CN109293564B - 1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物及其制备方法和应用 - Google Patents
1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物及其制备方法和应用 Download PDFInfo
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- CN109293564B CN109293564B CN201811487169.9A CN201811487169A CN109293564B CN 109293564 B CN109293564 B CN 109293564B CN 201811487169 A CN201811487169 A CN 201811487169A CN 109293564 B CN109293564 B CN 109293564B
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
-
- A—HUMAN NECESSITIES
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Abstract
本发明涉及医药和食品领域,具体涉及一种1‑脱氧野尻霉素‑羟基肉桂酸甲酯杂合体衍生物及其制备方法和应用。1‑脱氧野尻霉素‑羟基肉桂酸甲酯杂合体衍生物具有式(I)所示结构,经体外试验证明,该类化合物为强效α‑葡萄糖苷酶抑制剂,对α‑葡萄糖苷酶的抑制活性显著高于目前最常用的餐后血糖控制剂‑阿卡波糖。由于此类化合物能强效抑制α‑葡萄糖苷酶等糖类消化酶的活性,能够有效地降低餐后血糖,因此在降糖药物和辅助降糖食品中具有非常好的应用前景。
Description
技术领域
本发明涉及医药和食品领域,具体涉及1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物及其制备方法和应用。
背景技术
高血糖是导致糖尿病并发症的重要原因,控制血糖水平对于高血糖患者是非常重要的。服用α-葡萄糖苷酶和淀粉酶等糖类消化酶抑制剂是控制餐后血糖和治疗Ⅱ型糖尿病的首选方法之一,因此研发高活性糖类消化酶抑制剂具有十分重要的意义。已报道的糖类消化酶抑制剂主要是通过天然产物筛选来发现的,从自然资源特别是具有降糖活性作用的天然动植物和微生物资源中发掘α-葡萄糖苷酶抑制剂,是近几十年来食品和医药研究者开发抑制餐后高血糖新型化合物和功能食品最为常用的方法和手段。目前,国内市场上常见的α-葡萄糖苷酶抑制剂主要有阿卡波糖(Acarbose)、伏格列波糖(Voglibose)和米格列醇(Miglitol),均为低聚糖或单糖结构类似物。阿卡波糖是一种生物合成的假性四糖,能竞争性地抑制小肠上皮刷状缘上的葡萄糖淀粉酶、麦芽糖酶、蔗糖酶及α-淀粉酶,延缓淀粉、蔗糖等的消化吸收,从而达到抑制餐后高血糖的效果。伏格列波糖是一种氨基糖类似物,主要抑制双糖水解酶,如蔗糖酶、麦芽糖酶和异麦芽糖酶,而对淀粉酶的抑制作用较小。米格列醇的抑制作用比阿卡波糖及伏格列波糖更为广泛,对麦芽糖酶、异麦芽糖酶、葡萄糖淀粉酶、蔗糖酶、α-淀粉酶、海藻糖酶及乳糖酶均有抑制效果。
阿卡波糖、伏格列波糖和米格列醇是目前最常见的三种α-葡萄糖苷酶抑制剂,为低聚糖或单糖结构类似物,是竞争性的抑制剂,但这三种抑制剂均可能引起胃肠胀气、腹泻、腹痛等胃肠道反应,伏格列波糖相对较轻;偶有低血糖出现;服用阿卡波糖及伏格列波糖后偶尔会出现转氨酶升高的现象,而米格列醇排泄快,对肝脏无损害。因此,高效、低副作用的新型糖类消化酶抑制剂的研发成为了行业关注的焦点。1-脱氧野尻霉素(1-DNJ)是其中当前研究较多的一种亚氨基糖类,其具有与葡萄糖类似的化学结构,与α-葡萄糖苷酶的亲和力大于二糖,可阻碍二糖的分解,为强效的竞争性α-葡萄糖苷酶抑制剂,但该物质在体内吸收速度快,很快地被代谢,因此体内抑制餐后血糖升高的效果一般。基于此,研究开发1-脱氧野尻霉素的结构衍生物来发现新的降糖活性成分非常必要。
发明内容
本发明的目的在于提供一系列结构新颖的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物,本发明还提供该衍生物的制备方法,其是以1-脱氧野尻霉素和羟基肉桂酸甲酯为主要原料,通过化学合成制备得到。本发明提供的上述衍生物,经体外试验证明,该类化合物为强效α-葡萄糖苷酶抑制剂,其中DMC-6的活性显著高于目前最常用的餐后血糖控制剂-阿卡波糖,其抑制常数Ki仅为阿卡波糖的1/2。由于此类化合物能强效抑制α-葡萄糖苷酶等糖类消化酶的活性,能够有效地降低餐后血糖,因此在降糖药物和辅助降糖食品中具有非常好的应用前景。
本发明的上述目的是采用以下技术方案来实现:
本发明提供一种具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物及其药学上可接受的盐:
其中,M表示C1-C30的直链或者支链的烷基;
R1、R2、R3、R4和R5各自独立地表示氢、卤素原子、羟基、羧基、氨基、苯基、C1-C5的直链或支链烷基或C1-C5的直链或支链的取代烷基;且R1可以在苯环任意可能的位置。
需要说明的是,上述的取代烷基上的取代基例如可以是卤素原子、羟基、羧基、氨基和苯基等;M表示C1-C30的直链或者支链的烷基,非限制性实施例包括,甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、正壬基…,及其各种支链异构体等。
本发明优选方案,所述M为C1-C30的直链烷基;所述R1为氢。在本发明中,1-脱氧野尻霉素母核基团和羟基肉桂酸甲酯母核基团之间的连接桥的C原子个数,取值为1~30之间的整数,相对应的30个化合物的命名分别为DMC-1、DMC-2、DMC-3、……、DMC-30,以此类推。
进一步优选地,所述衍生物为
经体外活性试验证明,DMC-6的活性显著高于目前最常用的餐后血糖控制剂-阿卡波糖,其抑制常数Ki仅为阿卡波糖的1/2,并且上述化合物在体内可能具有更慢的代谢速度。
本发明还提供一种制备所述衍生物的方法,包括以下步骤:
(1)将式(II)化合物与式(III)化合物进行取代反应制备得到式(IV)化合物;
(2)式(IV)化合物与式(V)化合物进行取代反应制备得到式(I)化合物;
其中:
X表示卤族元素;
M表示C1-C30的直链或者支链的烷基;
R1、R2、R3、R4和R5各自独立地表示氢、卤素原子、羟基、羧基、氨基、苯基、C1-C5的直链或支链烷基或C1-C5的直链或支链的取代烷基;且R1可以在苯环任意可能的位置。
在式(V)化合物中,当R2、R3、R4和R5为氢时,式(V)化合物为1-脱氧野尻霉素(1-DNJ)。
需要说明的是,卤族元素非限制性实施例包括氟、氯、溴、碘;优选地,该卤族元素为溴。
本发明优选方案,步骤(1)所述反应的反应溶剂为丙酮,催化剂为碳酸盐,反应温度为45~90℃。
本发明优选方案,步骤(2)所述反应的溶剂为DMF,催化剂为碳酸盐,反应温度为60~100℃。
具体地,在上述反应中,所述碳酸盐可以是碳酸钾或碳酸钠。
本发明还提供含所述衍生物的药物组合物、保健品或食品,其含有至少一种式(I)所述化合物作为活性成分。
本发明的优选方案,其活性成分为DMC-6;在具体的实施方式中,药物组合物的剂型为固体制剂或液体制剂。进一步优选地,所述药物组合物为片剂、胶囊剂或冲剂。
在具体的实施方式中,所提供的药物组合物为片剂,其处方包括:活性成分DMC-6;辅料:微晶纤维素、环糊精、玉米淀粉、甜菊糖和硬脂酸镁。按活性成分计,片剂的规格为50mg/片。
在另一具体的实施方式中,所提供的药物为胶囊,其处方包括:活性成分DMC-6,辅料微晶纤维素和环糊精。按活性成分计,胶囊的规格为50mg/个。
在另一具体的实施方式中,所提供的药物组合物为冲剂,其处方包括:活性成分DMC-6,辅料β-环糊精、甜菊糖和乙醇。
在另一具体的实施方式中,所述食品是以淀粉为主要成分的原料加工而成的制品,例如以各种谷物为原料加工获得的米面制品,例如馒头、面条、蛋糕等等,本发明提供的具体实施例为馒头。
本发明还提供所述衍生物在制备降低餐后血糖或调控血糖的药物、保健品或食品中的应用。
本发明提供的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物的优点:本发明公开的一系列新颖的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物,是α-葡萄糖苷酶等糖类消化酶的强效抑制剂,以其中的一个、两个或多个衍生物作为主要活性成分制成药物或制剂可有效地降低餐后血糖或调控血糖,具有非常好的效果。经实验证明,这些化合物对α-葡萄糖苷酶的抑制活性显著高于目前最常用的餐后血糖控制剂-阿卡波糖,其中DMC-6的抑制常数Ki仅为阿卡波糖的1/2。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将对本发明实施例中的技术方案进行清楚、完整地描述。实施例中未注明具体条件者,按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者,均为可以通过市售购买获得的常规产品。本发明的己知的起始原料可以采用或按照本领域已知的方法来合成。
以下结合实施例对本发明的特征和性能作进一步的详细描述。
实施例1:1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物DMC-2的制备
(1)接入连接桥的羟基肉桂酸甲酯的中间体制备:
往250mL的圆底烧瓶里加入4g(22.44mmol)对羟基肉桂酸甲酯和8.4g(44.88mmol)1,2-二溴乙烷原料,再加入6g(44.88mmol)碳酸钾和100mL丙酮,于65℃的条件下搅拌进行反应,直至反应结束;反应结束后,将上述反应液倒入水中,以20mL乙酸乙酯进行萃取,重复萃取3次,合并有机相;以无水硫酸钠进行干燥,然后脱溶拌样,采用硅胶柱层析法进行分离,洗脱剂为石油醚/乙酸乙酯=20:1,制得接入了2个碳原子的连接桥的对羟基肉桂酸甲酯的中间体;1H NMR(500MHz,DMSO)δ7.68(d,J=8.7Hz,2H),7.63(d,J=16.0Hz,1H),7.01(d,J=8.7Hz,2H),6.51(d,J=16.0Hz,1H),4.42–4.33(m,2H),3.85–3.77(m,2H),3.71(s,3H).13C NMR(125MHz,DMSO)δ167.34,160.24,144.64,130.65,127.57,115.89,115.48,68.35,51.78,31.71.HRMS(ESI)m/z:calcd for C12H13BrO3[M+H]+ 284.0121,found284.0121。
(2)目标物DMC-2的制备:
往100mL的圆底烧瓶中加入1.44g(5mmol)上述中间体和0.815g(5mmol)1-DNJ原料,再加入1.38g(10mmol)碳酸钾和50mL DMF,在80℃条件下连续搅拌,直至反应结束;反应结束后,进行脱溶拌样,然后以硅胶柱层析分离,洗脱剂为二氯甲烷/甲醇=25:2,制得目标化合物DMC-2。1H NMR(500MHz,DMSO)δ7.66(d,J=6.5Hz,2H),7.61(dd,J=16.0,2.3Hz,1H),6.97(t,J=8.0Hz,2H),6.48(dd,J=16.0,3.4Hz,1H),4.71(d,J=17.4Hz,3H),4.28(s,1H),4.13(d,J=6.3Hz,2H),3.71(d,J=1.7Hz,3H),3.59(s,1H),3.22(s,1H),3.17(d,J=5.2Hz,1H),3.03(s,1H),2.95(s,2H),2.86(s,1H),2.18(d,J=10.6Hz,1H),2.09(s,2H).13C NMR(125MHz,DMSO)δ167.40,161.10,144.84,130.62,126.92,115.40,115.32,79.66,71.22,69.89,68.09,67.33,59.52,57.24,52.00,51.76.HRMS(ESI)m/z:calcd forC18H25NO7[M+Na]+ 389.1523,found 389.1526。
实施例2:1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物--DMC-6的制备
(1)接入连接桥的羟基肉桂酸甲酯的中间体制备:
往250mL的圆底烧瓶里加入4g(22.44mmol)对羟基肉桂酸甲酯和10.95g(44.88mmol)1,6-二溴己烷原料,再加入6g(44.88mmol)碳酸钾和100mL丙酮,于65℃的条件下搅拌进行反应,直至反应结束;反应结束后,将上述反应液倒入水中,以20mL乙酸乙酯进行萃取,重复萃取3次,合并有机相;以无水硫酸钠进行干燥,然后脱溶拌样,采用硅胶柱层析法进行分离,洗脱剂为石油醚/乙酸乙酯=20:1,制得接入了6个碳原子的连接桥的对羟基肉桂酸甲酯的中间体;1H NMR(500MHz,DMSO)δ7.66(d,J=8.4Hz,2H),7.61(d,J=16.0Hz,1H),6.97(d,J=8.4Hz,2H),6.48(d,J=16.0Hz,1H),4.02(t,J=6.3Hz,2H),3.71(s,3H),3.54(t,J=6.7Hz,2H),1.88–1.78(m,2H),1.77–1.65(m,2H),1.50–1.39(m,4H).13CNMR(125MHz,DMSO)δ167.39,161.06,144.81,130.61,126.95,115.46,115.29,68.02,51.75,35.55,32.64,28.87,27.74,25.09.HRMS(ESI)m/z:calcd for C16H21BrO3[M+H]+340.0747,found 340.0745。
(2)目标物DMC-6的制备:
往100mL的圆底烧瓶中加入1.7g(5mmol)上述中间体和0.815g(5mmol)1-DNJ原料,再加入1.38g(10mmol)碳酸钾和50mL DMF,在80℃条件下连续搅拌,直至反应结束;反应结束后,进行脱溶拌样,然后以硅胶柱层析分离,洗脱剂为二氯甲烷/甲醇=25:2,制得目标化合物DMC-6。1H NMR(500MHz,DMSO)δ7.65(d,J=8.6Hz,2H),7.61(d,J=16.0Hz,1H),6.97(d,J=8.6Hz,2H),6.47(d,J=16.0Hz,1H),4.99(s,4H),4.01(t,J=6.2Hz,2H),3.71(s,3H),3.66(s,1H),3.17(s,2H),3.03(s,2H),2.90(s,2H),2.17(d,J=7.5Hz,1H),1.74–1.69(m,2H),1.43(dd,J=14.7,7.2Hz,4H),1.32–1.27(m,2H).13C NMR(125MHz,DMSO)δ167.42,161.08,144.84,132.64,130.63,126.90,116.64,115.42,115.30,68.09,67.97,66.94,52.50,51.77,51.62,28.98,26.96,25.78,23.93,21.63.HRMS(ESI)m/z:calcd forC22H33NO7[M+H]+ 423.2330,found 423.2327。
实施例3:1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物DMC-5的制备
(1)接入连接桥的羟基肉桂酸甲酯的中间体制备:
往250mL的圆底烧瓶里加入4g(22.44mmol)对羟基肉桂酸甲酯和10.31g(44.88mmol)1,5-二溴戊烷原料,再加入6g(44.88mmol)碳酸钾和100mL丙酮,于65℃的条件下搅拌进行反应,直至反应结束;反应结束后,将上述反应液倒入水中,以20mL乙酸乙酯进行萃取,重复萃取3次,合并有机相;以无水硫酸钠进行干燥,然后脱溶拌样,采用硅胶柱层析法进行分离,洗脱剂为石油醚/乙酸乙酯=20:1,制得接入了5个碳原子的连接桥的对羟基肉桂酸甲酯的中间体;1H NMR(500MHz,DMSO)δ7.66(d,J=8.7Hz,2H),7.61(d,J=16.0Hz,1H),6.97(d,J=8.7Hz,2H),6.48(d,J=16.0Hz,1H),4.03(t,J=6.4Hz,2H),3.71(s,3H),3.56(t,J=6.7Hz,2H),1.92–1.82(m,2H),1.80–1.70(m,2H),1.54(t,J=7.6Hz,2H).13C NMR(125MHz,DMSO)δ167.39,161.03,144.80,130.61,126.98,115.48,115.30,67.97,51.75,35.49,32.40,28.16,24.71.HRMS(ESI)m/z:calcd for C15H19BrO3[M+H]+326.0590,found 326.0588。
(2)目标物DMC-5的制备:
往100mL的圆底烧瓶中加入1.63g(5mmol)上述中间体和0.815g(5mmol)1-DNJ原料,再加入1.38g(10mmol)碳酸钾和50mL DMF,在80℃条件下连续搅拌,直至反应结束;反应结束后,进行脱溶拌样,然后以硅胶柱层析分离,洗脱剂为二氯甲烷/甲醇=25:2,制得目标化合物DMC-5。1H NMR(500MHz,DMSO)δ7.66(d,J=8.7Hz,2H),7.61(d,J=16.0Hz,1H),6.96(t,J=8.2Hz,2H),6.48(d,J=16.0Hz,1H),4.84–4.66(m,3H),4.18(s,1H),4.01(t,J=6.4Hz,2H),3.74(s,1H),3.71(s,3H),3.55(d,J=11.2Hz,1H),3.21(s,1H),3.04(d,J=4.1Hz,1H),2.93(d,J=8.8Hz,1H),2.82(dd,J=11.1,4.8Hz,1H),2.76(d,J=7.1Hz,1H),2.39(s,1H),1.79–1.67(m,2H),1.43(d,J=6.2Hz,2H),1.35(dd,J=16.3,8.7Hz,2H),1.24(s,2H).13C NMR(125MHz,DMSO)δ167.40,161.09,144.84,130.62,126.89,115.41,115.29,79.69,71.24,69.91,68.18,67.23,59.58,57.36,52.43,51.76,29.00,24.74,23.96.HRMS(ESI)m/z:calcd for C21H31NO7[M+H]+ 409.2173,found 409.2170。
实施例4:药效试验例
为了验证本发明提供的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物对α-葡萄糖苷酶的抑制活性,下面以DMC-6为例进行试验:
(1)试剂配制
①0.1mmol/L磷酸缓冲液(PB)配制:取4.559g磷酸氢二钾和7.646g磷酸氢二钾,以超纯水溶解,定容至500mL,调pH至6.8,4℃冷藏备用。
②10mmol/L PNPG配制:取PNPG 0.0301g,以PB缓冲液溶解,定容至10mL,4℃冷藏备用。
③α-葡萄糖苷酶:将α-葡萄糖苷酶冻干粉溶于含50%甘油的PB中,配制成100U/mL的酶溶液,分装,-20℃冻存备用。
④待测抑制剂溶液:以DMSO溶解,Triton X-100助溶,PB缓冲液稀释。
(2)PNP测定标准曲线的绘制
吸取不同体积的PNP标准溶液,加入到96孔板中,以PB补足至200μL,得到0、0.15、0.03、0.06、0.15、0.3、0.6、1.5、0.8、3、6、12、24、48、96(×10-6mmol)的系列标准浓度;于405nm波长下测定吸光值;测定设置4个平行,取平均值,以吸光值(OD值)为横坐标,PNP物质的量为纵坐标,绘制测定标准曲线。所得的测定用线性回归方程为Y=48.5782*X,R2=0.999,式中Y表示PNP物质的量,X表示吸光值,R2表示决定系数。
(3)抑制常数Ki的测定
依次往96孔板中加入160μL PB缓冲液、待测样(DMC-6和参照物阿卡波糖的终浓度梯度均设置为1.0mM、0.5mM、0.3mM)和α-葡萄糖苷酶(1U/mL)10μL,37℃孵育20min;加入PNPG(终浓度分别设置为1.00mM、0.90mM、0.75mM、0.60mM、0.45mM、0.30mM、0.25mM),37℃孵育反应9min,于405nm波长下测定吸光值;每个待测样设置4个平行测试,重复测定3次;按照上述(2)所述的测定回归方程计算PNP的生成速度,据此计算反应速度;采用Lineweaver-Burk作图方法,计算各待测物的抑制常数Ki。
(4)测定结果
经检测,DMC-6和阿卡波糖的抑制常数Ki分别为0.15mM和0.30mM;DMC-5的抑制常数Ki仅为阿卡波糖的1/2。
实施例5:以DMC-6为活性成分制备的降糖胶囊
(1)制粒:按3:4:3的比例分别称取化合物DMC-6(1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体)、微晶纤维素和环糊精,以混匀机进行混匀10分钟,置于干法制粒机中进行制粒,过20目筛,制得的颗粒用于胶囊灌装;
(2)灌制胶囊:以2号胶囊进行灌装,装量控制在250mg,制得以1-脱氧野尻霉素-羟基肉桂酸甲酯类杂合体化合物DMC-6为主要活性成分的胶囊。
实施例6:以DMC-6和DMC-5为活性成分制备的降糖片剂
(1)按4:4:2的比例分别称取微晶纤维素、环糊精、玉米淀粉,再加入0.18%的甜菊糖,得到混合粉1;
(2)以6:2:2的比例称取上述混合粉1、化合物DMC-6和化合物化合物DMC-5,混匀得混合粉2;
(3)称取上述混合粉2,加入2%的硬脂酸镁,混匀后得粉3;
(4)称取上述混合粉3,按200mg每片的规格压片,制得以1-脱氧野尻霉素-羟基肉桂酸甲酯类杂合体化合物DMC-6和DMC-5组合物为主要活性成分的片剂。
实施例7:以DMC-6为活性成分制备的降糖冲剂
(1)按6:2的比例分别称取β-环糊精和化合物DMC-6,再称取0.8%甜菊糖,混匀;
(2)以50%的乙醇调整上述混合物料的湿度,制得软材,软材的软硬度以手捏成团、轻压则散为宜。
(3)将制好的上述软材投入到摇摆式颗粒机中,进行造粒;
(4)将上述造好的颗粒过16目筛网,得湿颗粒;
(5)将上述湿颗粒置于干燥机中干燥,80℃干燥20分钟,制得以1-脱氧野尻霉素-羟基肉桂酸甲酯类杂合体化合物DMC-6为主要活性成分的冲剂。
实施例8:以DMC-6化合物为活性成分的低血糖生成指数食品的制备以“低血糖生成指数馒头”为例,制作工艺和主要操作步骤如下:
制作工艺:主辅原料→称量→混合→和面→发酵→压面→分割→整形→醒发→蒸制→成品馒头。
主要操作步骤:
(1)称量、混合:称取面粉2000g、DMC-6化合物2.5g,加入20g酵母,混合均匀;
(2)和面:往上述混合粉中加入适量的水,置于和面机中慢速搅拌3分钟,再快速搅拌10分钟;
(3)发酵:将上述和好的面团放置于醒发箱中,在37℃、90%的相对湿度的条件下发酵1小时;
(4)压面:将上述发酵好了的面团置于压面机中,压10次;
(5)分割、整形:将压好的面团分割至适当太小,手搓成型;
(6)醒发:将上述成形的馒头放置于醒发箱中,在37℃、90%的相对湿度的条件下进行醒发,时间为15分钟;
(7)蒸制:将上述醒发好了的生馒头放进沸腾的蒸锅中,蒸制30分钟,制得成品--低血糖生成指数馒头。
以上所描述的实施例是本发明一部分实施例,而不是全部的实施例。本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围,而是仅仅表示本发明的选定实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
Claims (11)
3.一种药物组合物,其特征在于,含有至少一种权利要求1所述具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物作为活性成分。
4.根据权利要求3所述的一种药物组合物,其特征在于,所述药物组合物为固体制剂和液体制剂。
5.根据权利要求4所述的一种药物组合物,其特征在于,所述药物组合物为片剂、胶囊剂或冲剂。
6.一种保健品,其特征在于,含有至少一种权利要求1所述具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物作为活性成分。
7.一种食品,其特征在于,含有至少一种权利要求1所述具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物作为活性成分。
8.根据权利要求7所述的一种食品,其特征在于,所述食品是以淀粉为主要成分的原料加工而成的制品。
9.权利要求1所述一种具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物在制备降低餐后血糖或调控血糖的药物中的应用。
10.权利要求1所述一种具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物在制备降低餐后血糖或调控血糖的保健品中的应用。
11.权利要求1所述一种具有式(I)结构的1-脱氧野尻霉素-羟基肉桂酸甲酯杂合体衍生物在制备降低餐后血糖或调控血糖的食品中的应用。
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CN106102464A (zh) * | 2013-05-02 | 2016-11-09 | 牛津大学之校长及学者 | 采用亚氨基糖的糖脂抑制 |
CN106748970A (zh) * | 2016-12-01 | 2017-05-31 | 陕西师范大学 | N‑芳基‑1‑脱氧野尻霉素衍生物及其在制备治疗糖尿病药物中的应用 |
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