Lactic acid for use in the treatment of injuries of the musculoskeletal system

Abstract

In a first aspect, the present invention is related to lactic acid or a pharmaceutically acceptable salt thereof for use in the prevention and / or treatment of a musculoskeletal injury in a subject. In a second aspect, the present invention is related to an injectable composition for use in the treatment of a musculoskeletal injury in a subject characterized in that it comprises lactic acid or a pharmaceutically acceptable salt thereof and a suitable solvent. In a preferred embodiment, the musculoskeletal injury is selected from the group consisting of tendon injury, joint injury, cartilage injury and muscle injury.

Description

[0001] Lactic acid for use in the treatment of injuries of the musculoskeletal system

[0002] Field of the invention

[0003] The present invention refers to the field of medicine. In particular, the present invention is related to the prevention and / or treatment of muscle related diseases and disorders.

[0004] Background of the invention

[0005] Musculoskeletal conditions are prevalent across all age groups and are a significant burden on human well-being. These conditions encompass a wide array of diseases that commonly result in pain, discomfort, and limitations in the bones, joints, muscles, and supporting tissues. They can manifest as acute or chronic issues, affecting specific areas or spreading throughout the body. Such conditions often lead to disabilities or impairments that can impact individuals' daily lives.

[0006] Muscle injuries are frequent in sports, with athletes experiencing them through a range of mechanisms, including direct injuries such as lacerations and contusions, as well as indirect injuries linked to ischemia and neurological dysfunction.

[0007] When muscles sustain injury, they typically undergo a cycle of degeneration and regeneration. Initially, the injured muscle fibers experience necrosis, wherein damaged myofibrils are eliminated by macrophages. Subsequently, regeneration of new muscle fibers occurs within the muscle's connective tissue. While muscles possess the capacity to regenerate post-injury, the healing process is often prolonged and may result in incomplete functional recovery.

[0008] Nowadays, the available treatment options for musculoskeletal diseases and disorders primarily involve the use of pharmacological agents such as steroids or non-steroidal anti-inflammatory drugs (NSAIDs), along with surgical interventions. However, it is important to note that these medications alleviate clinical symptoms rather than addressing the underlying progression of the muscular degeneration or injury.

[0009] To date, there are several therapeutic agents and therapeutic methods to treat musculoskeletal injuries by promoting tissue regeneration. The patent application WO2012118192A1 refers to an aqueous solution used in a preferably injectable pharmaceutical composition to treat arthritis, knee osteoarthritis and scapulohumeral periarthritis, comprises hyaluronic acid and carboxylic acid. The carboxylic acids may be inter alia lactic, succinic or citric.

[0010] The patent application W02010138095A1 refers to a pharmaceutical composition comprising hyaluronic acid (0.5-60 g / l), sodium succinate (1-40 g / l), succinic acid (0.001- 10 g / l) and sodium chloride (1-10 g / l) in water.

[0011] The patent application US2012238521A1 discloses a pharmaceutical composition useful for the treatment of musculoskeletal injuries, diseases or disorders comprising a citrate analogue compound complexed with metal ions. The compounds and compositions of the present invention can be administered by any suitable means, intranasal, oral, inhalation, intramuscular, intrapleural, intraventricular, intraperitoneal, ophthalmic, intravenous, etc.

[0012] The patent application DE102005018887A1 refers to a method and composition of therapy for pain resulting from local calcification deposits, using a pharmaceutical formulation containing phosphocitrate or a complex salt with phosphocitrate as a biological calcium chelator.

[0013] The article “Postconditioning with Lactate- Enriched Blood in Patients with ST-Segment Elevation Myocardial Infarction”. Cardiology. 2019;142(2):79-80. doi: 10.1159 / 000499036. Epub 2019 Apr 18. This article discloses a modified postconditioning protocol of intermittent reperfusion and timely coronary injections of lactated Ringer’s solution.

[0014] However, none of these documents describes a composition as the one disclosed in the present document with the effect of recovering the musculoskeletal injuries reducing the necessary time required for recovering from such injuries.

[0015] Brief description of the invention

[0016] In a first aspect, the present invention is related to lactic acid or a pharmaceutically acceptable salt thereof for use in the treatment of a musculoskeletal injury in a subject. In some embodiments, the present invention is related to the lactic acid or a pharmaceutically acceptable salt thereof for use in the treatment of a musculoskeletal injury which is selected from the group consisting of tendon injury, joint injury, cartilage injury and muscle injury.

[0017] The term “musculoskeletal system” refers to the musculoskeletal tissues and comprises bones, muscles, and joints, as well as cartilage, tendons, ligaments, and other connective tissues.

[0018] The term “musculoskeletal injuries” are disorders of muscles, nerves, tendons, joints, cartilage and spinal discs. The musculoskeletal injuries that are common in athletes include fractures, dislocations, sprains, strains, tendinitis or bursitis.

[0019] As used herein, the terms "treat", "treatment" and "treating" refer to the amelioration of one or more symptoms associated with a disorder that results from the administration of a therapeutically effective amount of the conditioned media of the invention or a pharmaceutical composition comprising same, to a subject in need of said treatment. Thus, "treatment" as used herein covers any treatment of a disorder, disease or condition of a mammal, particularly a human, and includes: (a) preventing the disease or condition from occurring in a subject which may be predisposed to the disease or condition but has not yet been diagnosed as having it; (b) inhibiting the disease or condition, i.e., arresting its development; or (c) relieving the disease or condition, i.e., causing regression of the disease or condition or amelioration of one or more symptoms of the disease or condition. The population of subjects treated by the method includes a subject suffering from the undesirable condition or disease, as well as subjects at risk for development of the condition or disease. Thus, one of skill in the art realizes that a treatment may improve the patient's condition but may not be a complete cure of the disease. As used herein, the terms "disorder" and "disease" are used interchangeably to refer to an abnormal or pathological condition in a subject that impairs bodily functions and can be deadly.

[0020] In an embodiment the amelioration of one or more symptoms associated with a muscle injury is measured as an increase in the size of the muscle fibers, particularly as an increase in the cross-sectional area of muscle regenerating fibers. In a more preferred embodiment said measurement is carried out according to the method disclosed in Figure 1 and Example 1. In another embodiment the amelioration of one or more symptoms associated with a muscle injury is measured as a decrease in the degree of fibrosis. Preferably the degree of fibrosis is measured in collagen I immunofluorescence images by determining the area of collagen type I fibrosis marker respective to the total area in microphotographs. More preferably said measurement is carried out according to the method disclosed in Figure 2 and Example 1.

[0021] The term “recovery time” refers to the duration of recovery that varies based on the severity of the injury, typically vary from 6 to 15 days.

[0022] The term "subject" refers to an animal, preferably a mammal including a non-primate (e.g. a cow, pig, horse, cat, dog, rat, or mouse) and a primate (e.g. a monkey or a human). In a preferred embodiment, the subject is a human.

[0023] The term "mammal" as used in this invention means any of various warm-blooded vertebrate animals of the class Mammalia, including humans, characterized by a covering of hair on the skin and, in the female, milk-producing mammary glands for nourishing the young.

[0024] The term “pharmaceutically acceptable” refers to those properties and / or substances which are acceptable to the patient from a pharmacological / toxicological point of view and to the manufacturing pharmaceutical chemist from a physical / chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability.

[0025] The term “salt” must be understood as any form of an active compound used in accordance with this invention in which said compound is in ionic form or is charged an coupled (associated) to a counter-ion (a cation) or is in solution.

[0026] The term “pharmaceutically acceptable salt”, as used herein, refers to salts of lactic acid with a pharmaceutically acceptable base. A pharmaceutically acceptable salt can be synthesized by reacting a free acid with a stoichiometric amount of the appropriate base in water or in an organic solvent, or in a mixture of the two; non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile can be useful. Non-limiting examples of pharmaceutically acceptable bases include, but are not limited to, hydroxides of alkali metals such as sodium, potassium, and lithium; hydroxides of alkaline earth metals such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia, and organic amines, such as unsubstituted or hydroxy-substituted mono-, di- , or tri-alkylamines, dicyclohexylamine; tributyl amine; pyridine; N-methyl, N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-hydroxy substituted lower alkylamines), such as mono-; bis-, or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert- butylamine, or tris-(hydroxymethyl)methylamine, N,N-di-lower alkyi-N-(hydroxy lower alkyl)-amines, such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2- hydroxyethyl)amine; N-methyl-O-glucamine; and amino acids such as arginine or lysine. The term “pharmaceutically acceptable salt” also includes a hydrate. In a particular embodiment, the pharmaceutically acceptable salt is selected from sodium lactate, potassium lactate, calcium lactate and magnesium lactate. In a preferred embodiment the pharmaceutically acceptable salt is sodium lactate.

[0027] In a preferred embodiment, the expression “in the area of the musculoskeletal injury”, when it refers to a muscle injury, preferably to the rupture of muscle fibers, is the area wherein the injury is produced, which can be identified by symptoms such as pain, swelling, bruising, muscle weakness, limited range of motion, inflammatory response or imaging techniques such as MRI or ultrasound. In a more preferred embodiment, the area of the musculoskeletal injury is the hypoechoic or hyperechoic mass identified by MRI or ultrasound, more preferably the geometric center of the lesion image identified by MRI or ultrasound, preferably by ultrasound. In a preferred embodiment, the area of the musculoskeletal injury obtained between 24 and 48 hours after the injury is seen by ultrasound as a discontinuity of the echogenic perimysial striae around either the myotendinous junction or the myofascial junction, preferably is an intramuscular hematoma that is seen as an ill-defined muscle laceration separated by hypoechoic fluid with marked increased reflectivity in the surrounding muscle that may display increased echogenity in comparison to the surrounding muscle. In a more preferred embodiment, the area of the musculoskeletal injury is identified as previously described by Guermazi A. et al. (Guermazi et al. 2017. Radiology, 282(3): 646-663).

[0028] FIGURES

[0029] To complement the description being made and in order to aid in a better understanding of the features of the invention, there is attached as an integral part of said description, a set of drawings wherein, with illustrative and non-limiting character, the following has been represented. Figure 1. Analysis of cross-sectional area of Muscle regenerating fibers after treatments. Cross-sectional area (CSA) of newly formed muscle fibers was measured in collagen I immunofluorescence microphotographs. Three images were randomly selected within the injured area of gastrocnemius muscle cross sections by use of a BX- 61 microscope equipped with a DP72 camera and CellSens Digital Imaging software. The CSA values of 200-300 fibers per muscle were calculated with Image J software, based on a ratio of calibrated pixels to actual size (mm). Values are presented as median ± SD. Statistical analysis was performed with IBM SPSS Statistics version 20.0 (IBM). The normality and homoscedasticity of the data were studied for each parameter to apply the correct statistical method (parametric or nonparametric). The Shapiro-Wilk test was used to verify the normal distribution of the data. A Kruskal-Wallis test (with Dunn's multiple comparison test) was used to evaluate statistical significance in nonparametric comparisons between the different groups of myofiber CSA. Intergroup comparisons: *p=0,0332, **p=0,0021, ***p=0,0002, ****p<0,0001 .

[0030] Figure 2. Analysis of Fibrosis in rat Muscle after treatments. The degree of fibrosis was evaluated in collagen I immunofluorescence images by determining the area of collagen type I fibrosis marker respective to the total area in microphotographs. The percentage of collagen I area was measured by using the Threshold Colour plugin for Image J software as an average between 3 and 4 images in every muscle sample. The same threshold set was used for all samples analyzed. Values are presented as median ± SD. Statistical analysis was performed with IBM SPSS Statistics version 20.0 (IBM). The normality and homoscedasticity of the data were studied for each parameter to apply the correct statistical method (parametric or nonparametric). The Shapiro-Wilk test was used to verify the normal distribution of the data. A welch ANOVA (Dunnett's T3 multiple comparisons test) was used for comparisons of collagen I percentage in animal groups at 14 days, and One-way ANOVA (Dunnett's multiple comparisons test) was used for comparisons of collagen I percentage in animal groups at 21 days. Intergroup comparisons: **p=0,0021.

[0031] Description of the invention

[0032] The inventors have surprisingly found that this composition is useful in regenerating injuries to the musculoskeletal system, preferably muscle injuries, more preferably, injuries caused by the rupture of muscle fibers. The composition object of the invention accelerates the regeneration process of injuries to the musculoskeletal system and, therefore, decreases the recovery times required or associated with such injuries.

[0033] Therefore, in a first aspect, the present invention is related to lactic acid or a pharmaceutically acceptable salt thereof for use in the prevention and / or treatment of a musculoskeletal injury in a subject.

[0034] In a second aspect, the present invention is related to an injectable composition for use in the treatment of a musculoskeletal injury in a subject characterized in that it comprises lactic acid or a pharmaceutically acceptable salt thereof and a suitable solvent. In a preferred embodiment, the subject is a mammal.

[0035] In an embodiment of the present invention, the musculoskeletal injury is selected from the group consisting of tendon injury, joint injury, cartilage injury and muscle injury. In a more preferred embodiment, the musculoskeletal injury is a muscle injury. In a more preferred embodiment, the muscle injury is a rupture of the muscle fibers.

[0036] In an embodiment of the first and second aspects of the invention, the composition comprises lactic acid. In another embodiment of the first and second aspects, the composition comprises a salt of lactic acid, preferably sodium lactate.

[0037] In some embodiments of the present invention, the composition comprises a suitable solvent selected from the group consisting of physiological saline phosphate buffered saline (PBS) and solutions comprising thickening agents and / or solubilizing agents. In these preferred embodiments, the solubilizing agents are selected from the group consisting of glucose, polyethylene glycol, polypropyleneglycol, and mixtures thereof. In another more preferred embodiments, the thickening agents are selected from the group consisting of starches, polysaccharides, and proteins. In a preferred embodiment, the suitable solvent is phosphate buffered saline (PBS).

[0038] In an embodiment the PBS comprises, preferably consists of, sodium phosphate, sodium chloride and potassium phosphate. In another embodiment the PBS does not comprise calcium, magnesium and potassium chloride.

[0039] In an embodiment the composition consists of lactic acid or a pharmaceutically acceptable salt thereof and PBS. In an embodiment the pH of the composition is a physiological pH.

[0040] In a preferred embodiment, the injectable composition object of the invention comprises lactic acid or a pharmaceutically acceptable salt thereof in a concentration of at least 5mM.

[0041] In a preferred embodiment, the injectable composition object of the invention comprises a concentration of at least 10 mM of lactic acid or a pharmaceutically acceptable salt thereof. In a preferred embodiment, the injectable composition object of the invention comprises from 10mM to 40mM of lactic acid or a pharmaceutically acceptable salt thereof. In a more preferred embodiment, the composition comprises from 16mM to 32mM of lactic acid or a pharmaceutically acceptable salt thereof, and more preferred embodiment, the composition comprises from 20mM to 28mM of lactic acid or a pharmaceutically acceptable salt thereof. In another embodiment, the composition comprises from 20 mM to 32 mM, preferably from 24 to 32 mM, even more preferably at least 32 mM of lactic acid or a pharmaceutically acceptable salt thereof. In an embodiment the concentration of lactic acid or a pharmaceutically acceptable salt thereof is 16 mM. In another embodiment the concentration of lactic acid or a pharmaceutically acceptable salt thereof is 24 mM. In another embodiment the concentration of lactic acid or a pharmaceutically acceptable salt thereof is 32 mM. In an embodiment said concentrations are concentrations of lactic acid. In another embodiment said concentrations are concentration of a salt of lactic acid, preferably sodium lactate.

[0042] In a preferred embodiment, the present invention is related to the composition for use in the treatment of a musculoskeletal injury. Furthermore, the present invention refers to the use of the composition according to second aspect of the invention for the manufacture of a medicament for treating a musculoskeletal injury. Additionally, the present invention, refers to the method of treatment of a musculoskeletal injury that comprises the administration to a subject of the composition according to the second aspect of the invention.

[0043] Therefore, it is a preferred embodiment of the present invention the composition according to the invention for use in the treatment of a musculoskeletal injury wherein the composition is administered by injection to a subject. Preferably, the injection is an ultrasound-guided injection. In another preferred embodiment, the composition is administered by injection in the area of the musculoskeletal injury.

[0044] In a more preferred embodiment, the injection is an intramuscular injection.

[0045] It is well-known that after a tissue injury, several pro-inflammatory and anti-inflammatory signals take place, which are responsible for the activation of pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2), respectively. Each of these signals initiates unique gene regulatory networks downstream, influenced by the surrounding context, and can serve specific functions. In fact, transitioning from M1 to M2 has been observed due to the sequence of activation that control the macrophage activity.

[0046] The inventors have found that the technical effect of injecting lactic acid is to polarize the macrophages M1 involved in the healing of muscle tissue. Therefore, they surprisingly have proven that the intervention in the damaged tissue after the first 24 hours from the time of injury took place, and up to a time limit of 48 from the time of injury, causes a polarization of macrophages M1 towards the area of damage, intervening in the recovery and regeneration of the tissue.

[0047] Therefore, in a preferred embodiment of the present invention, the composition is administered within 24 to 48 hours after the injury. In a more preferred embodiment, the composition is administered within 30 to 40 hours, more preferable, within 32 to 36 hours after the injury, even more preferably 36 hours after the injury.

[0048] The inventors have surprisingly found that the composition of the invention is effective with a single administration and that its effect lasts for at least 14 days. In a preferred embodiment, the present invention refers to the injectable composition for use in the treatment of a musculoskeletal injury wherein the composition is administered once to a subject, i.e., the treatment is administered as a single injection and no other further injections are needed.

[0049] In another preferred embodiment, the composition is administered once every 3 days. In a more preferred embodiment, the first administration of the composition is within 24 to 48 hours after the injury, preferably, within 30 to 40 hours, and more preferably, within 32 to 36 hours after the injury, even more preferably 36 hours after the injury.

[0050] In a preferred embodiment, the subject is a mammal, and more preferred, the subject is a human. In another preferred embodiment, the subject is a primate, a mouse, a rat, a dog or a cat.

[0051] In an embodiment, the invention refers to the composition for use in the treatment of a musculoskeletal injury wherein the subject is a human and the amount of the composition administered is between 2 to 10mL. In a more preferred embodiment, the amount administered is comprised between 4 to 8m L, and more preferred is 5 to 6m L.

[0052] Finally, the present invention refers to an in vitro method for the treatment of a musculoskeletal injury that comprises administering the composition according to the first aspect of the invention to a biological sample. In a preferred embodiment, the biological sample is from a mammal.

[0053] EXAMPLES

[0054] The purpose of the examples given below is illustrative and is not intended to limit in any way the scope of the invention.

[0055] Example 1 : Evaluation of AL therapy in the treatment of muscle injury in rats

[0056] The objective of the efficacy study is to evaluate AL therapy in the treatment of muscle injury in rats. The treatment was administered 36 hours post-injury by ultrasound- guided injection in the injured area. At 14- and 21-days post-injury, the histological study of the morphology and muscle structure in the tissue after the treatments performed was carried out. The treatment was carried out with lactic acid or sodium lactate.

[0057] IN VIVO MUSCLE INJURY AND TREATMENT

[0058] As an animal model, 2-month-old male Wistar rats (Envigo) were used, with N=6 animals for each group. The animals were divided into 5 groups at 2 different times to perform the euthanasia of the animals and the histological analyzes at 14- and 21-days post-injury (in total 10 groups of animals).

[0059] The groups of animals in the study (N=6 / group) were: G1. Untreated injury 14 days post-injury

[0060] G2. Injury with treatment with dissolution medium (PBS) 14 days post-injury

[0061] G3. Injury treated with AL Molarity of 16mM 14 days post-injury

[0062] G4. Injury treated with AL Molarity of 24mM 14 days post-injury

[0063] G5. Injury treated with AL Molarity of 32mM 14 days post-injury

[0064] G6. Untreated injury 21 days post-injury

[0065] G7. Injury with treatment with dissolution medium (PBS) 21 days post-injury

[0066] G8. Injury treated with AL Molarity of 16mM at 21 days post-injury

[0067] G9. Injury treated with AL Molarity of 24mM at 21 days post-injury

[0068] G10. Injury treated with AL Molarity of 32mM at 21 days post-injury.

[0069] All in vivo procedures were performed in accordance with current Spanish legislation (Royal Decree 53 / 2013) and European (2010 / 63 / EU) and approved by the Department of Agriculture, Branches, Fisheries, Food and Natural Medicine of the Generalitat of Catalonia.

[0070] After anesthesia of the animals, the muscle injury was generated as previously described by our research group (Contreras, et al. Int J Sports Med. 2016 Mar; 37(3): 183-90). Treatments with AL (30 pl) and control (PBS) were administered 36 h post-injury by ultrasound-guided injection in the injury area.

[0071] HISTOLOGICAL ANALYSIS

[0072] After treatment by administration of AL at 14- and 21-days post-injury, the animals were sacrificed by intraperitoneal injection of an overdose of ketamine (75 mg / kg) and xylazine (10 mg / kg). The gastrocnemius muscles were excised and immediately frozen in 2-methylbutane (Alfa Aesar. A Johnson Matthey Company, Karlsruhe, Germany), which was previously supercooled in liquid nitrogen and stored at -80 °C until analysis. Frozen medial gastrocnemius was transversely sectioned (10 pm thick) with a cryotome (Leica Microsystems, Wetzlar, Germany) at less than -20°C and mounted on Polylisine™ glass slides (VWR, Leuven, Belgium). Consecutive sections of frozen muscle were used for histological and immunofluorescence analysis. For histological analysis, rat skeletal muscle sections were stained with hematoxylin-eosin (1 min hematoxylin and 15 s eosin), washed in water, dehydrated with graded ethanol solutions (1 min 50 % ethanol, 1 min of 70 % ethanol twice, 1 min of 90 % ethanol, 1 min of 100 % ethanol twice) and rinsed in xylene (5 s). After air drying for 5 minutes, the guides were mounted with DPX mounting medium and a coverslip (VWR, Madrid, Spain). The Harris Hematoxylin solution was purchased from Casa Alvarez (Casa Alvarez, Madrid, Spain) and the eosin solution was prepared by dissolving 0.5 g of Eosina Amarillenta (Panreac Quimica S.A., Barcelona, Spain) in 100 ml of water with 200 pl of glacial acetic acid (Sigma-Aldrich Quimica S.A., Madrid, Spain). Absolute ethanol and xylene were obtained from VWR (VWR, Leuven, Belgium). For immunofluorescence analysis, frozen muscle sections were fixed in cold acetone (-20 °C) (Sigma-Aldrich Quimica SA, Madrid, Spain) for 5 min, air dried and blocked in PBS containing 3 % BSA (bovine serum albumin, Sigma-Aldrich Quimica SA, Madrid, Spain) for 10 min at room temperature and then incubated with primary antibodies diluted 1 :100 in PBS (phosphate-buffered saline, Biowest, Barcelona, Spain). The primary antibodies used were against rabbit collagen I antibody (Abeam, Cambridge, United Kingdom), for 16 h in a humid chamber at 4 °C. Samples were washed 3 times in PBS and incubated with Alexa Fluor® 568 anti-mouse or Alexa Fluor® 488 anti-rabbit secondary antibodies (Invitrogen, Oregon, USA) diluted 1 :1000 in PBS in a dark, humid chamber for 1 hour at room temperature. Finally, the slides were washed 3 times with PBS and mounted using a coverslip and Fluoromount- G mounting medium (Southern Biotech, Madrid, Spain). Fluorescence was assessed using a BX-61 microscope (Olympus), a DP72 camera (Olympus), and CellSens® Digital Imaging software (version 1.9).

[0073] ANALYSIS OF THE RESULTS, STATISTICAL STUDY

[0074] To analyze the effectiveness of the proposed therapy, the size of the muscle fibers was quantified at each time of the experimental study. During the regeneration process, muscle fibers increase in size until they reach their pre-injury size.

[0075] Graphpad Prism version 10 software was used, first evaluating normality (Shapiro- Wilk) and homoscedasticity (Levene) in each group in order to apply the most appropriate statistical test. Due to the heterogeneity of the results, it was decided to perform a non-parametric analysis using the Kruskal-Wallis test. Differences were considered statistically significant for P<0.05. After carrying out the analysis of the results obtained in the study, graphs and figures were composed.

Claims

CLAIMS1. Lactic acid or a pharmaceutically acceptable salt thereof for use in the prevention and / or treatment of a musculoskeletal injury in a subject.

2. Lactic acid or a pharmaceutically acceptable salt thereof for use according to claim 1 , wherein the musculoskeletal injury is selected from the group consisting of tendon injury, joint injury, cartilage injury and muscle injury.

3. Lactic acid or a pharmaceutically acceptable salt thereof for use according to claim 2, wherein the musculoskeletal injury is a muscle injury.

4. An injectable composition for use in the treatment of a musculoskeletal injury in a subject characterized in that it comprises lactic acid or a pharmaceutically acceptable salt thereof and a suitable solvent.

5. The composition for use according to claim 4, wherein the suitable solvent is selected from the group consisting of physiological saline, phosphate buffered saline (PBS), and a solution comprising thickening agents and / or solubilizing agents.

6. The composition for use according to claim 4 or 5, wherein the suitable solvent is phosphate buffered saline (PBS).

7. The composition for use according to claims 4 to 6, wherein the composition comprises lactic acid or a pharmaceutically acceptable salt thereof in a concentration of at least 5mM.

8. The composition for use according to any of claims 4 to 7, wherein the composition is administered in the area of the musculoskeletal injury.

9. The composition for use according to any of claims 4 to 8, wherein the composition is administered within 24 to 48 hours after the injury.

10. The composition for use according to any of claims 4 to 9, wherein the composition is administered once to the subject.

11. The composition for use according to any of claims 4 to 9, wherein the composition is administered once every 3 days.

12. The composition for use according to any of claims 4 to 11 , wherein the injection is an intramuscular injection.

13. The composition for use according to any of claims 4 to 12, wherein the subject is a mammal.

14. The composition for use according to any of claims 4 to 13, wherein the subject is a human and the amount of the composition administered is between 2 to 10mL.

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