The inventors anticipate that, depending on the nature of the muscle atrophy, such as its extent and / or degree, a single application of a composition containing L-LA can effectively treat disorders, diseases, and / or conditions characterized by muscle atrophy.

[0204] Conversely, repeated application of compositions containing D-LA but not L-LA failed to induce effective muscle tissue regeneration in skeletal muscle, where muscle atrophy had already been induced by physical fixation. Therefore, these data indicate that compositions containing D-LA but not L-LA are ineffective in treating muscle atrophy in vivo.

[0205] Results and conclusions related to changes in molecular markers associated with muscle tissue regeneration, muscle atrophy, and / or inflammation were analyzed using histochemical and standard biochemical and molecular biological methods, and were generally as described in Example 1 (e.g., Masson's staining and H&E staining, RT-PCR analysis, and blood analysis).

[0206] The results and conclusions of these analyses are expected to support the experimental data on the muscle atrophy index presented in Example 3, as well as the therapeutic effects demonstrated by compositions comprising L-LA or its polymers. Most desirable results are expected to be obtained using compositions comprising L-LA or L-LA polymers, such as compositions comprising microspheres of PLLA homopolymer.

[0207] Example 4.

[0208] Treatment of muscle atrophy using PLLA-PEG microspheres.

[0209] This embodiment describes an in vivo experiment in which the composition comprises PLLA-PEG microspheres. Following induction of muscle atrophy, a single dose of the composition was administered to animals. The muscle atrophy index was measured as the primary indicator of muscle atrophy.

[0210] Materials and Methods

[0211] Preparation of the composition:

[0212] Synthesis of PLLA-PEG:

[0213] mPEG 2000 (3.5 g) and L-lactide (LLA) (21.6 g) were dissolved in anhydrous toluene and catalyzed by the addition of stannous octoate (relative to mPEG) as a catalyst. 2000 (0.5 molar equivalents) starting LLA and mPEG as a macromolecular initiator 2000 Ring-opening polymerization.

[0214] The molecular weight of PLLA-PEG is 16,000 g / mol (i.e., 16 kDa), of which PEG is 2,000 g / mol (i.e., 2 kDa) and PLLA is 14,000 g / mol (i.e., 14 kDa).

[0215] Preparation of PLLA-PEG microspheres:

[0216] PLLA-PEG microspheres were prepared using an oil / water emulsion strategy. 10 mg of PLLA-PEG was dispersed in 1 mL of dichloromethane, and the solution was added to 10 mL of a 3% PVA aqueous solution to generate an oil / water emulsion through emulsification pretreatment. The mixture was then added to a 1.5% PVA solution under stirring, and the dichloromethane was removed by rotary evaporation. The microspheres were separated by centrifugation at 7000 rpm and obtained by lyophilization.

[0217] Experimental model:

[0218] Eight-week-old Sprague-Dawley rats were kept in a temperature-controlled chamber (22±2℃) with a 12-hour dark-light cycle for 7 days to allow them to acclimatize.

[0219] After a 7-day acclimatization period, on day 8, the left hind limb of the animals was immobilized with a plaster cast to maintain the muscles of the calf in a relaxed position, thereby establishing a muscle atrophy model. Immobilization was discontinued and the plaster cast removed after 18 days of this physical immobilization. Each group of rats received either treatment or saline solution. According to Table 6, each animal received an intramuscular injection of the composition. Animals in groups A3 and B3 received intramuscular injections of 10 mg saline solution and PLLA-PEG microspheres (dispersed in saline solution, with a smooth surface and a particle size of 40-65 μm), respectively.

[0220] Table 4. Experimental groups in Example 4

[0221]

[0222] * The control group animals (Group A3) received only intramuscular administration of saline solution, with the same volume as the composition administered in Group B3.

[0223] ** The microspheres are dispersed in physiological saline solution. The microspheres have a smooth surface and a particle size of 40-65 μm with a roughly normal distribution.

[0224] Fourteen days after a single intramuscular administration of the composition, rats were sacrificed, and the gastrocnemius and brachialis muscles (biceps brachii) were dissected from the right and left hind limbs and samples were taken for further analysis. The absolute mass of the gastrocnemius and brachialis muscles of the left hind limb was measured and divided by the total body weight to calculate the relative muscle index. The rate of decrease was calculated based on the index ratio.

[0225] result

[0226] Figure 8 A and Figure 8 B shows that the muscle atrophy indices (mean ± SD, evaluated by unpaired t-test) of the gastrocnemius and biceps brachii muscles in the control group (A3 group) were significantly higher than those in the PLLA-PEG-treated group (B3 group). Therefore, Figure 8 The results presented indicate that, compared with group A3 (control group), PLLA-PEG treatment effectively reduced muscle atrophy induced by immobilized left hind leg in group B3.

[0227] in conclusion

[0228] based on Figure 8 A and Figure 8 B. It can be concluded that PLLA-PEG microspheres effectively reduce atrophy of the gastrocnemius and biceps brachii muscles in animal models. The results of this experiment confirm that a single application of the composition containing PLLA-PEG microspheres is effective in treating muscle atrophy in vivo, and that the application will also be effective in preventing muscle atrophy in vivo.

[0229] List of implementation plans item by item

[0230] 1. An L-lactic acid and / or its polymer thereof for the treatment of muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy.

[0231] 2. The L-lactic acid and / or its polymers for use according to claim 1, wherein the polymers are selected from the group consisting of: poly-L-lactic acid, poly-D,L-lactic acid, and any copolymers containing L-lactic acid but not D-lactic acid.

[0232] 3. The L-lactic acid and / or its polymers according to claim 1 or 2, wherein the polymers are selected from the group consisting of poly-L-lactic acid and poly-D,L-lactic acid.

[0233] 4. The L-lactic acid and / or its polymer according to claim 2 or 3, wherein the concentration of L-lactic acid in the poly-D,L-lactic acid is at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0234] The ratio of L-lactic acid to D-lactic acid in the polyD,L-lactic acid is at least about 1:5, such as the ratio being about 1:1.

[0235] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0236] 5. L-lactic acid and / or its polymers according to claim 1 or 2, wherein the polymers are selected from the group consisting of poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid.

[0237] 6. L-lactic acid and / or its polymers according to any one of claims 1, 2 and 5, wherein the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%;

[0238] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0239] 7. L-lactic acid and / or its polymers according to any one of claims 1, 2, 5 and 6, wherein said copolymers do not contain glycolic acid.

[0240] 8. L-lactic acid and / or its polymers for use according to any one of claims 1, 2, and 5 through 7, wherein said polymers are selected from the group consisting of: poly-L-lactic acid; any copolymer comprising L-lactic acid and ethylene glycol; any copolymer comprising L-lactic acid, ethylene glycol, and glycolic acid; any copolymer comprising L-lactic acid and taurine; any copolymer comprising L-lactic acid and chitosan; and any copolymer comprising L-lactic acid and ε-caprolactone; such as those selected from the group consisting of poly-L-lactic acid and any copolymers comprising L-lactic acid and ethylene glycol.

[0241] 9. The L-lactic acid and / or its polymers according to claim 8, wherein the concentration of the L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0242] The concentration of L-lactic acid in the copolymer is at least about 30%, such as about 30%;

[0243] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0244] 10. L-lactic acid and / or its polymers according to any one of claims 1 to 3, 5 and 8, wherein the polymer is poly-L-lactic acid.

[0245] 11. L-lactic acid and / or its polymer for use according to any one of the preceding claims, wherein said polymer has a molecular weight of at least about 400 Da, such as at least about 500 Da, such as at least about 1 kDa, such as at least about 2 kDa, such as at least about 5 kDa, such as at least about 10 kDa, such as at least about 20 kDa, such as at least about 30 kDa, such as at least about 40 kDa, such as at least about 50 kDa, such as at least about 100 kDa, such as at least about 150 kDa, such as at least about 200 kDa, such as at least about 250 kDa, such as at least about 300 kDa; and / or

[0246] Molecules ranging from about 400 Da to about 300 kDa, such as about 500 Da to about 300 kDa, such as about 1000 Da to about 300 kDa, such as about 1500 Da to about 275 kDa, such as about 2000 Da to about 250 kDa, such as about 2500 Da to about 225 kDa, such as about 3000 Da to about 200 kDa, such as about 3500 Da to about 175 kDa, such as about 4000 Da to about 150 kDa, such as about 4500 Da to about 125 kDa, such as about 5000 Da to about 100 kDa.

[0247] 12. A composition for treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy, said composition comprising L-lactic acid and / or a polymer thereof, wherein said L-lactic acid and / or said polymer thereof are as defined in any of the preceding claims; and wherein said composition comprises at least one pharmaceutically acceptable carrier and / or excipient.

[0248] 13. The composition for use according to claim 12, wherein the composition comprises at least about 1%, such as at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of the L-lactic acid; and / or

[0249] At least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of the L-lactic acid polymer;

[0250] The percentage (%) corresponds to the concentration as a weight-to-volume ratio.

[0251] 14. The composition for use according to claim 12 or 13, wherein the composition is formulated as a solution, suspension, gel and / or implant.

[0252] 15. The composition for use according to any one of claims 12 to 14, wherein the composition is formulated as a suspension, such as an injectable suspension.

[0253] 16. A composition for use according to any one of claims 12 to 15, wherein the composition comprises particles of the L-lactic acid and / or the polymer thereof.

[0254] 17. The composition for use according to claim 16, wherein the particles are selected from the group consisting of microcells, nanoparticles and microspheres, such as those selected from the group consisting of nanoparticles and microspheres.

[0255] 18. The composition for use according to claim 16 or 17, wherein the particles are microspheres.

[0256] 19. The composition for use according to any one of claims 16 to 18, wherein the particles have a particle size of at least about 10 µm, such as at least about 15 µm, such as at least about 20 µm, such as at least about 25 µm, such as at least about 30 µm, such as at least about 35 µm, such as at least about 40 µm, such as at least about 45 µm, such as at least about 50 µm, such as at least about 55 µm, such as at least about 60 µm; and / or a particle size of about 1 to about 100 µm, such as about 2 to about 90 µm, such as about 5 to about 85 µm, such as about 10 to about 80 µm, such as about 15 to about 75 µm, such as about 20 to about 70 µm, such as about 25 to about 65 µm, such as about 30 to about 60 µm; and / or a particle size of about 45 µm ± 15 µm, such as a particle size of about 45 µm.

[0257] 20. The composition for use according to any one of claims 17 to 19, wherein the microspheres have a smooth surface.

[0258] 21. The composition for use according to any one of the preceding claims, wherein the composition does not contain D-lactic acid and / or its polymers.

[0259] 22. The composition for use according to any one of the preceding claims, wherein the L-lactic acid and / or the polymer thereof are the sole active ingredients.

[0260] 23. The composition for use according to any one of the preceding claims, wherein the composition does not contain glycolic acid.

[0261] 24. The composition for use according to any one of the preceding claims, wherein the pharmaceutically acceptable carrier and / or excipient is selected from the group consisting of physiological saline solution, surfactant and stabilizer.

[0262] 25. The composition for use according to claim 24, wherein the pharmaceutically acceptable carrier and / or excipient is a physiological saline solution.

[0263] 26. L-lactic acid and / or its polymers for use according to any one of claims 1 to 11, or a composition for use according to any one of claims 12 to 25, wherein the L-lactic acid and / or its polymers, or the composition is formulated for oral, nasal, transdermal, ocular, intramuscular, and / or subcutaneous administration, such as the L-lactic acid and / or its polymers, or the composition is formulated for intramuscular and / or subcutaneous administration.

[0264] 27. L-lactic acid and / or its polymers for use according to any one of claims 1 to 11 and 26, or a composition for use according to any one of claims 12 to 26, wherein the use comprises administering the L-lactic acid and / or its polymers, or the composition, to a subject in need at least once.

[0265] 28. L-lactic acid and / or its polymers as described in claim 27, or a composition as described in claim 27, wherein the at least one application is intramuscular, such as wherein the at least one application is intramuscular injection.

[0266] 29. L-lactic acid and / or its polymers as described in claim 27 or 28, or the composition as described in claim 27 or 28, wherein at least one administration does not induce a significant inflammatory response in the subject.

[0267] 30. L-lactic acid and / or its polymers according to any one of claims 27 to 29, or a composition according to any one of claims 27 to 29, wherein the at least one application does not induce significant fibrosis and / or scar tissue formation in the subject.

[0268] 31. L-lactic acid and / or its polymers according to any one of claims 27 to 30, or a composition according to any one of claims 27 to 30, wherein the dose of said L-lactic acid is administered during said at least one administration, wherein said dose is about 2.25 to about 1152 mg / kg, such as about 112.5 to about 576 mg / kg, such as about 375 to about 500 mg / kg; and / or

[0269] The dosage of the L-lactic acid polymer is administered during the at least one administration, wherein the dosage is about 22.5 to about 57,600 mg / kg, such as about 1,125 to about 28,800 mg / kg, such as about 1,250 to about 1,667 mg / kg.

[0270] 32. L-lactic acid and / or its polymers according to any one of claims 27 to 31, or a composition according to any one of claims 27 to 31, wherein the at least one application is a single application.

[0271] 33. L-lactic acid and / or its polymers according to any one of claims 27 to 31, or a composition according to any one of claims 27 to 31, wherein the at least one application is a repeated application.

[0272] 34. L-lactic acid and / or its polymers as described in claim 33, or a composition as described in claim 33, wherein the administration is performed once daily to a patient in need for at least 2 days, such as at least 3 days, such as at least 4 days, such as at least 5 days, such as at least 6 days, such as at least 7 days, such as at least 8 days, such as at least 9 days, such as at least 10 days, such as at least 11 days, such as at least 12 days, such as at least 13 days, such as at least 14 days.

[0273] 35. L-lactic acid and / or its polymers according to any one of claims 1 to 11 and 26 to 34, or a composition according to any one of claims 12 to 34, wherein the muscle injury is characterized by muscle atrophy.

[0274] 36. L-lactic acid and / or its polymers for use according to any one of items 1 to 11 and 26 to 35, or a composition for use according to any one of items 12 to 35, wherein the treatment is a preventive and / or therapeutic treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0275] 37. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11 and 26 to 36, or a composition available for use according to any one of items 12 to 36, wherein the treatment is a preventive treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0276] 38. L-lactic acid and / or its polymers as described in claim 36 or 37, or the composition as described in claim 36 or 37, wherein the preventive treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or muscle strength reduction.

[0277] 39. L-lactic acid and / or its polymers available for use according to any one of claims 1 to 11 and 26 to 36, or a composition available for use according to any one of claims 12 to 36, wherein the treatment is a therapeutic treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0278] 40. L-lactic acid and / or its polymers as described in claim 36 or 39, or a composition as described in claim 36 or 39, wherein the therapeutic treatment induces muscle tissue regeneration.

[0279] 41. L-lactic acid and / or its polymers for use according to any one of claims 1 to 11 and 26 to 40, or a composition for use according to any one of claims 12 to 40, wherein the injury, disease, ailment and / or disorder is characterized by a decrease in muscle mass, wasting and / or thinning and / or a reduction in muscle strength.

[0280] 42. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11 and 26 to 41, or a composition available for use according to any one of items 12 to 41, wherein the treatment is a treatment for a disease, condition and / or disorder characterized by muscle atrophy.

[0281] 43. L-lactic acid and / or its polymers for use according to any one of claims 1 to 11 and 26 to 42, or a composition for use according to any one of claims 12 to 42, wherein the disease, condition or disorder is selected from the group consisting of: disuse atrophy, age-related atrophy, malnutrition-induced atrophy, muscle disorders and neurological disorders.

[0282] 44. L-lactic acid and / or its polymers for use according to any one of claims 1 to 11 and 26 to 43, or a composition for use according to any one of claims 12 to 43, wherein the disease, symptom or ailment is a myopathy.

[0283] 45. L-lactic acid and / or its polymers as described in claim 44, or a composition as described in claim 44, wherein the myopathy is a hereditary myopathy and / or an acquired myopathy.

[0284] 46. ​​L-lactic acid and / or its polymers as described in claim 45, or a composition as described in claim 45, wherein the hereditary myopathy is selected from the group consisting of: congenital myopathy, mitochondrial myopathy, metabolic myopathy and muscular dystrophy.

[0285] 47. L-lactic acid and / or its polymers as described in claim 45, or a composition as described in claim 45, wherein the acquired myopathy is selected from the group consisting of: autoimmune / inflammatory myopathy, toxic myopathy, endocrine myopathy, infectious myopathy, electrolyte imbalance-related myopathy, and critical illness myopathy.

[0286] 48. L-lactic acid and / or its polymers according to any one of claims 1 to 11 and 26 to 47, or a composition according to any one of claims 12 to 47, wherein the muscle atrophy is skeletal muscle atrophy.

[0287] 49. L-lactic acid and / or its polymers according to any one of claims 27 to 48, or a composition according to any one of claims 27 to 48, wherein the subject is a person and / or an animal, such as wherein the subject is a person.

[0288] 50. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11 and 26 to 41, or a composition available for use according to any one of items 12 to 41, wherein the treatment is a treatment for muscle injury, such as preventive and / or therapeutic treatment for muscle injury.

[0289] 51. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11, 26 to 41 and 50, or a composition available for use according to any one of items 12 to 41 and 50, wherein the treatment is a preventive treatment for muscle injury.

[0290] 52. The L-lactic acid and / or its polymers as described in claim 50 or 51, or the composition as described in claim 50 or 51, wherein the preventive treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or muscle strength reduction.

[0291] 53. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11, 26 to 41 and 50, or a composition available for use according to any one of items 12 to 41 and 50, wherein the treatment is a therapeutic treatment for muscle injury.

[0292] 54. The L-lactic acid and / or its polymers as described in claim 50 or 53, or the composition as described in claim 50 or 53, wherein the therapeutic treatment induces muscle tissue regeneration.

[0293] 55. L-lactic acid and / or its polymers available for use according to any one of items 1 to 11, 26 to 41 and 50 to 54, or a composition available for use according to any one of items 12 to 41 and 50 to 54, wherein the muscle injury is an acute and / or chronic muscle injury.

[0294] 56. L-lactic acid and / or its polymers for use according to any one of items 1 to 11, 26 to 41 and 50 to 55, or a composition for use according to any one of items 12 to 41 and 50 to 55, wherein the muscle injury is selected from the group consisting of abrasions, sprains, tears, spasms and cuts, such as the group consisting of sprains, tears and cuts.

[0295] 57. L-lactic acid and / or its polymers available for use according to any one of claims 1 to 11, 26 to 41 and 50 to 56, or a composition available for use according to any one of claims 12 to 41 and 50 to 56, wherein the muscle injury is a skeletal muscle injury.

[0296] 58. Use of L-lactic acid and / or its polymers for the manufacture of a medicament for the treatment of muscle injuries and / or diseases, conditions and / or disorders characterized by muscle atrophy.

[0297] 59. The use according to claim 58, wherein the polymer is selected from the group consisting of: poly-L-lactic acid, poly-D,L-lactic acid, and any copolymer containing L-lactic acid but not D-lactic acid.

[0298] 60. The use according to item 58 or 59, wherein the polymer is selected from the group consisting of poly-L-lactic acid and poly-D,L-lactic acid.

[0299] 61. The use according to item 59 or 60, wherein the concentration of L-lactic acid in the poly-D,L-lactic acid is at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0300] The ratio of L-lactic acid to D-lactic acid in the polyD,L-lactic acid is at least about 1:5, such as the ratio being about 1:1.

[0301] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0302] 62. The use according to item 58 or 59, wherein the polymer is selected from the group consisting of poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid.

[0303] 63. The use according to any one of claims 58, 59 and 62, wherein the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%;

[0304] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0305] 64. The use according to any one of items 58, 59, 62 and 63, wherein the copolymer does not contain glycolic acid.

[0306] 65. The use according to any one of claims 58, 59, and 62 through 64, wherein said polymer is selected from the group consisting of: poly-L-lactic acid; any copolymer comprising L-lactic acid and ethylene glycol; any copolymer comprising L-lactic acid, ethylene glycol, and glycolic acid; any copolymer comprising L-lactic acid and taurine; any copolymer comprising L-lactic acid and chitosan; and any copolymer comprising L-lactic acid and ε-caprolactone; such as those selected from the group consisting of poly-L-lactic acid and any copolymer comprising L-lactic acid and ethylene glycol.

[0307] 66. The use according to claim 65, wherein the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0308] The concentration of L-lactic acid in the copolymer is at least about 30%;

[0309] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0310] 67. The use according to any one of items 58 to 60, 62 and 65, wherein said polymer is poly-L-lactic acid.

[0311] 68. The use according to any one of items 58 to 67, wherein said polymer has a molecular weight of at least about 400 Da, such as at least about 500 Da, such as at least about 1 kDa, such as at least about 2 kDa, such as at least about 5 kDa, such as at least about 10 kDa, such as at least about 20 kDa, such as at least about 30 kDa, such as at least about 40 kDa, such as at least about 50 kDa, such as at least about 100 kDa, such as at least about 150 kDa, such as at least about 200 kDa, such as at least about 250 kDa, such as at least about 300 kDa; and / or

[0312] Molecules ranging from about 400 Da to about 300 kDa, such as about 500 Da to about 300 kDa, such as about 1000 Da to about 300 kDa, such as about 1500 Da to about 275 kDa, such as about 2000 Da to about 250 kDa, such as about 2500 Da to about 225 kDa, such as about 3000 Da to about 200 kDa, such as about 3500 Da to about 175 kDa, such as about 4000 Da to about 150 kDa, such as about 4500 Da to about 125 kDa, such as about 5000 Da to about 100 kDa.

[0313] 69. Use of a composition comprising L-lactic acid and / or its polymers, the composition being used to manufacture a medicament for treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy, wherein the L-lactic acid and / or its polymers are as defined in any one of items 58 to 68; and wherein the composition comprises at least one pharmaceutically acceptable carrier and / or excipient.

[0314] 70. The use according to claim 69, wherein said composition comprises at least about 1%, such as at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of said L-lactic acid; and / or

[0315] At least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of the L-lactic acid polymer;

[0316] The percentage (%) corresponds to the concentration as a weight-to-volume ratio.

[0317] 71. The use according to item 69 or 70, wherein the composition is formulated as a solution, suspension, gel and / or implant.

[0318] 72. The use according to any one of claims 69 to 71, wherein the composition is formulated as a suspension, such as an injectable suspension.

[0319] 73. The use according to any one of claims 69 to 72, wherein the composition comprises particles of the L-lactic acid and / or the polymer thereof.

[0320] 74. The use according to claim 73, wherein the particles are selected from the group consisting of microcells, nanoparticles and microspheres, such as those selected from the group consisting of nanoparticles and microspheres.

[0321] 75. The use according to item 73 or 74, wherein the particles are microspheres.

[0322] 76. The use according to any one of items 73 to 75, wherein said particles have a particle size of at least about 10 µm, such as at least about 15 µm, such as at least about 20 µm, such as at least about 25 µm, such as at least about 30 µm, such as at least about 35 µm, such as at least about 40 µm, such as at least about 45 µm, such as at least about 50 µm, such as at least about 55 µm, such as at least about 60 µm; and / or

[0323] Particle sizes such as about 1 to about 100 µm, such as about 2 to about 90 µm, such as about 5 to about 85 µm, such as about 10 to about 80 µm, such as about 15 to about 75 µm, such as about 20 to about 70 µm, such as about 25 to about 65 µm, such as about 30 to about 60 µm; and / or

[0324] Particle size of approximately 45 µm ± 15 µm, such as a particle size of approximately 45 µm.

[0325] 77. The use according to any one of items 74 to 76, wherein the microspheres have a smooth surface.

[0326] 78. The use according to any one of items 58 to 77, wherein the composition does not contain D-lactic acid and / or its polymers.

[0327] 79. The use according to any one of items 58 to 78, wherein the L-lactic acid and / or the polymer thereof are the sole active ingredients.

[0328] 80. The use according to any one of items 58 to 79, wherein the composition does not contain glycolic acid.

[0329] 81. The use according to any one of items 58 to 80, wherein the pharmaceutically acceptable carrier and / or excipient is selected from the group consisting of physiological saline solution, surfactant and stabilizer.

[0330] 82. According to the use described in item 81, wherein the pharmaceutically acceptable carrier and / or excipient is a physiological saline solution.

[0331] 83. The use according to any one of items 58 to 82, wherein the L-lactic acid and / or the polymer thereof, or the composition is formulated for oral, nasal, transdermal, ocular, intramuscular and / or subcutaneous administration, such as the L-lactic acid and / or the polymer thereof, or the composition being formulated for intramuscular and / or subcutaneous administration.

[0332] 84. The use according to any one of claims 58 to 83, wherein said use comprises administering the L-lactic acid and / or its polymer, or the composition, to a subject in need at least once.

[0333] 85. The use according to claim 84, wherein the at least one application is intramuscular application, such as wherein the at least one application is intramuscular injection.

[0334] 86. The use as described in item 84 or 85, wherein the at least one administration does not induce a significant inflammatory response in the subject.

[0335] 87. The use according to any one of claims 84 to 86, wherein the at least one administration does not induce a significant fibrotic response and / or scar tissue formation in the subject.

[0336] 88. The use according to any one of claims 84 to 87, wherein the dose of said L-lactic acid is administered during said at least one administration, wherein said dose is about 2.25 to about 1152 mg / kg, such as about 112.5 to about 576 mg / kg, such as about 375 to about 500 mg / kg; and / or

[0337] The dosage of the L-lactic acid polymer is administered during the at least one administration, wherein the dosage is about 22.5 to about 57,600 mg / kg, such as about 1,125 to about 28,800 mg / kg, such as about 1,250 to about 1,667 mg / kg.

[0338] 89. The use according to any one of items 84 to 88, wherein the at least one application is a single application.

[0339] 90. The use according to any one of items 84 to 88, wherein the at least one application is repeated application.

[0340] 91. The use according to item 90, wherein the administration is administered once daily to a patient in need for at least 2 days, such as at least 3 days, such as at least 4 days, such as at least 5 days, such as at least 6 days, such as at least 7 days, such as at least 8 days, such as at least 9 days, such as at least 10 days, such as at least 11 days, such as at least 12 days, such as at least 13 days, such as at least 14 days.

[0341] 92. The use according to any one of items 58 to 91, wherein the muscle injury is characterized by muscle atrophy.

[0342] 93. The use according to any one of items 58 to 92, wherein the treatment is a preventive and / or therapeutic treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0343] 94. The use according to any one of items 58 to 93, wherein the treatment is a preventive treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0344] 95. The use according to item 93 or 94, wherein the preventive treatment prevents muscle tissue degeneration; muscle loss, muscle wasting and / or thinning; and / or muscle strength reduction.

[0345] 96. The use according to any one of items 58 to 93, wherein the treatment is a therapeutic treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0346] 97. The use according to claim 93 or 96, wherein the therapeutic treatment induces muscle tissue regeneration.

[0347] 98. The use according to any one of items 58 to 97, wherein the injury, disease, ailment or disorder is characterized by a decrease in muscle mass, wasting and / or thinning and / or a reduction in muscle strength.

[0348] 99. The use according to any one of items 58 to 98, wherein the treatment is a treatment for a disease, condition and / or disorder characterized by muscle atrophy.

[0349] 100. The use according to any one of items 58 to 99, wherein the disease, symptom or ailment is selected from the group consisting of: disuse atrophy, age-related atrophy, malnutrition-induced atrophy, muscle disorders and neurological disorders.

[0350] 101. The use according to any one of items 58 to 100, wherein said disease, symptom or ailment is a myopathy.

[0351] 102. The use according to claim 101, wherein the myopathy is a hereditary myopathy and / or an acquired myopathy.

[0352] 103. According to the use described in item 102, the hereditary myopathy is selected from the group consisting of: congenital myopathy, mitochondrial myopathy, metabolic myopathy and muscular dystrophy.

[0353] 104. According to the use described in item 102, the acquired myopathy is selected from the group consisting of: autoimmune / inflammatory myopathy, toxic myopathy, endocrine myopathy, infectious myopathy, myopathy associated with electrolyte imbalance, and critical illness myopathy.

[0354] 105. The use according to any one of claims 58 to 104, wherein the muscle atrophy is skeletal muscle atrophy.

[0355] 106. The use according to any one of claims 84 to 105, wherein the subject is a person and / or an animal, such as wherein the subject is a person.

[0356] 107. The use according to any one of items 58 to 98, wherein said treatment is a treatment for muscle injury, such as preventive treatment and / or therapeutic treatment for muscle injury.

[0357] 108. The use according to any one of items 58 to 98 and 107, wherein said treatment is a preventive treatment for muscle injury.

[0358] 109. The use according to item 107 or 108, wherein the preventive treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or muscle strength reduction.

[0359] 110. The use according to any one of items 58 to 98 and 107, wherein said treatment is a therapeutic treatment for muscle injury.

[0360] 111. The use according to any one of claims 107 or 110, wherein the therapeutic treatment induces muscle tissue regeneration.

[0361] 112. The use according to any one of items 58 to 98 and 107 to 111, wherein the muscle injury is an acute and / or chronic muscle injury.

[0362] 113. The use according to any one of items 58 to 98 and 107 to 112, wherein the muscle injury is selected from the group consisting of abrasions, sprains and lacerations, such as being selected from the group consisting of sprains, tears and lacerations.

[0363] 114. The use according to any one of items 58 to 98 and 107 to 113, wherein the muscle injury is a skeletal muscle injury.

[0364] 115. A method of treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy using L-lactic acid and / or its polymers.

[0365] 116. The method according to claim 115, wherein the polymer is selected from the group consisting of: poly-L-lactic acid, poly-D,L-lactic acid, and any copolymer containing L-lactic acid but not D-lactic acid.

[0366] 117. The method according to claim 115 or 116, wherein the polymer is selected from the group consisting of poly-L-lactic acid and poly-D,L-lactic acid.

[0367] 118. The method according to claim 116 or 117, wherein the concentration of L-lactic acid in the poly-D,L-lactic acid is at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0368] The ratio of L-lactic acid to D-lactic acid in the polyD,L-lactic acid is at least about 1:5, such as the ratio being about 1:1.

[0369] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0370] 119. The method according to claim 115 or 116, wherein the polymer is selected from the group consisting of poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid.

[0371] 120. The method according to any one of claims 115, 116, and 119, wherein the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%;

[0372] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0373] 121. The method according to any one of claims 115, 116, 119 and 120, wherein the copolymer does not contain glycolic acid.

[0374] 122. The method according to any one of claims 115, 116, and 119 through 121, wherein said polymer is selected from the group consisting of: poly-L-lactic acid; any copolymer comprising L-lactic acid and ethylene glycol; any copolymer comprising L-lactic acid, ethylene glycol, and glycolic acid; any copolymer comprising L-lactic acid and taurine; any copolymer comprising L-lactic acid and chitosan; and any copolymer comprising L-lactic acid and ε-caprolactone; such as the group consisting of poly-L-lactic acid and any copolymer comprising L-lactic acid and ethylene glycol.

[0375] 123. The method according to claim 122, wherein the concentration of L-lactic acid in the copolymer is at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%; and / or

[0376] The concentration of L-lactic acid in the copolymer is at least about 30%;

[0377] The percentage (%) corresponds to the concentration expressed as a weight-to-weight ratio.

[0378] 124. The method according to any one of claims 115 to 117, 119 and 122, wherein the polymer is poly-L-lactic acid.

[0379] 125. The method according to any one of claims 115 to 124, wherein said polymer has a molecular weight of at least about 400 Da, such as at least about 500 Da, such as at least about 1 kDa, such as at least about 2 kDa, such as at least about 5 kDa, such as at least about 10 kDa, such as at least about 20 kDa, such as at least about 30 kDa, such as at least about 40 kDa, such as at least about 50 kDa, such as at least about 100 kDa, such as at least about 150 kDa, such as at least about 200 kDa, such as at least about 250 kDa, such as at least about 300 kDa; and / or

[0380] Molecules ranging from about 400 Da to about 300 kDa, such as about 500 Da to about 300 kDa, such as about 1000 Da to about 300 kDa, such as about 1500 Da to about 275 kDa, such as about 2000 Da to about 250 kDa, such as about 2500 Da to about 225 kDa, such as about 3000 Da to about 200 kDa, such as about 3500 Da to about 175 kDa, such as about 4000 Da to about 150 kDa, such as about 4500 Da to about 125 kDa, such as about 5000 Da to about 100 kDa.

[0381] 126. A method of treating muscle injury and / or disease, condition and / or disorder characterized by muscle atrophy using a composition comprising L-lactic acid and / or its polymers as defined in any one of claims 115 to 125; and wherein the composition comprises at least one pharmaceutically acceptable carrier and / or excipient.

[0382] 127. The method according to claim 126, wherein the composition comprises at least about 1%; such as at least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of said L-lactic acid; and / or

[0383] At least about 5%, such as at least about 10%, such as at least about 15%, such as at least about 20%, such as at least about 25%, such as at least about 30%, such as at least about 35%, such as at least about 40%, such as at least about 45%, such as at least about 50%, such as at least about 55%, such as at least about 60%, such as at least about 65%, such as at least about 70%, such as at least about 75%, such as at least about 80%, such as at least about 85%, such as at least about 90%, such as at least about 95%, such as about 100% of the L-lactic acid polymer;

[0384] The percentage (%) corresponds to the concentration as a weight-to-volume ratio.

[0385] 128. The method according to claim 126 or 127, wherein the composition is formulated as a solution, suspension, gel and / or implant.

[0386] 129. The method according to any one of claims 126 to 128, wherein the composition is formulated as a suspension, such as an injectable suspension.

[0387] 130. The method according to any one of claims 126 to 129, wherein the composition comprises particles of the L-lactic acid and / or the polymer thereof.

[0388] 131. The method according to claim 130, wherein the particles are selected from the group consisting of microcells, nanoparticles and microspheres, such as the group consisting of nanoparticles and microspheres.

[0389] 132. The method according to claim 130 or 131, wherein the particle is a microsphere.

[0390] 133. The method according to any one of claims 130 to 132, wherein said particles have a particle size of at least about 10 µm, such as at least about 15 µm, such as at least about 20 µm, such as at least about 25 µm, such as at least about 30 µm, such as at least about 35 µm, such as at least about 40 µm, such as at least about 45 µm, such as at least about 50 µm, such as at least about 55 µm, such as at least about 60 µm; and / or

[0391] Particle sizes such as about 1 to about 100 µm, such as about 2 to about 90 µm, such as about 5 to about 85 µm, such as about 10 to about 80 µm, such as about 15 to about 75 µm, such as about 20 to about 70 µm, such as about 25 to about 65 µm, such as about 30 to about 60 µm; and / or

[0392] Particle size of approximately 45 µm ± 15 µm, such as a particle size of approximately 45 µm.

[0393] 134. The method according to any one of claims 131 to 133, wherein the microspheres have a smooth surface.

[0394] 135. The method according to any one of items 115 to 134, wherein the composition does not contain D-lactic acid and / or its polymers.

[0395] 136. The method according to any one of claims 115 to 135, wherein the L-lactic acid and / or its polymer are the only active ingredients.

[0396] 137. The method according to any one of claims 115 to 136, wherein the composition does not contain glycolic acid.

[0397] 138. The method according to any one of claims 115 to 137, wherein the pharmaceutically acceptable carrier and / or excipient is selected from the group consisting of physiological saline solution, surfactant and stabilizer.

[0398] 139. The method according to claim 138, wherein the pharmaceutically acceptable carrier and / or excipient is a physiological saline solution.

[0399] 140. The method according to any one of claims 115 to 139, wherein the L-lactic acid and / or the polymer thereof, or the composition is formulated for oral, nasal, transdermal, ocular, intramuscular, and / or subcutaneous administration, such as the L-lactic acid and / or the polymer thereof, or the composition being formulated for intramuscular and / or subcutaneous administration.

[0400] 141. The method according to any one of claims 115 to 140, wherein the method comprises administering the L-lactic acid and / or its polymer, or the composition, to a subject in need at least once.

[0401] 142. The method according to claim 141, wherein the at least one application is intramuscular application, such as wherein the at least one application is intramuscular injection.

[0402] 143. The method according to claim 141 or 142, wherein the at least one administration does not induce a significant inflammatory response in the subject.

[0403] 144. The method according to any one of claims 141 to 143, wherein the at least one administration does not induce a significant fibrotic response and / or scar tissue formation in the subject.

[0404] 145. The method according to any one of claims 141 to 144, wherein the dose of said L-lactic acid is administered during said at least one administration, wherein said dose is about 2.25 to about 1152 mg / kg, such as about 112.5 to about 576 mg / kg, such as about 375 to about 500 mg / kg; and / or

[0405] The dosage of the L-lactic acid polymer is administered during the at least one administration, wherein the dosage is about 22.5 to about 57,600 mg / kg, such as about 1,125 to about 28,800 mg / kg, such as about 1,250 to about 1,667 mg / kg.

[0406] 146. The method according to any one of claims 141 to 145, wherein the at least one application is a single application.

[0407] 147. The method according to any one of items 141 to 145, wherein the at least one application is a repeated application.

[0408] 148. The method according to claim 147, wherein the administration is given once daily to the patient in need for at least 2 days, such as at least 3 days, such as at least 4 days, such as at least 5 days, such as at least 6 days, such as at least 7 days, such as at least 8 days, such as at least 9 days, such as at least 10 days, such as at least 11 days, such as at least 12 days, such as at least 13 days, such as at least 14 days.

[0409] 149. The method according to any one of claims 115 to 148, wherein the muscle injury is characterized by muscle atrophy.

[0410] 150. The method according to any one of claims 115 to 149, wherein the treatment is a preventive and / or therapeutic treatment for the injury, disease, symptom, and / or ailment characterized by muscle atrophy.

[0411] 151. The method according to any one of claims 115 to 150, wherein the treatment is a preventive treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0412] 152. The method according to claim 150 or 151, wherein the preventive treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or muscle strength reduction.

[0413] 153. The method according to any one of claims 115 to 150, wherein the treatment is a therapeutic treatment for the injury, disease, symptom and / or ailment characterized by muscle atrophy.

[0414] 154. The method according to claim 150 or 153, wherein the therapeutic treatment induces muscle tissue regeneration.

[0415] 155. The method according to any one of claims 115 to 154, wherein the injury, disease, ailment or disorder is characterized by a decrease in muscle mass, consumption and / or thinning and / or a reduction in muscle strength.

[0416] 156. The method according to any one of claims 115 to 155, wherein the treatment is a treatment for a disease, condition and / or disorder characterized by muscle atrophy.

[0417] 157. The method according to any one of claims 115 to 156, wherein the disease, symptom or disorder is selected from the group consisting of: disuse atrophy, age-related atrophy, malnutrition-induced atrophy, muscle disorders and neurological disorders.

[0418] 158. The method according to any one of claims 115 to 157, wherein the disease, symptom, or ailment is a myopathy.

[0419] 159. The method according to claim 158, wherein the myopathy is a hereditary myopathy and / or an acquired myopathy.

[0420] 160. The method according to claim 159, wherein the hereditary myopathy is selected from the group consisting of: congenital myopathy, mitochondrial myopathy, metabolic myopathy and muscular dystrophy.

[0421] 161. The method according to claim 159, wherein the acquired myopathy is selected from the group consisting of: autoimmune / inflammatory myopathy, toxic myopathy, endocrine myopathy, infectious myopathy, myopathy associated with electrolyte imbalance, and critical illness myopathy.

[0422] 162. The method according to any one of claims 115 to 161, wherein the muscle atrophy is skeletal muscle atrophy.

[0423] 163. The method according to any one of claims 141 to 162, wherein the subject is a person and / or an animal, such as wherein the subject is a person.

[0424] 164. The method according to any one of claims 115 to 155, wherein the treatment is a treatment for muscle injury, such as preventive and / or therapeutic treatment for muscle injury.

[0425] 165. The method according to any one of items 115 to 155 and 164, wherein the treatment is a preventive treatment for muscle injury.

[0426] 166. The method according to claim 164 or 165, wherein the preventive treatment prevents muscle tissue degeneration; muscle mass reduction; muscle loss and / or thinning; and / or muscle strength reduction.

[0427] 167. The method according to any one of items 115 to 155 and 164, wherein the treatment is a therapeutic treatment for muscle injury.

[0428] 168. The method according to claim 164 or 167, wherein the therapeutic treatment induces muscle tissue regeneration.

[0429] 169. The method according to any one of items 115 to 155 and 164 to 168, wherein the muscle injury is an acute and / or chronic muscle injury.

[0430] 170. The method according to any one of claims 115 to 155 and 164 to 169, wherein the muscle injury is selected from the group consisting of abrasions, sprains and lacerations, such as the group consisting of sprains, tears and lacerations.

[0431] 171. The method according to any one of claims 115 to 155 and 164 to 170, wherein the muscle injury is a skeletal muscle injury.

Claims

1. Use of an L-lactic acid polymer, wherein the L-lactic acid polymer is used to manufacture a medicament for treating diseases and / or conditions characterized by muscle atrophy, wherein the L-lactic acid polymer is an active ingredient.

2. The use according to claim 1, wherein the polymer is selected from the group consisting of: poly-L-lactic acid, poly-D,L-lactic acid, and any copolymer containing L-lactic acid but not D-lactic acid.

3. The use according to claim 1 or 2, wherein the polymer is selected from the group consisting of poly-L-lactic acid and poly-D,L-lactic acid.

4. The use according to claim 2, The ratio of L-lactic acid to D-lactic acid in the poly-D,L-lactic acid is at least 1:

5.

5. The use according to claim 4, The ratio of L-lactic acid to D-lactic acid in the poly-D,L-lactic acid is 1:

1.

6. The use according to claim 1 or 2, wherein the polymer is selected from the group consisting of poly-L-lactic acid and any copolymers containing L-lactic acid but not D-lactic acid.

7. The use according to claim 2, wherein the copolymer does not contain glycolic acid.

8. The use according to claim 1 or 2, wherein the polymer is selected from the group consisting of: poly-L-lactic acid; any copolymer comprising L-lactic acid and ethylene glycol; any copolymer comprising L-lactic acid, ethylene glycol and glycolic acid; any copolymer comprising L-lactic acid and taurine; any copolymer comprising L-lactic acid and chitosan; and any copolymer comprising L-lactic acid and ε-caprolactone.

9. The use according to claim 8, wherein the polymer is selected from the group consisting of poly-L-lactic acid and any copolymer of L-lactic acid and ethylene glycol.

10. The use according to claim 1 or 2, wherein the polymer is poly-L-lactic acid.

11. The use according to claim 1 or 2, wherein the disease or condition is muscle injury.

12. Use of a composition comprising an L-lactic acid polymer for manufacturing a medicament for treating diseases and / or conditions characterized by muscle atrophy, wherein the L-lactic acid polymer is as defined in any one of claims 1 to 11; and wherein the composition comprises at least one pharmaceutically acceptable carrier, the L-lactic acid polymer being the active ingredient.

13. The use according to claim 12, wherein the composition is formulated as a solution, suspension, gel or implant.

14. The use according to claim 12 or 13, wherein the composition is formulated as an injectable suspension.

15. The use according to claim 12 or 13, wherein the composition comprises particles of the L-lactic acid polymer.

16. The use according to claim 15, wherein the particles are selected from the group consisting of microcells, nanoparticles and microspheres.

17. The use according to claim 16, wherein the particles are selected from the group consisting of nanoparticles and microspheres.

18. The use according to claim 15, wherein the particle is a microsphere.

19. The use according to claim 15, wherein the particles have a particle size of 1 to 100 µm.

20. The use according to claim 15, wherein the particles have a particle size of 30 to 60 µm.

21. The use according to claim 16, wherein the microspheres have a smooth surface.

22. The use according to claim 12, wherein the composition does not contain D-lactic acid and / or its polymers.

23. The use according to claim 12, wherein the L-lactic acid polymer is the only active ingredient.

24. The use according to claim 22 or 23, wherein the composition does not contain glycolic acid.

25. The use according to claim 1 or 12, wherein the L-lactic acid polymer, or the composition, is formulated for oral, nasal, transdermal, ocular, intramuscular, or subcutaneous administration.

26. The use according to claim 1 or 12, wherein the L-lactic acid polymer, or the composition, is formulated for intramuscular or subcutaneous application.

27. The use according to claim 1 or 12, wherein the use comprises administering the L-lactic acid polymer, or the composition, to a subject in need at least once.

28. The use according to claim 27, wherein the at least one application is intramuscular.

29. The use according to claim 28, wherein the at least one administration is an intramuscular injection.

30. The use according to claim 27, wherein the at least one administration does not induce a significant inflammatory response in the subject.

31. The use according to claim 27, wherein the at least one administration does not induce a significant fibrotic response and / or scar tissue formation in the subject.

32. The use according to claim 27, The dosage of the L-lactic acid polymer is administered during the at least one administration, wherein the dosage is 22.5 to 57,600 mg / kg.

33. The use according to claim 32, wherein the dosage is 1125 to 28800 mg / kg.

34. The use according to claim 32, wherein the dosage is 1250 to 1667 mg / kg.

35. The use according to claim 27, wherein the at least one application is a single application.

36. The use according to claim 27, wherein the at least one application is repeated application.

37. The use according to claim 1 or 12, wherein the treatment is a preventive and / or therapeutic treatment for the disease and / or condition characterized by muscle atrophy.

38. The use according to claim 37, wherein the treatment is a preventive treatment for the disease and / or condition characterized by muscle atrophy.

39. The use according to claim 38, wherein the preventive treatment prevents muscle tissue degeneration.

40. The use according to claim 38, wherein the preventive treatment prevents muscle loss.

41. The use according to claim 38, wherein the preventive treatment prevents a decrease in muscle strength.

42. The use according to claim 38, wherein the preventive treatment prevents muscle loss.

43. The use according to claim 38, wherein the preventive treatment prevents muscle loss.

44. The use according to claim 37, wherein the treatment is a therapeutic treatment for the disease and / or condition characterized by muscle atrophy.

45. The use according to claim 44, wherein the therapeutic treatment induces muscle tissue regeneration.

46. ​​The use according to claim 1 or 12, wherein the disease or condition is characterized by a decrease in muscle mass.

47. The use according to claim 1 or 12, wherein the disease or condition is characterized by decreased muscle strength.

48. The use according to claim 1 or 12, wherein the disease or symptom is characterized by muscle loss.

49. The use according to claim 1 or 12, wherein the disease or symptom is characterized by thinning of muscle mass.

50. The use according to claim 1 or 12, wherein the disease or condition is selected from the group consisting of: disuse atrophy, age-related atrophy, malnutrition-induced atrophy, muscle disorders, and neurological disorders.

51. The use according to claim 1 or 12, wherein the disease or condition is myopathy.

52. The use according to claim 1 or 12, wherein the muscle atrophy is skeletal muscle atrophy.

53. The use according to claim 27, wherein the subject is a human and / or an animal.

54. The use according to claim 1 or 12, wherein the treatment is a treatment for muscle injury.

55. The use according to claim 54, wherein the treatment is a preventive and / or therapeutic treatment for muscle injury.

56. The use according to claim 55, wherein the treatment is a preventive treatment for muscle injury.

57. The use according to claim 56, wherein the preventive treatment prevents muscle tissue degeneration.

58. The use according to claim 56, wherein the preventive treatment prevents muscle loss.

59. The use according to claim 56, wherein the preventive treatment prevents a decrease in muscle strength.

60. The use according to claim 56, wherein the preventive treatment prevents muscle loss.

61. The use according to claim 56, wherein the preventive treatment prevents muscle loss.

62. The use according to claim 55, wherein the treatment is a therapeutic treatment for muscle injury.

63. The use according to claim 62, wherein the therapeutic treatment induces muscle tissue regeneration.

64. The use according to claim 54, wherein the muscle injury is selected from the group consisting of abrasions, sprains and lacerations.

65. The use according to claim 54, wherein the muscle injury is a tear.

66. The use according to claim 54, wherein the muscle injury is a skeletal muscle injury.

67. The use according to claim 64, wherein the muscle injury is a skeletal muscle injury.

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