CN113730379A - 一种含白花丹提取物的巴布剂及其制备方法 - Google Patents
一种含白花丹提取物的巴布剂及其制备方法 Download PDFInfo
- Publication number
- CN113730379A CN113730379A CN202111118465.3A CN202111118465A CN113730379A CN 113730379 A CN113730379 A CN 113730379A CN 202111118465 A CN202111118465 A CN 202111118465A CN 113730379 A CN113730379 A CN 113730379A
- Authority
- CN
- China
- Prior art keywords
- extract
- parts
- plumbum preparatium
- cataplasm
- plumbago
- 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.)
- Granted
Links
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 53
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229940119217 chamomile extract Drugs 0.000 claims abstract description 27
- 229940069521 aloe extract Drugs 0.000 claims abstract description 26
- 235000020221 chamomile extract Nutrition 0.000 claims abstract description 26
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims abstract description 16
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 11
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 11
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 claims abstract description 10
- 239000008367 deionised water Substances 0.000 claims abstract description 10
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 10
- 239000010439 graphite Substances 0.000 claims abstract description 10
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 46
- 241000368424 Plumbago scandens Species 0.000 claims description 43
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 238000002156 mixing Methods 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 20
- 239000012530 fluid Substances 0.000 claims description 17
- 239000004745 nonwoven fabric Substances 0.000 claims description 17
- 239000011248 coating agent Substances 0.000 claims description 16
- 238000000576 coating method Methods 0.000 claims description 16
- -1 dihydroxyaminoacetic acid aluminum Chemical compound 0.000 claims description 15
- 235000019198 oils Nutrition 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 239000003208 petroleum Substances 0.000 claims description 14
- VCMMXZQDRFWYSE-UHFFFAOYSA-N plumbagin Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1O VCMMXZQDRFWYSE-UHFFFAOYSA-N 0.000 claims description 14
- 238000002791 soaking Methods 0.000 claims description 14
- 238000001914 filtration Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 238000000605 extraction Methods 0.000 claims description 12
- 238000002386 leaching Methods 0.000 claims description 12
- 235000019476 oil-water mixture Nutrition 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000741 silica gel Substances 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 9
- 241000209456 Plumbago Species 0.000 claims description 9
- 239000004698 Polyethylene Substances 0.000 claims description 9
- 229920000573 polyethylene Polymers 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 230000001681 protective effect Effects 0.000 claims description 8
- ZMOIGGHUSNHCAB-UHFFFAOYSA-N Isoplumbagin Natural products C1=CC(O)=C2C(=O)C(C)=CC(=O)C2=C1 ZMOIGGHUSNHCAB-UHFFFAOYSA-N 0.000 claims description 7
- ALPCEXCHMFUSAN-UHFFFAOYSA-N beta-Dihydroplumbagin Natural products C1=CC=C2C(=O)C(C)CC(=O)C2=C1O ALPCEXCHMFUSAN-UHFFFAOYSA-N 0.000 claims description 7
- 238000004809 thin layer chromatography Methods 0.000 claims description 7
- BDOYKFSQFYNPKF-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;sodium Chemical compound [Na].[Na].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O BDOYKFSQFYNPKF-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000004440 column chromatography Methods 0.000 claims description 6
- 229940069328 povidone Drugs 0.000 claims description 6
- 238000005303 weighing Methods 0.000 claims description 6
- 229920003082 Povidone K 90 Polymers 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 238000011068 loading method Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 240000000451 Zingiber zerumbet Species 0.000 claims description 4
- 235000014687 Zingiber zerumbet Nutrition 0.000 claims description 4
- 229960001484 edetic acid Drugs 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 238000010828 elution Methods 0.000 claims description 4
- 230000007480 spreading Effects 0.000 claims description 4
- 238000003892 spreading Methods 0.000 claims description 4
- 230000005526 G1 to G0 transition Effects 0.000 claims description 2
- 229920005654 Sephadex Polymers 0.000 claims description 2
- 239000012507 Sephadex™ Substances 0.000 claims description 2
- 238000000643 oven drying Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims 2
- 208000002193 Pain Diseases 0.000 abstract description 13
- 206010005963 Bone formation increased Diseases 0.000 abstract description 12
- 208000024891 symptom Diseases 0.000 abstract description 7
- 206010040880 Skin irritation Diseases 0.000 abstract description 5
- 231100000475 skin irritation Toxicity 0.000 abstract description 5
- 230000036556 skin irritation Effects 0.000 abstract description 5
- 206010040830 Skin discomfort Diseases 0.000 abstract description 4
- 230000008685 targeting Effects 0.000 abstract description 4
- 230000004060 metabolic process Effects 0.000 abstract description 2
- 230000036285 pathological change Effects 0.000 abstract description 2
- 231100000915 pathological change Toxicity 0.000 abstract description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 abstract 1
- 240000003936 Plumbago auriculata Species 0.000 abstract 1
- 235000011187 glycerol Nutrition 0.000 description 13
- 239000003814 drug Substances 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 7
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 5
- 230000007794 irritation Effects 0.000 description 5
- 208000008558 Osteophyte Diseases 0.000 description 4
- 229910000004 White lead Inorganic materials 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 201000010934 exostosis Diseases 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 3
- 244000042664 Matricaria chamomilla Species 0.000 description 3
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 238000005520 cutting process Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 210000000629 knee joint Anatomy 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000011505 plaster Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000006820 Arthralgia Diseases 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000014104 aloe vera supplement Nutrition 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229940076810 beta sitosterol Drugs 0.000 description 2
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 2
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229950005143 sitosterol Drugs 0.000 description 2
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 2
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 2
- 206010063409 Acarodermatitis Diseases 0.000 description 1
- 206010060934 Allergic oedema Diseases 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061246 Intervertebral disc degeneration Diseases 0.000 description 1
- 241000533950 Leucojum Species 0.000 description 1
- 241001676573 Minium Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010057178 Osteoarthropathies Diseases 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- 240000003377 Shepherdia canadensis Species 0.000 description 1
- 235000018324 Shepherdia canadensis Nutrition 0.000 description 1
- 208000004078 Snake Bites Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000893966 Trichophyton verrucosum Species 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 208000018180 degenerative disc disease Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229940124600 folk medicine Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 description 1
- NKMDIWKRKQFYPH-VIUFNMEASA-N lupane Chemical compound C1CCC(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C(C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C NKMDIWKRKQFYPH-VIUFNMEASA-N 0.000 description 1
- MQYXUWHLBZFQQO-QGTGJCAVSA-N lupeol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C MQYXUWHLBZFQQO-QGTGJCAVSA-N 0.000 description 1
- PKGKOZOYXQMJNG-UHFFFAOYSA-N lupeol Natural products CC(=C)C1CC2C(C)(CCC3C4(C)CCC5C(C)(C)C(O)CCC5(C)C4CCC23C)C1 PKGKOZOYXQMJNG-UHFFFAOYSA-N 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 208000005687 scabies Diseases 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Images
Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- 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
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- 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
-
- 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
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
-
- 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
- A61K2236/55—Liquid-liquid separation; Phase separation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明提供一种含白花丹提取物的巴布剂及其制备方法，其巴布剂包括如下原料：白花丹精制提取物0.5～1份，洋甘菊提取物0.2～0.5份，芦荟提取物0.1～0.3份，聚丙烯酸钠4.8～5.2份，二羟基氨基乙酸铝0.2～0.4份，2,3‑二羟基丁二酸0.2～0.4份，甘油28～32份，乙二胺四乙酸二钠0.05～0.09份，聚维酮K‑902～4份和去离子水58～62份；本发明实现了白花丹巴布剂的直接病变部位给药，加快病灶新陈代谢，增强治疗骨质增生的靶向性，治愈率高，并且其粘黏度适中，皮肤追随性好，揭扯疼痛感低，可反复粘结且皮肤的刺激性低，无皮肤不适症状，无残留。
Description
技术领域
本发明涉及中医药制剂技术领域，特别涉及一种含白花丹提取物的巴布剂及其制备方法。
背景技术
骨质增生又称为骨刺，主要就是由于人到了一定的年龄，身体出现了退化，发生骨质增生以后会导致关节出现疼痛，肿胀等情况，其属于中老年的常见病、多发病。中医学属于痹症的范围，主要的命名有骨关节病、椎间盘退变、增生性关节炎、骨关节退行性疾病、骨刺等。
巴布剂是一种外用贴膏剂，它源于日本民间惯用的泥罨剂，我国在上世纪八十年代初，由原上海中药三厂将巴布剂引入中药，制成关节镇痛膏巴布剂，是国内最早的中药巴布剂品种。由于橡皮膏、黑膏药等传统膏药的缺点日益突出，使得巴布剂的整体优越性突显。巴布剂由于具有载药量大、生物利用度高、起效快以及使用简便等优势，将在很多方面展现良好开发价值和市场应用前景。
白花丹又称白雪花、白皂药、猛老虎，其具有清热解毒，祛风除湿，活血化瘀等功效。属于民间常用药，用以治疗风湿跌打、筋骨疼痛、癣疥恶疮和蛇咬伤，并用以灭孑孓、蝇蛆。但由于植物白花丹的药性强烈，若直接外敷，则容易灼烧皮肤，而不适用于白花丹作为主要药效成分的外敷贴药剂，仅常见于白花丹止痛喷雾剂，但其治疗效果不佳，渗透性差，限定了白花丹药物的直接病变部位给药的方式。因此，制备一种可有效质量骨质增生且刺激性低的白花丹巴布剂制剂，有利于实现骨质增生的靶向性治疗，增强其直接病变部位给药的疗效，提高治愈率。
发明内容
鉴以此，本发明提出一种含白花丹提取物的巴布剂及其制备方法，实现了白花丹巴布剂的直接病变部位给药，增强治疗骨质增生的靶向性，治愈率高，并且其粘黏度适中，皮肤追随性好，揭扯疼痛感低，可反复粘结且皮肤的刺激性低，无皮肤不适症状，无残留。
本发明的技术方案是这样实现的：
一种含白花丹提取物的巴布剂，按照重量份数比，包括如下原料：白花丹精制提取物0.5～1份，洋甘菊提取物0.2～0.5份，芦荟提取物0.1～0.3份，聚丙烯酸钠4.8～5.2份，二羟基氨基乙酸铝0.2～0.4份，2,3-二羟基丁二酸0.2～0.4份，甘油28～32份，乙二胺四乙酸二钠0.05～0.09份，聚维酮K-902～4份和去离子水58～62份。
更优选的，按照重量份数比，包括如下原料：白花丹精制提取物0.8份，洋甘菊提取物0.4份，芦荟提取物0.2份，聚丙烯酸钠5.0份，二羟基氨基乙酸铝0.3份，2,3-二羟基丁二酸0.3份，甘油30份，乙二胺四乙酸二钠0.07份，聚维酮K-90 3份和去离子水60份。
进一步说明，所述白花丹精制提取物是由5～18倍质量的质量浓度为95％乙醇溶液冷浸提取，并经过进行柱层析分离提取和薄层色谱法合并相同项，所得的白花丹精制提取物；其中，固定相为正相硅胶或葡聚糖凝胶，流动相为石油醚：乙酸乙酯＝1:0-0:1,v/v，或者氯仿：甲醇＝1:1-0:1，v/v。
进一步说明，所述白花丹提取物的制备方法，包括如下步骤：
(1)冷浸提取：取白花丹干燥粉末，加入质量浓度为95％乙醇溶液，于26～28℃下冷浸泡提取3次，每7天/次，合并提取液，过滤、减压浓缩，得到白花丹浸膏；
(2)柱层析：按照质量比1:1将白花丹浸膏与硅胶进行拌样，挥发溶剂，上样至含有10-15倍质量的层析硅胶柱上，采用石油醚：乙酸乙酯＝1:0-0:1,v/v进行梯度洗脱，石油醚：乙酸乙酯的比值依次为：1:0，20:1，10:1，5:1，3:1，2:1，1:1，0:1，得到洗脱液；
(3)将洗脱液减压浓缩回收溶剂，进行TLC色谱法，展开剂为石油醚：乙酸乙酯＝1:0-0:1，V/V进行展开，合并斑点相同的洗脱液，得到白花丹精制提取物。
该白花丹精制提取物主要包括Fr-1，Fr-2，Fr-3，Fr-4和Fr-5组分，其中，Fr-1组份，经纯石油醚硅胶柱层析可得到化合物白花丹素；Fr-2组份，以石油醚-乙酸乙酯(30:1,v/v)为洗脱溶剂，经正相硅胶柱色谱分离，可获得2,2′-氧双(1,4)-二叔丁基苯)和羽扇豆醇；Fr-3组分，经正相硅胶柱色谱(石油醚:乙酸乙酯＝8:1,v/v)，半制备高效液相色谱(乙腈:水＝70:30,v/v)分离，可获得香草酸、β-谷甾醇和3-isopropyl-5-acetoxycyclohexene-2-one。
进一步说明，步骤(1)中，所述浸泡提取3次，其乙醇溶液的用量分别为白花丹粉末的10～18倍体积、8-16倍体积和5-15倍体积。
进一步说明，所述洋甘菊提取物是由5～10倍质量的质量浓度为80～85％乙醇溶液浸提，过滤，减压浓缩而得的洋甘菊浸膏；
所述芦荟提取物是由5～8倍质量的质量浓度为90～95％乙醇溶液浸提，过滤，减压浓缩而得的芦荟浸膏。
一种含白花丹提取物的巴布剂的制备方法，包括如下步骤：
S1、按配比称取甘油，将二羟基氨基乙酸铝和乙二胺四乙酸二钠溶于甘油中，混合均匀，加入聚丙烯酸钠混合，作为油相；
S2、按配比称取2,3-二羟基丁二酸加水溶解，再加入聚维酮K-90混合，作为水相；
S3、将油相持续搅拌8～12min后，在搅拌状态下，缓慢倒入水相，搅拌1.5～2h，得到油水混合物；
S4、向油水混合物中依次加入白花丹提取物、洋甘菊提取物和芦荟提取物，充分搅拌均匀成粘稠的流体后，立即涂布于无纺布上，室温放置24小时后盖上聚乙烯保护膜放烘箱40-60℃烘干，得到含白花丹提取物的巴布剂。
进一步说明，步骤S4中，涂布的厚度为0.4～0.6mm。
与现有技术相比，本发明的有益效果是：
(1)在本发明的巴布剂处方中，通过采用以一定工艺精制而得的白花丹精制提取物，联合洋甘菊、芦荟提取物作为主要功效成分进行复配，不仅实现了直接病变部位给药，缓解疼痛部位的疼痛感，能加快病灶新陈代谢，促进疼痛部位瘀血散去，增强治疗骨质增生的靶向性，治愈率高，而且极大降低药物外敷的刺激性，舒缓肌肤过敏度，改善肌肤对冷热刺激的敏感度，促进药物有效成分的吸收，同时增强皮肤胶元蛋白的恢复功能，保持皮肤屏障，避免皮肤无红肿过敏等现象。
(2)本发明所制得的含白花丹提取物的巴布剂呈清爽的淡绿色，其结合了以聚丙烯酸钠与二羟基氨基乙酸铝作为粘合交联剂，以甘油作为保湿剂，以2,3-二羟基丁二酸作为皮肤酸碱调节剂，以乙二胺四乙酸二钠和聚维酮K-90作为稳定剂，使巴布剂的粘黏度适中，且皮肤追随性好，揭扯疼痛感低，可反复粘结且皮肤的刺激性低，无皮肤不适症状，无残留。
附图说明
图1为本发明白花丹精制提取物中的活性成分化学结构式；
图2为临床实验病例用药前的膝关节骨质增生情况图；
图3为临床实验用于用药后的膝关节骨质增生情况图；
具体实施方式
为了更好理解本发明技术内容，下面提供具体实施例，对本发明做进一步的说明。
本发明实施例所用的实验方法如无特殊说明，均为常规方法。
本发明实施例所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1
本实施例白花丹巴布剂，由以下原料配方制得：白花丹精制提取物0.5g，洋甘菊提取物0.2g，芦荟提取物0.1g，聚丙烯酸钠4.8g，二羟基氨基乙酸铝0.2g，2,3-二羟基丁二酸0.2g，甘油28g，乙二胺四乙酸二钠0.05g，聚维酮K-902g和去离子水58g。
该白花丹精制提取物是通过以下方法制备：
(1)冷浸提取：称取白花丹干燥粉末，回流提取3次；第1次加10-倍体积的95％乙醇溶液浸泡提取7天后；第2次用8倍体积的95％乙醇溶液浸泡提取7天后；第3次用5倍体积的95％乙醇溶液浸泡提取7天，每次用3层纱布滤过，得到白花丹浸膏；
(2)柱层析：按照质量比1:1将白花丹浸膏与硅胶进行拌样，挥发溶剂，上样至含有10倍质量的层析硅胶柱上，采用石油醚：乙酸乙酯＝1:0-0:1,v/v进行梯度洗脱，得到洗脱液；
(3)将洗脱液减压浓缩回收溶剂，进行TLC色谱法，展开剂为石油醚：乙酸乙酯＝1:0-0:1，V/V进行展开，合并斑点相同的洗脱液，得到白花丹精制提取物。
洋甘菊提取物是由5倍质量的质量浓度为80％乙醇溶液浸提，过滤，减压浓缩而得的洋甘菊浸膏，备用。
芦荟提取物是由5倍质量的质量浓度为90％乙醇溶液浸提，过滤，减压浓缩而得的芦荟浸膏，备用。
一种含白花丹提取物巴布剂的制备工艺，包括以下步骤：
S1、将二羟基氨基乙酸铝、乙二胺四乙酸二钠溶入甘油中，混合均匀；再加入聚丙烯酸钠混匀，作为油相；
S2、将2,3-二羟基丁二酸溶解于水中，再将聚维酮K-90溶解于水中混合，作为水相；
S3、将油相持续搅拌8～12min后，在搅拌状态下，缓慢倒入水相，搅拌1.5～2h，得到油水混合物；
S4、向油水混合物中依次加入白花丹提取物、洋甘菊提取物和芦荟提取物，充分搅拌均匀成粘稠的流体后，立即涂布于无纺布上，涂布操作时要用玻璃棒趁热均匀涂布在自制的7×10cm无纺布上，厚度为0.4～0.6mm，涂布完毕后，26～28℃室温下放置24小时后盖上聚乙烯保护膜放烘箱40-60℃烘干，切割、包装，即得含白花丹提取物的巴布剂。
实施例2
本实施例白花丹巴布剂，由以下原料配方制得：白花丹精制提取物1g，洋甘菊提取物0.5g，芦荟提取物0.3g，聚丙烯酸钠5.2g，二羟基氨基乙酸铝0.4g，2,3-二羟基丁二酸0.4g，甘油32g，乙二胺四乙酸二钠0.09g，聚维酮K-904g和去离子水62g。
该白花丹精制提取物是通过以下方法制备：
(1)冷浸提取：称取白花丹干燥粉末，回流提取3次；第1次加18倍体积的95％乙醇溶液浸泡提取7天后；第2次用16倍体积的95％乙醇溶液浸泡提取7天后；第3次用15倍体积的95％乙醇溶液浸泡提取7天，每次用3层纱布滤过，得到白花丹浸膏；
(2)柱层析：按照质量比1:1将白花丹浸膏与硅胶进行拌样，挥发溶剂，上样至含有15倍质量的层析硅胶柱上，采用石油醚：乙酸乙酯＝1:0-0:1,v/v进行梯度洗脱，得到洗脱液；
(3)将洗脱液减压浓缩回收溶剂，进行TLC色谱法，展开剂为石油醚：乙酸乙酯＝1:0-0:1，V/V进行展开，合并斑点相同的洗脱液，得到白花丹精制提取物。
洋甘菊提取物是由10倍质量的质量浓度为85％乙醇溶液浸提，过滤，减压浓缩而得的洋甘菊浸膏，备用。
芦荟提取物是由8倍质量的质量浓度为95％乙醇溶液浸提，过滤，减压浓缩而得的芦荟浸膏，备用。
一种含白花丹提取物巴布剂的制备工艺，包括以下步骤：
S1、将二羟基氨基乙酸铝、乙二胺四乙酸二钠溶入甘油中，混合均匀；再加入聚丙烯酸钠混匀，作为油相；
S2、将2,3-二羟基丁二酸溶解于水中，再将聚维酮K-90溶解于水中混合，作为水相；
S3、将油相持续搅拌8～12min后，在搅拌状态下，缓慢倒入水相，搅拌1.5～2h，得到油水混合物；
S4、向油水混合物中依次加入白花丹提取物、洋甘菊提取物和芦荟提取物，充分搅拌均匀成粘稠的流体后，立即涂布于无纺布上，涂布操作时要用玻璃棒趁热均匀涂布在自制的7×10cm无纺布上，厚度为0.4～0.6mm，涂布完毕后，26～28℃室温下放置24小时后盖上聚乙烯保护膜放烘箱40-60℃烘干，切割、包装，即得含白花丹提取物的巴布剂。
实施例3
本实施例白花丹巴布剂，由以下原料配方制得：白花丹精制提取物0.8g，洋甘菊提取物0.4g，芦荟提取物0.2g，聚丙烯酸钠5.0g，二羟基氨基乙酸铝0.3g，2,3-二羟基丁二酸0.3g，甘油30g，乙二胺四乙酸二钠0.07g，聚维酮K-90 3g和去离子水60g。
该白花丹精制提取物、洋甘菊提取物和芦荟提取物的制备方法如实施例2。
一种含白花丹提取物巴布剂的制备工艺，包括以下步骤：
S1、将二羟基氨基乙酸铝、乙二胺四乙酸二钠溶入甘油中，混合均匀；再加入聚丙烯酸钠混匀，作为油相；
S2、将2,3-二羟基丁二酸溶解于水中，再将聚维酮K-90溶解于水中混合，作为水相；
S3、将油相持续搅拌8～12min后，在搅拌状态下，缓慢倒入水相，搅拌1.5～2h，得到油水混合物；
S4、向油水混合物中依次加入白花丹提取物、洋甘菊提取物和芦荟提取物，充分搅拌均匀成粘稠的流体后，立即涂布于无纺布上，涂布操作时要用玻璃棒趁热均匀涂布在自制的7×10cm无纺布上，厚度为0.4～0.6mm，涂布完毕后，26～28℃室温下放置24小时后盖上聚乙烯保护膜放烘箱40-60℃烘干，切割、包装，即得含白花丹提取物的巴布剂。
对比例1
如实施例3的含白花丹提取物巴布剂的制备工艺，区别在于：区别在于：其原料配方为：白花丹精制提取物0.8g，洋甘菊提取物0.4g，芦荟提取物0.2g，聚丙烯酸钠8.0g，二羟基氨基乙酸铝0.5g，2,3-二羟基丁二酸0.5g，甘油30g，乙二胺四乙酸二钠0.07g，聚维酮K-90 2g和去离子水60g。
该白花丹精制提取物、洋甘菊提取物和芦荟提取物的制备方法如实施例2。
对比例2
如实施例3的含白花丹提取物巴布剂的制备工艺，区别在于：其原料配方为：白花丹精制提取物0.8g，聚丙烯酸钠5.0g，二羟基氨基乙酸铝0.3g，2,3-二羟基丁二酸0.3g，甘油30g，乙二胺四乙酸二钠0.07g，聚维酮K-90 3g和去离子水60g，即未加入洋甘菊提取物和芦荟提取物；
该白花丹精制提取物的制备方法如实施例2。
对比例3
如实施例3的含白花丹提取物巴布剂的制备工艺，区别在于：其原料配方中，采用白花丹浸膏0.8g替代白花丹精制提取物，该白花丹浸膏，由白花丹干燥粉末，回流提取3次；第1次加18倍体积的95％乙醇溶液浸泡提取7天后；第2次用16倍体积的95％乙醇溶液浸泡提取7天后；第3次用15倍体积的95％乙醇溶液浸泡提取7天，每次用3层纱布滤过而得，该洋甘菊提取物和芦荟提取物的制备方法如实施例2，其余与实施例3相同。
对比例4
如实施例3的含白花丹提取物巴布剂的制备工艺，区别在于：其原料配方中，采用0.8g白花丹干燥粉末、0.4g洋甘菊粉末、0.2g芦荟干燥粉末替代白花丹精制提取物、洋甘菊提取物和芦荟提取物，于步骤S4中加入至油水混合物中，其余与实施例3相同。
1、按照《中国药典》2015年通则0952贴膏剂黏附力的测定方法，对本发明实施例和对比例所制备的白花丹巴布剂进行初黏力和剥离强度测定，其结果如下表。
由上表可知，本发明所制得的白花丹巴布剂进行初黏力均可在2.0g，同时剥离强度在4.5N以下，表明本发明的白花丹巴布剂黏性好，且易剥离，不易伤及皮肤，而在对比例1中，其平均剥离度达4.93，容易导致药剂剥离过程引起的不适。
2、将本发明实施例和对比例所制备的白花丹巴布剂由10名受试志愿者进行皮肤追随性、皮肤症状、基质残留和反复揭贴性等进行综合感官评价。
评分标准为：
皮肤追随性：将白花丹巴布剂贴于手腕背部处，用力甩10下不脱落，平行5份试验；均无脱落记10分，3片以内脱落记5分，5片均脱落记1分；
皮肤症状：无过敏发红现象记10分，轻度勉强可见过红斑水肿，记5分，明显严重过敏水肿现象记1分；
基质残留：将白花丹巴布剂以180°剥离，是否在聚乙烯薄膜上有残留。无残留记10分，残留＜30％记5分，残留＞60％记1分；
反复揭贴性：取白花丹巴布剂反复贴上、揭下各10次，平行5份样品；最终仍具有稳定粘性记10分，最终具有轻微粘性记5分，完全无粘性记1分。
其结果如下表：
由上表可知，本发明实施例制备的白花丹巴布剂的皮肤追随性好，揭扯疼痛感低，可反复粘结且皮肤的刺激性低，无皮肤不适症状，无残留。而在对比例1中，其易出现基质残留和反复揭贴性性差，对比例2～4中其药剂的皮肤刺激较高，长时间黏贴引起了不同程度的红斑水肿，因此，表明了本发明以白花丹精制提取物，联合洋甘菊、芦荟提取物作为主要功效成分进行复配，可降低了药物外敷的刺激性，舒缓肌肤过敏度，改善肌肤对冷热刺激的敏感度，利于药物有效成分的吸收。
3、治疗效果实验
选取50名膝关节处骨质增生患者，随机分为两组，每组25名，分别采用由实施例3和对比例4所制备的白花丹巴布剂，贴于疼痛部位，每天1贴，7天为一个疗程，治疗2个疗程。
疗效判定标准：显效，疼痛消失；有效，疼痛缓解；无效，症状依旧。结果见表1：
由上表可以看出，相比传统直接以药材原料进行复配而言，本发明通过对白花丹的精制提取，并结合洋甘菊、芦荟提取物进行有效组合，可有效实现了直接病变部位给药，缓解疼痛部位的疼痛感，增强治疗骨质增生的靶向性，治愈率高，疼痛发作频次明显减少。其骨质增生患者的骨刺用药情况如图2和3所示，可以看出患者用药前和用药过后相比，用药前骨刺明显紧密，如图2，用药后骨刺明显疏松，如图3。
4.本发明对白花丹精制提取物主要化学成分的氢谱和碳谱测定香草酸的1H和13CNMR数据
3-isopropyl-5-acetoxy-2-cyclohexene-1-one的1H和13C NMR数据
2,2′-氧双(1,4)-二叔丁基苯的1H和13C NMR数据
羽扇豆烷的1H和13C NMR数据
β-谷甾醇的1H和13C NMR数据
其中，所得白花丹素与白花丹素标准品共薄层色谱检测相一致得以确认。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (8)
1.一种含白花丹提取物的巴布剂，其特征在于：按照重量份数比，包括如下原料：白花丹精制提取物0.5～1份，洋甘菊提取物0.2～0.5份，芦荟提取物0.1～0.3份，聚丙烯酸钠4.8～5.2份，二羟基氨基乙酸铝0.2～0.4份，2,3-二羟基丁二酸0.2～0.4份，甘油28～32份，乙二胺四乙酸二钠0.05～0.09份，聚维酮K-902～4份和去离子水58～62份。
2.如权利要求1所述的一种含白花丹提取物的巴布剂，其特征在于：按照重量份数比，包括如下原料：白花丹精制提取物0.8份，洋甘菊提取物0.4份，芦荟提取物0.2份，聚丙烯酸钠5.0份，二羟基氨基乙酸铝0.3份，2,3-二羟基丁二酸0.3份，甘油30份，乙二胺四乙酸二钠0.07份，聚维酮K-90 3份和去离子水60份。
3.如权利要求1所述的一种含白花丹提取物的巴布剂，其特征在于：所述白花丹精制提取物是由5～18倍质量的质量浓度为95％乙醇溶液冷浸提取，并经过进行柱层析分离提取和薄层色谱法合并相同项，所得的白花丹精制提取物；其中，固定相为正相硅胶或葡聚糖凝胶，流动相为石油醚：乙酸乙酯＝1:0-0:1,v/v，或者氯仿：甲醇＝1:1-0:1，v/v。
4.如权利要求3所述的一种含白花丹提取物的巴布剂，其特征在于：所述白花丹提取物的制备方法，包括如下步骤：
(1)冷浸提取：取白花丹干燥粉末，加入质量浓度为95％乙醇溶液，于26～28℃下冷浸泡提取3次，每7天/次，合并提取液，过滤、减压浓缩，得到白花丹浸膏；
(2)柱层析：按照质量比1:1将白花丹浸膏与硅胶进行拌样，挥发溶剂，上样至含有10-15倍质量的层析硅胶柱上，采用石油醚：乙酸乙酯＝1:0-0:1,v/v进行梯度洗脱，得到洗脱液；
(3)将洗脱液减压浓缩回收溶剂，进行TLC色谱法，展开剂为石油醚：乙酸乙酯＝1:0-0:1，V/V进行展开，合并斑点相同的洗脱液，得到白花丹精制提取物。
5.如权利要求4所述的一种含白花丹提取物的巴布剂，其特征在于：步骤(1)中，所述浸泡提取3次，其乙醇溶液的用量分别为白花丹粉末的10～18倍体积、8-16倍体积和5-15倍体积。
6.如权利要求1所述的一种含白花丹提取物的巴布剂，其特征在于：所述洋甘菊提取物是由5～10倍质量的质量浓度为80～85％乙醇溶液浸提，过滤，减压浓缩而得的洋甘菊浸膏；
所述芦荟提取物是由5～8倍质量的质量浓度为90～95％乙醇溶液浸提，过滤，减压浓缩而得的芦荟浸膏。
7.一种如权利要求1～6中任意一项所述的含白花丹提取物的巴布剂的制备方法，其特征在于：包括如下步骤：
S1、按配比称取甘油，将二羟基氨基乙酸铝和乙二胺四乙酸二钠溶于甘油中，混合均匀，加入聚丙烯酸钠混合，作为油相；
S2、按配比称取2,3-二羟基丁二酸加水溶解，再加入聚维酮K-90混合，作为水相；
S3、将油相持续搅拌8～12min后，在搅拌状态下，缓慢倒入水相，搅拌1.5～2h，得到油水混合物；
S4、向油水混合物中依次加入白花丹提取物、洋甘菊提取物和芦荟提取物，充分搅拌均匀成粘稠的流体后，立即涂布于无纺布上，室温放置24小时后盖上聚乙烯保护膜放烘箱40-60℃烘干，得到含白花丹提取物的巴布剂。
8.如权利要求7所述的一种含白花丹提取物的巴布剂的制备方法，其特征在于：步骤S4中，涂布的厚度为0.4～0.6mm。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111118465.3A CN113730379B (zh) | 2021-09-24 | 2021-09-24 | 一种含白花丹提取物的巴布剂及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111118465.3A CN113730379B (zh) | 2021-09-24 | 2021-09-24 | 一种含白花丹提取物的巴布剂及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113730379A true CN113730379A (zh) | 2021-12-03 |
| CN113730379B CN113730379B (zh) | 2023-12-12 |
Family
ID=78740547
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111118465.3A Active CN113730379B (zh) | 2021-09-24 | 2021-09-24 | 一种含白花丹提取物的巴布剂及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113730379B (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020046329A (ko) * | 2000-12-12 | 2002-06-21 | 성재갑 | 아토피성 피부염 개선용 화장료 조성물 |
| CN1626168A (zh) * | 2003-12-08 | 2005-06-15 | 西南民族大学 | 白花丹（白雪花）制剂 |
| JP2010159213A (ja) * | 2009-01-06 | 2010-07-22 | B & C Laboratories Inc | 抗酸化剤 |
| CN104258067A (zh) * | 2014-09-12 | 2015-01-07 | 皖南医学院 | 一种用于巴布剂的药物组合物、巴布剂及其制备工艺 |
| CN107693779A (zh) * | 2017-05-10 | 2018-02-16 | 广州润虹医药科技股份有限公司 | 一种祛疤组合物及其制备方法 |
| CN109512847A (zh) * | 2018-12-29 | 2019-03-26 | 广州医科大学附属第医院 | 白花丹在用于制备治疗肺纤维化疾病药物中的用途 |
-
2021
- 2021-09-24 CN CN202111118465.3A patent/CN113730379B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20020046329A (ko) * | 2000-12-12 | 2002-06-21 | 성재갑 | 아토피성 피부염 개선용 화장료 조성물 |
| CN1626168A (zh) * | 2003-12-08 | 2005-06-15 | 西南民族大学 | 白花丹（白雪花）制剂 |
| JP2010159213A (ja) * | 2009-01-06 | 2010-07-22 | B & C Laboratories Inc | 抗酸化剤 |
| CN104258067A (zh) * | 2014-09-12 | 2015-01-07 | 皖南医学院 | 一种用于巴布剂的药物组合物、巴布剂及其制备工艺 |
| CN107693779A (zh) * | 2017-05-10 | 2018-02-16 | 广州润虹医药科技股份有限公司 | 一种祛疤组合物及其制备方法 |
| CN109512847A (zh) * | 2018-12-29 | 2019-03-26 | 广州医科大学附属第医院 | 白花丹在用于制备治疗肺纤维化疾病药物中的用途 |
Non-Patent Citations (2)
| Title |
|---|
| 林世源 等: "白花丹巴布剂的基质处方优选及其体外透皮吸收研究", 中国现代应用药学, vol. 37, no. 16, pages 47 - 51 * |
| 蔡立民 等: "白花丹止痛喷雾剂的抗炎镇痛作用研究", 广州中医药大学学报, vol. 34, no. 05, pages 724 - 728 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113730379B (zh) | 2023-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100490828C (zh) | 一种治疗痔疮的外用药物及其制备工艺和质量检测方法 | |
| WO2010032269A2 (en) | Anti-inflammatory activity of the iridoid glycosides | |
| CN105250366B (zh) | 香青兰提取物及其制备方法和用途 | |
| CN102872288B (zh) | 一种治疗风湿骨痛乳香风湿气雾剂及其制备方法 | |
| CN115381912B (zh) | 一种降低癌性疼痛的外用中药复方制剂及其制备方法 | |
| CN113730379A (zh) | 一种含白花丹提取物的巴布剂及其制备方法 | |
| CN100467025C (zh) | 积雪草总苷、积雪草苷或羟基积雪草苷在制备防治心、脑血管疾病药物中的用途 | |
| CN1966064A (zh) | 一种伤湿祛痛软膏及其制备方法 | |
| CN102998412A (zh) | 一种伤科接骨外用制剂的检测方法 | |
| CN100335094C (zh) | 镇痛膏及其制备方法 | |
| CN109419823A (zh) | 红豆杉植物提取物及其在制备治疗类风湿性关节炎外用药物中的应用 | |
| CN1218693C (zh) | 中药贴膜剂及其制备方法 | |
| CN102579696B (zh) | 治疗输液静脉炎的中药复方制剂及其制备方法和应用 | |
| CN102688368B (zh) | 一种用于治疗外伤止血或顽固性溃疡的中药 | |
| CN110812401A (zh) | 一种用于软组织损伤的中药组合物及其检测方法 | |
| CN111759905A (zh) | 一种治疗骨关节炎的巴布剂及其制备方法 | |
| CN1539493A (zh) | 一种治疗呼吸***疾病的中药组合物及其制备方法 | |
| CN109985120A (zh) | 一种治疗湿疹的中药组合物及其应用 | |
| CN100362994C (zh) | 治疗过敏性鼻炎和哮喘的制剂 | |
| CN111298075A (zh) | 一种中药组合物及其制备方法与应用 | |
| CN101904831B (zh) | 紫草素及其组合物的应用 | |
| CN105997848A (zh) | 山莨菪麝香凝胶剂及其制备方法 | |
| CN1626064A (zh) | 伤口止血消炎用无菌干粉喷剂及生产方法 | |
| CN101161268B (zh) | 丹参和蒲黄的药用组合物 | |
| CN106063802A (zh) | 水柏枝有效部位、其制备方法及其用途 |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |