COMPOSITION IN MICRO-ENCAPSULATED FORM, BASED ON N-BUTYRICACID OR DERIVATIVES THEREOF, FOR TREATING CROHNS DISEASE OR ULCERATIVE RECTAL COLITIS

Abstract

A composition in micro-encapsulated form, comprising a core based on n- butyric acid or a derivative thereof, and a coating based on a lipid matrix which surrounds the core, in which the matrix has a content of C14-C22 long chain saturated fatty acids between 40% and 95%, is used for the treatment of ulcerative rectal colitis or Crohn's disease.

Claims

1. A composition in micro-encapsulated form, comprising a core based on n-butyric acid or a derivative thereof, and a coating based on a lipid matrix which surrounds the core, in which the matrix has a content of C14-C22 long chain saturated fatty acids between 40% and 95%, for the treatment of ulcerative rectal colitis or Crohn's disease.

2. The composition according to claim 1, wherein the C14-C22 long chain saturated fatty acids which are present in the matrix are in the form of glycerides and constitute at least 80% by weight of the matrix.

3. The composition according to claim 2, wherein the glycerides of saturated fatty acids are derived from hydrogenated palm oil.

4. The composition according to claim 1, wherein the matrix comprises a mineral agent in an amount between 1% and 20% by weight, with respect to the matrix, the mineral agent comprising a fraction of calcium sulphate dihydrate greater than 20% by weight.

5. The composition according to claim 4, wherein the fraction of the calcium sulphate dihydrate in the mineral agent is greater than 50%.

6. The composition according to any onc of thc prcceding claims, claim 1 wherein the compound is the sodium salt of n-butyric acid.

7. The composition according to any onc of the preceding claims, claim 1 for the treatment of ulcerative rectal colitis or Crohn's disease in a light or moderate activity phase.

8. The composition according to any onc of thc prcceding claims, claim 7, wherein the treatment of ulcerative rectal colitis or Crohn's disease provides for a daily dose of the composition between 500 and 2000 mg/day.

9. The composition according to claim 8, wherein the treatment of ulcerative rectal colitis or Crohn's disease provides for a daily dose of the composition between 1000 and 1700 mg/day.

Description

EXAMPLE

[0046] The micro-encapsulated composition to which the invention relates has been subjected to a study in order to evaluate the therapeutic potential thereof in relation to Crohn's disease and ulcerative rectal colitis.

[0047] The study involved subjects who are affected by Crohn's disease and ulcerative rectal colitis and who were subdivided into two different groups (selected randomly), a first group treated with a micro-encapsulated composition of sodium butyrate and a second group treated with a placebo substance (corn starch).

[0048] The treatment lasted 12 weeks and provided for taking two capsules per day, each one containing 550 mg of a micro-encapsulated composition based on sodium butyrate (equal to approximately 200 mg of sodium butyrate per capsule) or an equal quantity of the placebo substance. The daily dose of micro-encapsulated composition based on sodium butyrate or placebo substance (excluding the weight of the capsule which contains it) was therefore approximately 1100 mg.

[0049] The micro-encapsulated composition based on sodium butyrate used in the study is commercially available under the trade name Butyrose , produced by the same Applicant.

[0050] All the subjects have been subjected just before the start of the treatment (time T0) and at the end of the treatment (time T1) to an examination of the faeces, directed towards analysing the microbial composition of the intestine (intestinal microbiota) and the presence of faecal calprotectin, a recognized biological indicator of intestinal inflammation.

[0051] Furthermore, all the subjects have expressed an evaluation of their quality of life before and after the treatment period, by means of an IBDQ questionnaire (Inflammatory Bowel Disease Questionnaire).

[0052] The results of the study are set out and commented upon below.

Intestinal microbiota analysis

[0053] The analysis was carried out by comparing the bactericidal strains prevalent at the time TO and at the time T1, after their identification by means of the method of Sparse Partial Least Squares Discriminant Analysis (SPLS-DA). In Table 1 below, there are set out the bacterial species prevalent at the time T0 and at the time T1 for the subjects who are affected by Crohn's disease and who are treated with the micro-encapsulated composition based on sodium butyrate.

TABLE-US-00001 TABLE 1 Bacterial species Per- Bacterial species Per- prevalent at the time = T0 centage prevalent at the time = T1 centage Lachnospiraceae- 2.55 Ruminococcaceae- 0.77 Lachnoclostridium Subdoligranulum Ruminococcaceae- 2.17 Lachnospiraceae- 0.57 Flavonifractor plautii Blautia Desulfovibrionaceae- 0.3 Ruminocaccaceae- Bilophila_wadsworthia Butyricicoccus 0.47 Bacteroidaceae-Bacteroides 2.41 uniformis Fusobacteriaceae- 2.59 Fusobacterium-varium Streptococcaceae- 2.79 Streptococcus Erysipelotrichaceae- 0.71 Erysipelotrichaceae-UGC- 003

[0054] An examination of Table 1 shows that, at the time T0 (just before the start of treatment), the prevalent bacterial species which are producers of SCFA (Lachnospiraceae—Lachnoclostridium and Ruminococcaceae—Flavonifractor p/autii) are equal to approximately 35% of the total of prevalent bacterial species while, at the time T1(end of treatment), the prevalent bacterial species are all producers of SCFA (100% of the total of prevalent bacterial species).

[0055] It can be seen particularly clearly that the prevalent bacterial species are highly butyrogenic.

[0056] In Table 2 below there are set out the bacterial strains prevalent at the time T0 and at the time T1for the subjects who are affected by ulcerative rectal colitis with the micro-encapsulated composition based on sodium butyrate.

TABLE-US-00002 TABLE 2 Bacterial species Per- Bacterial species prev- Per- prevalent at the time = T0 centage alent at the time = T1 centage Bacteroidaceae- 2.73 Lachnospiraceae- 0.81 Bacteroides uniformis Lachnospira Streptococcaceae- 0.3 Lachnospiraceae- 0.265 Streptococcus Lachnospiraceae Ruminococcaceae- 0.41 NK4A136 group Ruminoclostridium-5 Lachnospiraceae- 0.47 Ruminococcaceae 0.11 Lachnoclostridium Erysipelotrichaceae- 0.55 Lachnospiraceae- 0.44 Erysipelotrichaceae UGC003 Lachnospiraceae UCG- Lachnospiraceae- 0.57 010 Coporococcus Erysipelotrichaceae- 0.04 Turicibacter sanguinis

[0057] An examination of Table 2 shows that, at the time TO (just before the start of treatment), the prevalent bacterial species which are producers of SCFA (Ruminococcaceae-Ruminoclostridium-5, Ruminococcaceae and Lachnospiraceae-Coporococcus) are equal to approximately 23% of the total of prevalent bacterial species while, at the time T1(end of treatment), the prevalent bacterial species are all producers of SCFA (100% of the total of prevalent bacterial species).

[0058] In both groups of subjects treated with the micro-encapsulated composition based on sodium butyrate (both the ones affected by Crohn's disease and those affected by ulcerative rectal colitis), it has further been found how the variation of the intestinal microbiota has been particularly effective in subjects in which the activity of the disease was at a light or moderate level, while, in subjects in which the disease was in a remission phase, this effect was only slightly relevant.

Faecal calprotectin analysis

[0059] The analysis of the faecal calprotectin in subjects who are affected by Crohn's disease and who are subjected to treatment with the micro-encapsulated composition based on sodium butyrate has shown that, for approximately 67% of them, there has been a significant reduction (greater than or equal to 30% in patients with initial values greater than 250 μg/g) of the value of the faecal calprotection.

[0060] In subjects who are affected by Crohn's disease and who are subjected to treatment with the placebo, this significant reduction of the value of faecal calprotectin was found to be only 33% of the total.

[0061] The analysis of the faecal calprotectin in subjects who are affected by ulcerative rectal colitis and who are subjected to treatment with the micro-encapsulated composition based on sodium butyrate has not shown particular differences from the subjects subjected to treatment with a placebo.

Quality of life

[0062] All the subjects have expressed evaluations on their quality of life by means of responses to the IBDQ questionnaire (Inflammatory Bowel Disease Questionnaire) before and after the treatment.

[0063] The results collected and processed have shown a substantial increase which is statistically significant (p value=0.0071) of the quality of life in the subjects who are affected by ulcerative rectal colitis and who are treated with the micro-encapsulated composition based on sodium butyrate with respect to the subjects who are affected by the same pathology and who are treated with a placebo.

[0064] In the subjects who are affected by Crohn's disease, however, there have been found no appreciable differences in the evaluation of the quality of life between the subjects who are treated with the micro-encapsulated composition based on sodium butyrate and those treated with a placebo. In conclusion, the study has shown that a treatment with the micro-encapsulated composition based on sodium butyrate according to the present invention is effective in treating Crohn's disease and ulcerative rectal colitis, modifying the intestinal microbiota so as to promote and increase the species which produce SCFA and especially, in the case of Crohn's disease, of the bacterial species which produce n-butyric acid.

[0065] Furthermore, there has been found a substantial reduction in the intestinal inflammatory activity in the case of treatment of Crohn's disease and a significant increase in the subjective perception of the quality of life in the case of treatment of ulcerative rectal colitis.