Gonadotropin-releasing hormone agonist (GnRH)

曲普瑞林对雷公藤多苷诱导的小鼠卵巢细胞损伤具有保护作用 [2]。

曲普瑞林对雷公藤引起的雌性小鼠卵巢功能损害具有保护作用[2]。

For qualified, healthy SD female mice, the vaginal exfoliated cell method was used to select 30 mice with normal estrous cycle as test animals, which were randomly divided into 3 groups of 10 mice each: • Group A: blank control group, where 0.35 mL of saline was administered to the stomach once daily for 11 weeks; • Group B: tripterygium glycoside group, where 0.35 mL of tripterygium glycoside solution was administered to the stomach from the 8th day; once a day for 10 weeks; • Group C: triptolide + triptorelin group: 0.1 mg/kg daily subcutaneous injection of triptorelin injection; once a day; continuous injection for 11 weeks; from the 8th day, the triptolide solution was administered to the stomach 0.35 mL, once daily for 10 weeks. From the first day of the experiment, the general conditions of the mice were observed and recorded, including energy, activity, hair, food intake, water intake, stomach appetite, second stool, etc. The mice were weighed once a week to observe changes in body weight. The vagina exfoliation cell method, simple to operate, was used to observe the estrous cycle. After 11 weeks of treatment, the drug was stopped for 3 weeks and all mice were sacrificed. The ovaries were then obtained by laparotomy, and the ovarian wet weight was measured using an electronic analytical balance. The ovarian index was calculated by ovarian wet weight (mg) / mouse weight (g) × 100%. After weighing, the ovaries were fixed in a 4% paraformaldehyde solution for 3 days, and were routinely dehydrated, xylene-transparented, wax-impregnated, embedded, sectioned (4 µm), and operated according to the instructions of immunohistochemistry kit. Immunohistochemical average optical density (average optical) analysis method: each slice in each group randomly selected at least three positions with a 200× field of view (FoV) for photographing. When taking pictures, FoV was selected to ensure that the testing tissue fully filled the view. In addition, the background illumination of each photo was kept as consistent as possible. Image-Pro Plus 6.0 software was used to select the same brown-yellow color as the uniform standard for determining the positives of all photos. Each photo was analyzed to obtain the Integrated Optical Density (IOD) and the pixel area (AREA). The average optical density (AO) was obtained by AO = IOD/AREA. (1) The larger the AO value, the higher the positive expression level. [2]

Absorption, Distribution and Excretion
Following IV administration of triptorelin, triptorelin is completely absorbed.
Elimination of triptorelin involves both the kidneys and the liver.
After a single IV dose of 0.5mg, the volume of distribution of triptorelin peptide in healthy males was 30 - 33L.
In healthy male volunteers, total clearance of triptorelin was 211.9 mL/min.

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Metabolism / Metabolites
The metabolism of triptorelin in humans is not well understood; however, metabolism likely does not involve hepatic enzymes such as cytochrome P450. Whether or not triptorelin affects, or how it affects other metabolizing enzymes is also poorly understood. Triptorelin has no identified metabolites.

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Biological Half-Life
The pharmacokinetics of triptorelin follows a 3 compartment model. The half lives are estimated to be 6 minutes, 45 minutes, and 3 hours respectively.

Hepatotoxicity
Long term triptorelin is associated with serum enzyme elevations in 2% to 5% of patients, although the elevations are rarely above three times the upper limit of normal (
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Protein Binding
Triptorelin does not bind to plasma proteins at clinically relevant concentrations.

[1]. Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty.2016 Nov 1;29(11):1241-1248.
[2]. www.ejgo.net/articles/10.31083/j.ejgo.2021.02.2299

Triptorelin is an oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, D-tryptophyl, leucyl, arginyl, prolyl and glycinamide residues joined in sequence. It is an agonist analogue of gonadotropin-releasing hormone. It has a role as a gonadotropin releasing hormone agonist, an antineoplastic agent and a contraceptive drug.
Triptorelin is a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion. After chronic, continuous administration, this agent effects sustained decreases in LH and FSH production and testicular and ovarian steroidogenesis. Serum testosterone concentrations may fall to levels typically observed in surgically castrated men.
Triptorelin is a gonadotropin releasing hormone (GnRH) agonist that is a potent inhibitor of the synthesis of testosterone (in men) and estrogen (in women) and is used to treat advanced prostate cancer. Triptorelin is associated with a low rate of transient serum enzyme elevations during therapy, but has not been linked convincingly to cases of clinically apparent acute liver injury.
Triptorelin is a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion. After chronic, continuous administration, this agent effects sustained decreases in LH and FSH production and testicular and ovarian steroidogenesis. Serum testosterone concentrations may fall to levels typically observed in surgically castrated men. (NCI04)
A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE with D-tryptophan substitution at residue 6.
See also: Triptorelin Pamoate (active moiety of); Triptorelin Acetate (active moiety of).

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Drug Indication
Triptorelin is indicated for the palliative treatment of advanced prostate cancer.
FDA Label
For the synchronisation of ovulation in weaned sows to enable a single fixed-time artificial insemination.

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Mechanism of Action
Triptorelin is a synthetic agonist analog of gonadotropin releasing hormone (GnRH). Animal studies comparing triptorelin to native GnRH found that triptorelin had 13 fold higher releasing activity for luteinizing hormone, and 21-fold higher releasing activity for follicle-stimulating hormone.

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Pharmacodynamics
The first administration of triptorelin is followed by a transient surge of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol,and testosterone. The time, peak and decline of testosterone in the body varies depending on the dose administered. This initial surge is often responsible for worsening of prostate cancer symptoms such as urethral or bladder outlet obstruction, bone pain, spinal cord injury and hematuria in the early stages. A sustained decrease in FSH and LH, and significant reduction of testicular steroidogenesis is usually seen 2-4 weeks post-initiation of therapy. This result is a reduction of serum testosterone to levels which are typically seen in surgically castrated men. Ultimately, tissues and functions that require these hormones become inactive. The effects of triptorelin can usually be reversed once the drug is discontinued.

C64H82N18O13

1311.4487

1310.63

C, 58.61; H, 6.30; N, 19.22; O, 15.86

57773-63-4

2240176-35-4 (TFA); 140194-24-7 (acetate); 57773-63-4; 124508-66-3 (pamoate)

25074470

Solid powder

1.5±0.1 g/cm3

1.723

-0.41

487.92

17

15

33

95

2710

9

O=C([C@]([H])(C([H])([H])C([H])([H])C([H])([H])/N=C(\N([H])[H])/N([H])[H])N([H])C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C([C@]([H])(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])N([H])C([C@]([H])(C([H])([H])O[H])N([H])C([C@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C([C@]([H])(C([H])([H])C1=C([H])N=C([H])N1[H])N([H])C([C@]1([H])C([H])([H])C([H])([H])C(N1[H])=O)=O)=O)=O)=O)=O)=O)=O)N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(N([H])C([H])([H])C(N([H])[H])=O)=O

VXKHXGOKWPXYNA-PGBVPBMZSA-N

InChI=1S/C64H82N18O13/c1-34(2)23-46(56(88)75-45(13-7-21-69-64(66)67)63(95)82-22-8-14-52(82)62(94)72-31-53(65)85)76-58(90)48(25-36-28-70-42-11-5-3-9-40(36)42)78-57(89)47(24-35-15-17-39(84)18-16-35)77-61(93)51(32-83)81-59(91)49(26-37-29-71-43-12-6-4-10-41(37)43)79-60(92)50(27-38-30-68-33-73-38)80-55(87)44-19-20-54(86)74-44/h3-6,9-12,15-18,28-30,33-34,44-52,70-71,83-84H,7-8,13-14,19-27,31-32H2,1-2H3,(H2,65,85)(H,68,73)(H,72,94)(H,74,86)(H,75,88)(H,76,90)(H,77,93)(H,78,89)(H,79,92)(H,80,87)(H,81,91)(H4,66,67,69)/t44-,45-,46-,47-,48+,49-,50-,51-,52-/m0/s1

5-Oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-tryptophyl-L-leucyl-L-arginyl-L-prolylglycinamide

Triptoreline; Arvekap; Triptorelina

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)

DMSO: > 10mM

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。