Urolon is a Bioresorbable Urethral Implant for the treatment of stress urinary incontinence (SUI) and inherently different from traditional urethral bulking agents due to its unique performance, mode of action and bioresorption profile. It is a minimally invasive treatment using non-permanent materials that is very suitable as a first-choice treatment option before using permanent injectables or surgical interventions.
Dual action of:
1. immediate bulking effect by the gel carrier
2. sustained performance by the polycaprolactone microspheres and related mechanism of action
Urolon can be administered non-surgically using a transurethral approach via cystoscopy. Urolon offers the following performance properties:
- Immediate bulking effect
- Sustained performance
- Lower associated-risks when compared to surgery (Ref: Pitt CG. Poly (ε-caprolactone) and its copolymers. In: Chassin M, Langer R, editors. Biodegradable polymers as drug delivery systems. New York: Dekker ;1990:71-119.)
Immediate bulking effect
Most noticeable is the ability of Urolon to restore lost volume around the urethra by providing an immediate bulking effect due to the optimum visco-elastic gel carrier.
A sustained performance is achieved through the unique mode of action of Urolon and its bioresorption profile.
What is Urolon™
Urolon represents a new class of urethral injectable products: Bioresorbable Urethral Implants. It is an injectable device, indicated for submucosal implantation for the treatment of stress urinary incontinence (SUI) in adult females. It is a sterile, non-pyrogenic, totally bioresorbable, non-permanent implant, whose principle component is synthetic polycaprolactone (PCL) microspheres suspended in a carboxymethylcellulose (CMC) gel carrier (Figure 1a and 1b).
PCL is a well-known totally bioresorbable soft medical polymer. PCL has been used in numerous CE-marked and FDA approved commercial bioresorbable product applications and has demonstrated an excellent safety profile.
Figures 1a and 1b show light and scanning electron micrograph of PCL microspheres
The Bioresorption Process
The PCL microspheres bioresorb into the non-toxic degradation products of carbon dioxide and water and are excreted through normal metabolic pathways (representing total bioresorbability). The complete and controlled bioresorption of PCL has been proven via radio-labelled PCL microsphere implantation studies (3H- and C14-labelled).
The mechanism of bioresorption of the polycaprolactone (PCL) microspheres is defined by two predictable and controlled phases;
- During the initial phase, the PCL chain-length is reduced by chain scission (hydrolysis), but is not yet resorbed, keeping the microsphere intact with no volume or mass loss
- During the second phase, total bioresorption takes place through volume and mass loss and excretion occurs through the normal metabolic pathways (citric acid cycle) as carbon dioxide and water.
Mode of Action
The main constituent of the sub-urethral wall is fibrous connective tissue. Collagen of types I, III, and VI are the predominant component of this connective tissue. As women with SUI often have a change in their connective tissue metabolism, resulting in altered collagen content, stimulation of collagen production has the potential to replace lost collagen in women with SUI, restoring urinary continence by improving outlet resistance.
Urolon induces a controlled foreign body response and has the potential to induce neocollagenesis in urethral tissue. Studies have shown that an injection of Urolon induces the formation of collagen type I and III. Collagen type III, over several months, is replaced by the more stable collagen type I. This newly formed collagen scaffold embeds the microspheres in the tissue, limiting the risk of dislocation.
Advantages of Urolon™
Bioresorbable Urethral Implant with a unique composition
- 70% CMC gel
- 30% Polycaprolactone (PCL) microspheres
Minimally invasive procedure
Proven safety and efficacy
- Safe product components with a long safety history in numerous CE marked and FDA approved bioresorbable medical devices
- Soft bioresorbable (non-cross-linked) medical polymer: polycaprolactone, in a tailor made aqueous CMC gel carrier
- Gel carrier components Generally Recognized As Safe (GRAS) by the USA FDA
- Sensitivity testing not required due to a non-animal, non-bacterial and non-human derived product
- Due to microsphere size, spherical shape, smooth surface and chain scission (hydrolysis) as opposed to degradation
Bi-phasic hydrolytic bioresorption
- Purely hydrolysis-based; non-enzymatic process
- PCL microspheres remain in-situ, resulting in stable and sustained performance
- Second-phase results in full bioresorption of small PCL chains (6-hydroxy caproic acid) via the normal citric acid cycle; reduction to CO2 and H2O)
- Non-permanent microspheres
- As shown by radio-labelled PCL studies
- Reduced risk of long-term complications when compared to permanent implants
Urolon is a new class of urethral injectables. Its composition gives an immediate bulking effect primarily from the CMC gel carrier (70%) and sustained performance due to highly biocompatible PCL microspheres (30%). Combined, these unique advantages position Urolon as an ideal, first-choice and minimally invasive treatment option for women with mild to moderate SUI.
Treatment for SUI
Stress Urinary Incontinence Spectrum
Injectable products have an important role to play within the SUI treatment offerings. However, current UBAs are mostly a last resort treatment option for women unable or unwilling to undergo a surgical procedure, or after a failed surgical intervention. Urolon now represents a new opportunity for these women. Urolon has the potential to address a much wider population of women suffering with SUI; especially those who currently do not come forward for treatment, opting to try to manage their condition alone, or prefer not to have a non-resorbable, permanent implant.
The below graph shows the position of Urolon in the SUI treatment spectrum: start with a minimally invasive bioresorbable urethral implant! Keep surgical and permanent options for later!
Minimally Invasive Treatment
Urolon represents a minimally invasive treatment opportunity for women with mild to moderate SUI where pelvic floor muscle training is not sufficient or adherence to training is not met. This same group may not feel ready to consider a surgical option, yet would benefit from a treatment that aims at symptom reduction and prevention.