IT202100030170A1 - Transdermal patch, and use of said patch in a method of treating a disorder, or disorder, or pathology, of a tendon - Google Patents

Description

DESCRIPTION of the invention entitled: ?Transdermal patch, and use of said patch in a method of treating a disorder, or disorder, or pathology, of a tendon?

The present invention relates to a transdermal patch comprising: (i) a support layer delimiting an external surface and an internal surface; (ii) an adhesive layer attached to the internal surface; (iii) a protective layer, releasably connected to at least a portion of said adhesive layer; (iv) a composition located at said internal surface, wherein said composition comprises or, alternatively, consists of: (a) a mixture of cetylated fatty acids; and (b) optionally pharmaceutical grade additives or excipients. Furthermore, the present invention refers to said patch in which said composition is a composition for use in a method of treating a disorder, or disorder, or pathology, of a tendon selected from tendinopathy, tendonitis, and tenosynovitis, preferably tendinopathy, in a subject. Finally, the present invention refers to a composition in the form of a cream for external topical use, said cream being for use in a treatment method (i) for the reduction of joint and musculoskeletal pain, (ii) for the recovery of motility? in the consequent rehabilitation periods and (iii) to recover movement in the event of sports injuries to the joints; said cream composition comprising or, alternatively, consisting of: (a) a mixture of cetylated fatty acids; and (b) optionally pharmaceutical grade additives or excipients.

The advancement of the physiopathological knowledge of tendon structures has shown that, in conditions of overload (probably associated with oxidative stress mechanisms), there are both degenerative phenomena, such as the production of metalloproteases which degrade the extracellular matrix, and apoptosis of tendon cells and neoangiogenesis with vascular infiltration, both regenerative and protective phenomena, such as the production of insulin-like growth factor-1 (IGF-1; insulin-like growth factor-1) and nitric oxide. A tendinopathy? the result of an imbalance between degenerative phenomena and regenerative and protective phenomena, which leads to degeneration, weakening and cracking of the tendons, associated with local pain.

The substantial inadequacy of traditional therapies has favored the proliferation of more therapeutic proposals. or not based on pathophysiological knowledge. Currently the treatment of tendinopathy? mainly entrusted to:

(I) oral administration of non-steroidal anti-inflammatory drugs (NSAIDs);

(II) corticosteroid infiltrations;

(III) extracorporeal shock wave therapy (Extracorporeal Shock Wave Therapy, in short ?shock waves?);

(IV) physical therapies (laser and/or ultrasound).

However, the available literature suggests that, in the absence of an overt inflammatory process, the oral administration of NSAIDs is not capable of altering the course of chronic tendinopathy.

Regarding corticosteroid infiltrations, proposed therapeutic mechanisms include anti-inflammatory effects, effects on local tissue metabolism, relaxation of reflex muscle spasm, pain reduction, improvement of movement and a placebo effect. Several studies have evaluated the quality of this therapeutic intervention but, despite the improvements observed in the majority of patients, numerous cases of tendon rupture have been reported.

Shock waves, initially used to treat patients with kidney stones, have also become popular in recent years for the treatment of soft tissue disorders, including calcific rotator cuff tendinopathy, epicondylitis, plantar fasciitis, patellar and Achilles tendinopathy , etc.

However, an analysis of the literature shows that, even for this treatment approach, the results are ambiguous, mainly due to the different protocols applied.

As regards physical therapies (laser and/or ultrasound), there are numerous studies that demonstrate their effectiveness in reducing pain symptoms and inflammation, however there are many pathological conditions (mainly cancer) that contraindicate and limit their use .

In this context, ? It is important to underline that some studies have shown the effectiveness of cetylated fatty acids (CFA) administered topically in improving articulation, functionality, strength and endurance, as well as in reducing pain symptoms and in the absence of side effects.

? therefore felt by the operators of the sector, the need? to be able to have a therapeutic solution that is effective in the treatment of tendon disorders, or disorders, or pathologies, which is in an easy-to-use form, and which can be used by any subject without contraindications.

The Applicant, after a long and intense activity? of research and development, has developed a transdermal patch capable of providing an adequate response to existing limitations, inconveniences and problems.

Therefore, the subject of the present invention is a transdermal patch (Patch) comprising: (i) a support layer which delimits an external surface and an internal surface; (ii) an adhesive layer attached to the internal surface; (iii) a protective layer, releasably connected to at least a portion of said adhesive layer; (iv) a composition located at said internal surface, wherein said composition comprises or, alternatively, consists of: (a) a mixture of cetylated fatty acids; and (b) optionally pharmaceutical grade additives or excipients, having the characteristics as defined in the attached claims.

Furthermore, the object of the present invention is called a plaster in which said composition is a composition for use in a method of treating a disorder, or disorder, or pathology, of a tendon selected from tendinopathy, tendinitis, and tenosynovitis, preferably tendinopathy, in a subject, having the characteristics as defined in the attached claims.

Said patch (Cetilar<? >Patch), thanks to its formulation based on cetyl esters (CFA) of plant origin - applied on a support comprising acrylate copolymers, in the presence of menthol (CAS 89-781/1490-04-6/ 2116-51-5; C10H20O; PM 156.3) , ? advantageously indicated in the treatment of osteo-arthritic joint diseases, to improve functionality? articulation and the ability? of movement and to reduce painful symptoms. Also, said patch? able to reduce joint and musculoskeletal pain quickly as well as being useful for the recovery of motility? during rehabilitation periods following inflammatory phenomena or joint trauma. Finally, said patch? useful in case of sports injuries to the joints to recover natural movement.

Furthermore, the subject of the present invention is a composition in the form of a cream for external topical use, said cream being for use in a treatment method (i) for the reduction of joint and musculoskeletal pain, (ii) for the recovery of motility? in the consequent rehabilitation periods and (iii) to recover movement in the event of sports injuries to the joints; said cream composition comprising or, alternatively, consisting of: (a) a mixture of cetylated fatty acids; and (b) optionally pharmaceutical grade additives or excipients.

Said composition in cream form (Cetilar? Cream) ? indicated in the treatment of osteo-arthritic joint diseases, to improve functionality? articulation and the ability? of movement, and to reduce painful symptoms.

Preferred embodiments of the present invention will be described below by way of example, and therefore without limitation, with the aid of the tables, in which:

- Figure 1: flow diagram of the study referred to in Example 2;

- Figure 2: Constant-Murley (CS) score with graphical representation of all its indices (Example 2);

- Figure 3: percentage of patients who reported changes in the Constant-Murley score (Example 2);

- Figure 4: percentage increase in CS between V0 and V1 (Example 2); each dot represents a patient;

- Figure 5: variation in CS in male and female genders (Example 2);

- Figure 6: patients' response to question A1 related to pain frequency (Example 2);

- Figure 7: patients' response to question B1 regarding limitation of activities? of daily life (Example 2);

- Figure 8: sectional view of a transdermal patch object of the present invention, according to a first possible embodiment;

- Figure 9: sectional view of a transdermal patch object of the present invention, according to a second possible embodiment.

The object of the present invention is therefore a transdermal patch 1 comprising: (i) a support layer 2 which delimits an external surface 4 and an internal surface 6; (ii) an adhesive layer 8 connected to the internal surface 6; (iii) a protection layer 10, releasably connected to at least a portion of said adhesive layer 8; and (iv) a composition placed in correspondence with said internal surface 6.

Said transdermal patch 1? preferably an occlusive plaster. In other words, said support layer 2? preferably an air-tight layer, and composition, whereby air, water and composition are prevented from passing through a thickness of said support layer 2 towards the outside.

The support layer 2 delimits the external surface 4 and the internal surface 6 through its thickness.

The external surface 4? preferably a surface which, during the use of said transdermal patch, lies externally, in sight on the skin of a subject. The internal surface 6 ? preferably a surface opposite to the external surface 4 which, during the use of said transdermal patch, is facing the subject's skin.

Support layer 2 ? preferably at least partially elasticized.

Preferably, the support layer 2? made up of a fabric or non-woven fabric (TNT), more? preferably from TNT, even more? preferably from spunbond type TNT.

More? preferably, said support layer 2 could be made up of polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), polyurethane (PU), or latex.

The adhesive layer 8 ? connected to the internal surface 6. Preferably, the adhesive layer 8 is in direct or indirect contact with the internal surface 6, where said indirect contact is? carried out via a porous membrane 12 of said transdermal patch 1, said porous membrane 12 being at least partially interposed between said adhesive layer 8 and said internal surface 6.

Preferably, the adhesive layer 8 can be made using non-crosslinkable acrylic copolymers, as a pressure sensitive adhesive, in the presence of volatile organic solvents, such as ethyl acetate, hexane or heptane. For example, can be an adhesive of the type available on the market, such as Duro-Tak387-2353/87-2353.

Preferably, the adhesive layer 8 overlaps at least in part on said internal surface 6, more preferably predominantly or substantially completely.

Within this description the expression ?predominantly? means that the adhesive layer 8 overlaps the internal surface 6 by 51% to 100% of the surface area of the internal surface 6.

Within this description the expression ?substantially complete? means that the adhesive layer 8 overlaps the internal surface 6 by 90% to 100%, preferably by 95% to 100%, more? preferably from 98% to 100% of the surface area of the internal surface 6.

According to the embodiment shown in Figure 8, the adhesive layer 8 has a surface area substantially coinciding with the surface area of the internal surface 6.

According to the embodiment shown in Figure 9, the adhesive layer 8 has a perimeter contact area with the internal surface 6.

The adhesive layer 8 preferably comprises an adhesive substance, preferably an acrylic adhesive substance. More? preferably, called acrylic adhesive substance? of acrylic, methacrylic and/or epoxy-diacrylic type. Preferably, the adhesive substance mainly or substantially completely covers said internal surface 6.

The adhesive substance? preferably mixed with said composition (for example, refer to the embodiment of figure 8, which shows a single layer marked by the number 8), so that said adhesive substance acts as a controlled release matrix for said composition through the subject's skin .

Preferably, said adhesive substance and said composition are mixed in a weight ratio [adhesive substance]:[composition] ranging from 10:1 to 1:3, preferably ranging from 5:1 to 1:2, even more? preferably ranging from 2:1 to 1:1.

Preferably, the transdermal patch 1 comprises the porous membrane 12 which is permeable to said composition and which, preferably, is at least partially covered by the adhesive layer 8 (for example predominantly or substantially completely).

Preferably, said porous membrane 12 and said support layer 2 jointly circumscribe a containment compartment 14 (or tank) for said composition. According to this embodiment, the composition is therefore confined in the containment compartment 14 and, since said porous membrane 12 is permeable, said composition can? pass through a thickness of the porous membrane 12 to reach ? under conditions of controlled release - on the subject's skin.

Said controlled release can? be adjusted through parameters such as thickness, size and/or density? of the pores of the porous membrane 12.

The protection layer 10 ? releasably connected to at least a portion of said adhesive layer 8. Preferably, the protection layer 10 is a removable layer of the transdermal patch 1, which is removed (or peeled) from the adhesive layer 8 before said patch 1 is applied to the subject's skin.

The protection layer 10 preferably comprises a base material coated with a film of an anti-adhesive (or de-adhesive) agent on a surface of said protection layer 10 facing the adhesive layer 8. Said base material? preferably paper or a polymeric material, more? preferably paper.

Said anti-adhesive agent? preferably of the silicone type.

Said composition located in correspondence with said internal surface 6 includes or, alternatively, consists of:

(a) a mixture of cetylated fatty acids; And

(b) optionally pharmaceutical grade additives or excipients.

By way of example, this mixture of cetylated fatty acids of vegetal origin? obtained with a process and a system according to the previous document no. WO 17/029580 A1 which is incorporated herein by reference.

In particular, said (a) mixture of cetylated fatty acids can? be obtained with method I (page 6, last paragraph - page 7, penultimate paragraph) or with method II (page 7, last paragraph - page 10, second paragraph) of the previous document no. WO 17/029580 A1, the aforementioned passages of which are to be considered incorporated into this description by reference.

Preferably, said (a) mixture of cetylated fatty acids in the composition object of the present invention? a ?refined MF final blend? (final refined mixture MF) obtained at the end of method II disclosed in the previous document no. WO 17/029580 A1.

Preferably, said (a) mixture of cetylated fatty acids comprises or, alternatively, consists of cetyl myristate and/or cetyl oleate.

In particular, said cetyl myristate and/or cetyl oleate are obtained through an esterification reaction respectively between myristic acid and/or oleic acid and cetyl alcohol, in the presence of a catalyst, and in the absence of solvent (such as for example, in the absence of water, or in the absence of any organic solvent or inorganic solvent).

Preferably, myristic acid can be a myristic acid with a purity of 90% to 99%, preferably 94% to 98%. More? preferably, myristic acid has a percentage composition (GLC): - lauric acid C12:0 ? 1%;

- myristic acid C14:0 ? 99%;

- palmitic acid C16:0 ? 1%.

Even more? preferably, myristic acid? tetradecanoic acid (CAS 544-63-8, EINECS 208-875-2).

Preferably, oleic acid can be an oleic acid with a purity of between 70% and 95%, preferably between 75% and 90%, even more? preferably from 80% to 85%. More? preferably, oleic acid has a percentage composition (GLC):

- lauric acid myristic acid C12:0+C14:0 ? 0.5;

- oleic acid C18:1 ? 78%;

- linoleic acid C18:2 ? 15;

- other C18:3 ? 1.

Even more? preferably, oleic acid can? be the compound CAS 112-80-1 (EINECS 204-007-1).

Cetyl alcohol can be a cetyl alcohol with a purity of 80% to 99%, preferably 90% to 98%. More? preferably, cetyl alcohol? 1-hexadecanol (CAS 36653-82-4; EINECS 253-149-0).

In a preferred embodiment, a mixture of fatty acids to be esterified with cetyl alcohol can comprise from 50% to 99% by weight of myristic acid, and from 1% to 50% by weight of oleic acid.

In another preferred embodiment, a mixture of fatty acids to be esterified with cetyl alcohol can comprise from 60% to 90% by weight of myristic acid, and from 10% to 40% by weight of oleic acid.

Said catalyst? preferably a metal catalyst, more? preferably zinc powder. In one embodiment, the catalyst employed is ? powdered metallic zinc. The quantity? of catalyst used in the esterification reaction? ranging from 0.05% to 0.3% by weight with respect to the total weight of the reaction reagents (i.e. fatty acid or mixture of fatty acids and cetyl alcohol). Preferably, the quantity? of catalyst added? ranging from 0.1% to 0.25% by weight, even more? preferably ranging from 0.15% to 0.20% by weight. Said catalyst could be present in minimal traces within said (a) mixture of cetylated fatty acids.

Said composition preferably includes or, alternatively, consists of:

(a) said mixture of cetylated fatty acids;

(b) so called optional pharmaceutical grade additives or excipients; And

(c) one or more? vegetable oils.

Preferably, in said composition? menthol present (CAS 89-78-1/1490-04-6/2116-51-5; C10H20O; PM 156.3.

Preferably, a weight ratio (a):(c) ? ranging from 10:1 to 1:1, preferably ranging from 5:1 to 2:1, more? preferably between 4:1 and 2:1, even more? preferably 3:1.

Said (c) one or more? vegetable oils includes or, alternatively, consists of vegetable oils with high oleic acid content from olive oil, palm oil and/or sunflower oil (SOHO), preferably olive oil, plus? preferably refined olive oil. Said composition which is the object of the present invention can? include, in addition to (a), optionally (b) and optionally (c):

(d) a mixture of tocopherols; and/or

(e) lecithin.

Said (d) mixture of tocopherols can? be present in a quantity? by weight ranging from 1% to 5%, preferably from 2% to 3%, with respect to the total weight of said composition.

Said (e) lecithin can? be present in a quantity? by weight ranging from 1% to 10%, preferably in a quantity? from 1% to 5%, compared to the total weight of said composition.

In a particularly preferred embodiment, the composition of the present invention comprises 5% by weight of lecithin, 20% by weight of a refined olive oil, 74% by weight of cetylated fatty acids, and 1% by weight of a mixture of tocopherols compared to the total weight of said composition.

Furthermore, the object of the present invention is called transdermal patch 1, in which said composition is a composition for use in a method of treating a disorder, or disorder, or pathology, of a tendon in a subject.

Preferably, called disorder, or disorder, or pathology? selected between tendinopathy, bursitis, tendonitis, and tenosynovitis, preferably bursitis and/or tendinopathy, plus? preferably shoulder tendinopathy, even more so? preferably tendinopathy of the dominant shoulder.

Preferably, said subject has a Constant-Murley score (CS; Constant-Murley score) less than 45 (CS < 45), preferably CS < 40, more? preferably CS < 35.

The Constant-Murley score? a tool to evaluate overall shoulder function and evaluates four aspects related to shoulder pathology; two subjective ones: pain and activity? of daily living (ADL, activities of daily living) and two objectives: amplitude of movement (ROM, range of motion) and strength. The first two parts can receive up to 35 points and the second two 65, resulting in a possible maximum total score of 100 points (best function).

More? preferably, said subject ? a female subject suffering from shoulder tendinopathy (preferably the dominant shoulder) with CS < 40, preferably with CS < 35.

Preferably, said treatment method involves application of a transdermal patch 1 per day for a time ranging from 4 hours to 12 hours for a number of days from 5 to 15; preferably for a time ranging from 6 hours to 10 hours for a number of days from 8 to 12; more? preferably for a time ranging from 7 hours to 9 hours for a number of days from 9 to 11; even more? preferably for a period of 8 hours for a number of 10 days.

Preferably, a quantity? of said composition to be administered via said transdermal patch 1? ranging from 1 mg/kg to 15 mg/kg of body weight per day, more? preferably between 3 mg/kg and 10 mg/kg of body weight per day, even more? preferably ranging from 5 mg/kg to 8 mg/kg of body weight per day.

Below are some examples, provided by way of example and not by way of limitation, of the present invention.

EXAMPLES

EXAMPLE 1: A prospective observational study on beneficial effects and tolerability? of a complex of cetylated fatty acids (CFA) in a patch formulation for shoulder tendon disorders. The purpose of this study? evaluate the effectiveness and tolerability? of a transdermal patch - object of the present invention - comprising cetylated fatty acids (CFA) in the control of acute pain localized to the shoulder and in the recovery of function in patients with tendinopathies.

METHODS

A prospective, single-center, non-profit observational study conducted according to good clinical practices.

Patients with recent onset (1-3 months) shoulder pain symptoms related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination, were evaluated for shoulder pain and function using the Constant Murley.

Patients used a patch containing a complex of cetylated fatty acids (CFA) based mainly on cetyl myristate and cetyl oleate, and preferably menthol, for 8 hours a day for 10 days. At 10 days (V1) and 35 days (V2) after a first visit (V0), the Constant-Murley score, compliance and to the treatment and tolerability? of the product.

More? precisely, this was a prospective, monocentric, non-profit observational study conducted at the Rehabilitation Department of the North West Tuscany Local Health Authority (Italy). The aim of this study was to evaluate the efficacy and tolerability of the product. of the CFA patch formulation in controlling acute pain localized to the shoulder in patients with tendinopathies. I study ? was approved by the local Ethics Committee (protocol code 2018RIAB105) and conducted according to good clinical practices and the ethical principles outlined in the Declaration of Helsinki.

All patients signed the informed consent document. Patients were included, referred to the center between 1? October 2019 and July 31, 2020 who had suffered from recent onset (1-3 months) shoulder pain symptoms related to bursitis and tenosynovitis, with a diagnosis of shoulder tendon pathology confirmed by ultrasound examination. All enrolled patients have never been treated with NSAIDs or other self-medication products or instrumental techniques for their tendinopathy. Were all patients with hypersensitivity excluded? known to CFA or one of the excipients of the product, or with damaged skin in the shoulder area, or who have used NSAIDs and corticosteroid infiltrations during treatment. Patients with cognitive impairment or complete tendon damage were also excluded. At the first visit (V0) patients were examined by ultrasound examination and shoulder pain and function were assessed using the Constant-Murley score (CS). The CS? a tool to evaluate overall shoulder function and evaluates four aspects related to shoulder pathology; two subjective ones: pain and activity? of daily living (ADL, activities of daily living) and two objectives: amplitude of movement (ROM, range of motion) and strength. The first two parts can receive up to 35 points and the second two 65, resulting in a possible maximum total score of 100 points (best function).

To all patients? The use of a patch containing CFA (Cetilar<? >Patch, Pharmanutra S.p.A, Pisa, Italy) was prescribed for 8 hours a day for 10 consecutive days. Two follow-up visits were carried out: the first (V1) 10 days after the first visit, the second (V2) 35 days after the first. At each visit the Constant-Murley score, compliance and to the treatment and tolerability? of the product (by recording any undesirable effects). Figure 1 shows the flowchart of the study.

The sample size was based on both the primary endpoint (evaluating the effectiveness of the transdermal patch of the present invention in controlling acute pain localized to the shoulder in patients with tendinopathies) and secondary endpoints. ? a change of at least 3 points in the Constant-Murley score was estimated, setting an error of type ? = 0.05 and taking as a starting point a test power (?) of 0.9 (90%), determining a sample size of at least 30 subjects in order to ensure adequate statistical robustness of the study. Continuous variables were expressed as means and standard deviations, differences over time and subgroups were assessed with the unpaired Student's t test for continuous variables. In all cases, a p value less than 0.05? was considered significant. The statistical analysis? was carried out using Excel 2020

and GraphPad Prism version 8.3.1

RESULTS

A total of thirty-two (32) patients ? been recruited. Thirty (30) patients completed the study. Not a patient? managed to complete the treatment due to a localized irritative reaction, another was not? unable to return to follow-up due to an accident (bone fracture) during the observation period. Table 1 shows the characteristics of the enrolled patients.

Table 1

The sample was mainly represented by women (19 compared to 11 men); Most study participants had pain in their dominant shoulder. There were no significant differences in age? average between the two groups (p = 0.4749). At V0 the average Constant-Murley Score (CS) was 32.37 ? 11.86.

The Constant-Murley score? a 100-point scale that defines the level of pain and ability to carry out normal activities? daily lives of the patient, where the higher the score, the higher the quality? of the function. This score is often used to determine functionality? after treatment of a shoulder injury. Proof ? divided into four subscales: two subjective: pain (15 points) and activity? of daily life (20 points) and two objectives: range of motion (40 points) and strength (25 points). The maximum achievable score (100) represents an optimal condition.

The average CS in the subjects who underwent the present study? given by the sum of the above four variables with the following value: Pain = 3.3? 2.76; Activities? of daily living (ADL) = 8.07 ? 3.95; Range of motion (ROM)= 17.60 ? 6.65; Strength = 3.40 ? 2.65. These are very low values, considering that healthy subjects of the same age? and sex should have a CS that ? ranging from 70 points to 90 points.

At V1, the mean CS value was 50.68 ? 14.30, and was composed as follows: Pain = 7.65 ? 3.78; ADL = 15.33? 4.86; ROM = 24.07 ? 8.04; Strength = 3.63 ? 2.61. The second visit? was performed on average 12 days after the first visit.

At V2, the mean CS value was 51.07 ? 15.29, and was composed as follows: Pain = 7.60 ? 3.40; ADL = 14.90? 5.43; ROM = 24.93 ? 8.25; Strength = 3.63 ? 2.61. The third follow-up visit? was performed on average 35 days after the first visit.

The value of CS? increased significantly between V0 and V1 (p < 0.0001), while ? stationary result between V1 and V2 (p = 0.7162). All other indices followed the same trend as the total score. The temporal variations of the CS value are shown in Figure 2.

By analyzing the increases in the value of CS, we can? observe how 20 patients (66.7%) reported an increase of at least 10 points, 7 patients reported an increase of at least 2 points, 2 patients reported no change in CS and only 1 patient reported a decrease in CS. (Figure 3).

In percentage there? There was an average increase in CS value of 68% between V1 compared to V0. Only 3 (three) patients (10%) did not report an increase in CS value, while 14 patients (46.7%) reported an increase of more than 50% (Figure 4).

Between V2 and V1, almost all patients reported no significant change in CS value, except for three patients who reported a large increase in CS value at V1. Since? the sample was not homogeneous from a gender point of view, ? A gender-specific analysis was performed, which showed differences between the groups. Baseline CS (V0) was significantly (p = 0.009) lower in women (28.2 - 7.4) than in men (39.5 - 14.8). At V1 the CS value was 49.7 ? 15.6 for women and 52.4? 12.29 for men, while at V2 the CS value was 48.3 ? 17.0 for the female group and 55.91? 10.9 for the men's group. In both groups there is There was a significant increase between V0 and V1 and therefore a stable score at V2, but in women the increase in the CS value was ? been more higher (+21.4 points) than in men (+12.9 points). The trend of the two groups? shown in Figure 5.

Analyzing each parameter making up the CS, it emerges that 17 patients (56.7%) reported a score of 0 to the first question of the "Pain" section. (A1) to V1, which on a pain frequency scale represents "permanent" pain, without forcing; among these, only 5 (16.7%) still suffered from "permanent" pain. at V1 and only 3 (10%) at V2 (Figure 6).

If we analyze the first question of the "activities of daily living" section (B1), which evaluates the patients' limitation for activities daily, can you? observe how 21 patients (70%) reported a serious limitation of their work or activities? daily at the first visit, while only 5 (16.7%) reported the same limitation in V1 (Figure 7).

Tolerability? of the product ? was excellent: only 1 case of skin irritation? was reported with the use of the transdermal patch object of the present invention and, although the irritation was temporary and resolved spontaneously indicating an effect not related to the product, the patient preferred not to continue with the study.

CONCLUSIONS

The application of the patch object of the present invention for 10 consecutive days in patients with shoulder tendinopathies is was effective in reducing local pain and resulted in good recovery of function. The results obtained were maintained in the follow-up period.

After the first observation period, during which ? was the biggest change observed? significant, the value of CS is ? stabilized in the follow-up period. There? could be explained by the fact that the 10 day treatment ? an appropriate period of time why? CFAs result in effective pain reduction and allow physiological changes in tendons, probably due to stabilization of the tissue membrane; these improvements were sufficient to be maintained during the followup observation period. Furthermore, subjects who felt better shoulder condition after the 10-day treatment were able to resume their normal activities. work or hobbies, starting to use and "stress" the shoulder again, which was very often the dominant one. ? Interestingly, initial differences were observed between male and female subjects. The women started from a worse condition, but after the first period of treatment their recovery? was greater than men (+21.4 F points compared to 12.9 M points), reaching on average a very similar CS value after 10 days. At follow-up, however, men's CS value continued to improve, while women's CS value continued to improve. stabilized.

A possible explanation for this gender difference can? reside in the fact that the value of CS ? on average more? high for men: since? one of the parameters that make up the total index? strength, usually greater in men of this age population, this could explain both the difference in V0 and the faster recovery? effective at follow-up.

LIST OF REFERENCE NUMBERS

1 transdermal patch

2 layer support

4 external surface

6 internal surface

8 adhesive layer

10 layer of protection

12 porous membrane

14 containment compartment or tank

Claims (10)

1. One transdermal patch (1) comprising: (i) a support layer (2) delimiting an external surface (4) and an internal surface (6); (ii) an adhesive layer (8) connected to the internal surface (6); (iii) a protection layer (10), releasably connected to at least a portion of said adhesive layer (8); (iv) a composition placed in correspondence with said internal surface (6), wherein said composition comprises or, alternatively, consists of: (a) a mixture of cetylated fatty acids; And (b) optionally pharmaceutical grade additives or excipients. 2. The transdermal patch (1) according to the previous claim, wherein said (a) mixture of cetylated fatty acids comprises or, alternatively, consists of cetyl myristate and/or cetyl oleate. 3. The transdermal patch (1) according to any of the preceding claims, wherein said composition comprises or, alternatively, consists of: (a) said mixture of cetylated fatty acids; (b) so called optional pharmaceutical grade additives or excipients; And (c) one or more? vegetable oils; where a weight ratio (a):(c) ? ranging from 10:1 to 1:1, preferably ranging from 5:1 to 2:1, more? preferably between 4:1 and 2:1, even more? preferably 3:1. 4. The transdermal patch (1) according to claim 3, wherein said (c) one or more? vegetable oils includes or, alternatively, consists of vegetable oils with high oleic acid content from olive oil, palm oil and/or sunflower oil (SOHO), preferably olive oil, plus? preferably refined olive oil. 5. The transdermal patch (1) according to any of claims 1-4, wherein said adhesive layer (8) comprises an adhesive substance, preferably an acrylic adhesive substance, wherein said adhesive substance is? mixed with said composition such that said adhesive substance acts as a controlled release matrix for said composition. 6. The transdermal patch (1) according to any of claims 1-4, comprising: (v) a porous membrane (12), at least partially covered by the adhesive layer (8) and permeable to said composition; wherein said porous membrane (12) and said support layer (2) jointly circumscribe a containment space (14) for said composition. 7. The transdermal patch (1) according to any of the previous claims, wherein said composition is? a composition for use in a method of treating a disorder, or disorder, or pathology, of a tendon selected from tendinopathy, bursitis, tendinitis, and tenosynovitis, preferably bursitis and/or tendinopathy, plus? preferably shoulder tendinopathy, in one subject. 8. The transdermal patch (1) for use according to claim 7, wherein said subject has a Constant-Murley score (CS; Constant-Murley score) less than 45 (CS < 45), preferably CS < 40, more? preferably CS < 35. 9. The transdermal patch (1) for use according to claim 8, wherein said subject is? a female subject suffering from dominant shoulder tendinopathy with CS < 40, preferably with CS < 35. 10. The transdermal patch (1) for use according to any of claims 7-9, wherein said treatment method provides for an application of a transdermal patch (1) per day for a time ranging from 4 hours to 12 hours for a number of days from 5 to 15; preferably for a time ranging from 6 hours to 10 hours for a number of days from 8 to 12; more? preferably for a time ranging from 7 hours to 9 hours for a number of days from 9 to 11; even more? preferably for a period of 8 hours for a number of 10 days.