CN107115408A - 一种降低甲氨蝶呤副作用的药物 - Google Patents
一种降低甲氨蝶呤副作用的药物 Download PDFInfo
- Publication number
- CN107115408A CN107115408A CN201710365573.8A CN201710365573A CN107115408A CN 107115408 A CN107115408 A CN 107115408A CN 201710365573 A CN201710365573 A CN 201710365573A CN 107115408 A CN107115408 A CN 107115408A
- Authority
- CN
- China
- Prior art keywords
- parts
- methotrexate
- mtx
- medicine
- side effect
- 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.)
- Withdrawn
Links
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 title claims abstract description 40
- 229960000485 methotrexate Drugs 0.000 title claims abstract description 40
- 239000003814 drug Substances 0.000 title claims abstract description 23
- 230000000694 effects Effects 0.000 title claims abstract description 18
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 14
- 239000003124 biologic agent Substances 0.000 claims abstract description 9
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 7
- 229940085605 saccharin sodium Drugs 0.000 claims abstract description 7
- 239000011734 sodium Substances 0.000 claims abstract description 7
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 6
- 229940057948 magnesium stearate Drugs 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 claims description 2
- 241001191006 Phlomoides rotata Species 0.000 claims description 2
- 241001103621 Psychotria Species 0.000 claims description 2
- 241000208000 Striga Species 0.000 claims description 2
- 229960003896 aminopterin Drugs 0.000 claims description 2
- 238000007796 conventional method Methods 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 238000007654 immersion Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000008107 starch Substances 0.000 claims 1
- 235000019698 starch Nutrition 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 12
- 208000005987 polymyositis Diseases 0.000 abstract description 9
- 241000700159 Rattus Species 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 6
- 238000007689 inspection Methods 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 206010044008 tonsillitis Diseases 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- HNXQXTQTPAJEJL-UHFFFAOYSA-N 2-aminopteridin-4-ol Chemical compound C1=CN=C2NC(N)=NC(=O)C2=N1 HNXQXTQTPAJEJL-UHFFFAOYSA-N 0.000 description 2
- 206010000087 Abdominal pain upper Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000007665 chronic toxicity Effects 0.000 description 2
- 231100000160 chronic toxicity Toxicity 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 201000001881 impotence Diseases 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 208000013220 shortness of breath Diseases 0.000 description 2
- 239000008354 sodium chloride injection Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000820 toxicity test Toxicity 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 206010001580 Albuminuria Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010024572 Lip ulceration Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030302 Oliguria Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 201000010878 atypical lipomatous tumor Diseases 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000037308 hair color Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- HLUCICHZHWJHLL-UHFFFAOYSA-N hematein Chemical compound C12=CC=C(O)C(O)=C2OCC2(O)C1=C1C=C(O)C(=O)C=C1C2 HLUCICHZHWJHLL-UHFFFAOYSA-N 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940125698 hormone suppressant Drugs 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 208000022752 well-differentiated liposarcoma Diseases 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
-
- 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)
- A61K36/80—Scrophulariaceae (Figwort family)
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种降低甲氨蝶呤副作用的药物，属于药物技术领域。该药物由甲氨蝶呤、羟甲基淀粉钠、生物制剂、硬脂酸镁、微晶纤维素、糖精钠制成。经临床试验，可较好的克服了普通甲氨蝶呤临床治疗多发性肌炎易产生副作用的问题。
Description
技术领域
本发明涉及医药技术领域，尤其涉及一种在临床治疗多发性肌炎时降低甲氨蝶呤副作用的药物。
背景技术
多发性肌炎是一种自身免疫性疾病，其发生与细菌、病毒、真菌等感染有关，属祖国医学“肌痿”范畴。为肝、脾、肾三脏失和, 气血失调, 气机不利, 肌失所荣，髓海失养，发为痿证。多发性肌炎以对称性四肢近端、咽部以及颈肌肌肉无力为主要临床表现，病因尚不明确。其一般会出现肌肉压痛和血清酶上升等特征，属于弥漫性肌肉炎症疾病，绝大多数观点认为与自身免疫系统有关，多数学者认为本病与自身免疫紊乱有关。也有部分学者认为与病毒感染或遗传因素有关。多为亚急性起病，任何年龄均可发病，中年以上多见，女性略多。目前西医主要应用激素或免疫抑制剂治疗，效果不理想，特别是长期服用，副作用大。甲氨蝶呤是目前常用的治疗多发性肌炎的药物之一，但由其引起的毒副作用明显，如口腔炎、口唇溃疡、咽喉炎、恶心、呕吐、腹痛、腹泻、黄疸、丙氨酸氨基转移酶、碱性磷酸酶，脂肪肝、纤维化甚至肝硬变、蛋白尿、尿少、咳嗽、气短、肺炎、脱发、皮肤发红、瘙痒或皮疹等。因此如何解决甲氨蝶呤副作用问题是目前研究的重点和热点。为解决甲氨蝶呤的副作用问题，发明人在多年的临床治疗实践中，不断探索研究，研制出一种在临床治疗多发性肌炎时降低甲氨蝶呤副作用的药物。
发明内容
本发明的目的是提供一种在临床治疗多发性肌炎时降低甲氨蝶呤副作用的药物。
本发明的目的是通过以下技术方案实现的，该降低甲氨蝶呤副作用的药物由甲氨蝶呤3-7份、羟甲基淀粉钠38-48份、生物制剂28-34份、硬脂酸镁1-2份、微晶纤维素35-45份、糖精钠12-20份制成。
将甲氨蝶呤、羟甲基淀粉钠、生物制剂、硬脂酸镁、微晶纤维素、糖精钠均过100目筛，按重量份称取甲氨蝶呤和生物制剂先于羟甲基淀粉钠以等量递加法混匀，接着加入微晶纤维素混匀，然后加入糖精钠和硬脂酸镁混匀，按常规方法压制成片。
所述生物制剂是由独一味30份、独脚柑18份、穿根藤28份加10倍重量份的蒸馏水浸泡40min，加热至沸腾文火保持20min，用六层纱布过滤，药渣再加6倍重量份蒸馏水，加热至沸腾文火保持30min，六层纱布过滤，合并2次滤液浓缩干燥，高压灭菌制成。
本发明所述药物片剂的质量检查
本研究制得3个批次的供试品，并按照《中国药典》的各项方法检查对其进行了崩解时限、溶出度和稳定性考察。
①崩解时限考察
按照《中国药典》2005 年版二部附录Ⅹ A 崩解时限检查法项下方法检查[5]，3 批次的平均崩解时限分别为（8.10±2.20）min、（8.12±2.17）min、（8.07±2.21）min，均不超过15 min，符合规定。
②溶出度考察
按照 《中国药典》2005 年版二部附录ⅩC 溶出度第一法项下方法检查[5]，45 min 时3 批次的平均溶出度分别为（85.23 ±6.16）% 、（85.20 ±6.33）% 、（85.20 ±6.20）% ，均超 过70%，符合规定。
③稳定性考察
按照 《中国药典》2005年版二部附录ⅪⅩC原料药与药物制剂稳定性试验指导原则[5]，对自制本发明所述药物片剂进行加速试验考察。 实验条件：供试品3批，按市售包装，在温度（40±3）℃、相对湿度（75±6）%（Na Cl饱和溶液）的条件下放置 6 个月。 在试验期间第 1、2、3、6 个月末各取样 1 次，按稳定性考察项目检查。 结果表明：本品在高温、高湿条件下稳定性较好，考察的各项指标均无明显变化，结果符合规定。
毒性试验
1、实验动物 清洁级健康SD雌性大鼠60只，体质量(203±5)g，用作慢性毒理实验；清洁级健康昆明雌性小白鼠40只，体质量(24±2)g，用作急性毒理实验。喂以普通饲料，普通饮水。室温控制在(21±3)℃，湿度(52±4)％，自然光照。
2、急性毒理实验，选用清洁级健康昆明雌性小白鼠40只，随机分为2组，试验组和空白对照组各20只。试验组按正常成人每天口服本发明药物的药量折算成小白鼠的剂量，每日灌服2次。空白对照组予1mL／20g体质量0.9％氯化钠注射液灌服。
3、慢性毒性实验 清洁级健康SD雌性大鼠60只，随机分为4组，对照组及试验组的小、中、大剂量各15只。对照组予1mI／20g体质量0.9％氯化钠注射液，试验组的小、中、大剂量组是成人正常用量折算成大鼠剂量的10、20、30倍，均为灌胃给药。每日2次，实验周期为3个月。
4、 急性毒性实验结果 小白鼠在给药7d内无死亡，给药后观察小鼠外观、毛色、光泽正常，社会行为、反应均正常，摄食、排泄正常。7d后人工处死解剖，观察其心脏、肝脏、脾脏、肺脏、肾脏、脑、卵巢、子宫均未见异常。病理学检查：苏木精一伊红(HE)染色，试验组脏器表面光滑，组织结构排列有序，细胞大小、形态正常，胞浆、胞核染色清晰，与空白对照组比较差异无统计学意义(P>0.05)。
5、慢性毒理实验结果 试验组的小、中、大剂量组和正常对照组大鼠的外观、毛色，社会行为、刺激性等和对周围环境、食物、水的兴趣等比较差异均无统计学意义(P>0.05)。4组大鼠实验后体质量均较本组实验前增加(P<0.05)，但4组实验后体质量比较差异均无统计学意义(P<0.05)，4组大鼠实验后血液细胞学指标、血液生化学指标、重要脏器系数比较差异均无统计学意义(P>0.05)。4组大鼠处死后重要脏器行病理切片染色检查，HE染色。试验组大鼠脏器组织结构排列有序，细胞大小、形态正常，胞浆、胞核染色清晰，与对照组比较差异无统计学意义(P>0.05)。
毒性试验表明，本发明所述药物给药大、小白鼠后未见毒性反应。
临床资料
1、一般资料 选自2010年2月～2014年7月来我院就诊的180例患者，其中男100例，女80例；年龄36～67岁，病程5个月～5年。在患者知情和自愿的基础上，只采用本发明药物加以治疗的设为治疗组，只采用甲氨蝶呤片加以治疗的设为对照组，统计学对比各组患者年龄、性别、病程无显著性差异（P<0.05）可以进行对比研究。
2、治疗方法 治疗组口服按本发明实施方式二制得的药物加以治疗，成人一次15mg，一日1次；对照组口服市售普通甲氨蝶呤片加以治疗，成人一次15mg，一日1次；各组4周为一疗程，各组患者均治疗2个疗程后进行疗效比较。
3、疗效评定标准 显效：机体的各项症状和体征基本或全部消失；有效：各项临床症状明显减缓且临床体征得到显著改善；无效：症状以及体征无明显改善或加重。
4、治疗结果：
| 组别 | 例数 | 日服药量 | 显效 | 有效 | 无效 | 复发率 | 副作用 | 总有效率（%） |
| 治疗组 | 90 | 15mg | 45 | 40 | 5 | 0 | 0 | 94.4 |
| 对照组 | 90 | 15mg | 44 | 39 | 7 | 15 | 21例 | 92.2 |
通过以上临床资料可知，治疗组总有效率虽然稍高于对照组，但毒性降低，没有出现毒副作用，无复发；而对照组中有15例复发，出现5例腹痛、4例咽喉炎、2例气短、5例恶心、6例出现不同程度的肝功能损伤。由此说明本发明的药物较好的克服了市售普通甲氨蝶呤临床使用中易产生副作用的问题。
当对治疗组患者进行随访时，其中有4例自述“服用本发明的药物后，不但治好了多发性肌炎，而且扁桃体炎也得到了有效的治疗”。得到这一消息后，我们随即对50例患有不同程度扁桃体炎患者，采用本发明实施方式二制得的药物加以治疗。疗效判断标准治愈：扁桃体发炎、肿胀以及因扁桃体炎症所引发的发热、疼痛等症状消失，机体免疫能力恢复正常； 好转：上述症状有所缓解，机体免疫能力有所恢复；无效：症状无变化。结果：50例患者中，治愈35例，好转13例，无效2例，总有效率按治愈和好转计为96%。由此可知，服用本发明的药物，不但治疗多发性肌炎疗效显著，而且对扁桃体炎具有很好的治疗效果。
Claims (3)
1.一种降低甲氨蝶呤副作用的药物，其特征在于该药物由甲氨蝶呤3-7份、羟甲基淀粉钠38-48份、生物制剂28-34份、硬脂酸镁1-2份、微晶纤维素35-45份、糖精钠12-20份制成。
2.如权利要求1所述的一种降低甲氨蝶呤副作用的药物的制备方法，其特征在于将甲氨蝶呤、羟甲基淀粉钠、生物制剂、硬脂酸镁、微晶纤维素、糖精钠均过100目筛，按重量份称取甲氨蝶呤和生物制剂先于羟甲基淀粉钠以等量递加法混匀，接着加入微晶纤维素混匀，然后加入糖精钠和硬脂酸镁混匀，按常规方法压制成片。
3.如权利要求1所述的一种降低甲氨蝶呤副作用的药物，其特征在于所述生物制剂是由独一味30份、独脚柑18份、穿根藤28份加10倍重量份的蒸馏水浸泡40min，加热至沸腾文火保持20min，用六层纱布过滤，药渣再加6倍重量份蒸馏水，加热至沸腾文火保持30min，六层纱布过滤，合并2次滤液浓缩干燥，高压灭菌制成。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710365573.8A CN107115408A (zh) | 2017-05-22 | 2017-05-22 | 一种降低甲氨蝶呤副作用的药物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710365573.8A CN107115408A (zh) | 2017-05-22 | 2017-05-22 | 一种降低甲氨蝶呤副作用的药物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107115408A true CN107115408A (zh) | 2017-09-01 |
Family
ID=59728666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710365573.8A Withdrawn CN107115408A (zh) | 2017-05-22 | 2017-05-22 | 一种降低甲氨蝶呤副作用的药物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107115408A (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107752002A (zh) * | 2017-10-10 | 2018-03-06 | 陈仲亮 | 一种增强免疫力的桦茸硒片 |
| CN109078129A (zh) * | 2018-08-20 | 2018-12-25 | 沂南县迎辉农业开发有限公司 | 一种降低阿奇霉素临床治疗扁桃体炎副作用的药物 |
-
2017
- 2017-05-22 CN CN201710365573.8A patent/CN107115408A/zh not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107752002A (zh) * | 2017-10-10 | 2018-03-06 | 陈仲亮 | 一种增强免疫力的桦茸硒片 |
| CN109078129A (zh) * | 2018-08-20 | 2018-12-25 | 沂南县迎辉农业开发有限公司 | 一种降低阿奇霉素临床治疗扁桃体炎副作用的药物 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102145126B (zh) | 治疗干眼症的药物组合物 | |
| CN101444611A (zh) | 治疗腰腿痛、腰椎间盘突出症的中药组合物及其制备方法 | |
| CN104667044A (zh) | 一种治疗痹症的中药制剂及其制备方法 | |
| CN105327287A (zh) | 一种治疗精神病的药物组合物及其制备工艺 | |
| CN107115408A (zh) | 一种降低甲氨蝶呤副作用的药物 | |
| CN100528214C (zh) | 治疗癫痫病的胶囊及制备方法 | |
| CN105769789A (zh) | 用于治疗精神分裂症的氯氮平片及其制备方法 | |
| CN103191331A (zh) | 用于治疗支气管哮喘缓解期的中药组合物 | |
| CN105919991B (zh) | 泽兰素在制备治疗抑郁症药物中的应用 | |
| CN104524245B (zh) | 用于治疗儿童多动症的中药组合物及其制剂 | |
| CN1209162C (zh) | 治疗痤疮、黄褐斑的药物组合物 | |
| CN102579785B (zh) | 肺康丸 | |
| CN107669931A (zh) | 一种降低呋喃唑酮临床治疗慢性肠炎副作用的药物 | |
| CN105687835A (zh) | 一种治疗躁狂症的中药及制备方法 | |
| CN107007590A (zh) | 淫羊藿苷元在制备预防或治疗帕金森病药物中的用途 | |
| CN106177461A (zh) | 一种治疗神经衰弱综合征的中西药复方制剂及制备方法 | |
| CN106109541A (zh) | 一种提高机体免疫力、抗疲劳的保健品 | |
| CN107661387A (zh) | 一种降低硝酸甘油临床治疗心绞痛副作用的药物 | |
| CN107158107A (zh) | 一种降低来佛米特副作用的药物 | |
| CN104116836B (zh) | 一种用于治疗抑郁症的中药组合物及其制备方法 | |
| CN104996685A (zh) | 一种保健茶饮料及其制备方法 | |
| CN105213398B (zh) | 一种治疗糖尿病的药物组合物 | |
| CN115245549A (zh) | 一种改善体质的中药组合物 | |
| CN107929508A (zh) | 一种解郁中药组合物及其制备方法 | |
| CN109078129A (zh) | 一种降低阿奇霉素临床治疗扁桃体炎副作用的药物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20170901 |
|
| WW01 | Invention patent application withdrawn after publication |