Pilocarpine HCl
(Synonyms: 盐酸毛果芸香碱) 目录号 : GC17256
A muscarinic acetylcholine receptor agonist
Cas No.:54-71-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
C.albicans SC5314 |
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Preparation Method |
Standardized C. albicans SC5314 (1×106 cells/ml) were inoculated in RPMI with or without Pilocarpine HCl on Thermanox coverslips (13mm) within a 24-well tissue culture plate and then incubated for 24h at 37℃. |
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Reaction Conditions |
0-50mM |
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Applications |
Light microscopy revealed that Pilocarpine HCl inhibited filamentation and biofilm formation in a dose-dependent manner. Furthermore, visually, in the presence of increasing concentrations of Pilocarpine HCl, more C.albicans cells maintained a yeast morphology, suggesting that Pilocarpine HCl was inhibiting the yeast-to-hypha transition. Scanning electron microscopy analysis further confirmed the fact that Pilocarpine HCl inhibited biofilm formation due to inhibition of the yeast-to-hypha transition in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats, seven-week-old |
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Preparation Method |
Each rat was fasted overnight before the experiment, but had free access to drinking water. The rat was anaesthetized with urethane (1.25 g/kg, s.c.) and its body temperature was maintained at 37℃ during the subsequent experiment. After intubating the trachea, the duct of the right parotid gland was cannulated for the collection of saliva. Pilocarpine hydrochloride (0.05, 0.1, 0.2 or 0.4mg/kg in 1mL) or distilled water was administered intraduodenally and the saliva was collected for 120min after this administration |
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Dosage form |
0.05, 0.1, 0.2 or 0.4mg/kg in 1mL |
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Applications |
The mean salivary output for 120min without pilocarpine hydrochloride was 1.58±0.99μL (n=6). Pilocarpine hydrochloride (0.05-0.4mg/kg, intraduodenal) dose-dependently increased salivary output for 120 min in normal rats, the total volumes being 3.02±0.73 μL (0.05 mg/kg; n = 6), 3.91±0.50 μL (0.1 mg/kg; n = 6; P < 0.05 vs control), 5.74±0.99 μL (0.2 mg/kg; n = 6; P < 0.05 vs control) and 23.65±3.25 μL (0.4 mg/kg; n = 6; P < 0.05 vs control). |
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References: [1]. Nile C, Falleni M, et al. Repurposing Pilocarpine Hydrochloride for Treatment of Candida albicans Infections. mSphere. 2019;4(1):e00689-18. Published 2019 Jan 23. [2]. Asari T, Komatsu Y, et al. Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats. Clin Exp Pharmacol Physiol. 2001;28(7):545-550. |
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Pilocarpine HCl is a miotic drug that acts as a M3-type muscarinic acetylcholine receptor (M3 muscarinic receptor) agonist, causing ciliary muscle contraction that opens up the trabecular meshwork which allows aqueous humour drainage and a resultant reduction in IOP[1]. Pilocarpine HCl is a hydrophilic drug used for managing IOP in the treatment of glaucoma[2]
Pilocarpine HCl encapsulated by liposomes can keep their integrity and physicochemical properties for at least 15 month[3].Pilocarpine HCl specifically inhibits Candida albicans biofilm formation and pathogenicity through interaction with a muscarinic-like receptor[4]. Pilocarpine HCl has acaricidal activity on larvae (LC50=2.6 mg?mL-1) and engorged females (LC50=11.8 mg?mL-1) of R.(B.) microplus[5]
Pilocarpine HCl have apparent functional protective effects in xerostomia models: an increase in the volume of saliva without any change in salivary content. This prophylactic action of pilocarpine HCl may provide a new clinical treatment for irradiation xerostomia in patients with head and neck cancer[6]. Oral activity responses to pilocarpine HCl are enhanced in neonatal 6-OHDA-treated rats[7]
References:
[1]. Jain N, Verma A, et al. Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits. Drug Deliv. 2020;27(1):888-899.
[2]. Owodeha-Ashaka K, Ilomuanya MO, et al. Evaluation of sonication on stability-indicating properties of optimized pilocarpine hydrochloride-loaded niosomes in ocular drug delivery [published correction appears in Prog Biomater. 2021 Oct 5;:]. Prog Biomater. 2021;10(3):207-220.
[3]. Monem AS, Ali FM, et al. Prolonged effect of liposomes encapsulating pilocarpine HCl in normal and glaucomatous rabbits. Int J Pharm. 2000;198(1):29-38.
[4]. Nile C, Falleni M, et al. Repurposing Pilocarpine Hydrochloride for Treatment of Candida albicans Infections. mSphere. 2019;4(1):e00689-18. Published 2019 Jan 23.
[5]. Castro KN, Lima DF, et al. In vitro effects of Pilocarpus microphyllus extracts and pilocarpine hydrochloride on Rhipicephalus (Boophilus) microplus. Rev Bras Parasitol Vet. 2016;25(2):248-253.
[6]. Asari T, Komatsu Y, et al. Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats. Clin Exp Pharmacol Physiol. 2001;28(7):545-550.
[7]. Kostrzewa RM, Neely D. Enhanced pilocarpine-induced oral activity responses in neonatal 6-OHDA treated rats. Pharmacol Biochem Behav. 1993;45(3):737-740.
盐酸毛果芸香碱是一种缩瞳药，作为 M3 型毒蕈碱型乙酰胆碱受体（M3 毒蕈碱受体）激动剂，引起睫状肌收缩，打开小梁网，允许房水排出，从而降低眼压 [1]。盐酸毛果芸香碱是一种亲水性药物，在治疗青光眼时用于控制眼压[2]
脂质体包封的盐酸毛果芸香碱可保持其完整性和理化性质至少 15 个月[3]。盐酸毛果芸香碱通过与毒蕈碱样受体相互作用特异性抑制白色念珠菌生物膜形成和致病性[4]。盐酸毛果芸香碱对幼虫(LC50=2.6 mg•mL-1)和饱食雌虫(LC50=11.8 mg•mL)具有杀螨活性-1) 的 R.(B.) microplus[5]
盐酸毛果芸香碱对口干症模型具有明显的功能性保护作用:唾液量增加而唾液含量没有任何变化。盐酸毛果芸香碱的这一预防作用可能为头颈癌患者的辐照口干症提供一种新的临床治疗方法[6]。新生 6-OHDA 处理的大鼠对盐酸毛果芸香碱的口腔活动反应增强[7]
| Cas No. | 54-71-7 | SDF | |
| 别名 | 盐酸毛果芸香碱 | ||
| 化学名 | (3S,4R)-3-ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydrofuran-2(3H)-one hydrochloride | ||
| Canonical SMILES | Cl[H].O=C1OC([H])([H])[C@@](C([H])([H])C2=C([H])N=C([H])N2C([H])([H])[H])([H])[C@]1([H])C([H])([H])C([H])([H])[H] | ||
| 分子式 | C11H16N2O2.HCl | 分子量 | 244.72 |
| 溶解度 | 50 mg/mL in DMSO(Need ultrasonic); 20mg/mL in Water | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0863 mL | 20.4315 mL | 40.863 mL |
| 5 mM | 0.8173 mL | 4.0863 mL | 8.1726 mL |
| 10 mM | 0.4086 mL | 2.0432 mL | 4.0863 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Solid-state epimerisation and disproportionation of pilocarpine HCl: Why we need a 5-stage approach to validate melting point measurements for heat-sensitive drugs
Int J Pharm.2020 Jan 25;574:118869.PMID:31765787DOI: 10.1016/j.ijpharm.2019.118869.
Melting points for new drugs are reported in regulatory documents, e.g. investigational brochures, and frequently in published research; however, the authors do not typically consider that heat-induced degradation can affect the melting point measurement. Applying a single heating rate is not adequate, and thus many melting points in the literature and regulatory documentation are not valid. Our aim was to validate a five-stage approach for the melting point measurement of heat-sensitive drugs. These stages are; (1) observe melting; (2) record mass loss; (3) measure melting points at different heating rates; (4) characterise degradation and (5) test for potential isomerisation. Applying this approach to pilocarpine HCl illustrated the sensitivity of a melting point to thermal degradation. Due to salt disproportionation & loss of HCl gas, pilocarpine's melting point decreased by 14 °C when the heating rate was lowered from 20 to 1 °C/min. Epimerization occurred before melting was reached. Increasing the heating rate diminished disproportionation; however, this did not remove epimerization. Thus, the melting point of pilocarpine HCl of 205.5 ± 0.4 °C measured at 20 °C/min represents the melt of a racemic mixture containing inactive isopilocarpine. Heating above the melting point accelerated degradation, a rate of 5 °C/min recovered just 38 ± 1% of pilocarpine. Such data predicted a shelf-life of 6.6 years. Pilocarpine successfully validated the multistage approach by providing new knowledge concerning its thermal stability. Our 5-stage approach must be applied to all new drugs especially if their formulation requires heat. For example, thermal stability is an infrequently considered pre-requisite in the emerging field of 3D printing.
Oral pilocarpine HCl stimulates labial (minor) salivary gland flow in patients with Sjögren's syndrome
Oral Dis.1997 Jun;3(2):93-8.PMID:9467349DOI: 10.1111/j.1601-0825.1997.tb00019.x.
Pilocarpine HCl has been shown to stimulate parotid and submandibular gland salivary flow. The purpose of this study was to determine whether this cholinergic-muscarinic drug also stimulates labial (minor) salivary gland (LSG) flow and to relate that with whole unstimulated salivary (WUS) flow rates. Subjects diagnosed with primary Sjögren's syndrome (SS-1; n = 9) or secondary Sjögren's syndrome (SS-2; n = 9) were enrolled in this study after meeting stringent enrollment criteria. An age-gender matched control group was also enrolled. The labial saliva was collected in a standardized manner on Periopaper for 5 min and the volume was analysed by the Periotron. Whole unstimulated salivary samples were collected for 5 min by the method of Mandel and Wotman (1976). Each subject was dosed with pilocarpine HCl (5 mg; tablets; p.o.). After 60 min the LSG flow as well as the WUS flow was determined again as previously. The results indicated a significant (> 180%) increase in both labial salivary gland flow as well as whole salivary flow in the SS-1 and SS-2 subjects (mean +/- s.e.m.): [SS-1: WUS = 0.1080 +/- 0.03 vs 0.2242 +/- 0.03 ml per 5 min; LSG = 93.1 +/- 22.2 vs 167.8 +/- 15.9 microliters/5 min; P < 0.001; SS-2: WUS = 0.1384 +/- 0.02 vs 0.2775 +/- 0.09 ml per 5 min; LSG = 97.7 +/- 20.2 vs 182.8 +/- 17.9 microliters per 5 min; P < 0.001]. These results indicate a significant increase in labial salivary gland flow as well as whole salivary flow as stimulated by pilocarpine HCl in Sjögren's syndrome patients.
Prolonged effect of liposomes encapsulating pilocarpine HCl in normal and glaucomatous rabbits
Int J Pharm.2000 Mar 30;198(1):29-38.PMID:10722948DOI: 10.1016/s0378-5173(99)00348-8.
The possibility of using liposomes as an ophthalmic drug delivery carrier for the lipophilic drug, pilocarpine HCl, was investigated on the eyes of normal and glaucomatous pigmented rabbits. The intraocular pressure (IOP) of rabbits was measured, using a Shi∅tz tonometer, as a function of time after topical administration with free drug, neutral and negatively charged multilamellar vesicles (MLVs) encapsulating pilocarpine HCl. The results showed that administration with neutral MLVs displayed the most prolonged effect with respect to negatively charged MLVs and free drug. The efficiency of MLVs encapsulating pilocarpine HCl, measured using spectrophotometric technique, was found to be 96% in our modified preparations. The storage stability of MLVs encapsulating pilocarpine HCl was investigated by measuring phase transition and size distribution using light scattering technique. The results show that liposomes encapsulating pilocarpine HCl have kept their integrity and physicochemical properties for at least 15 months, which makes them suitable for commercial use.
A comparison of the efficacy of various metipranolol-pilocarpine combinations in patients with ocular hypertension and primary open-angle glaucoma
J Ocul Pharmacol.1994 Summer;10(2):411-20.PMID:7916025DOI: 10.1089/jop.1994.10.411.
We compared the ocular hypotensive effects of four fixed-dose metipranolol-pilocarpine combinations in nineteen ocular hypertensive subjects and glaucoma patients. Each patient was tested with all of the study medications: vehicle alone, 0.1% metipranolol HCl + 2% pilocarpine HCl, 0.1% metipranolol HCl + 4% pilocarpine HCl, 0.3% metipranolol HCl + 2% pilocarpine HCl, and 0.3% metipranolol HCl + 4% pilocarpine HCl, in a single dose, randomized, double-masked, cross-over placebo-controlled trial. In addition, another eight age and baseline intraocular pressure (IOP)-matched subjects received 0.1% or 0.3% metipranolol HCl, while a similar group of 14 volunteers received 2% or 4% pilocarpine HCl. A two week washout period was instituted between the various groups of treatments. All four metipranolol-pilocarpine combinations were more effective than placebo or either medication alone in reducing the average IOP for up to 8 hours (p < 0.05 for each treatment group). Metipranolol HCl 0.3%, regardless of the pilocarpine concentration, demonstrated the most significant IOP lowering effect, reducing the IOP by 4.9 mm Hg or about 20% from baseline. However, 0.1% metipranolol HCl in combination with 4% pilocarpine HCl was found almost as effective with a 18.5% reduction in IOP from baseline, but a shorter duration of action. In conclusion, all metipranolol-pilocarpine combinations were more efficacious than either medication alone in a single-dose trial. Additional multiple-dose studies are needed to determine the long-term effectiveness and tolerance of combining 0.3% metipranolol HCl with either 2% or 4% pilocarpine HCl.
Preparation and characterization of polymeric and lipid nanoparticles of pilocarpine HCl for ocular application
Pharm Dev Technol.2013 May-Jun;18(3):701-9.PMID:22813238DOI: 10.3109/10837450.2012.705298.
Pilocarpine is used topically in the treatment of glaucoma. Various studies were performed to improve the bioavailability and prolong the residence time of drugs in ocular drug delivery. Drug loaded polymeric and lipid nanoparticles offer several favourable biological properties, such as biodegradability, nontoxicity, biocompatibility and mucoadhesiveness. Therefore, preparing positively-charged pilocarpine HCl-loaded polymeric and lipid nanoparticles was the purpose of this study. Nanoparticles were prepared by quasi-emulsion solvent evaporation technique. The non-biodegradable positively-charged polymer Eudragit(®) RS 100 and semi-solid lipid excipient Gelucire(®) 44/14 were used as a vehicle, the cationic lipid octadecylamine was used as a cationic agent. The formulations were evaluated in terms of particle size, size distribution, zeta potential measurement, thermal behavior (Differential Scanning Calorimetry DSC), entrapment efficacy and pH. Characterizations of nanoparticles were analyzed during the storage period of 6 months for stability tests. Polymeric and lipid nanoparticles could be prepared successfully promising their use for ophthalmic delivery.