CN105311004B - 姜黄素及其药用盐的应用 - Google Patents
姜黄素及其药用盐的应用 Download PDFInfo
- Publication number
- CN105311004B CN105311004B CN201510227963.XA CN201510227963A CN105311004B CN 105311004 B CN105311004 B CN 105311004B CN 201510227963 A CN201510227963 A CN 201510227963A CN 105311004 B CN105311004 B CN 105311004B
- Authority
- CN
- China
- Prior art keywords
- curcumin
- acid
- drug
- cancer
- pharmaceutical salts
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 title claims abstract description 102
- 235000012754 curcumin Nutrition 0.000 title claims abstract description 52
- 239000004148 curcumin Substances 0.000 title claims abstract description 51
- 229940109262 curcumin Drugs 0.000 title claims abstract description 51
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 150000003839 salts Chemical class 0.000 title claims abstract description 19
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 22
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 210000000952 spleen Anatomy 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 241000699670 Mus sp. Species 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000008187 granular material Substances 0.000 claims description 4
- 210000000214 mouth Anatomy 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 238000013268 sustained release Methods 0.000 claims description 4
- 239000012730 sustained-release form Substances 0.000 claims description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- -1 electuary Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 206010019695 Hepatic neoplasm Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 39
- 208000007502 anemia Diseases 0.000 abstract description 20
- 208000029522 neoplastic syndrome Diseases 0.000 abstract description 15
- 201000011510 cancer Diseases 0.000 abstract description 7
- 238000002512 chemotherapy Methods 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 230000004614 tumor growth Effects 0.000 abstract description 4
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 18
- 230000000694 effects Effects 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 102000001554 Hemoglobins Human genes 0.000 description 9
- 108010054147 Hemoglobins Proteins 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000005534 hematocrit Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 244000163122 Curcuma domestica Species 0.000 description 3
- 235000003392 Curcuma domestica Nutrition 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000001772 blood platelet Anatomy 0.000 description 3
- 235000003373 curcuma longa Nutrition 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000013976 turmeric Nutrition 0.000 description 3
- 229940052016 turmeric extract Drugs 0.000 description 3
- 235000020240 turmeric extract Nutrition 0.000 description 3
- 239000008513 turmeric extract Substances 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000035126 Facies Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 206010019842 Hepatomegaly Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 244000273928 Zingiber officinale Species 0.000 description 2
- 235000006886 Zingiber officinale Nutrition 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940125644 antibody drug Drugs 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 230000025084 cell cycle arrest Effects 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000008397 ginger Nutrition 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 244000144993 groups of animals Species 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229940125645 monoclonal antibody drug Drugs 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- KKAJSJJFBSOMGS-UHFFFAOYSA-N 3,6-diamino-10-methylacridinium chloride Chemical compound [Cl-].C1=C(N)C=C2[N+](C)=C(C=C(N)C=C3)C3=CC2=C1 KKAJSJJFBSOMGS-UHFFFAOYSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 208000032420 Latent Infection Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010041649 Splenic injury Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000011805 ball Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 235000021438 curry Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940044652 phenolsulfonate Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000015067 sauces Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/10—Natural spices, flavouring agents or condiments; Extracts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
- A23V2250/2112—Curcumin, turmeric
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明涉及姜黄素及其药用盐在制备抗肿瘤相关性综合症药物中的应用。与目前常规的抗肿瘤化疗药物不但无法避免或减轻肿瘤相关性综合症、而且能够显著提高贫血等肿瘤相关性综合症的发生率和发病程度的作用特点不同，姜黄素具有在抑制肿瘤生长的同时、显著地抑制肿瘤相关性综合症的作用，为抗肿瘤相关性综合症药物的开发提供了新的思路。
Description
技术领域
本发明涉及一种抗肿瘤剂，特别是，涉及姜黄素及其药用盐在制备抗肿瘤相关性综合症药物中的应用。
背景技术
肿瘤相关性综合症严重影响病人的生存质量，是导致肿瘤患者死亡的一个重要原因。肿瘤相关性综合症包括：造血功能障碍、内分泌失调、腹水、肝脏损伤、脾脏损伤、肾功能损伤、胃肠道功能紊乱、肌肉萎缩等。以贫血为例，贫血是恶性肿瘤患者常见的并发症，据报道超过50％的肿瘤病人患有贫血。贫血的严重程度与许多因素有关，包括疾病进展和使用的化疗药物的种类，以及年龄的增加和潜在感染的发生等。各种肿瘤贫血发生率为：妇科肿瘤为81％，肺癌为77％，淋巴瘤与骨髓瘤为73％，胃肠道肿瘤为61％，乳腺癌为62％，泌尿生殖系肿瘤为51％。化疗疗程与贫血发生率和贫血程度有明显关系，Coiffier等对超过1000名肿瘤患者的调查显示化疗1个月后贫血发生率开始增长，接受化疗10～12个月的病人发生中度(血红蛋白8～10.0g/dl)或重度(血红蛋白＜8.0g/dl)贫血者在50％以上。有效控制和治疗贫血等肿瘤相关性综合症在肿瘤的综合治疗中具有重要意义。
发明内容
本发明要解决的技术问题是：提供一种姜黄素的新用途，具体涉及姜黄素及其药用盐在制备抗肿瘤相关性综合症药物中的应用。
为解决上述技术问题，本发明采用的技术方案如下：
姜黄素及其药用盐在制备抗肿瘤相关性综合症药物中的应用。
优选地，所述肿瘤为纤维肉瘤或非小细胞肺癌。
优选地，所述抗肿瘤相关性综合症药物的制剂形式为液体制剂、颗粒剂、片剂、冲剂、胶丸、胶囊、缓释剂、口崩制剂或注射剂。
优选地，所述姜黄素药用盐为姜黄素与无机酸形成的盐。
优选地，所述无机酸为盐酸、氢溴酸、硫酸、硝酸和磷酸中任一种或几种。
优选地，所述姜黄素药用盐为姜黄素与有机酸形成的盐。
优选地，所述有机酸为甲酸、乙酸、丙酸、草酸、丙二酸、琥珀酸、富马酸、马来酸、乳酸、苹果酸、酒石酸、柠檬酸、苦味酸、甲磺酸和甲基苯磺酸中任一种或几种。
优选地，所述姜黄素药用盐为姜黄素与酸性氨基酸的酸形成的盐。
优选地，所述酸性氨基酸为天门氨酸或谷氨酸。
以姜黄素为主要成分的植物在制备抗肿瘤相关性综合症药物或食品中的应用。
本发明的有益效果在于：
1、与目前常规的抗肿瘤化疗药物不但无法避免或减轻肿瘤相关性综合症、而且能够显著提高贫血等肿瘤相关性综合症的发生率和发病程度的作用特点不同，姜黄素具有在抑制肿瘤生长的同时、显著地抑制肿瘤相关性综合症的作用，为抗肿瘤相关性综合症药物的开发提供了新的思路；
2、姜黄素药用盐具有相同的功效条件下，使得姜黄素具有更多的保存状态，适用范围更大；
3、姜黄素及其药用盐在抗肿瘤相关性综合症药物中作为主要成分，保证了抗肿瘤的同时，显著地抑制肿瘤相关性综合症，具有更好的药用效果，便于大规模生产和推广应用；
4、姜黄素是从姜黄的根茎中提取的一种酚类色素，在食品生产中用于肠类制品、罐头、酱卤制品等产品的着色，由于姜黄素同时是一种食品原料，因此，以姜黄素为主要活性成分的植物能够用以制备具有抗肿瘤相关性综合症的食品或者药物。
附图说明
图1为姜黄素治疗肿瘤动物模型实验结果；
图2为姜黄素治疗对小鼠肿瘤重量及肝脾系数实验结果；
图3为姜黄素治疗对小鼠贫血症状分析实验结果。
具体实施方式
实施例1抗肿瘤动物模型实验
目前常规的抗肿瘤药物在产生抗肿瘤效果的同时，一般都具有毒副作用。本实验中我们评价了姜黄素的抗肿瘤效果，同时通过治疗后动物体重的变化考察了药物的毒性。鉴于化疗药物治疗及其疗程与肿瘤相关性综合症发生率及其严重程度有明显关系，本实验中阳性对照采用目前国际上最为先进的抗肿瘤抗体药物作为对照。T241-VEGF是一种肿瘤生长快速、并且肿瘤相关性综合症明显的肿瘤模型。
我们将雌性C57BL/6小鼠(SPF级，6-8周龄，上海斯莱克实验动物有限责任公司生产)适应饲养2-3天，皮下接种前一天用剃毛器剃除背颈部体毛以便进行肿瘤细胞皮下接种。将肿瘤细胞T241-VEGF收集，并用PBS洗涤2次后，用PBS重悬，计数后用PBS稀释为1*107个cells/ml，冰上放置准备接种。小鼠用7％水合氯醛进行麻醉，0.1ml/只，腹腔注射；待小鼠完全麻醉后，用1ml医用一次性注射器对小鼠进行背颈部皮下接种肿瘤细胞T241-VEGF，1*106/只。将接种后的小鼠随机分组(每组8只)，称重，分组及给药治疗。本试验中姜黄素(Sigma公司生产,cat no.C1386-10G)用DMSO配置为1mol/L，给药之前用20％Tween-80(PBS配置)分别稀释为2.5mM，5mM和10mM。具体情况及给药方案如下：对照组(Control)：20％Tween-80，0.1ml/只；姜黄素低剂量组(Curcumin-2.5mM)：2.5mM Curcumin,0.1ml/只，连续给药14天；姜黄素中剂量组(Curcumin-5mM)：5mM Curcumin,0.1ml/只，连续给药14天；姜黄素高剂量组(Curcumin-10mM)：10mM Curcumin,0.1ml/只，连续给药14天；阳性对照组(PC：人源化抗VEGF单克隆抗体药物，江苏先声药业有限公司生产)：2mg/ml,0.1ml/只，每周2次，共给药4次。动物隔天称重，肿瘤长起后，用游标卡尺隔天量瘤体积。
结果如图1-A所示。姜黄素高中低三剂量均能抑制T241-VEGF肿瘤的生长，其中5mM和10mM剂量与对照组相比，最终的肿瘤体积呈显著差异(p<0.01或p<0.001),2.5mM组小鼠的肿瘤体积亦有一定的抑制。与肿瘤体积结果相对应的肿瘤重量结果见图1-B，结果显示，5mM和10mM剂量组的肿瘤重量与对照组呈显著差异，表明5mM和10mM两个剂量的姜黄素能够显著抑制T241-VEGF肿瘤的生长。无论是姜黄素高中低剂量组的体重都没有降低，而且显著好于阳性对照药物，显示其毒性甚至显著好于目前国际上最为先进的抗肿瘤抗体药物。姜黄素高中低三个剂量组动物的体重都与同期饲养的正常动物体重变化一致，而阳性对照药物组动物的体重在治疗则显著低于正常动物及姜黄素高中低三个剂量组动物。
实施例2各组小鼠肿瘤重量及肝脾系数实验
为了进一步确证姜黄素各剂量组的抗肿瘤效果、及其对肝脾的影响。我们在给药结束后隔天，处理各组动物，解剖得到肿瘤，肝脏，脾脏和肾脏，称重，将各组织进行固定保存。结果如图2，姜黄素对由于T241-VEGF肿瘤引发的肝脏肿大和脾脏肿大的改善结果明显。结果显示，肿瘤对照组小鼠的肝脏系数和脾脏系数与正常小鼠相比呈显著差异(p<0.01),5mM和10mM姜黄素能显著改善肝脏肿大(p<0.05)，同时10mM姜黄素能显著改善脾脏肿大(p<0.05)。
实施例3各组小鼠贫血症状分析实验
给药结束后隔天，处理各组动物，称重后摘眼球取血(存放入已加入20ul 0.5MEDTA的1.5ml EP管)，进行血相分析，评价姜黄素对肿瘤相关性综合症贫血指标--小鼠红细胞数(RBC)，血红蛋白(HGB)，红细胞比容(HCT)和血小板数(PLT)的改善结果。
对于由T241-VEGF肿瘤动物模型诱发的肿瘤相关性综合症--小鼠贫血症状，我们对各组小鼠血液进行血相分析，结果见图3显示：与正常小鼠相比，对照组小鼠红细胞数(RBC)，血红蛋白(HGB)，红细胞比容(HCT)和血小板数(PLT)显著降低，表明T241-VEGF肿瘤模型能够产生肿瘤相关性综合症、即荷瘤鼠贫血症状。阳性单克隆抗体药物能够显著改善荷瘤鼠的贫血症状，但是阳性单克隆抗体药物能够产生小鼠红细胞数(RBC)、血红蛋白(HGB)、红细胞比容(HCT)过度升高的现象；姜黄素高中低三个剂量小鼠贫血症状改善非常明显，与对照组相比均呈显著差异，其中红细胞数，血红蛋白和红细胞比容与正常小鼠无统计学差异，10mM剂量的血小板与正常小鼠无统计学差异，表明姜黄素能够显著改善由肿瘤引发的贫血症状。
本发明同时以非小细胞肺癌A549为肿瘤模型进行了与上述实验完全相同的实验研究，获得了几乎完全相同的研究结果。
这个结果充分说明：按照目前已知的姜黄素抗肿瘤的6个作用机制，即诱导细胞凋亡，诱导细胞周期阻滞，阻断肿瘤细胞的生长信号传导，抑制肿瘤血管生成，抑制黏附分子的表达，增加化疗药物对癌细胞的敏感性(国际肿瘤学杂志2013,v40(11):823-826)，姜黄素应当与化疗药物类似(诱导细胞凋亡，诱导细胞周期阻滞，阻断肿瘤细胞的生长信号传导，增加化疗药物对癌细胞的敏感性，这是许多小分子化疗药物共有的作用特征)、具有提高肿瘤相关性综合症发生率及其严重程度的作用。但是本发明出乎意料地发现，姜黄素能够在显著抑制肿瘤生长的同时，能非常显著地抑制肿瘤相关性综合症，同时荷瘤动物的体重像正常动物一样增长，未发生任何毒副作用现象。
将姜黄素与盐酸、氢溴酸、硫酸、硝酸、磷酸等无机酸形成的药用盐，和与甲酸、乙酸、丙酸、草酸、丙二酸、琥珀酸、富马酸、马来酸、乳酸、苹果酸、酒石酸、柠檬酸、苦味酸、甲磺酸、对甲基苯磺酸等有机酸和天门氨酸、谷氨酸等酸性氨基酸的酸形成的药用盐进行实施例1-3的实验发现，姜黄素药用盐与姜黄素具有相同的效果。在进一步应用中，可以根据实际需要，将含有姜黄素及其药用盐的抗肿瘤相关性综合症药物的制剂形式为液体制剂、颗粒剂、片剂、冲剂、胶丸、胶囊、缓释剂、口崩制剂或注射剂。
以富含姜黄素的姜、芥末、咖哩等原料制备而成的动物食品进行实施例1-3的实验发现，富含姜黄素的食品与姜黄素具有相类似的效果。在进一步应用中，可以根据实际需要，将富含姜黄素的抗肿瘤相关性综合症食品的形态为液体口服液、颗粒剂、片剂、冲剂、胶丸、胶囊、缓释剂、口崩制剂。
综上所述，姜黄素具有在抑制肿瘤生长的同时、能显著地抑制肿瘤相关性综合症的作用，为抗肿瘤相关性综合症药物的开发提供了新的思路。
Claims (2)
1.姜黄素及其药用盐在制备抗纤维肉瘤或非小细胞肺癌相关性综合症药物中的应用，其特征在于，所述纤维肉瘤或非小细胞肺癌相关综合症为荷瘤鼠肝脏肿大、脾脏肿大或贫血。
2.如权利要求1所述的应用，其特征在于，所述抗肿瘤相关性综合症药物的制剂形式为颗粒剂、片剂、冲剂、胶丸、胶囊、缓释剂、口崩制剂或注射剂。
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510227963.XA CN105311004B (zh) | 2015-05-06 | 2015-05-06 | 姜黄素及其药用盐的应用 |
| US15/572,066 US20180214391A1 (en) | 2015-05-06 | 2016-04-11 | Use of curcumin and pharmaceutically acceptable salt thereof |
| PCT/CN2016/000188 WO2016177013A1 (zh) | 2015-05-06 | 2016-04-11 | 姜黄素及其药用盐的应用 |
| JP2017558371A JP2018515505A (ja) | 2015-05-06 | 2016-04-11 | クルクミン及びその薬用塩の応用 |
| EP16789007.8A EP3292865A1 (en) | 2015-05-06 | 2016-04-11 | Use of curcumin and pharmaceutically acceptable salt thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510227963.XA CN105311004B (zh) | 2015-05-06 | 2015-05-06 | 姜黄素及其药用盐的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105311004A CN105311004A (zh) | 2016-02-10 |
| CN105311004B true CN105311004B (zh) | 2018-12-11 |
Family
ID=55239970
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510227963.XA Active CN105311004B (zh) | 2015-05-06 | 2015-05-06 | 姜黄素及其药用盐的应用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20180214391A1 (zh) |
| EP (1) | EP3292865A1 (zh) |
| JP (1) | JP2018515505A (zh) |
| CN (1) | CN105311004B (zh) |
| WO (1) | WO2016177013A1 (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105311004B (zh) * | 2015-05-06 | 2018-12-11 | 江苏靶标生物医药研究所有限公司 | 姜黄素及其药用盐的应用 |
| WO2018159852A1 (ja) * | 2017-03-03 | 2018-09-07 | 三栄源エフ・エフ・アイ株式会社 | クルクミン含有製剤 |
| CN109942395B (zh) * | 2019-03-29 | 2021-09-21 | 四川大学 | 一种姜黄素类离子液体及其应用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1994286A (zh) * | 2006-12-29 | 2007-07-11 | 神威药业有限公司 | 总姜黄素在制备预防及延缓慢性肾功能衰竭药物中的应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1118262A (zh) * | 1994-09-08 | 1996-03-13 | 刘凤江 | 治癌合剂 |
| JP2002080338A (ja) * | 2000-06-20 | 2002-03-19 | Shiseido Co Ltd | 老化防止用皮膚外用剤 |
| JP2004075666A (ja) * | 2002-05-15 | 2004-03-11 | Keio Gijuku | 造血器腫瘍の治療薬、免疫抑制剤、およびｐ５３を標的分子とする分子標的治療薬 |
| AU2003253681B2 (en) * | 2002-06-24 | 2008-05-01 | Research Development Foundation | Treatment of human multiple myeloma by Curcumin |
| JP2014148474A (ja) * | 2013-01-31 | 2014-08-21 | Chube Univ | Ｇｌｐ−１分泌促進剤 |
| CN103404667A (zh) * | 2013-08-19 | 2013-11-27 | 北京绿源求证科技发展有限责任公司 | 一种改善营养性贫血的食品养血茶冲剂 |
| CN105311004B (zh) * | 2015-05-06 | 2018-12-11 | 江苏靶标生物医药研究所有限公司 | 姜黄素及其药用盐的应用 |
-
2015
- 2015-05-06 CN CN201510227963.XA patent/CN105311004B/zh active Active
-
2016
- 2016-04-11 JP JP2017558371A patent/JP2018515505A/ja active Pending
- 2016-04-11 EP EP16789007.8A patent/EP3292865A1/en not_active Withdrawn
- 2016-04-11 WO PCT/CN2016/000188 patent/WO2016177013A1/zh active Application Filing
- 2016-04-11 US US15/572,066 patent/US20180214391A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1994286A (zh) * | 2006-12-29 | 2007-07-11 | 神威药业有限公司 | 总姜黄素在制备预防及延缓慢性肾功能衰竭药物中的应用 |
Non-Patent Citations (5)
| Title |
|---|
| Induction of apoptosis in human lung cancer cells by curcumin;Radhakrishna Pillai G等;《Cancer Letter》;20041231;第208卷(第2期);第163-170页 * |
| 姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素对人肝癌细胞HepG2 中MMP-2、MMP-9 蛋白表达的影响;徐玉峰;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20140915;第8页前言最后1段至第9页第1段 * |
| 姜黄素抗癌机制研究进展;张博，叶丽红;《中医药学报》;20131231;第41卷(第1期);第121-123页 * |
| 生姜药理作用研究进展;孙永金;《现代中西医结合杂志》;20070228;第16卷(第4期);第561-563页 * |
| 生姜药理作用研究进展;武彩霞 等;《临沂医学院专科学校学报》;20041231;第26卷(第6期);第445-447页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2018515505A (ja) | 2018-06-14 |
| EP3292865A1 (en) | 2018-03-14 |
| US20180214391A1 (en) | 2018-08-02 |
| CN105311004A (zh) | 2016-02-10 |
| WO2016177013A1 (zh) | 2016-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105311004B (zh) | 姜黄素及其药用盐的应用 | |
| Hou et al. | In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment | |
| CN111870609A (zh) | 一种肠道菌群调节剂及其应用 | |
| CN105983097B (zh) | 一种抗肿瘤制剂及其制备方法 | |
| CN104398526A (zh) | 雷公藤甲素和雷公藤红素在制备抗肿瘤药物中的应用 | |
| CN107007594A (zh) | 维生素c和奥沙利铂联用在抗肿瘤中的作用 | |
| CN105380956B (zh) | 一种治疗白血病的含艾德拉尼的药物组合物及应用 | |
| Maeda et al. | Inhibitory effects of preventive and curative orally administered spinach glycoglycerolipid fraction on the tumor growth of sarcoma and colon in mouse graft models | |
| CN109528731B (zh) | 具有协同作用治疗多发性骨髓瘤的药物组合物及其应用 | |
| CN107929712A (zh) | 一种治疗肝癌的联合药物 | |
| TWI646964B (zh) | 用於降低癌症治療藥物副作用之醫藥組合物、製備方法及其用途 | |
| CN102846868B (zh) | 藏药仁青芒觉在制备抗肿瘤药物中的用途 | |
| CN111249274B (zh) | 银杏内酯b在制备胶质瘤细胞活性抑制剂中的应用 | |
| EP3127544A1 (en) | Anti-tumor drug containing anti-tumor platinum complex, and anti-tumor effect enhancer | |
| TW201306833A (zh) | 包含康布列塔司他汀（ｃｏｍｂｒｅｔａｓｔａｔｉｎｓ）族衍生物及西妥昔單抗（ｃｅｔｕｘｉｍａｂ）之組合 | |
| CN106806382B (zh) | 抗癌组合物 | |
| CN104367581B (zh) | 二水合水杨酸锌在制备用于治疗乳腺癌药物中的应用 | |
| CN110215460B (zh) | 一种抗肿瘤的联用组合药物 | |
| CN106974910B (zh) | 含索拉非尼和gsk2656157的药物组合物及用途 | |
| CN108309990A (zh) | 雷公藤内酯酮用于制备Gli基因抑制剂和防治肝癌药物的生物医药用途 | |
| CN101011399A (zh) | 汉防已甲素作为治疗胃癌的化疗药物增敏剂的应用 | |
| US20190099424A1 (en) | Pharmaceutical Composition for Decreasing The Side Effects of Pancreatic Cancer Drug, and Manufacturing Method and Uses Thereof | |
| Li et al. | The Synergistic Inhibitory Effect of Combination Drug Treatment of Enteromorpha Prolifera Polysaccaharide and Doxorubicin Hydrochloride on A549 Cell | |
| CN105769888A (zh) | 竹节人参皂苷IVa在制备抗肿瘤药物中的应用 | |
| KR20180030200A (ko) | 항종양 약물 제조에서의 다이하이드록시아세톤의 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |