CN111467435A - 一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 - Google Patents
一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 Download PDFInfo
- Publication number
- CN111467435A CN111467435A CN201910070503.9A CN201910070503A CN111467435A CN 111467435 A CN111467435 A CN 111467435A CN 201910070503 A CN201910070503 A CN 201910070503A CN 111467435 A CN111467435 A CN 111467435A
- Authority
- CN
- China
- Prior art keywords
- preparation
- water
- sieving
- adjuvants
- sarcandra
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 241001076416 Dendrobium tosaense Species 0.000 title claims abstract description 6
- 241000736026 Sarcandra Species 0.000 title description 9
- 241001633680 Polygonatum odoratum Species 0.000 title description 2
- 206010013781 dry mouth Diseases 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 13
- 230000002285 radioactive effect Effects 0.000 claims abstract description 11
- 240000004274 Sarcandra glabra Species 0.000 claims abstract description 9
- 235000010842 Sarcandra glabra Nutrition 0.000 claims abstract description 9
- 239000002671 adjuvant Substances 0.000 claims abstract description 8
- 239000012530 fluid Substances 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 210000003681 parotid gland Anatomy 0.000 claims abstract description 8
- 238000007873 sieving Methods 0.000 claims abstract description 8
- 230000006378 damage Effects 0.000 claims abstract description 6
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 5
- 208000014674 injury Diseases 0.000 claims abstract description 5
- 229920001353 Dextrin Polymers 0.000 claims abstract description 4
- 239000004375 Dextrin Substances 0.000 claims abstract description 4
- 235000019425 dextrin Nutrition 0.000 claims abstract description 4
- 238000001035 drying Methods 0.000 claims abstract description 4
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000843 powder Substances 0.000 claims abstract description 4
- 230000005855 radiation Effects 0.000 claims description 2
- 208000005946 Xerostomia Diseases 0.000 abstract description 9
- 230000001681 protective effect Effects 0.000 abstract description 3
- 238000001959 radiotherapy Methods 0.000 description 21
- 239000008187 granular material Substances 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 9
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 9
- 210000003743 erythrocyte Anatomy 0.000 description 9
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 231100000915 pathological change Toxicity 0.000 description 5
- 230000036285 pathological change Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 108050006400 Cyclin Proteins 0.000 description 3
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 210000003924 normoblast Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000011455 3D conformal radiation therapy Methods 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 2
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 2
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 102000055102 bcl-2-Associated X Human genes 0.000 description 2
- 108700000707 bcl-2-Associated X Proteins 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 210000001995 reticulocyte Anatomy 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 229940116269 uric acid Drugs 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 238000002729 3-dimensional conformal radiation therapy Methods 0.000 description 1
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 208000010470 Ageusia Diseases 0.000 description 1
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 1
- 108010082126 Alanine transaminase Proteins 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003011 Appendicitis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007882 Cellulitis Diseases 0.000 description 1
- 241000758719 Chloranthaceae Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 102100033223 Nicotinamide phosphoribosyltransferase Human genes 0.000 description 1
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 1
- 229960001097 amifostine Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- -1 coumarin, lactone Chemical class 0.000 description 1
- 229930182485 cyanogenic glycoside Natural products 0.000 description 1
- 150000008142 cyanogenic glycosides Chemical class 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000004980 dosimetry Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229930182486 flavonoid glycoside Natural products 0.000 description 1
- 150000007955 flavonoid glycosides Chemical class 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000006303 immediate early viral mRNA transcription Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002721 intensity-modulated radiation therapy Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000018343 nutrient deficiency Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 230000000693 radiobiological effect Effects 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 230000003537 radioprotector Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000003442 weekly effect Effects 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
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8969—Polygonatum (Solomon's seal)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8984—Dendrobium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明属于医药技术领域，尤其涉及到一种中药复方制剂的制备及其用途。本发明的目的，是提供一种安全有效、价廉、方便服用的解决放射性口干的复方制剂。为到达此目的之技术方案是：九节茶650g、玉竹250g、铁皮石斛100g，以上三味加水煎煮三次，每次加水15000ml，第一次煎煮1.5小时，第二次和第三次煎煮均为1小时。合并水煎液，浓缩至65℃下相对密度为1.28～1.32的清膏，按糊精与糖粉之重量比4∶1为辅料，清膏与辅料之重量比1∶4混匀，加5倍重量的70％乙醇‑水溶液制软材，过筛制成颗粒，干燥，过筛，制成1500g，即得。实验结果表明，本发明制剂对放射性腮腺损伤有保护作用，能减轻放射性口干。
Description
技术领域
本发明属于医药技术领域，尤其涉及到一种中药复方制剂的制备及其用途。
背景技术
鼻咽癌(Nasopharyngeal Carcinoma)是一种发生于鼻咽腔或上咽喉部的癌症，死亡率很高。鼻咽癌好发于华人和爱斯基摩人，罹病机率远高于欧美及日韩等民族，而中国东南沿海及台湾等地的居民罹病机率又高于中国北方，特别是广东和广西地区。目前鼻咽癌的首选治疗方式为放射治疗，其方式主要有常规二维放疗(2D-CRT)、三维适形放疗(3D-CRT)、调强适形放疗(IMRT)等。尽管IMRT在剂量学和放射生物效应方面较2D-CRT技术更具优势，造成口干副反应也较轻。但是，受到地方经济、放疗技术、设备以及从业人员水平等各方面条件的限制，IMRT难以大范围推广，因此目前放射治疗模式仍以2D-CRT为主，仅少部分病人接受3D-CRT和IMRT。2D-CRT对腮腺功能的损害较大，几乎所有接受2D-CRT放疗的鼻咽癌患者都会出现不同程度的唾液腺功能低下或永久丧失导致的口干症，进而导致龋齿、真菌感染、味觉丧失、吞咽及交谈困难、营养缺乏等一系列并发症，严重影响患者生活质量，目前国内外尚没有针对放射性腮腺损伤的放射防护剂，现有的治疗手段如阿米福汀、还原型谷胱甘肽、超氧化物歧化酶及其类似物、褪黑激素等，则因较大的毒副作用或价格昂贵而难以推广。因此探求解决放射性口干的方法成为鼻咽癌治疗一个重要课题，寻找能有效减轻放疗并发症的方法迫在眉睫。
九节茶(又名：肿节风、草珊瑚、接骨木)系金粟兰科(Chloranthaceae)草珊瑚属植物草珊瑚Sarcandra glabra(Thunb.)Nakai的干燥全草，其主要成分包括黄酮苷类、挥发油、氰苷、香豆素、内酯等，药理作用主要有抗菌消炎、抑制肿瘤、改善免疫功能等，临床常用于咽喉炎、肺炎、阑尾炎、蜂窝组织炎等的治疗。本课题组在长期的临床观察和前期研究中发现：九节茶的水提取物能够减轻鼻咽癌患者经放疗引起的口干症状。但是，使用单一的九节茶服用剂量较大且效果较差，将其与其他中药配伍制成复方制剂能克服这些缺点。
发明内容
本发明的目的，是提供一种安全有效、价廉、方便服用的解决放射性口干的复方制剂。
本发明是通过以下技术方案解决问题：
九节茶650g、玉竹250g、铁皮石斛100g，以上三味加水煎煮三次，每次加水15000ml，第一次煎煮1.5小时，第二次和第三次煎煮均为1小时。合并水煎液，浓缩至65℃下相对密度为1.28～1.32的清膏，按糊精与糖粉之重量比4∶1为辅料，清膏与辅料之重量比1∶4混匀，加5倍重量的70％乙醇-水溶液制软材，过筛制成颗粒，干燥，过筛，制成1500g，即得。
具体实施方式
下面结合实施例对本发明作进一步描述。
实施例1
制剂工艺：
九节茶650g、玉竹250g、铁皮石斛100g，以上三味加水煎煮三次，每次加水15000ml，第一次煎煮1.5小时，第二次和第三次煎煮均为1小时。合并水煎液，浓缩至65℃下相对密度为1.28～1.32的清膏，按糊精与糖粉之重量比4∶1为辅料，清膏与辅料之重量比1∶4混匀，加5倍重量的70％乙醇-水溶液制软材，过筛制成颗粒，干燥，过筛，制成1500g，即得。
实施例2
复方九节茶颗粒对SD大鼠放射性腮腺损伤的保护作用
97只雄性大鼠随机分成5组：空白对照组、单纯照射组、复方九节茶颗粒(FJJC颗粒)低、中、高剂量组。药照组于照射前一周开始按体重灌胃给予FJJC颗粒，给药至腮腺取出，空白组和照射组按照体重给予等量的生理盐水，直至观察结束。大鼠以3％戊巴比妥钠(按照30mg·kg-1)腹腔麻醉，于某大型三甲医院放疗科进行放疗。于照射后第10天、40天、70天3个时间点，分别随机取每组5只、9只、6只腹主动脉取血，随后离心，取血清对AST、ALT、LDH、ALP、BUN、CR六个指标进行检测；HE染色观察腮腺组织的病理学变化；透射电镜观察腮腺组织的超微结构变化；TUNEL法检测细胞凋亡情况；蛋白免疫印迹法检测腮腺组织中Bcl-2、Bax、PCNA、TNF-a的蛋白表达；RT-PCR法检测腮腺组织中IL-1β、CCL-2、MMP-1、PDGF、NamptmRNA的表达。
结果表明：FJJC颗粒对大鼠AST、ALT、ALP、BUN有一定的降低作用，差异具有统计学意义(P＜0.05)，对LDH、CR降低作用不明显，差异无统计学意义(P＞0.05)；HE和透射电镜结果显示FJJC颗粒能改善大鼠放射线引起的腮腺损伤病理变化；FJJC颗粒可以上调Bcl-2、PCNA蛋白的表达，下调Bax、PCNA、TNF-α蛋白的表达；降低IL-1β、CCL-2、PDGFmRNA的表达，升高MMP-1、Nampt mRNA的表达。结果表明FJJC颗粒对大鼠放射性腮腺损伤有明显的保护作用。
实施例3
复方九节茶颗粒急性毒性试验
以最大给药量法进行供试品单次给药毒性试验。通过给昆明小鼠一日内灌服最大浓度最大体积的受试药物，观察该药物对动物产生的毒性反应、中毒程度、性质、恢复情况及死亡分布，为临床用药安全提供可靠依据。
结果表明：给药后至观察期14天结束，对照组及给药组动物行为活动及体征表现均正常；给药组动物体重与对照组无显著差异；且无一死亡。试验结束后，给药组和对照组动物经大体解剖所见：心脏、肺脏、肝脏、脾脏、肾脏和胃肠，诸脏器均未发生异常改变。结果表明一日内给昆明小鼠灌胃高于临床剂量约213.6倍的90.0g·kg-1九节茶提取物(相当于143.1g生药·kg-1)后，即刻至整个观察期过程中未见动物出现任何不良反应及死亡。认为该供试品给小鼠经灌胃给药的LD50剂量大于最大给药剂量(90.0g·kg-1)。
实施例4
复方九节茶颗粒长期毒性试验
将80只SD大鼠随机分成空白对照组和三个供试品组，每组40只，雌雄各半。选用13.4g·kg-1、26.8g·kg-1、40.2g·kg-1复方九节茶颗粒提取物作为本次实验的给药剂量。每天灌胃给药1次，每周7天，连续灌胃给药90天，对照组灌胃等体积的蒸馏水。每目观察动物自主活动、精神状态、皮毛、粪便情况；每周称量体重、记录摄食量。给药结束后，每组雌雄各取7只动物，进行血液学、血生化及电解质等各项指标检测；解剖取脏器进行称重，计算脏器系数；并进行病理组织学检查。于恢复期结束时，每组雌雄各取3只动物，用同样方法取血、剖杀，进行与给药结束时相同的各项检查。
结果表明：
1.一般临床表现 给药期至恢复期结束，各实验组动物行为活泼，自主活动规律，外观体征、皮肤、粘膜及粪便颜色形态正常，腺体无异常分泌物，且无一死亡。
2.体重与进食量 在整个实验过程中，各给药组大鼠的体重、进食量等指标均未见与药物相关的异常降低趋势，变化值均属正常范围内的波动。
3.临床病理学检验所见 血液学检测结果显示：本实验中各时期检测数据显示，在给药90天后，雄性大鼠中剂量组的高荧光网织红细胞(HFR)高于对照组；高剂量组的血小板压积(HCT)、中性粒细胞比率(NEUT％)、红细胞分布宽度-变异系数(RDW-CV)、高荧光网织红细胞(HFR)高于对照组；平均血红蛋白浓度(MCHC)、淋巴细胞比率(LYMPH％)低于对照组。雌性大鼠中剂量的红细胞分布宽度(RDW-SD)低于对照组；高剂量的血小板压积(PCT)、单核细胞在白细胞中的百分比(MONO％)、淋巴细胞比率(LYMPH％)、红细胞分布宽度-变异系数(RDW-CV)、红细胞分布宽度(RDW-SD)、外周血有核红细胞分数(NRBC％)低于对照组。恢复期结束后，雄性大鼠高剂量的网织红细胞绝对数(RET#)、有核红细胞绝对值(NRBC#)、网织红细胞比例(RET％)、低荧光强度比率(LFR)、中荧光强度比率(MFR)、未完全成熟网织红细胞分数(IRF)高于对照组；雌性大鼠高剂量的网织红细胞绝对数(RET#)、有核红细胞绝对值(NRBC#)、网织红细胞比例(RET％)、低荧光强度比率(LFR)、高荧光网织红细胞(HFR)、未完全成熟网织红细胞分数(IRF)高于对照组。因检测值未超出正常值范围，且无剂量及时效的相关性，故不认为与药物作用有关，不具有毒理学意义。血液生化检测结果显示：给药结束后，雄性高剂量组的白球比(A/G)、肌酐(CR)高于对照组；钠离子(Na+)低于对照组；雌性高剂量组的白球比(A/G)、尿酸(UA)高于对照组；丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、球蛋白(GLB)、钠离子(Na+)低于对照组。给药结束时，雌性大鼠中剂量乳酸脱氢酶(LDH)高于对照组，高剂量组碱性磷酸酶(ALP)高于对照组。因检测值未超出正常值范围，且无剂量及时效的相关性，故不认为与药物作用有关。本次血液生化指标的变化值与本机构的测试背景资料数据相符，可认为上述改变属正常生理范围的波动，而并无毒理学意义。在试验各阶段中，三个剂量组的网织细胞计数及脏器系数检查均未见与供试品相关的病理性改变。
4.组织病理学结果所见 在试验各时期，各组均有个别动物出现肾肺脏的间质性炎症，恢复期雌性高剂量组出现一例轻度脾脏充血和一例卵巢间质轻度充血，以上现象实属大鼠常见的自发性病变，并无毒理学意义，且对照组与给药组间的发生率和病变程度无明显差别，与给予受试物无明显相关性。在本试验条件下，连续给SD大鼠复方九节茶颗粒提取物90天，各给药组动物的诸项生理指标均未出现因药物引起的毒性反应和与给药相关的病理改变。经停药3周的观察，各项检测指标也均未显现出因给药而引发延迟毒性或蓄积性毒性反应。器官组织的病理改变与给药相关性分析认为：在试验的各时期，均未发现与给予受试物相关的病理改变。本次实验复方九节茶颗粒提取物的无毒性反应剂量为40.2g·kg-1。
实施例5
复方九节茶颗粒减轻放射性口干的临床疗效观察
某大型三甲医院放疗科收治的初治鼻咽癌患者60例，经病理确认，符合疗前骨髓、肝肾功能正常，Karnofsky评分≥70，无远处转移，无严重内科合并症。随机分为实验组：同步放化疗+复方九节茶颗粒(30例)，对照组：同步放化疗组(30例)。
放疗方法：采用调强放射治疗，靶区勾画、照射剂量及计划评估按照专家共识。
化疗方案：采用同步化疗(放疗第一天开始进行)DDP 80mg·m-2，分成两天使用d1-2，21天为一周期，共行3-4个周期。
复方九节茶颗粒干预：放疗前3天开始口服复方九节茶颗粒，一次10g，一日3次。持续到放疗结束。放疗后3、6、12、18和24个月唾液分泌量，并观察口干分级情况。以评价复方九节茶颗粒对放疗导致的口干患者是否具有防护作用，并评价药物安全性。
结果表明：实验组在治疗期间对复方九节茶颗粒适应性良好，未观察到显著的复方九节茶颗粒相关的药物不良反应。放疗结束时，实验组发生I级口干19人，II级口干11人；对照组发生I级口干9人，II级口干21人，两组比较，实验组发生II级口干人数明显低于对照组，差异有统计学意义(P＝0.01)。结果提示复方九节茶颗粒对放疗导致的放射性口干具有一定的防护作用，可显著预防放疗导致的急性放射性口干，而远期效应尚需长期随访验证。
Claims (3)
1.一种复方制剂的制备方法，其特征在于：九节茶650g、玉竹250g、铁皮石斛100g，以上三味加水煎煮三次，每次加水15000ml，第一次煎煮1.5小时，第二次和第三次煎煮均为1小时；合并水煎液，浓缩至65℃下相对密度为1.28～1.32的清膏，按糊精与糖粉之重量比4∶1为辅料，清膏与辅料之重量比1∶4混匀，加5倍重量的70％乙醇-水溶液制软材，过筛制成颗粒，干燥，过筛，制成1500g，即得。
2.如权利要求1所述复方制剂保护放射性腮腺损伤的用途。
3.如权利要求1所述复方制剂减轻放射性口干的用途。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910070503.9A CN111467435A (zh) | 2019-01-24 | 2019-01-24 | 一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910070503.9A CN111467435A (zh) | 2019-01-24 | 2019-01-24 | 一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111467435A true CN111467435A (zh) | 2020-07-31 |
Family
ID=71743722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910070503.9A Pending CN111467435A (zh) | 2019-01-24 | 2019-01-24 | 一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111467435A (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106729656A (zh) * | 2016-12-07 | 2017-05-31 | 江山 | 一种治疗口干的口腔护理组合物及其在牙膏中的应用 |
-
2019
- 2019-01-24 CN CN201910070503.9A patent/CN111467435A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106729656A (zh) * | 2016-12-07 | 2017-05-31 | 江山 | 一种治疗口干的口腔护理组合物及其在牙膏中的应用 |
Non-Patent Citations (2)
| Title |
|---|
| 韦波等: "肿节风水提物减轻放射性口干的临床疗效观察", 《广西医科大学学报》 * |
| 马姗姗等: "肿节风防治鼻咽癌诱导放化疗毒副反应", 《中国实验方剂学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101074158B1 (ko) | 간 보호 또는 간 질환의 예방 및 치료용 인삼다당체 조성물 | |
| CN102697035A (zh) | 虫草褔寿丹 | |
| JPH11322616A (ja) | 天然化学物質六酸化四砒素の新規の抗腫瘍治療剤としての用途及びその薬学的組成物 | |
| CN102258679B (zh) | 一种中药组合物、制备方法及其应用 | |
| CN103169843B (zh) | 一种具有抗辐射保护作用的复方药物 | |
| CN1895337B (zh) | 党参黄芪组合物提高晚期肿瘤患者生存质量的制药用途 | |
| KR20000061327A (ko) | 간질환 예방 및 치료용 생약조성물 | |
| CN105126030B (zh) | 一种辅助抗肺癌的壮药组合物 | |
| CN111467435A (zh) | 一种含有九节茶、铁皮石斛和玉竹的复方制剂的制备及其用途 | |
| TWI601535B (zh) | 牛樟段木栽培牛樟芝子實體及固態培養菌絲體水及乙醇萃取物之組合物應用於抗癌藥輔助劑 | |
| Ramachandran et al. | A review on antitumor action of amygdalin on various types of cancers | |
| CN100406026C (zh) | 一种治疗慢性胃炎、胃癌的药物及其制备方法 | |
| CN102793731A (zh) | 九节茶提取物在降低流感病毒易感性上的应用 | |
| CN102580065A (zh) | 虎眼万年青皂甙osw-i口服抗癌制剂及其制备方法 | |
| CN112022896A (zh) | 一种抗肿瘤中药复方软胶囊制剂及其制备方法和应用 | |
| KR102559079B1 (ko) | 한약재 복합 추출물을 유효 성분으로 포함하는 암 예방 또는 치료용 약학적 조성물 | |
| CN113181173B (zh) | 药用组合物及其在制备用于预防和/或治疗肝癌的产品中的应用 | |
| CN105030798B (zh) | 一种抗肿瘤的药物组合物及其制备方法和应用 | |
| US20060039999A1 (en) | Pharmaceutical composition for inhibition of tumor growth or metastasis | |
| CN110123871B (zh) | 一种提升白细胞及排毒作用的中药组合物制剂及制备方法 | |
| CN103705547A (zh) | 一种灵芝孢子的破壁处理剂 | |
| US20060177520A1 (en) | Compositions and methods for reducing cytotoxicity and inhibiting angiogenesis | |
| CN103585485B (zh) | 一种抗癌药物及其制备方法与应用 | |
| CN112107649B (zh) | 一种治疗抗肿瘤药物所致口腔粘膜损伤的中药组合物 | |
| CN102327421B (zh) | 治疗食管癌的活血行气中药制剂及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200731 |