CN115429848A - Application of traditional Chinese medicine composition in preparation of medicine for treating osteoporosis - Google Patents
Application of traditional Chinese medicine composition in preparation of medicine for treating osteoporosis Download PDFInfo
- Publication number
- CN115429848A CN115429848A CN202111397663.8A CN202111397663A CN115429848A CN 115429848 A CN115429848 A CN 115429848A CN 202111397663 A CN202111397663 A CN 202111397663A CN 115429848 A CN115429848 A CN 115429848A
- Authority
- CN
- China
- Prior art keywords
- parts
- root
- ginseng
- traditional chinese
- chinese medicine
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 43
- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 28
- 239000000203 mixture Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 5
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 75
- 241000208340 Araliaceae Species 0.000 claims abstract description 54
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 claims abstract description 54
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 54
- 235000008434 ginseng Nutrition 0.000 claims abstract description 54
- 206010027476 Metastases Diseases 0.000 claims abstract description 53
- 230000009401 metastasis Effects 0.000 claims abstract description 53
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims abstract description 45
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 35
- 201000005202 lung cancer Diseases 0.000 claims abstract description 35
- 208000020816 lung neoplasm Diseases 0.000 claims abstract description 35
- 229960004276 zoledronic acid Drugs 0.000 claims abstract description 35
- 238000005728 strengthening Methods 0.000 claims abstract description 34
- 241000405414 Rehmannia Species 0.000 claims abstract description 14
- 235000002722 Dioscorea batatas Nutrition 0.000 claims abstract description 8
- 235000006536 Dioscorea esculenta Nutrition 0.000 claims abstract description 8
- 240000001811 Dioscorea oppositifolia Species 0.000 claims abstract description 8
- 235000003416 Dioscorea oppositifolia Nutrition 0.000 claims abstract description 8
- 244000197580 Poria cocos Species 0.000 claims abstract description 8
- 235000008599 Poria cocos Nutrition 0.000 claims abstract description 8
- 241000405911 Rehmannia glutinosa Species 0.000 claims abstract 2
- 239000007788 liquid Substances 0.000 claims description 34
- 208000024891 symptom Diseases 0.000 claims description 11
- 241000209020 Cornus Species 0.000 claims description 6
- 206010034156 Pathological fracture Diseases 0.000 claims description 6
- 208000005250 Spontaneous Fractures Diseases 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 244000003416 Asparagus officinalis Species 0.000 claims description 4
- 235000005340 Asparagus officinalis Nutrition 0.000 claims description 4
- 206010006002 Bone pain Diseases 0.000 claims description 4
- 208000037147 Hypercalcaemia Diseases 0.000 claims description 4
- 240000005001 Paeonia suffruticosa Species 0.000 claims description 4
- 235000003889 Paeonia suffruticosa Nutrition 0.000 claims description 4
- 235000001188 Peltandra virginica Nutrition 0.000 claims description 4
- 206010041549 Spinal cord compression Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 230000000148 hypercalcaemia Effects 0.000 claims description 4
- 208000030915 hypercalcemia disease Diseases 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 241000049624 Alisma plantago-aquatica subsp. orientale Species 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 241000759833 Cornus officinalis Species 0.000 claims 1
- 229930195210 Ophiopogon Natural products 0.000 claims 1
- 244000248557 Ophiopogon japonicus Species 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 229940126680 traditional chinese medicines Drugs 0.000 abstract description 2
- 240000006766 Cornus mas Species 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 29
- 230000000694 effects Effects 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 210000000689 upper leg Anatomy 0.000 description 7
- 230000037182 bone density Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 206010061289 metastatic neoplasm Diseases 0.000 description 6
- 238000000465 moulding Methods 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 3
- 108010022452 Collagen Type I Proteins 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000000010 osteolytic effect Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 206010027452 Metastases to bone Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000009102 absorption Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 244000248539 Asparagus cochinchinensis Species 0.000 description 1
- 235000009292 Asparagus cochinchinensis Nutrition 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 240000002948 Ophiopogon intermedius Species 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000011579 SCID mouse model Methods 0.000 description 1
- 206010041497 Spermatorrhoea Diseases 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 210000004349 growth plate Anatomy 0.000 description 1
- 210000003692 ilium Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000010603 microCT Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 238000012809 post-inoculation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000011127 radiochemotherapy Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000886 tinnitus Toxicity 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
- A61K36/076—Poria
-
- 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)
- A61K36/40—Cornaceae (Dogwood 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)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- 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)
- A61K36/804—Rehmannia
-
- 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)
- A61K36/884—Alismataceae (Water-plantain 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)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/894—Dioscoreaceae (Yam family)
- A61K36/8945—Dioscorea, e.g. yam, Chinese yam or water yam
-
- 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
- A61K36/8965—Asparagus, e.g. garden asparagus or asparagus fern
-
- 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
- A61K36/8968—Ophiopogon (Lilyturf)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a ginseng root-strengthening traditional Chinese medicine composition prepared from ginseng, rehmannia glutinosa, poria cocos, moutan bark, prepared rehmannia root, dogwood, chinese yam, rhizoma alismatis, radix asparagi and radix ophiopogonis, and application of the ginseng root-strengthening traditional Chinese medicine composition combined with zoledronic acid in preparation of a medicine for treating lung cancer bone metastasis with osteoporosis.
Description
Technical Field
The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to application of ginseng root-strengthening oral liquid and zoledronic acid in lung cancer bone metastasis with osteoporosis.
Background
In recent years, the incidence and mortality of lung cancer have rapidly increased, and the lung cancer has become one of the most common malignant tumors. The highly metastatic character of lung cancer is one of the leading causes of poor treatment and death. The most common sites of metastasis for lung cancer are brain metastases and bone metastases. In advanced lung cancer, bone metastasis is predominant, and the metastatic sites are usually found in the spine, the bones of the limbs, the ilium, etc. The radiotherapy and chemotherapy and the like have adverse effects on bone metabolism, so that the loss of bone components is increased, osteoporosis is caused, the osteoporosis has high morbidity in elderly patients, the osteoporosis and bone metastasis mutually affect, clinical symptoms are aggravated, and the life quality of the patients is seriously affected. The clinical manifestations of lung cancer bone metastasis and osteoporosis are related to bone events such as dysfunction, pathological fracture, severe bone pain, spinal cord compression of vertebral body metastasis, hypercalcemia and the like. Bone metastasis prognosis is poor, so early detection of treatment is extremely important.
The current major therapies include chemoradiotherapy, radionuclides, bisphosphonates, analgesics, etc. Zoledronic acid (Zoledronic acid) is a latest generation of diphosphate type medicine, and has good prevention and treatment effects on malignant tumor bone metastasis and osteoporosis. The zoledronic acid can selectively inhibit osteoclast activity and bone destruction, induce apoptosis of various tumor cells, and reduce bone destruction, absorption and pathological fracture incidence; and can reduce the release of inflammatory mediators and pain factors such as prostaglandin, lactic acid and the like, relieve pain, and have the advantages of improving the survival rate and the life quality of patients and the like. Zoledronic acid combined with radiotherapy is a main therapy for lung cancer bone metastasis, and is widely used for preventing and treating various clinical bone metastasis tumors. However, the medicine has great medicine taking problems because the medicine is very poor in absorption and stimulates the esophagus, so that the medicine taking requirements are quite strict and accurate, and side effects are great.
Clinical research shows that the clinical curative effect of treating the lung cancer bone metastasis by combining traditional Chinese medicine and western medicine is more obvious than that of treating the bone metastasis by using simple western medicine. The ginseng root-strengthening oral liquid is prepared from ginseng, rehmannia root, poria cocos, moutan bark, prepared rehmannia root, dogwood fruit, chinese yam, rhizoma alismatis, asparagus and radix ophiopogonis, has the effects of nourishing yin and tonifying qi, and strengthening the body resistance and reinforcing primordial qi, and is mainly used for treating yin deficiency and qi weakness, consumptive cough, palpitation and short breath, bone steaming and tidal fever, waist soreness and tinnitus, spermatorrhea and night sweat, and dry stool. The applicant finds that the ginseng root-strengthening oral liquid and the zoledronic acid have better treatment effects in the bone metastasis of lung cancer and osteoporosis clinically, and the efficacy of the ginseng root-strengthening oral liquid is not reported in the previous literature.
Disclosure of Invention
The inventor finds that the traditional Chinese medicine product can prevent and treat the lung cancer bone metastasis with osteoporosis by combining with zoledronic acid on the basis of clinical use feedback of 'ginseng root-strengthening oral liquid'.
The invention aims to provide a ginseng root-strengthening traditional Chinese medicine composition, and an application of the ginseng root-strengthening traditional Chinese medicine composition in preparation of a combined medicine for preventing and/or treating lung cancer bone metastasis with osteoporosis.
The ginseng root-strengthening traditional Chinese medicine composition is used for preparing a medicine for preventing and/or treating lung cancer bone metastasis in combination with zoledronic acid.
The lung cancer bone metastasis with osteoporosis is also accompanied by at least one symptom of functional disorder, pathological fracture, severe bone pain, spinal cord compression of vertebral body metastasis or hypercalcemia.
The ginseng root-strengthening traditional Chinese medicine composition is prepared from ginseng, rehmannia root, poria cocos, moutan bark, prepared rehmannia root, dogwood, chinese yam, rhizoma alismatis, asparagus cochinchinensis and radix ophiopogonis. The traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: 60-90 parts of ginseng, 130-170 parts of rehmannia root, 130-170 parts of tuckahoe, 130-170 parts of tree peony bark, 130-170 parts of prepared rehmannia root, 130-170 parts of dogwood, 280-320 parts of Chinese yam, 130-170 parts of alisma orientale, 130-170 parts of asparagus and 130-170 parts of dwarf lilyturf tuber.
Further, the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: 70-80 parts of ginseng, 140-160 parts of rehmannia root, 140-160 parts of tuckahoe, 140-160 parts of tree peony bark, 140-160 parts of prepared rehmannia root, 140-160 parts of dogwood, 290-310 parts of Chinese yam, 140-160 parts of rhizoma alismatis, 140-160 parts of radix asparagi and 140-160 parts of radix ophiopogonis.
The ginseng root-strengthening oral liquid and zoledronic acid medicine can prevent or treat lung cancer bone metastasis with osteoporosis, and is also accompanied with at least one of the following symptoms: functional disorder, pathological fracture, severe bone pain, spinal cord compression of vertebral body metastasis or hypercalcemia.
The administration mode of the traditional Chinese medicine composition comprises preventive intervention administration or therapeutic administration.
The ginseng traditional Chinese medicine composition for consolidating the constitution also contains one or more pharmaceutically acceptable pharmaceutic adjuvants.
The traditional Chinese medicine composition can be prepared into an acceptable preparation form by directly adding pharmaceutically acceptable auxiliary materials through a conventional process.
The ginseng root-strengthening traditional Chinese medicine composition is processed into capsules, tablets, granules, powder, syrup, pills or oral liquid by the prior art.
Wherein, the clinically acceptable dosage forms comprise capsules, tablets, granules, pills or oral liquid.
Preferably, the clinically acceptable dosage form is an oral liquid.
Further preferably, the oral liquid is ginseng solid oral liquid.
Compared with the prior art, the invention has the following remarkable advantages:
the invention discloses a new application of a traditional Chinese medicine composition, namely ginseng root-strengthening oral liquid, in combination with zoledronic acid in preventing and treating lung cancer bone metastasis with osteoporosis for the first time. According to the invention, a lung cancer bone metastasis model is successfully established, and the combination of the ginseng root-strengthening oral liquid and the zoledronic acid can reduce the molding success rate of lung cancer bone metastasis and prevent the generation of the lung cancer bone metastasis with osteoporosis; the weight of the mice in the ginseng root-strengthening oral liquid and zoledronic acid group is maintained stably in the experimental process, and the vital signs are normal; enzyme-linked immunosorbent assay (ELISA) is used for detecting the serum type I collagen amino terminal peptide (NTX) level of each group of tumor-bearing nude mice, and the ginseng root-strengthening oral liquid and zoledronic acid group obviously reduce the serum NTX level (p is less than 0.05), which shows that the ginseng root-strengthening oral liquid and zoledronic acid can effectively inhibit the activity of osteolytic cells and reduce the damage of bone metastasis to bone quality.
Mice with successful lung cancer bone metastasis molding have a clinically common osteoporosis symptom. By carrying out bone density measurement on mice successfully molded before and after molding, the inventor finds that the zoledronic acid and ginseng root-strengthening oral liquid has significant difference compared with a control group when being used together, significantly improves the symptoms of lung cancer bone metastasis with osteoporosis, further improves the symptoms of lung cancer bone metastasis with osteoporosis compared with zoledronic acid, and plays a role in synergy; the microscopic CT analysis is carried out on the microstructure of the distal metaphyseal spongy bone of the femur, and the zoledronic acid and ginseng solid oral liquid further inhibits the reduction of the metaphyseal bone mass and the number of bone trabeculae of the femur, reduces the space between the bone trabeculae and can effectively improve the symptoms of bone metastasis of lung cancer with osteoporosis.
The ginseng root-strengthening oral liquid combined with zoledronic acid can effectively relieve the symptoms of lung cancer bone metastasis with osteoporosis, relieve pain, promote bone reconstruction, reduce the incidence rate of pathological fracture and inhibit a new bone metastasis, is safe and reliable in clinical application, good in patient tolerance and few in side effect, and is worthy of clinical use and popularization.
Detailed Description
The advantageous effects of the present invention will now be further described by the following examples, which should be understood as being for illustrative purposes only and not limiting the scope of the present invention, and that changes and modifications apparent to those of ordinary skill in the art in light of the present invention are also included within the scope of the present invention.
Example 1
Experimental animals: immunodeficient mice SCID mice (NIH-BNX mice), 70 mice, 8-10 weeks old, weighing 22 + -2 grams, were bred under SPF environment.
Tumor cell culture: preparing single cell suspension from human lung adenocarcinomse:Sub>A bone metastasis cell strain SPC-A-IBM in exponential growth phase. The single cell suspension is subjected to primary culture and then further amplified. The culture conditions were DMEM medium. Cell culture environment 37 deg.C, 5% 2 . Metastatic tumor model: the prepared cell suspension was inoculated into the left ventricle of 60 NIH-BNX mice (containing about 0.8X 10 viable cell count) at 0.2mL per cell 6 And (II) making into a lung cancer bone metastasis model.
Grouping and processing: according to the weight, 10 NIH-BNX mice are randomly selected as a normal control group without any treatment, the remaining 60 mice are prepared into a metastatic tumor model, the metastatic tumor model is randomly divided into 3 groups, each group is 20, and each mouse in the group is numbered by a toe-cutting method and is respectively 1-20. Dosing began on day 8 post-inoculation and was continued for a total of 5 weeks. The mice were weighed twice a week, observed for general conditions, sacrificed if they were imminent, and sacrificed at week 8.
Zoledronic acid group: zoledronic acid 0.2mg/kg2 times/w.times.5 w was administered by subcutaneous injection.
Zoledronic acid + ginseng solid oral liquid group: zoledronic acid 0.2mg/kg2 times/w is multiplied by 5w for subcutaneous injection administration, and ginseng solid oral liquid 3.6mL/kg for intragastric administration.
Control group: normal saline solution is injected in equal volume for administration.
Normal group: metastatic tumor modeling was not performed and saline was administered by equal volume injection.
Statistical treatment: all data were analyzed by SPSS16.0 for data processing and results
And (4) showing.
Evaluation indexes and results:
(I) evaluation index of bone metastasis
(1) Body weights were weighed and recorded twice weekly from the first drug injection to week 8 in the tumor cell inoculated murine model.
TABLE 1 weight change for each group
P <0.05 compared to control group
After inoculation of the tumor cells, mice in the control group began to experience wasting. By the 7 th week, the weight of the zoledronic acid group is remarkably different from that of the control group (p is less than 0.05), but the duration is short, the weight of mice in the zoledronic acid + ginseng root-fixing oral liquid group is remarkably different from that of the control group (p is less than 0.05) from the 4 th week and lasts until the 8 th week, which shows that the combined use of the zoledronic acid and the ginseng root-fixing oral liquid can maintain the weight of the mice at a certain level.
(2) Mice were sacrificed for pronucleus scanning by intravenous injection of 148MBq from the mouse tail 99 Mice were sacrificed by exsanguination after 5-6 hours and ECT scan with SPECTE. Matrix 256 × 256, zoom3.2, ims:0.1 mm. Times.2 cm. And observing the number of the bone metastasis mice by taking the nuclide concentration or deletion part as a bone metastasis positive part.
TABLE 2 number of tumor-bearing mice positive for each nuclide scan group
The bone metastasis of tumor-bearing mice is scanned by nuclides, and the number of the bone metastases in the control group is 16 at most, accounting for 80%. The number of mice with bone metastasis in the zoledronic acid group, the zoledronic acid group and the ginseng root-strengthening oral liquid group is 8 and 6 respectively, and results show that the zoledronic acid can prevent the bone metastasis to a certain extent, and the combined medication of the zoledronic acid and the ginseng root-strengthening oral liquid group has a synergistic effect on reducing the bone metastasis of lung cancer.
(3) Serum is reserved when the mice are sacrificed, the level of serum type I collagen amino-terminal peptide (NTX) of each group of tumor-bearing nude mice is detected by an enzyme-linked immunosorbent assay (ELISA), and the specific operation method is as provided in the NTX kit instruction provided by Haiyuan medical instrument company Limited.
TABLE 3 serum NTX levels in groups of tumor-bearing mice
| Group of | Number of tests (n) | Mean value (nM) |
| Zoledronic acid group | 8 | 9.867±3.493 |
| Zoledronic acid and ginseng oral liquid group for strengthening body resistance | 6 | 7.391±4.291* |
| Control group | 16 | 13.759±4.892 |
Compared with the control group, the compound of the formula, * p<0.05
the type I collagen amino-terminal peptide (NTX) is a bone metastasis marker representing the activity of osteolytic cells, the serum NTX level of each group of tumor-bearing mice is shown in table 3, and the zoledronic acid and ginseng solid oral liquid group obviously reduces the serum NTX level (p is less than 0.05), which indicates that the ginseng solid oral liquid and the zoledronic acid can effectively inhibit the activity of the osteolytic cells and reduce the damage of bone metastasis to bone quality. (II) evaluation index of osteoporosis after bone metastasis
And (3) measuring the osteoporosis degree related indexes of 60 modeling experiment mice, and selecting the data of mice with successful lung cancer bone metastasis according to the nuclide scanning condition after the measurement is finished, and finishing the data as follows.
(1) Bone Density (BMD) determination
Before molding, 60 mice divided into 3 groups were anesthetized with pentobarbital sodium in the abdominal cavity, and the supine position was examined for bone density by using a dual-energy X-ray bone densitometer, wherein the examination time was before molding (0 week), in the middle stage of drug intervention (4 weeks), and after sacrifice (8 weeks).
TABLE 4 comparison of Whole body BMD for each group
P <0.05, P <0.01, compared to control group
The bone density of the lung cancer bone metastasis mice in the control group continuously decreases along with the time; the bone density of mice administered with zoledronic acid decreased with time, and at week 8, the zoledronic acid group was significantly different from the control group (P < 0.05); the bone density of mice administered with the zoledronic acid + ginseng solid oral solution decreases less with time, and is significantly different from the control group at week 4 (P < 0.05) and significantly different from the control group at week 8 (P < 0.01). The experimental result shows that the zoledronic acid and the ginseng root-strengthening oral liquid have a synergistic effect and can obviously improve the symptoms of lung cancer bone metastasis with osteoporosis.
(2) The microstructure of the distal metaphyseal cancellous bone of the femur was analyzed by micro-CT. And 2-dimensional scanning is adopted to scan the cross section with the thickness of 9.43 mu m at the position 1.06mm below the far epiphyseal cartilage line of the femur, and the structure of the spongy bone is quantitatively analyzed, wherein the content comprises the bone mass/tissue mass of the spongy bone, the number of trabeculae and the distance between the trabeculae.
TABLE 5 comparison of distal femur spongy bone in groups of mice
| Group of | n | Bone mass/tissue mass (%) | Number of trabeculae (n/mm) | Bone trabecula spacing (mm) |
| Zoledronic acid group | 8 | 14.6±0.9*# | 2.7±0.3*# | 0.34±0.04 *# |
| Zoledronic acid and ginseng oral liquid group for strengthening body resistance | 6 | 16.3±1.1** | 3.7±0.3** | 0.29±0.02** |
| Control group | 16 | 8.7±1.4## | 1.8±0.4## | 0.49±0.07## |
| Normal group | 10 | 17.2±0.7** | 3.8±0.3** | 0.27±0.05** |
Comparing with control group * P<0.05， ** P<0.01; comparison with Normal group # P<0.05, ## P<0.01
Compared with the normal group, the bone mass and the number of trabeculae at the metaphysis of the femur of the control group are obviously reduced, and the spacing between the trabeculae is obviously increased; the zoledronic acid group inhibited the decrease in the amount of metaphyseal bone and number of trabeculae of the femur and maintained the trabecular spacing; the zoledronic acid and ginseng root-strengthening oral liquid group further inhibits the reduction of the metaphyseal bone mass of femoral bones and the number of bone trabeculae, reduces the spacing between the bone trabeculae, has no significance (P is more than 0.05) compared with the normal group, shows that the zoledronic acid and ginseng root-strengthening oral liquid have obvious combined effect and has synergistic effect on improving the symptoms of lung cancer bone metastasis and osteoporosis.
Claims (10)
1. Application of ginseng root-strengthening traditional Chinese medicine composition in preparing medicines for preventing and/or treating lung cancer bone metastasis with osteoporosis.
2. The use of claim 1, wherein the ginseng root-securing traditional Chinese medicine composition is used for preparing a medicine for preventing and/or treating lung cancer bone metastasis with osteoporosis in combination with zoledronic acid.
3. The use of claim 1, wherein the ginseng root-strengthening traditional Chinese medicine composition is used for preparing a medicine for preventing and/or treating lung cancer bone metastasis in combination with zoledronic acid.
4. The use of claim 2, wherein the lung cancer bone metastasis with osteoporosis is further accompanied by at least one symptom of a functional disorder, pathological fracture, severe bone pain, spinal cord compression of vertebral body metastasis, or hypercalcemia.
5. The use of claim 1, 2, 3 or 4, wherein the ginseng root-strengthening Chinese medicinal composition is prepared from ginseng, rehmannia glutinosa, poria cocos, moutan bark, prepared rehmannia root, cornus officinalis, chinese yam, alisma orientale, asparagus, and ophiopogon root.
6. The use of claim 5, wherein the ginseng root-strengthening traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: 60-90 parts of ginseng, 130-170 parts of rehmannia root, 130-170 parts of tuckahoe, 130-170 parts of tree peony bark, 130-170 parts of prepared rehmannia root, 130-170 parts of dogwood, 280-320 parts of Chinese yam, 130-170 parts of rhizoma alismatis, 130-170 parts of asparagus and 130-170 parts of radix ophiopogonis.
7. The use of claim 5, wherein the Chinese medicinal composition is prepared from the following medicinal materials in parts by weight: 70-80 parts of ginseng, 140-160 parts of rehmannia root, 140-160 parts of tuckahoe, 140-160 parts of tree peony bark, 140-160 parts of prepared rehmannia root, 140-160 parts of dogwood, 290-310 parts of Chinese yam, 140-160 parts of rhizoma alismatis, 140-160 parts of radix asparagi and 140-160 parts of radix ophiopogonis.
8. The use of claim 5, wherein the ginseng root-strengthening traditional Chinese medicine composition further comprises one or more pharmaceutically acceptable pharmaceutical excipients.
9. The use of claim 5, wherein the ginseng root-strengthening traditional Chinese medicine composition is processed into capsules, tablets, granules, powder, syrup, pills or oral liquid by the prior art.
10. The use of claim 9, wherein the ginseng root-securing traditional Chinese medicine composition is a ginseng root-securing oral liquid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2020113613930 | 2020-11-27 | ||
| CN202011361393 | 2020-11-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115429848A true CN115429848A (en) | 2022-12-06 |
Family
ID=84240124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111397663.8A Pending CN115429848A (en) | 2020-11-27 | 2021-11-24 | Application of traditional Chinese medicine composition in preparation of medicine for treating osteoporosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115429848A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1626228A (en) * | 2003-08-19 | 2005-06-15 | 中国人民解放军军事医学科学院毒物药物研究所 | Extractive from decoction of rehmannia including six elements, combination of medication, and medical use |
| CN1762237A (en) * | 2005-11-02 | 2006-04-26 | 江中药业股份有限公司 | Health care food capable of preventing osteoprosis and preparation method thereof |
| CN103566171A (en) * | 2013-11-14 | 2014-02-12 | 大连杰信生物科技有限公司 | Preparation method and medicinal use of paste containing rehmannia, ginseng, radix ophiopogonis and radix asparagi |
| CN111407847A (en) * | 2020-05-21 | 2020-07-14 | 鲁南制药集团股份有限公司 | Application of traditional Chinese medicine composition in treating gynecological diseases |
-
2021
- 2021-11-24 CN CN202111397663.8A patent/CN115429848A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1626228A (en) * | 2003-08-19 | 2005-06-15 | 中国人民解放军军事医学科学院毒物药物研究所 | Extractive from decoction of rehmannia including six elements, combination of medication, and medical use |
| CN1762237A (en) * | 2005-11-02 | 2006-04-26 | 江中药业股份有限公司 | Health care food capable of preventing osteoprosis and preparation method thereof |
| CN103566171A (en) * | 2013-11-14 | 2014-02-12 | 大连杰信生物科技有限公司 | Preparation method and medicinal use of paste containing rehmannia, ginseng, radix ophiopogonis and radix asparagi |
| CN111407847A (en) * | 2020-05-21 | 2020-07-14 | 鲁南制药集团股份有限公司 | Application of traditional Chinese medicine composition in treating gynecological diseases |
Non-Patent Citations (4)
| Title |
|---|
| 刘学;赵林林;: "归脾汤合六味地黄丸加减治疗晚期肺癌化疗骨髓抑制", 吉林中医药, no. 07, 15 July 2014 (2014-07-15), pages 705 - 707 * |
| 刘献祥等: "骨质疏松性骨折", 31 October 2008, 福建科学技术出版社, pages: 172 * |
| 国家药典委员会: "中华人民共和国药典临床用药须知：2010年版，中药饮片卷", 30 April 2011, 中国医药科技出版社, pages: 996 * |
| 陈吉生: "新编临床药物学", 31 August 2014, 中国中医药出版社, pages: 827 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6911221B2 (en) | Anti-neoplastic drug | |
| CN101890040B (en) | Composition with anti-fatigue effect and application thereof | |
| CN104306959A (en) | Medicine composition for treating osteoporosis and preparation method thereof | |
| CN100502936C (en) | Chinese medicinal compound preparation for inhibiting tumor and resisting insenescence | |
| CN102861193B (en) | Traditional Chinese medicine composition for treating gastric cancer | |
| CN115429848A (en) | Application of traditional Chinese medicine composition in preparation of medicine for treating osteoporosis | |
| CN101036708A (en) | Medicine composition for treatment of cardio-cerebralvascular disease | |
| CN114081923A (en) | Application of traditional Chinese medicine composition in preparation of medicine for treating muscular atrophy | |
| CN104491459A (en) | Traditional Chinese medicine composition for treating tumors | |
| CN101966235B (en) | Medicament for treating migraine and preparation method thereof | |
| CN116350674B (en) | Traditional Chinese medicine composition for preventing early lung metastasis of Lewis lung cancer and application thereof | |
| CN108815301A (en) | Has effects that composition of leukocytosis promoting and preparation method thereof | |
| CN109528886A (en) | A kind of Chinese medicinal composition preparation and its preparation and application preventing and treating Postmenopausal Osteoporosis | |
| CN116570702B (en) | Traditional Chinese medicine composition for resisting ejection fraction retention type heart failure and application thereof | |
| CN109106893B (en) | Traditional Chinese medicine compound preparation for regulating intestinal barrier function and preparation method thereof | |
| CN116763884B (en) | Traditional Chinese medicine mixture for treating sarcopenia-osteoporosis and preparation method thereof | |
| CN113041254B (en) | Chinese medicinal composition comprising herba Goodyearae Repentis and its preparation method | |
| CN108635498B (en) | Pharmaceutical composition for treating myelodysplastic syndrome and application thereof | |
| CN108743796B (en) | Traditional Chinese medicine composition for treating lung cancer and application thereof | |
| CN109908294B (en) | Pharmaceutical composition for treating stable stage of bronchiectasis and preparation method and application thereof | |
| CN114129656A (en) | New use of Ginseng radix oral liquid for preventing and treating radiation-induced lung injury | |
| CN105477373A (en) | Chinese patent medicine for treating myocardial infarction and preparation method thereof | |
| CN116688001A (en) | Traditional Chinese medicine composition for preventing and treating tumor bone metastasis and reducing osteoporosis and/or toxic and side effects of chemotherapy, and preparation method and application thereof | |
| CN109432226A (en) | It is a kind of to have effects that the composition of leukocytosis promoting | |
| CN104189846A (en) | Traditional Chinese medicine composition used as radiotherapy and chemotherapy sensitizing agent and preparation method thereof |
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 |