科研方向：

1. 神经肽生理与药理

神经肽是机体内一类重要的神经递质/调质，本实验室利用不同效能和效价的肽类分子作为药理学工具，来探讨内源性神经肽及其受体系统的生理学和药理学功能及其作用机制。

2. 神经肽与疼痛/痒觉

神经肽在躯体感觉的传导和调节中扮演重要的角色，本课题组利用分子、细胞和行为等多种研究手段来探讨神经肽在痛觉和痒觉调节过程中的作用及其具体机制。

3. 神经肽类新药创制

在神经肽结构和功能的研究基础上，以具有医药应用前景的内源性神经肽为化学模板而构建一系列的全新的肽类分子，以期筛选并获得具有高效、低副作用、镇痛（或止痒）等多肽药物的先导化合物用于多肽新药研发。

Research  Interests：

1. Neuropeptide Physiology & Pharmacology

2. Neuropeptide & Pain/Itch

3. Development of novel neuropeptide drugs

代表性科研项目：

1.主持国家自然科学基金委面上项目（82473760），G蛋白偏向性的Kappa-/Mu-阿片受体双靶点肽类激动剂的化学构建及其镇痛活性研究，2025.1-2028.12

2.甘肃省科技重大专项项目（23ZDNA007）的课题负责人，动物疫病防控关键技术创新与重大产品研发-兽用新型防控产品研究（课题3），2023.5-2024.3

3.主持甘肃省基础研究创新群体项目（20JR5RA310），原创性神经肽类镇痛新药创制，2020.11-2023.10；

4.主持国家自然科学基金委面上项目（81973159），具有口服镇痛活性的阿片/神经肽FF受体多靶点环肽分子的设计和合成及其药理学鉴定，2020.1-2023.12

5.主持国家自然科学基金委面上项目（81673282），以神经肽为模板的大麻/神经肽FF受体多靶点分子的化学构建和无耐受镇痛作用研究，2017.1-2020.12

6.主持best365官方网站登录入口“中央高校基本科研业务费专项资金”杰出人才项目（lzujbky-2018-ot02），神经肽类新药研究，2018.1-2019.12

7.主持国家自然科学基金委面上项目（81273355），阿片/神经肽FF 受体的双功能肽类配体的化学构建及其无耐受镇痛特性的研究，2013.1-2016.12

8.主持甘肃省青年科技研究基金项目一项（1208RJYA001），以神经肽FF和阿片肽为模板的嵌合肽构建及其在镇痛用新药研究中应用，2013.1-2015.12

9.主持国家自然科学基金委青年基金项目（20902041），环境敏感性荧光氨基酸在新型NPFF1和NPFF2高选择性配体的设计和合成中的应用，2010.1-2012.12

10.主持教育部高校博士点专项科研基金（新教师基金课题）（200807301028）, RFa肽家族的新成员—促摄食肽26RFa的构效关系及其生物活性的研究，2009.1-2011.12

发表论文（按年度）：

Publications

ORCID iD: https://orcid.org/0000-0003-0381-6796

已发表的主要论著目录已发表的主要论著目录：

1.Chen D, Zhang M, Zhang Q, Wu S, Yu B, Zhang X, Hu X, Zhang S, Yang Z, Kuang J, Xu B*, Fang Q^*. The blockade of neuropeptide FF receptor 1 and 2 differentially contributed to the modulating effects on fentanyl-induced analgesia and hyperalgesia in mice. European Journal of Pharmacology. 2024; 969: 176457.

2.Zhang QQ, Xu B, Chen D, Wu SY, Hu XR, Zhang XD, Yu BW, Zhang SC, Yang ZY, Zhang MN*, Fang Q^*. Structure-Activity Relationships of a Novel Cyclic Hexapeptide that Exhibits Multifunctional Opioid Agonism and Produces Potent Antinociceptive Activity, Journal of Medicinal Chemistry. 2024; 67(1): 272-288.

3.Zhang MN, Xu B, Li N, Zhang R, Zhang QQ, Chen D, Wu SY, Yu BW, Zhang XD, Hu XR, Zhang SC, Jing YH, Yang ZY, Jiang JH*, Fang Q^*. The All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting, Brain Permeant Analgesics with Diminished Side Effects, Journal of Medicinal Chemistry. 2023; 66(24):17138-17154.

4.Xu B, Zhang QQ, Chen D, Zhang MN, Zhang R, Zhao WD, Qiu Y, Xu KT, Xiao J, Niu JD, Shi YH, Li N, Fang Q^*. OCP002, a mixed agonist of opioid and cannabinoid receptors, produces potent antinociception with minimized side effects. Anesthesia & Analgesia. 2023; 136(2): 373-386.

5.Xu B, Zhang R, Zhang MN, Chen D, Zhang QQ, Zhang N, Shi YH, Hu XR, Li N, Fang Q^*. Nav1.7 Channel Blocker [Ala5, Phe6, Leu26, Arg28]GpTx-1 Attenuates CFA-induced Inflammatory Hypersensitivity in Rats via Endogenous Enkephalin Mechanism. The Journal of Pain. 2023; 24(5): 840-859.

6.Li N, Xiao J, Niu JD, Zhang MN, Shi YH, Yu BW, Zhang QQ, Chen D, Zhang N, Fang Q^*. Synergistic interaction between DAMGO-NH2 and NOP01 in peripherally acting antinociception in two mouse models of formalin pain Peptides. 2023; 161: 170943.

7.Zhang MN, Xu B, Li N, Zhang R, Zhang QQ, Chen D, Rizvi SFA, Xu KT, Shi YH, Yu BW, Fang Q^*. OFP011 Cyclic Peptide as a Multifunctional Agonist for Opioid/Neuropeptide FF Receptors with Improved Blood-Brain Barrier Penetration. ACS Chemical Neuroscience. 2022, 13(21): 3078-3092.

8.Zhang QQ, Li TT, Niu JD, Xiao J, Zhang MN, Zhang R, Chen D, Shi YH, Zhang XD, Hu XR, Yu BW, Feng J*, Fang Q^*. Inhibitory effects of antibiotic-induced gut microbiota depletion on acute itch behavior in mice. Brain Research Bulletin. 2022; 190: 50-61.

9.Zhang R, Xu B, Zhang N, Niu JD, Zhang MN, Zhang QQ, Chen D, Shi YH, Chen DN, Liu KD, Zhang XD, Li N, Fang Q^*. Spinal microglia-derived TNF promotes the astrocytic JNK/CXCL1 pathway activation in a mouse model of burn pain. Brain, Behavior, and Immunity. 2022, 102 (2022) 23-39.

10.Xiao J, Niu JD, Xu B, Zhang R, Zhang MN, Zhang N, Xu KT, Zhang QQ, Chen D, Shi YH, Fang Q^*, Li N^*. NOP01, a NOP receptor agonist, produced potent and peripherally restricted antinociception in a formalin-induced mouse orofacial pain model. Neuropeptides. 2022, 91: 102212.

11.Zhang MN, Xu B, Li N, Zhang R, Zhang QQ, Shi XR, Xu KT, Xiao J, Chen D, Niu JD, Shi YH, Fang Q^*. Development of Multifunctional and Orally Active Cyclic Peptide Agonists of Opioid/Neuropeptide FF Receptors that Produce Potent, Long-lasting Peripherally Restricted Antinociception with Diminished Side Effects. Journal of Medicinal Chemistry. 2021; 64(18): 13394-13409. 

12.Zhang T, Zhang R, Xu B, Zhang MN, Zhang QQ, Li N, Qiu Y, Chen D, Xu KT, Xiao J, Zhang N^*, Fang Q^*. Spinal endomorphins attenuate burn-injury pain in male mice by inhibiting p38 MAPK signaling pathway through the mu-opioid receptor. European Journal of Pharmacology. 2021; 903: 174139. 

13.Zhang MN, Xu B, Li N, Liu H, Shi XR, Zhang QQ, Shi YB, Xu KT, Xiao J, Chen D, Zhu HW, Sun YL, Zhang T, Zhang R, Fang Q^*. Synthesis and biological characterization of cyclic disulfide-containing peptide analogs of the multifunctional opioid/neuropeptide FF receptors agonist that produced long-lasting and nontolerant antinociception. Journal of Medicinal Chemistry 2020; 63(24): 15709-15725. (封面文章)

14.Xu B, Xiao J, Xu KT, Zhang QQ, Chen D, Zhang R, Zhang MN, Zhu HW, Niu JD, Zheng T, Li N, Zhang XY, Fang Q^*. VF-13, a chimeric peptide of VD-hemopressin(α) and neuropeptide VF, produces potent antinociception with reduced cannabinoid-related side effects. Neuropharmacology 2020; 175: 108178. 

15.Zhang R, Xu B, Zhang QQ, Chen D, Zhang MN, Zhao GH, Xu KT, Xiao J, Zhu HW, Niu JD, Li N*, Fang Q*. Spinal administration of the multi-functional opioid/neuropeptide FF agonist BN-9 produced potent antinociception without development of tolerance and opioid-induced hyperalgesia. European Journal of Pharmacology. 2020; 880: 173169.

16.Xu B, Guo YY, Zhang MN, Zhang R, Chen D, Zhang QQ, Xiao J, Xu KT, Li N, Qiu Y, Zhu HW, Niu JD, Zhang XY^*, Fang Q^*. Central and peripheral modulation of gastrointestinal transit in mice by DN-9, a multifunctional opioid/NPFF receptor agonist. Neurogastroenterology & Motility. 2020; 32(8): e13848. 

17.Wang ZL, Xu B, Jiang CY, Zhang T, Zhang MN, Li N, Zhang QQ, Xu KT, Chen D, Xiao J, Fang Q*. Spinal DN-9, a peptidic multifunctional opioid/neuropeptide FF agonist produced potent nontolerance forming analgesia with limited side effects. Journal of Pain. 2020; 21(3-4): 477-493.

18.Xu B, Zhang MN, Shi XR, Zhang R, Chen D, Chen Y, Wang ZL, Qiu Y, Zhang T, Xu KT, Zhang XY, Liedtke W*, Wang R*, Fang Q*. The multifunctional peptide DN-9 produced peripherally acting antinociception in inflammatory and neuropathic pain via mu and kappa opioid receptors. British Journal of Pharmacology. 2020; 177: 93-109.

19.Zhang T, Han Z, Shi X, Zhao W, Wang Z, Zhang R, Xu B, Zhang M, Zhang Q, Xiao J, Zhu H, Zheng T, Fang Q*. Discovery of two novel branched peptidomimetics containing endomorphin-2 and RF9 pharmacophores: Synthesis and neuropharmacological evaluation. Bioorganic & Medicinal Chemistry. 2019; 27: 630-643.

20.方泉，李宁，许彪，王锐^* 多靶点肽类镇痛药物的研究进展，药学进展；2019，43(10): 726-37

21.Zhang T¹, Zhang N¹, Zhang R, Zhao WD, Chen Y, Wang ZL, Xu B, Zhang MN, Shi XR, Zhang QQ, Guo YY, Xiao J, Chen D, Fang Q*. Preemptive intrathecal administration of endomorphins relieves inflammatory pain in male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines. Journal of Neuroinflammation. 2018; 15: 320. (¹: authors contributed equally to this work)

22.Zhang T, Zhao WD, Zhang MN, Xu B, Shi XR, Zhang QQ, Guo YY, Xiao J, Chen D, Zheng T, Fang Q*. Analgesic activities of the mixed opioid and NPFF receptors agonist DN-9 in a mouse model of formalin-induced orofacial inflammatory pain. Peptides. 2018; 110C: 30-39.

23.Chen C¹, Xu B¹, Shi XR, Zhang MN, Zhang QQ, Zhang T, Zhao WD, Zhang R, Wang ZL, Fang Q*. GpTx-1 and [Ala⁵, Phe⁶, Leu²⁶, Arg²⁸]GpTx-1, two peptide NaV1.7 inhibitors: analgesic and tolerance properties at the spinal level. British Journal of Pharmacology. 2018; 175(20): 3911-3927. (¹: authors contributed equally to this work)

24.Li N, Han ZL, Xu B, Zhang MN, Zhang T, Shi XR, Zhao WD, Guo YY, Zhang QQ, Fang Q*. Systemic administration of the bifunctional opioid/neuropeptide FF receptors agonist BN-9 produced peripheral antinociception in preclinical mouse models of pain. European Journal of Pharmacology. 2018; 837: 53-63. 

25.Wang P, Zheng T, Zhang MN, Xu B, Zhang R, Zhang T, Zhao WD, Shi XR, Zhang QQ, Fang Q*. Antinociceptive effects of the endogenous cannabinoid peptide agonist VD-hemopressin(β) in mice. Brain Research Bulletin. 2018; 139:48-55.

26.Zheng T¹, Zhang R¹, Zhang T, Zhang MN, Xu B, Song JJ, Li N, Tang HH, Wang P, Wang R*, Fang Q*. CB1 cannabinoid receptor agonist mouse VD-hemopressin(α) produced supraspinal analgesic activity in the preclinical models of pain. Brain Research. 2018; 1680: 155-164.

27.Zhang R, Xu B, Zhang MN, Zhang T, Wang ZL, Zhao G, Zhao GH, Li N, Fang Q*, Wang R^*. Peripheral and central sites of action for anti-allodynic activity induced by the bifunctional opioid/NPFF receptors agonist BN-9 in inflammatory pain model. European Journal of Pharmacology. 2017; 813:122-129.

28.Zheng T, Zhang T, Zhang R, Wang ZL, Han ZL, Li N, Li XH, Zhang MN, Xu B, Yang XL, Fang Q*, Wang R^*. Pharmacological characterization of rat VD-hemopressin(α), an α-hemoglobinderived peptide exhibiting cannabinoid agonist-like effects in mice. Neuropeptides 2017, 63: 83-90. 

29.Wang ZL, Pan JX, Song JJ, Tang HH, Yu HP, Li XH, Li N, Zhang T, Zhang R, Xu B, Zhang MN, Fang Q*, Wang R^*. Structure-based optimization of multifunctional agonists for opioid and neuropeptide FF receptors with potent non-tolerance forming analgesic activities. Journal of Medicinal Chemistry. 2016; 59(22):10198-10208.

30.Yu HP, Zhang N, Zhang T, Wang ZL, Li N, Tang HH, Zhang R, Zhang MN, Xu B, Fang Q^*, Wang R^*. Activation of NPFF2 receptor stimulates neurite outgrowth in Neuro 2A cells through activation of ERK signaling pathway. Peptides. 2016; 86: 24-32.

31.Li N¹, Han ZL¹, Wang ZL, Xing YH, Sun YL, Li XH, Song JJ, Zhang T, Zhang R, Zhang MN, Xu B, Fang Q*, Wang R^*. BN-9, a chimeric peptide with mixed opioid and NPFF receptors agonistic properties, produces nontolerance-forming antinociception in mice. British Journal of Pharmacology. 2016; 173(11): 1864-1880. (¹: authors contributed equally to this work)

32.Wang ZL¹, Li N¹, Wang P, Tang HH, Han ZL, Song JJ, Li XH, Yu HP, Zhang T, Zhang R, Xu B, Zhang MN, Fang Q*, Wang R^*. Pharmacological characterization of EN-9, a novel chimeric peptide of endomorphin-2 and neuropeptide FF that produces potent antinociceptive activity and limited tolerance. Neuropharmacology. 2016; 108: 364-372. (¹: authors contributed equally to this work)

33.Chen Y, Fang Q, Wang Z, Zhang JY, MacLeod AS, Hall RP, Liedtke WB*. Transient receptor potential vanilloid 4 ion channel functions as a pruriceptor in epidermal keratinocytes to evoke histaminergic itch. Journal of Biological Chemistry. 2016; 291:10252-10262.

34.Li XH¹, Lin ML¹, Wang ZL, Wang P, Tang HH, Lin YY, Li N, Fang Q*, Wang R*. Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice. Neurogastroenterology & Motility. 2016; 28: 891-899. (¹: authors contributed equally to this work)

35.Zhang XY, Chen Y, Li Lin, Qiao H, Wang R, Ni JM *, You JQ, Ma KK, Fan CC, Fang Q. Development and validation of a reversed phase liquid chromatographic method with fluorescence detection for the pharmacokinetic study of a new chimeric peptide. Analytical Methods. 2016; 8(12): 2620-2627.

36.Pan JX¹, Wang ZL¹, Li N, Zhang N, Wang P, Tang HH, Zhang T, Yu HP, Zhang R, Zheng T, Fang Q*, Wang R*. Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(α) in naive and cannabinoid-tolerant mice. European Journal of Pharmacology. 2015; 767(C):119-125. (¹: authors contributed equally to this work)

37.Han ZL, Wang ZL, Li XH, Li N, Pan JX, Zheng T, Fang Q*, Wang R*. Neuropeptide VF enhances cannabinoid agonist WIN55,212-2-induced antinociception in mice. Anesthesia & Analgesia. 2015; 121(5):1360-1368. 

38.Chen Y, Kanju P ², Fang Q ², Lee SH, Parekh PK, Lee W, Moore C, Brenner D, Gereau RW 4th, Wang F, Liedtke W^*. TRPV4 is necessary for trigeminal irritant pain and functions as a cellular formalin receptor. Pain. 2014; 155(12):2662-72. (²: authors contributed equally to this work)

39.Han ZL¹, Fang Q¹, Wang ZL, Li XH, Li N, Chang XM, Pan JX, Tang HZ, Wang R^*. Antinociceptive effects of central administration of the endogenous CB1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], a N-terminally extended hemopressin peptide. Journal of Pharmacology and Experimental Therapeutics. 2014; 348(2): 316-323. (¹: authors contributed equally to this work)

40.Wang ZL¹, Fang Q ¹, Han ZL, Pan JX, Li XH, Li N, Tang HH, Wang P, Zheng T, Chang XM, Wang R*. Opposite Effects of Neuropeptide FF on Central Antinociception Induced by Endomorphin-1 and Endomorphin-2 in Mice. PLoS One. 2014; 9(8): e103773. (¹: authors contributed equally to this work)

41.Pan JX, Wang ZL, Li N, Han ZL, Li XH, Tang HH, Wang P, Zheng T, Fang Q*, Wang R*. Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(α) and WIN55,212-2 at the supraspinal level in mice. Neuroscience Letters. 2014; 578: 187-191. 

42.Li XH¹, Li N¹, Wang ZL, Pan JX, Han ZL, Chang XM, Tang HH, Wang P, Wang R*, Fang Q*. The hypotensive effect of intrathecally injected (m)VD-hemopressin(α) in urethane-anesthetized rats. Peptides. 2014; 56(C): 45-51.

43.Han ZL, Wang ZL, Tang HZ, Li N, Fang Q*, Li XH, Yang XL, Zhang XY, Wang R^*. Neuropeptide FF attenuates the acquisition and the expression of conditioned place aversion to endomorphin-2 in mice. Behavioural Brain Research 2013; 248(1):51-56. 

44.Sun YL, Zhang XY, He N, Sun T, Zhuang Y, Fang Q*, Wang KR, Wang R*. Neuropeptide FF activated ERK and NF kappa B signal pathways in differentiated SH-SY5Y cells. Peptides 2012; 38(1):110-117. 

45.Li N ¹, Han ZL ¹, Fang Q*, Wang ZL, Tang HZ, Ren H, Wang R^*. Neuropeptide FF and related peptides attenuates warm-, but not cold-water swim stress-induced analgesia in mice. Behavioural Brain Research 2012; 233(2): 428-433. 

46.Fang Q, Han ZL, Li N, Wang ZL, He N, Wang R^*. Effects of neuropeptide FF system on CB₁ and CB₂ receptors mediated antinociception in mice. Neuropharmacology 2012; 62 (2): 855-864. 

47.Fang Q ¹, Jiang TN ¹, Li N, Han ZL, Wang R^*. Central administration of neuropeptide FF and related peptides attenuate systemic morphine analgesia in mice. Protein & Peptide Letters 2011; 18(4): 403-409. (¹: authors contributed equally to this work)

48.Fang Q ¹, Li N ¹, Jiang TN, Liu Q, Li YL, Wang R^*. Pressor and tachycardic responses to intrathecal administration of Neuropeptide FF in anesthetized rats. Peptides 2010; 31(4): 683-688. (¹: authors contributed equally to this work)

49.Fang Q ¹, Liu Q ¹, Li N, Jiang TN, Li YL, Yan X, Wang R^*. Cardiovascular effects of intravenous administered 26RFa, a novel RF-amide peptide ligand for GPR103, in anaesthetized rats. European Journal of Pharmacology 2009; 621(1-3): 61-66. (¹: authors contributed equally to this work)

50.Fang Q, Wang YQ, He F, Guo J, Guo J, Chen Q, Wang R^*. Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist. Regulatory Peptides 2008; 147(1-3): 45-51.

51.Fang Q, Zhang BZ, Wang R^*. Progress in the structure-activity relationship studies of neuropeptide FF. Progress in Chemistry 2007; 19: 1977-1985. (Review, in Chinese) 

52.Fang Q, He F, Wang YQ, Guo J, Zhang BZ, Chen Q, Wang R^*. Pharmacological effects of the dansylated neuropeptide FF analogues on body temperature and morphine analgesia. Neuropeptides 2007; 41(5): 339-347.

53.Fang Q, Guo J, He F, Peng YL, Chang M, Wang R^*. In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist. Peptides 2006; 27(9): 2207-2213.

54.Fang Q, Guo J, Peng YL, Chang M, He F, Chen Q, Wang R^*. In vitro and in vivo studies of dansylated compounds, the putative agonists and antagonists on neuropeptide FF receptors. Peptides 2006; 27(6): 1297-1304.

55.Fang Q, Guo J, Chang M, Chen LX, Chen Q, Wang R^*. Neuropeptide FF receptors exert contractile activity via inhibition of nitric oxide release in the mouse distal colon. Peptides 2005; 26(5): 791-797.

56.Chen LX , Fang Q, Chen Q, Guo J, Wang ZZ, Chen Y, Wang R. Study in vitro and in vivo of nociceptin/orphanin FQ(1-13)NH₂ analogues substituting N-Me-Gly for Gly² or Gly³. Peptides 2004; 25(8): 1349-1354.

57.Wang YQ, Guo J, Wang SB, Fang Q, He F, Wang R^*. Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice. Peptides 2008; 29(7): 1183-90.

58.Chen LX, Wang ZZ, Wu H, Fang Q, Chen Y, Guo J, Chen Y, Wang R^*. Effects of nociceptin (13-17) in pain modulation at supraspinal level in mice. Neuroscience Letters 2002; 331(2): 95-98.

59.Wang YQ, Wang SB, Ma JL, Guo J, Fang Q, Sun T, Zhuang Y, Wang R^*. Neuropeptide FF receptor antagonist, RF9, attenuates the fever induced by central injection of LPS in mice. Peptides. 2011; 32(4): 702-706.

60.Sun YL, Zhang XY, Sun T, He N, Li JY, Zhuang Y, Fang Q, Wang R. The anti-inflammatory potential of neuropeptide FF in vitro and in vivo. Peptides 2013; 47:124-132.

61.Sun YL, Sun T, Zhang XY, He N, Zhuang Y, Li JY, Fang Q, Wang KR, Wang R^*. NPFF2 receptor is involved in the modulatory effects of neuropeptide FF for macrophage cell line. Protein & Peptide Letters 2014; 21(5): 490-502.

参编书籍：

王 锐，方 泉，张 伟。参编中国科协组织2012-2013年的《生物化学与分子生物学学科发展报告》的“多肽学科发展报告”部分——“多肽科学研究进展”，中国科学技术出版社。

代表性专利成果：

1.王 锐，方 泉，李 宁，韩政岚；“基于内吗啡肽2和神经肽FF的嵌合肽及其合成和应用”， 国家发明专利，授权号：ZL201110097843.4，申请日期：2011年4月19日；公 开 (公告) 号：  CN102206285A，公开(公告)日： 2011.10.05。授权日期：2013年2月13日

2.王 锐，方 泉，韩政岚，王子龙，李宁；“基于阿片肽Biphalin和神经肽FF的嵌合肽及其合成和应用”，国家发明专利，授权专利号：ZL201210098832.2，授权日期：2014年5月21日。已申请国际专利，PCT/CN2013/070611

3.王 锐，方 泉，韩政岚，王子龙，李宁，李旭辉；“内源性大麻肽类激动剂(m)VD-Hpα在制备镇痛药物中的应用”，国家发明专利，授权专利号：ZL201310087565.3，授权日期：2015年4月22日。

4.王 锐，方 泉，李 宁，韩政岚，王子龙；“基于内吗啡肽2和NPFF受体拮抗剂RF9的分叉型杂交肽及其合成方法和应用”，国家发明专利，专利号： ZL201510123629.X，授权日期：2017年11月28日

5.王 锐，方 泉，王 沛，张 婷，王子龙，李宁；“基于内吗啡肽2或Biphalin的棕榈酰化修饰的阿片肽类似物及其合成和应用”， 国家发明专利，授权专利号： ZL201510619850.4，授权日期：2018年5月1日

6.王 锐，方泉，王子龙；“一类阿片和神经肽FF受体的多靶点肽类分子及其制备和应用”，国家发明专利，授权专利号： ZL201610252648.7，授权日期：2019年5月24日

7.方 泉，张梦娜，王 锐，许 彪，石学睿；“一类阿片和神经肽FF受体多靶点肽类分子BN-9的二硫键环化类似物及其制备方法和应用”，国家发明专利，授权专利号：ZL201810932993.4，授权日期：2020年7月31日

8.方 泉，张梦娜，王 锐，许 彪，石学睿；“一类阿片和神经肽FF受体多靶点分子BN-9的类似物及其制备方法与应用”，国家发明专利，授权专利号：ZL201810950987.1，授权日期：2020年5月8日

9.方 泉，许 彪，张梦娜，张 润，李宁；“一种基于大麻肽(r)VD-Hpα和神经肽FF的嵌合肽及其制备方法与应用”，国家发明专利，授权专利号：ZL201911323745.0，授权日期：2021年7月27日

10.方 泉，许 彪，张梦娜，张 润，李宁；“一类基于阿片肽和大麻肽的双功能肽及其制备方法与应用”，国家发明专利，授权专利号：ZL202110211993.7，授权日期：2023年8月4日

11.Rui Wang, Quan Fang, Zilong Wang, Biao Xu.; MULTI-TARGET PEPTIDE MOLECULES OF OPIOID AND NEUROPEPTIDE FF RECEPTOR, PREPARATION FOR MOLECULES, AND APPLICATIONS THEREOF；专利号：US 11,167,006 B2；授权日期： 2021.11.9