Sustained In-Vivo Release of Triptorelin Acetate from a Biodegradable Silica Depot: Comparison to Pamorelin® LA

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

ANALEPTIC APPLICATIONS OF PEPTIDES

Bioactive peptides are protein parts which positively affect the capacities and states of living creatures. Peptides have demonstrated a few helpful properties for human wellbeing, including antimicrobial, antifungal, antiviral, and antitumor exercises. These mixes are delivered by practically all types of life. Notwithstanding, they are delivered in restricted amounts in nature. Subsequently, scientists have attempted to integrate bioactive peptides to contemplate their properties and applications in different zones. This review delivers a concise portrayal of the applications utilized by peptides: Triptorelin Acetate, Thymosin Alpha 1, Leuprolide acetate, Liraglutide, Desmopressin Acetate, Teduglutide, Pramlintide, Oxytocin, Calcitonin, Octreotide and Triptorelin. Keywords: Triptorelin Acetate, Thymosin Alpha 1, Leuprolide acetate

Comparison of oocyte maturity rates in recombinant Human Chorionic Gonadotropin (HCG) and triptorelin acetate triggers: A prospective randomized study

Luteinizing Hormone (LH) like exposure in the mid cycle for inducing the oocyte maturation is the very crucial step in the success of ICSI treatment. Introduction of LH surge endogenously by GnRH-agonist for final oocyte maturation induction, may be more physiological compared with the administration of HCG. Since GnRH agonist would induce FSH surge also along with LH surge, as happens in natural cycle. However, the effects of giving HCG trigger for inducing only LH surge and giving GnRH agonist trigger for inducing both LH and FSH surge, in patients treated for ICSI with GnRH antagonists need more research. Sub fertile patients planned for ICSI, meeting the requirement of inclusion criteria, were started with recombinant FSH from day 2 of menstrual cycle. GnRH antagonists were started from day 6 of stimulation. FSH dose was adjusted according to the individual response. Trigger was planned when the lead follicle reaches 24 mm. For triggering, 100 patients were randomized to receive Recombinant HCG trigger and Triptorelin acetate trigger. Oocyte retrieval was done 36 hours after Recombinant hCG Trigger and 35 hours after Triptorelin acetate trigger. The oocyte maturity rate was assessed by the number of metaphase II oocytes retrieved.

MON-069 Uncontrolled Central Precocious Puberty Patient Against GnRH Agonist, After Showing Granuloma Formation and Sterile Abscess to Both Leuprorelin Acetate and Triptorelin Actate

For more than 30 years, Gonadotropin-releasing hormone (GnRH) agonist has been the treatment of choice for central precocious puberty (CPP) to expect regression of secondary sexual characteristics, delayed menarche, and maximization of linear growth. There are several kinds of GnRH agonists such as leuprorelin, triptorelin, goserelin and histrelin, etc. In Korea, leuprolide acetate and triptorelin acetate are most common used drugs, and a monthly depot preparation is typically used for suppression of the HPG axis. Local complications related to GnRH agonists, including erythematous macules, granulomas, subcutaneous nodules, and sterile abscesses, occur in 10~15% of patients, and sterile abscesses have been known to occur in less than 2~3% of patients. In present case, we would like to introduce a case of CPP patient who was treated with GnRH agonist, but not suppressed and experienced recurrent vaginal bleeding, after showing granuloma formation and sterile abscess to both leuprorelin acetate and triptoreline actate. A 8.9 year-old girl visited our clinic with breast development and vaginal bleeding. On physical examination, she had enlarged breasts (Tanner stage 4) with pigmentation of the areola. Her height and weight was measured as 144.4cm (98th percentile) and 44.2kg (98th percentile) respectively. Her bone age was advanced as 12~12.6 years of age by TW3 method. Therefore, Leuprolide acetate (Lorelin depot®, Dongkook pharm) 3.75mg was administered to the patient every 4 weeks, and until the 6th injection, she exhibited no other complications. However, after 7th injection, the patient presented with granuloma and subcutaneous nodule at the left injection site and elevated hormone levels. Although that we switched to triptorelin acetate from 8th injection, the patient also showed a sterile abscess at the injection site. We switched from triptorelin acetate to leuprolide acetate again, however, after 2 months of the switch, the patient showed abrupt vaginal bleeding and elevated hormone levels. Therefore, after assumption of unsuppression of HPG axis, leuprolide acetate 3.75mg was administered every 2 weeks for 2 months. However, her vaginal bleeding occurred monthly and hormonal level was still unsuppressed, and also, the granuloma appeared again at the injection site. So, we discussed with her parents about her uncontrolled symptoms, and we discontinued the treatment. There are many theories about the cause of local complications of GnRH agonist, but the mechanism has still not been revealed. Further studies are required to identify the mechanism and the relationship between treatment effect and local complications, which could induce uncontrolled CPP.

Relapse after conservative surgery combined with Triptorelin Acetate versus conservative surgery only in women with focal adenomyosis: study protocol for a multicenter, prospective, randomized controlled trial

Background: To preserve fertility or integrity of organs was on the rise for the most women with adenomyosis. Adenomyomectomy is now a widely applied conservative surgery, however relapse is a serious problem after operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the recurrence rate in patients. However, there is still a lack of evidence from randomized clinical trials comparing the efficacy of GnRHa for decreasing the postoperative recurrence rate. Method/Design：Relapse after conservative surgery combined with Triptorelin Acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse accessed with Visual Analogue Scale (VRS) and Numeric Rating Scale (NRS), Pictorial blood loss assessment chart (PBAC) score and the size of uterus and lesion are measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, and adverse events, assessing by Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels and anti-muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, 36 months after conservative surgery. Discussion：The result of this large multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation.

Comparison of Single, Fixed-Time Artificial Insemination in Gilts Using Two Different Protocols to Synchronize Ovulation

In order to efficiently have a consistent supply of service-ready gilts available to incorporate into each batch of breeding sows, it is necessary to manipulate the timing of estrus and possibly the timing of ovulation of gilts. Estrus can be synchronized by the withdrawal of altrenogest after at least 14 days of treatment. It is possible that protocols developed to induce ovulation, and therefore allow fixed-time artificial insemination (FTAI), can improve the predictability of gilt breeding. This study investigated the effect of two FTAI protocols in gilts on reproductive performance and timing of farrowing and piglet weaning weight compared to gilts bred based on signs of estrus after cessation of altrenogest. Puberty was induced in gilts, followed by treatment with altrenogest. Following altrenogest withdrawal, 180 gilts were assigned to one of three treatment groups. Group 1 gilts (LUT, n = 62) were treated with 600 IU equine chorionic gonadotropin 24 h after altrenogest withdrawal and 5 mg porcine luteinizing hormone (pLH) 80 h later, followed by a single FTAI 36 h after pLH. Group 2 gilts (TRI, n= 61) received 2 mL of a gonadotropin-releasing hormone agonist, triptorelin acetate, intravaginally 6 d after altrenogest withdrawal and were bred by a single FTAI 24 h later. Group 3 gilts (CON, n = 57) were observed for estrus and bred twice by AI, 24 h apart. LUT and TRI gilts farrowed closer together (2.4 ± 1.6 and 2.9 ± 1.2 d(days), respectively) compared to CON gilts (4.5 ± 3.3 d). Piglets in LUT were 80 g (p < 0.001) heavier and piglets in TRI were 64 g (p < 0.05) heavier at weaning than CON piglets, when controlling for birth weight. Results indicate that FTAI might be useful as a means of minimizing the time from the first to the last gilt farrowing in a breeding batch of gilts. However, modifications of the protocols may be required to ensure optimum farrowing rates and litter size.