The active moiety is 5-aminosalicylic acid (5-ASA), which is released in the colon. The specific molecular target is not detailed in this clinical study, but it exerts a topical anti-inflammatory action on the colonic mucosa. [2]

Balsalazide is a novel prodrug of 5-aminosalicylic acid (5-ASA) [2]. At the endpoint, colon tissue's synthesis of MIP-1β, MCP-1, IL-6, and IL-10 proteins reduced as the cytokines' plasma concentrations increased. Furthermore, p-STAT3 expression was lower in the medication treatment group when compared to the CAC group, and there was a large increase in BAX and a significant decrease in BCL2.

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In a 26-week, double-blind, multicenter, randomized trial of 133 patients with ulcerative colitis in remission, treatment with high-dose balsalazide (3.0 g twice daily) resulted in a significantly higher clinical remission rate (77.5%) compared to low-dose balsalazide (1.5 g twice daily; 43.8%; p=0.001) and mesalazine (0.5 g three times daily; 56.8%; p=0.045). [2]
The time to relapse was significantly longer in the high-dose balsalazide group (161 days) compared to the low-dose group (131 days; p=0.003). No significant difference was found between the high-dose balsalazide and mesalazine groups (144 days). [2]
Analysis of the final endoscopic score showed a significant difference between the two balsalazide treatment groups (p=0.005), favoring the higher dose. Differences between either balsalazide group and the mesalazine group were not statistically significant. [2]
Analysis of the final Clinical Activity Index (CAI) showed a significant difference between the high and low dose balsalazide groups (p=0.008). The final CAI was also dependent on the baseline CAI (p=0.023). [2]
Based on CAI data, the dose of balsalazide equivalent to mesalazine 0.5 g three times daily (1.5 g/day 5-ASA) was estimated to be 2.13 g twice daily (95% CI 1.16; 4.19), which corresponds chemically to 1.49 g/day of 5-ASA. [2]

Balsalazide is a prodrug where 5-aminosalicylic acid (5-ASA) is bound to an inert carrier molecule, 4-aminobenzoyl-β-alanine (4-ABA). The azo bond is split by colonic bacteria, releasing 5-ASA in the colon to exert its anti-inflammatory action. [2]
Urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was measured as a percentage of the oral 5-ASA dose. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine, although the differences were not statistically significant. The combined balsalazide groups showed a 5-ASA recovery rate of 11.5% (95% CI 8.0, 16.70) compared to 18.7% (95% CI 11.40, 30.60) for mesalazine (p=0.124). [2]
Urine samples (24-hour collection) were analyzed using a standardized high-performance liquid chromatography method. Samples were deproteinized with acetonitrile, followed by derivatization of 5-ASA and liquid-liquid extraction with ethyl acetate. Chromatography was performed on a Nucleosil 10 SB column with fluorescence detection. The calibration range was 50-2000 ng/ml for 5-ASA and 100-4000 ng/ml for N-Ac-5-ASA. Determinations were performed in duplicate. [2]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
While there is currently no information on whether balsalazine is excreted into breast milk, it is metabolized in breast milk to the active drug mesalazine. A small number of infants have been reported to experience diarrhea after taking mesalazine, but the incidence is low. Most experts and professional guidelines consider mesalazine derivatives safe for breastfeeding women. ◉ Effects on Breastfed Infants
Mesalazine, the active metabolite of balsalazine, may have been the cause of diarrhea in a 6-week-old infant who experienced four recurrences of diarrhea after the mother took balsalazine four times during breastfeeding.
In a prospective telephone follow-up study, eight breastfeeding mothers reported taking mesalazine (dosage and route of administration not specified). One mother reported diarrhea in her infant. No other adverse reactions were reported in the infants by the mothers.
A case-control study compared infants born to mothers receiving mesalazine (n = 117; mean dose, 2065 mg daily), olsalazine (n = 2), or sulfasalazine (n = 2) with infants born to a mother-matched control group (n = 121). Control group mothers did not receive any treatment known to be harmful to breastfed infants. The mean duration of breastfeeding exposure to mesalazine was 5.3 months (range: 3 days to 24 months). Infants were breastfed for approximately 7.4 months on average and followed up at a mean of approximately 22 months of age. There were no differences in the frequency or characteristics of maternally reported adverse events between the exposed and control groups.
◉ Effects on breastfeeding and breast milk
As of the revision date, no relevant published information was found.

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Adverse Events Leading to Discontinuation: Nine patients discontinued the trial due to adverse events: three in the balsalazide 1.5 g twice daily group (headache, hypertension, malaise, dizziness, abdominal pain, pruritus, skin rash), two in the balsalazide 3.0 g twice daily group (pancreatitis, gingivitis, alopecia, nail disorders), and four in the mesalazine group (palpitation, hypotension, tenesmus, nausea, impotence, diarrhoea, alopecia). [2]
Overall Adverse Events: The percentage of patients reporting any adverse event was 38% in the balsalazide 1.5 g twice daily group, 53% in the balsalazide 3.0 g twice daily group, and 45% in the mesalazine group. No clinically important new drug safety-related findings were identified. [2]
Nephrotoxicity Assessment: To assess potential renal tubular damage, several analyses were performed:
SDS-PAGE Urinary Protein Analysis: Morning urine samples were analyzed by SDS-PAGE. A positive result (indicative of tubular damage) was defined as a protein pattern showing tubular proteinuria. There was no evidence of any difference between groups in the proportion of patients with negative results at the start and positive results at the end (p=0.99).
Glutathione-S-transferase-π (GST-π): 24-hour urine collections were analyzed for GST-π, a marker of tubular damage. There were few positive measurements, and changes from baseline to the end of the study showed no evidence of any difference between the three groups (p=0.49).
The study concluded that there was no indication of tubular damage with either dose of balsalazide or with mesalazine. [2]

[1]. Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3. J Gastroenterol Hepatol. 2016 Aug;31(8):1453-61.

[2]. Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses. Gut, 2001. 49(6): p. 783-789.

Balsalazine disodium is the dihydrate of balsalazine disodium salt. It is a prodrug that releases the anti-inflammatory drug 5-aminosalicylic acid (mesalazine) in the colon for the treatment of ulcerative colitis. It has the effects of a gastrointestinal drug, an anti-ulcer drug, and a nonsteroidal anti-inflammatory drug. It is an organosoilane salt and hydrate. It contains the balsalazine (2-) ion. It is functionally related to balsalazine.
See also: Balsalazine disodium (note moved to).

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Balsalazide is a novel prodrug of 5-aminosalicylic acid (5-ASA) used for the treatment of ulcerative colitis. It consists of 5-ASA linked to an inert carrier molecule, 4-aminobenzoyl-β-alanine (4-ABA). [2]
Unlike other prodrugs such as sulphasalazine (which releases sulphapyridine) or olsalazine (which consists of two 5-ASA molecules linked together), the carrier molecule 4-ABA in balsalazide is pharmacologically inert and devoid of systemic effects. [2]
The study demonstrated that high-dose balsalazide (3.0 g twice daily) was superior to a lower dose (1.5 g twice daily) and to a standard dose of mesalazine (0.5 g three times daily) in maintaining remission in patients with ulcerative colitis. All three treatments were safe and well tolerated. [2]
The authors suggest that patients with more extensive disease or frequent relapses may benefit from a higher dose of maintenance therapy with balsalazide. [2]
While not statistically significant, the trend toward lower urinary excretion of 5-ASA and its metabolite with balsalazide compared to mesalazine may suggest a potential advantage in terms of reduced systemic exposure, which could be relevant for nephrotoxicity risk. [2]

C17H17N3NA2O8

437.3117

437.081

150399-21-6

Balsalazide;80573-04-2

135414247

Light yellow to yellow solid powder

0.303

4

10

6

30

539

0

XDCNKOBSQURQOZ-UHFFFAOYSA-L

InChI=1S/C17H15N3O6.2Na.2H2O/c21-14-6-5-12(9-13(14)17(25)26)20-19-11-3-1-10(2-4-11)16(24)18-8-7-15(22)23;;;;/h1-6,9,21H,7-8H2,(H,18,24)(H,22,23)(H,25,26);;;2*1H2/q;2*+1;;/p-2

disodium;3-[[4-[(3-carboxy-4-oxidophenyl)diazenyl]benzoyl]amino]propanoate;dihydrate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)