CN116650544B - A hot compress patch containing folium Ginkgo extract for promoting blood circulation for removing blood stasis and treating burn, and its preparation method - Google Patents
A hot compress patch containing folium Ginkgo extract for promoting blood circulation for removing blood stasis and treating burn, and its preparation method Download PDFInfo
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- CN116650544B CN116650544B CN202310786097.2A CN202310786097A CN116650544B CN 116650544 B CN116650544 B CN 116650544B CN 202310786097 A CN202310786097 A CN 202310786097A CN 116650544 B CN116650544 B CN 116650544B
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- China
- Prior art keywords
- leaf extract
- ginkgo leaf
- hot compress
- compound
- patch containing
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- 239000008280 blood Substances 0.000 title claims abstract description 17
- 210000004369 blood Anatomy 0.000 title claims abstract description 17
- 230000017531 blood circulation Effects 0.000 title claims abstract description 13
- 241000218628 Ginkgo Species 0.000 title claims description 20
- 235000011201 Ginkgo Nutrition 0.000 title claims description 20
- 235000008100 Ginkgo biloba Nutrition 0.000 title claims description 20
- 239000000284 extract Substances 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title abstract description 19
- 230000001737 promoting effect Effects 0.000 title abstract description 10
- 239000009429 Ginkgo biloba extract Substances 0.000 claims abstract description 131
- 229940125904 compound 1 Drugs 0.000 claims abstract description 59
- 239000000126 substance Substances 0.000 claims abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 52
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical group [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 claims description 49
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 49
- 229960001545 hydrotalcite Drugs 0.000 claims description 49
- -1 magnesium-nickel-aluminum Chemical compound 0.000 claims description 44
- 239000002994 raw material Substances 0.000 claims description 44
- 238000002156 mixing Methods 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 36
- 229910021389 graphene Inorganic materials 0.000 claims description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 28
- 238000003756 stirring Methods 0.000 claims description 28
- 229910001868 water Inorganic materials 0.000 claims description 28
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 26
- 235000010413 sodium alginate Nutrition 0.000 claims description 26
- 239000000661 sodium alginate Substances 0.000 claims description 26
- 229940005550 sodium alginate Drugs 0.000 claims description 26
- 239000012790 adhesive layer Substances 0.000 claims description 24
- 239000004745 nonwoven fabric Substances 0.000 claims description 24
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
- 239000010410 layer Substances 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 15
- 229910052902 vermiculite Inorganic materials 0.000 claims description 15
- 239000010455 vermiculite Substances 0.000 claims description 15
- 235000019354 vermiculite Nutrition 0.000 claims description 15
- 239000011780 sodium chloride Substances 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 238000004806 packaging method and process Methods 0.000 claims description 12
- 238000003825 pressing Methods 0.000 claims description 12
- 238000007789 sealing Methods 0.000 claims description 12
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical group [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229920000161 Locust bean gum Polymers 0.000 claims description 8
- 235000010420 locust bean gum Nutrition 0.000 claims description 8
- 239000000711 locust bean gum Substances 0.000 claims description 8
- 239000000654 additive Substances 0.000 claims description 6
- 235000010418 carrageenan Nutrition 0.000 claims description 6
- 239000000679 carrageenan Substances 0.000 claims description 6
- 229920001525 carrageenan Polymers 0.000 claims description 6
- 229940113118 carrageenan Drugs 0.000 claims description 6
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 5
- 235000007586 terpenes Nutrition 0.000 claims description 5
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 claims description 3
- 229930003944 flavone Natural products 0.000 claims description 3
- 150000002212 flavone derivatives Chemical class 0.000 claims description 3
- 235000011949 flavones Nutrition 0.000 claims description 3
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims 1
- 239000012730 sustained-release form Substances 0.000 claims 1
- 230000008961 swelling Effects 0.000 abstract description 35
- 230000000694 effects Effects 0.000 abstract description 34
- 206010014080 Ecchymosis Diseases 0.000 abstract description 32
- 239000013543 active substance Substances 0.000 abstract description 21
- 239000000463 material Substances 0.000 abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 7
- 230000002195 synergetic effect Effects 0.000 abstract description 7
- 238000004904 shortening Methods 0.000 abstract description 4
- 238000013329 compounding Methods 0.000 abstract description 2
- 231100000957 no side effect Toxicity 0.000 abstract 1
- 230000035876 healing Effects 0.000 description 47
- 210000002683 foot Anatomy 0.000 description 23
- 230000000052 comparative effect Effects 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 7
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 239000011149 active material Substances 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 241000411851 herbal medicine Species 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 229960000956 coumarin Drugs 0.000 description 3
- 235000001671 coumarin Nutrition 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 238000001027 hydrothermal synthesis Methods 0.000 description 3
- 230000008338 local blood flow Effects 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N methylquinoline Natural products C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000012928 buffer substance Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- 229940106580 ginkgo biloba leaf extract Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940118019 malondialdehyde Drugs 0.000 description 1
- 150000002815 nickel Chemical class 0.000 description 1
- SPIFDSWFDKNERT-UHFFFAOYSA-N nickel;hydrate Chemical compound O.[Ni] SPIFDSWFDKNERT-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 231100000075 skin burn Toxicity 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 125000001650 tertiary alcohol group Chemical group 0.000 description 1
- 230000037314 wound repair Effects 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
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F7/03—Compresses or poultices for effecting heating or cooling thermophore, i.e. self-heating, e.g. using a chemical reaction
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F7/00—Heating or cooling appliances for medical or therapeutic treatment of the human body
- A61F7/02—Compresses or poultices for effecting heating or cooling
- A61F2007/0261—Compresses or poultices for effecting heating or cooling medicated
- A61F2007/0263—Compresses or poultices for effecting heating or cooling medicated made of a substance with therapeutic action, e.g. copper or silver
-
- 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
Abstract
The application discloses a pharmaceutical composition containing ginkgo leaf extract, hot compress patch and a preparation method thereof, wherein the pharmaceutical composition containing ginkgo leaf extract comprises ginkgo leaf extract and a compound 1, and the chemical formula of the compound 1 is shown as follows:
Description
Technical Field
The application relates to the technical field of chemical pharmaceutical preparations, in particular to a pharmaceutical composition containing ginkgo leaf extract, hot compress and a preparation method thereof.
Background
The ginkgo leaf extract is a product with rich active ingredients extracted by taking dry leaves of ginkgo of the family ginkgo as raw materials and adopting proper solvents. The ginkgo leaf extract is light yellow brown flowable powder, has bitter taste, has the effects of activating blood circulation, removing blood stasis and dredging collaterals, and is widely applied to the fields of medicines, health products, food additives, functional beverages, cosmetics and the like. The ginkgo leaf extract mainly contains flavonoid and terpene lactone compounds as active ingredients. The flavonoid compound has the functions of resisting oxidation and scavenging active oxygen free radicals, so that the activity of superoxide dismutase can be improved, the generation of lipid peroxide malondialdehyde and oxidized low density lipoprotein can be reduced, and the terpene lactone compound has the function of resisting platelet aggregation.
The ginkgo leaf extract has great medicinal value, is widely applied to treatment such as activating blood circulation to dissipate blood stasis at present, is usually mixed with various Chinese herbal medicines for improving the effect, however, the addition of the Chinese herbal medicines often brings about some unknown side effects due to the complex components of the Chinese herbal medicines, and the Chinese herbal medicines are usually heavier in smell and poorer in sensory comfort, and especially can resist the preparation with pungent smell for children.
Therefore, it is necessary to provide a pharmaceutical preparation containing ginkgo extract with relatively definite ingredients and good effects.
Disclosure of Invention
The present invention aims to solve at least one of the problems of the prior art, and thus, in a first aspect of the present invention, the present invention provides a pharmaceutical composition comprising ginkgo leaf extract, comprising ginkgo leaf extract and compound 1, wherein the compound 1 has the formula:
the mass ratio of the ginkgo leaf extract to the compound 1 is (8.5-10.5) (9.5-11.5), preferably (8.7-10.3) (9.7-11.3).
In one or more embodiments of the present invention, the mass ratio of the ginkgo leaf extract to the compound 1 may be (8.7-9.6): (10.4-11.3), (9.6-10.3): (9.7-10.4).
In a specific embodiment of the present invention, the mass ratio of the ginkgo leaf extract to the compound 1 may be 9.6:10.4.
Through the technical scheme, after 3 days of continuous administration, the swelling degree can be controlled below 97mg, the ecchymosis dissipation time can be controlled below 82h, the healing rate after 5 days after burn can be controlled above 50%, and the healing rate after 8 days can be controlled above 75%. The trifluoromethyl substituted compound, especially the trifluoromethyl substituted tertiary alcohol skeleton, is widely applied to a series of drug molecules, has various biological activities such as anti-inflammatory and antibacterial, and the inventor selects compound 1 from innumerable compounds to solve the technical problems, and finds that the compound 1 and ginkgo leaf extract have remarkable synergistic effects in promoting blood circulation to remove blood stasis, reducing the swelling degree of feet, shortening the dissipation time of ecchymosis and curing burn. In addition, the compound 1 and the ginkgo leaf extract have definite components, no pungent smell, few side effects, few active components, convenient preparation and safe use.
In one or more embodiments of the present invention, the ginkgo leaf extract has a flavone content of more than 24wt% and a terpene lactone content of more than 6 wt%.
In one or more embodiments of the invention, compound 1 is prepared from trifluoroacetyl coumarin ketone and a methylquinoline compound at 70-90 ℃.
In a second aspect of the present invention, the present invention provides a hot compress patch containing ginkgo leaf extract, which is prepared from the following raw materials in parts by weight:
8.5-10.5 parts by weight of ginkgo leaf extract;
9.5 to 11.5 parts by weight of compound 1;
2-3 parts by weight of reduced iron;
0.1 to 0.15 part by weight of sodium chloride;
0.5-1.5 parts by weight of activated carbon;
0.8-1.3 parts by weight of vermiculite powder;
0.75-1 parts by weight of water;
the chemical formula of the compound 1 is shown as follows:
preferably, the hot compress patch containing ginkgo leaf extract is prepared by the following raw materials in parts by weight: 8.7-10.3 parts by weight of ginkgo leaf extract and 9.7-11.3 parts by weight of compound 1.
In one or more embodiments of the present invention, the hot compress patch containing ginkgo leaf extract is prepared by the following raw materials in parts by weight: 8.7-9.6 parts by weight of ginkgo leaf extract and 10.4-11.3 parts by weight of compound 1.
In one or more embodiments of the present invention, the hot compress patch containing ginkgo leaf extract is prepared by the following raw materials in parts by weight: 9.6-10.3 parts by weight of ginkgo leaf extract and 9.7-10.4 parts by weight of compound 1.
In a specific embodiment of the invention, the hot compress patch containing ginkgo leaf extract is prepared from the following raw materials in parts by weight: 9.6 parts by weight of ginkgo leaf extract and 10.4 parts by weight of compound 1.
According to the technical scheme, when the heating substances are added into the hot compress patch, the foot swelling degree is reduced, the ecchymosis dissipation time is shortened, the swelling degree after 3d administration can be controlled below 92mg, the ecchymosis dissipation time can be controlled below 76h, in addition, the healing rate after 5d and the healing rate after 8d are both high, the healing rate after 5d of burn administration can be controlled above 55%, and the healing rate after 8d can be controlled above 80%.
In one or more embodiments of the present invention, the raw material for preparing the hot compress patch containing ginkgo leaf extract further includes 0.08 to 0.13 parts by weight of a transdermal enhancer, which includes sodium alginate.
According to the technical scheme, when the transdermal enhancer sodium alginate is added into the hot compress patch, the foot swelling degree is reduced, the ecchymosis dissipating time is shortened, the swelling degree after 3d administration can be controlled below 73mg, the ecchymosis dissipating time can be controlled below 62h, in addition, the healing rate after 5d and the healing rate after 8d are both high, the healing rate after 5d of burn administration can be controlled above 58%, and the healing rate after 8d can be controlled above 88%.
In one or more embodiments of the present invention, the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.19-0.22 parts by weight of a slow release agent, wherein the slow release agent is selected from one or more of hydrotalcite and graphene.
According to the technical scheme, when the slow release agent is added into the hot compress, the swelling degree is reduced, the ecchymosis dissipation time is shortened, the swelling degree after 3d administration can be controlled below 70mg, the ecchymosis dissipation time can be controlled below 60h, in addition, the healing rate after 5d and the healing rate after 8d are both high, the healing rate after 5d of burn administration can be controlled above 62%, and the healing rate after 8d can be controlled above 90%.
In one or more embodiments of the present invention, the slow release agent includes hydrotalcite and graphene, the hydrotalcite is aluminum-magnesium hydrotalcite or magnesium-nickel-aluminum hydrotalcite, and the mass ratio of the hydrotalcite to the graphene is (0.65-3): 1.
In one or more embodiments of the invention, the mass ratio of hydrotalcite to graphene is (0.65-1): 1, (1-3): 1.
In a specific embodiment of the invention, the mass ratio of hydrotalcite to graphene is 1:1.
In one or more embodiments of the invention, the magnesium nickel aluminum hydrotalcite is prepared from magnesium salts, nickel salts, and aluminum salts by hydrothermal reaction with urea.
Preferably, the temperature of the hydrothermal reaction is controlled to be 95-105 ℃.
According to the technical scheme, when the slow release agent is added into the hot compress, the swelling degree is reduced, the ecchymosis dissipation time is shortened, the swelling degree after 3d administration can be controlled below 60mg, the ecchymosis dissipation time can be controlled below 54h, in addition, the healing rate after 5d and the healing rate after 8d are both high, the healing rate after 5d of burn administration can be controlled above 72%, and the healing rate after 8d can be controlled above 97%.
In one or more embodiments of the present invention, the raw material for preparing the hot compress patch containing ginkgo leaf extract further includes an additive selected from one or more of locust bean gum and carrageenan.
According to the technical scheme, when the additive is added into the hot compress, the swelling degree is reduced, the ecchymosis dissipating time is shortened, the swelling degree after 3d administration can be controlled below 51mg, and the ecchymosis dissipating time can be controlled below 49 h.
In a third aspect of the present invention, the present invention provides a method for preparing a hot compress patch containing ginkgo leaf extract according to the second aspect of the present invention, comprising the steps of:
step 1): mixing all the raw materials, and stirring;
step 2): placing the stirred raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
In one or more embodiments of the invention, the
In the step 1), the ginkgo leaf extract, the compound 1, sodium alginate and 40-60wt% of water are mixed and stirred to obtain a first mixture, other raw materials and the rest water are mixed and stirred to obtain a second mixture, and the first mixture and the second mixture are mixed and stirred.
Through the technical scheme, when the additive is added into the hot compress, the swelling degree is reduced, the ecchymosis dissipation time is shortened, and the healing rate after 5 days and the healing rate after 8 days are both high.
In a fourth aspect of the present invention, the present invention provides an application of the pharmaceutical composition containing ginkgo leaf extract according to the first aspect of the present invention or the hot compress patch containing ginkgo leaf extract according to the second aspect of the present invention in preparing a medicament for activating blood circulation to dissipate blood stasis and burn.
The invention has the beneficial effects that:
1. the invention provides a pharmaceutical composition containing ginkgo leaf extract, which comprises ginkgo leaf extract and a compound 1, wherein the ginkgo leaf extract and the compound 1 have remarkable synergistic effects in promoting blood circulation to remove blood stasis, relieving swelling degree of feet, shortening resolving time of ecchymosis and curing burn. In addition, the medicine composition has definite components, no pungent smell, few side effects, few active components, convenient preparation and safe use.
2. The invention provides a hot compress patch containing ginkgo leaf extract, which is added with heating substances to raise the temperature of hot compress parts on the body surface of a human body, on one hand, blood vessels are dilated, local blood circulation and drug absorption are promoted, on the other hand, the drug activity is improved, sodium alginate is added as a transdermal promoter, the transdermal effect of an active substance is enhanced, a specific slow release agent is added, a proper slow release effect is obtained through charge adsorption and specific double-layer structure and heat conduction activity of the active substance, an additive is added to be compounded with the transdermal promoter and the slow release agent, a certain glue connection is formed with the active substance coated by the sodium alginate, meanwhile, the active substance can be smoothly moved between slow release agent layers, and the bioavailability of the active substance and the curative effect can be obviously improved through compounding selection of auxiliary materials.
3. The invention provides a preparation method of the hot compress patch containing ginkgo leaf extract, which is simple and easy to prepare.
Detailed Description
The invention is further illustrated below with reference to specific examples, which are provided for illustration only and should not be construed as limiting the scope of the invention. The following examples are conducted under conventional conditions or conditions recommended by the manufacturer, and the methods used are conventional methods known in the art, and the consumables and reagents used are commercially available unless otherwise specified. Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any method or material similar or equivalent to those described may be used in the present invention.
Preparation example
Compound 1 is prepared from compound 2 and compound 3, and the reaction formula for preparing compound 1 from compound 2 and compound 3 is shown below:
the preparation procedure for compound 1 was as follows: trifluoroacetyl coumarin ketone (compound 2,0.20 mmol), methylquinoline compound (compound 3,0.4 mmol) and solvent (MeCN, 2.0 mL) are added into a 10mL sealed tube, the mixture is reacted for 9H at 90 ℃, the mixture is filtered by a sand core funnel with a diatomite pad, the solvent is removed under reduced pressure, the residue is separated by a silica gel column to obtain a product 3- (1, 1-trifluoro-2 hydroxy-3- (quinolyl) -2 pyranyl) -2H-2 coumarin ketone (compound 1), and the eluent used in the separation process is petroleum ether and ethyl acetate according to the proportion of 8:1.
Examples 1 to 5
Examples 1-5 provide a heat patch containing ginkgo leaf extract, prepared from the components and compositions described in table 1. Wherein the folium Ginkgo extract (obtained from Biotechnology Co., ltd.) has flavone content above 24wt% and terpene lactone content above 6wt%. Compound 1 was prepared from the preparation examples.
A method for preparing hot compress patch containing folium Ginkgo extract comprises the following steps:
step 1): mixing folium Ginkgo extract, compound 1, reduced iron, sodium chloride, activated carbon, vermiculite powder, and water, stirring, and mixing;
step 2): placing the stirred raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, shearing, and packaging to obtain the hot compress patch containing the ginkgo leaf extract.
Table 1 raw materials and addition amounts of Hot Patches containing Ginkgo biloba leaf extract were prepared in examples 1 to 5
Example 6
Example 6 is different from example 2 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract does not contain reduced iron, sodium chloride, activated carbon, vermiculite powder. The starch with equal mass is used for replacing the reduced iron, sodium chloride, active carbon and vermiculite powder.
Example 7
Example 7 is different from example 2 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises a transdermal enhancer comprising 0.1g of sodium alginate.
A method for preparing hot compress patch containing folium Ginkgo extract comprises the following steps:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder and the rest water to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 8
Example 8 is different from example 7 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.2g of aluminum magnesium hydrotalcite.
Example 8 preparation method of a hot compress patch containing ginkgo leaf extract comprises the following steps:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water and aluminum magnesium hydrotalcite to obtain a second mixture, adding the first mixture, stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 9
Example 9 is different from example 7 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.2g of magnesium nickel aluminum hydrotalcite.
The preparation method of the magnesium nickel aluminum hydrotalcite comprises the following steps: 11.53g of Mg (NO) was weighed out 3 ) 2 ﹒6H 2 O、6.54g Ni(NO 3 ) 2 ﹒6H 2 O and 8.43g Al (NO) 3 ) 3 ﹒9H 2 O, 150mL of deionized water was added, stirred, dissolved, and urea was added to make the molar concentration of urea equal to (Mg 2+ +Ni 2+ ) The molar concentration of the magnesium-nickel-aluminum hydrotalcite is the same, the magnesium-nickel-aluminum hydrotalcite is transferred into a hydrothermal reaction kettle, placed into a drying box at 100 ℃ for reaction for 12 hours, cooled, filtered, washed and dried, and then the magnesium-nickel-aluminum hydrotalcite is obtained.
Example 9 preparation method of a heat patch containing ginkgo leaf extract, comprising the following steps:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water and magnesium nickel aluminum hydrotalcite to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 10
Example 10 is different from example 7 in that the raw material for preparing the heat patch containing ginkgo leaf extract further comprises 0.2g of graphene.
Example 10 a method for preparing a heat patch containing ginkgo leaf extract, comprising the steps of:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water and graphene to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 11
Example 11 is different from example 7 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.1g of aluminum magnesium hydrotalcite and 0.1g of graphene.
Example 11 a method for preparing a heat patch containing ginkgo leaf extract, comprising the steps of:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water, graphene and aluminum magnesium hydrotalcite to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 12
Example 12 is different from example 7 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.1g of magnesium nickel aluminum hydrotalcite and 0.1g of graphene.
The preparation of magnesium nickel aluminum hydrotalcite was the same as in example 9.
Example 12 preparation method of a heat patch containing ginkgo leaf extract comprises the following steps:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water, graphene and magnesium nickel aluminum hydrotalcite to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 13
Example 13 differs from example 12 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.15g of magnesium nickel aluminum hydrotalcite and 0.05g of graphene.
Example 14
Example 14 is different from example 12 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.08g of magnesium nickel aluminum hydrotalcite and 0.12g of graphene.
Example 15
Example 15 is different from example 12 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract further comprises 0.06g locust bean gum.
Example 15 preparation method of a heat patch containing ginkgo leaf extract comprises the following steps:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water, graphene, magnesium nickel aluminum hydrotalcite and locust bean gum uniformly, stirring to obtain a second mixture, adding the first mixture, stirring, and mixing uniformly;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 16
Example 16 differs from example 12 in that the raw material for preparing the heat patch containing ginkgo leaf extract further comprises 0.06g of carrageenan.
Example 16A method for preparing a heat patch containing ginkgo leaf extract, comprising the steps of:
step 1): mixing sodium alginate and half of water, adding folium Ginkgo extract and compound 1, stirring, and mixing to obtain a first mixture;
step 2): stirring and uniformly mixing reduced iron, sodium chloride, active carbon, vermiculite powder, residual water, graphene, magnesium nickel aluminum hydrotalcite and carrageenan to obtain a second mixture, adding the first mixture, and stirring and uniformly mixing;
step 3): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Example 17
Example 17 differs from example 15 in the method of preparation.
Example 17 preparation method of a heat patch containing ginkgo leaf extract comprises the following steps:
step 1): stirring sodium alginate, water, folium Ginkgo extract, compound 1, reduced iron, sodium chloride, activated carbon, vermiculite powder, residual water, graphene, magnesium nickel aluminum hydrotalcite, and locust bean gum, and mixing;
step 2): placing the mixed raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
Comparative example 1
Comparative example 1 is different from example 2 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract does not contain ginkgo leaf extract. 20g of Compound 1 was used instead of 9.6g of ginkgo leaf extract and 10.4g of Compound 1.
Comparative example 2
Comparative example 2 is different from example 2 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract does not contain the compound 1. 9.6g of ginkgo leaf extract and 10.4g of compound 1 were replaced with 20g of ginkgo leaf extract.
Comparative example 3
Comparative example 3 is different from example 2 in that the raw material for preparing the hot compress patch containing ginkgo leaf extract does not contain ginkgo leaf extract and compound 1. The ginkgo leaf extract and the compound 1 are replaced by starch with equal quality.
Effect test:
I. the influence of hot compress containing ginkgo leaf extract provided by the embodiment and the comparative example on traumatic blood stasis swelling of the foot plantar part of a mouse is studied by the following test, the left hind foot of the mouse is vertically pressed by a cylinder with the inner diameter of 3.2cm and the length of 27cm, and the foot plantar part of the mouse is vertically hit by a 200g weight from top to bottom in the cylinder, so that acute traumatic blood stasis swelling of the foot plantar part of the left hind foot is caused. After modeling, mice were randomly grouped by body weight, sex, 10 mice per group, male and female halves. The administration was started after 1 hour, and the hot compress patch containing ginkgo leaf extract prepared in examples and comparative examples was administered. The hot compress patch containing folium Ginkgo extract is applied to the left hind foot plantar blood stasis swelling position of mice, once daily for more than 8 hr, and continuously for 3 days at a dose of 0.5g active substance/kg body weight of mice. 2 hours after the last administration, the mice were sacrificed, the left and right feet were cut off at 4mm on the ankle joint and weighed, the difference was the swelling degree, the ecchymosis dissipating time was observed, and the data of 10 mice were averaged. The results are shown in Table 2.
Table 2 examples and comparative examples therapeutic effects on the resolution of blood stasis swelling and ecchymoses in the plantar region of mice
Examples 1-3 are compared with the results of Table 2, it is clear that the swelling degree of feet and the resolving time of ecchymosis are changed when the mass ratio of the ginkgo leaf extract to the compound 1 is changed, and the swelling degree of feet is small, can be controlled within 92mg, and the resolving time of ecchymosis is short, can be controlled within 76h when the mass ratio of the ginkgo leaf extract to the compound 1 is (8.5-10.5): 9-11.5.
Examples 4-5 in combination with the results of table 2, it is understood that the swelling degree of feet and the dissipation time of ecchymosis are changed when the amount of the heating material is changed, which is probably because the hot compress heating material containing ginkgo leaf extract according to the present invention is a polymer synthesized from iron, vermiculite, activated carbon, inorganic salt, water, etc., and can react exothermically under the effect of oxygen in the air to generate heat, so that the active material ginkgo leaf extract and compound 1 have higher activity, and proper temperature and heating time are required to be ensured.
As can be seen from a comparison of the results of example 6 and example 2 in combination with Table 2, when no heating material is added to the hot compress patch containing ginkgo leaf extract, the swelling degree of the feet becomes large and the ecchymosis dissipating time becomes long. This is probably because, on the one hand, the exothermic material can dilate blood vessels and promote local blood circulation and drug absorption, and on the other hand, the active material ginkgo leaf extract and the compound 1 have higher activity at higher temperatures.
As can be seen from comparison of the results of example 7 and example 2 in combination with the results of table 2, when sodium alginate is added to the hot compress patch containing ginkgo leaf extract, the swelling degree of feet becomes smaller and the ecchymosis dissipating time becomes shorter, which is probably because the addition of sodium alginate can increase the transdermal effect of ginkgo leaf extract and compound 1, more active substances can be absorbed at the trauma site, which is beneficial to promoting blood circulation, removing blood stasis and promoting the recovery of trauma.
As can be seen from comparison of the results of example 8 and example 7 in combination with the results of table 2, when the hot compress patch containing ginkgo leaf extract is further added with aluminum magnesium hydrotalcite, the foot swelling degree becomes small and the ecchymosis dissipating time becomes short, which is probably because the layered structure forms a certain obstacle to the transfer of active substances in the hot compress patch containing ginkgo leaf extract when the aluminum magnesium hydrotalcite is added, a certain slow release effect is achieved, and the bioavailability of the active substances ginkgo leaf extract and the compound 1 is enhanced.
Example 9 and example 7 are compared with the results of table 2, it is understood that when the hot compress patch containing ginkgo leaf extract is further added with magnesium nickel aluminum hydrotalcite, the foot swelling degree becomes smaller and the ecchymosis dissipating time becomes shorter, which is probably because the slow release effect is different when zinc aluminum magnesium hydrotalcite is added with different electropositivity from magnesium aluminum hydrotalcite.
Comparison of the results of example 10 and example 7 in combination with Table 2 shows that when graphene is further added to the hot compress patch containing ginkgo leaf extract, the foot swelling degree is slightly reduced and the ecchymosis dissipating time is slightly shortened. This is probably because the layered structure of graphene has a certain slow release effect, and in addition, graphene can conduct heat, which is beneficial to heat transfer.
Comparison of the results of examples 11 and examples 7, 8 and 10 in combination with Table 2 shows that when the aluminum magnesium hydrotalcite and graphene are added simultaneously to the hot compress patch containing ginkgo leaf extract, the foot swelling degree becomes smaller and the ecchymosis dissipating time becomes shorter.
As can be seen from comparison of the results of examples 12-14 and examples 7, 9 and 10 in combination with table 2, when the hot compress containing ginkgo leaf extract is applied while magnesium nickel aluminum hydrotalcite and graphene are added, and the mass ratio of magnesium nickel aluminum hydrotalcite to graphene is controlled within a certain range, the foot swelling degree is remarkably reduced, and the ecchymosis dissipation time is remarkably shortened, which is probably because the magnesium nickel aluminum hydrotalcite and graphene can form a labyrinth structure with a certain degree of complexity under the action of the molecular force of the system, on one hand, the ginkgo leaf extract as an active substance and the compound 1 can have a good slow release effect at the same time, and on the other hand, the active molecules are orderly arranged, the accumulation is reduced, and the transdermal effect is promoted. The magnesium-nickel-aluminum hydrotalcite and the graphene have good synergistic effect in relieving the foot swelling degree and shortening the ecchymosis dissipating time.
As can be seen from comparison of the results of example 15 and example 12 in combination with the results of table 2, when locust bean gum is further added to the hot compress containing ginkgo leaf extract, the foot swelling degree becomes smaller and the ecchymosis dissipating time becomes shorter, which is probably because, when the buffer substance is added, the drug concentration is reduced in the later stage of the hot compress, the locust bean gum is compounded with the transdermal enhancer and the slow release agent at the temperature of about 40 ℃ for a long time, and forms a certain glue connection with the active substance coated by sodium alginate, and meanwhile, the active molecule can smoothly move between the slow release agent layers, so that the active molecule can be formed into the wound by transdermal penetration, the consistency of the release speed of the ginkgo leaf extract and the compound 1 of the active substance in the hot compress in the use period is improved, and the bioavailability of the ginkgo leaf extract and the compound 1 of the active substance is improved.
As can be seen from a comparison of the results of example 16 and example 12 in combination with the results of table 2, when carrageenan is further added to the hot compress containing ginkgo leaf extract, there is little change in the swelling degree of the feet and the ecchymosis dissipating time, probably because carrageenan exhibits a cohesive effect at the early stage of the hot compress application or no cohesive effect at the later stage, and little help in the release of the active substance.
As can be seen from comparison of the results of example 17 and example 15 in combination with the results of table 2, when ginkgo leaf extract, compound 1, sodium alginate and water in an amount of 40-60wt% in total are mixed, and the remaining raw materials are stirred, and the materials are mixed and stirred again, the swelling degree of feet is smaller, and the ecchymosis dissipation time is shorter, probably because the layering mixing is more favorable for coating the surface of the active molecules with the aqueous solution of sodium alginate, and the transdermal penetration of the active molecules is favorable.
As can be seen from the comparison of the results of example 2 and comparative examples 1-3 in combination with the results of table 2, the ginkgo leaf extract and the compound 1 have a synergistic effect in promoting blood circulation to remove blood stasis, and compared with the comparative example 1 added with only the active substance compound 1 and the comparative example 2 added with only the ginkgo leaf extract, the use of the active substance compound 1 and the ginkgo leaf extract simultaneously achieves a technical effect of 1+1 of more than 2 in reducing the swelling degree of feet and the resolving time of ecchymosis.
Study of effects of hot compress containing ginkgo leaf extract on skin burn of mice according to some examples and comparative examples of the present invention by taking experimental rats, performing burn treatment on their backs, the burn area was about 2 x 2cm 2 Making burn model, and making into capsuleThe rats were randomly grouped, 10 rats per group were treated with the hot compress patch containing ginkgo leaf extract of examples and comparative examples, respectively, once daily administration of the patch at a dose of 0.5g active substance/kg body weight of the mice, each time for 8 hours or more, wound healing conditions of the rats after 2d, 5d, 8d of treatment were recorded, wound sizes of each rat were measured, total wound areas of each rat group were recorded, and wound healing rate was calculated, wound healing rate = (wound area before treatment-wound area after treatment)/wound area before treatment x 100%,10 rats were averaged, and specific results are shown in table 3.
Table 3 results of some examples and comparative examples on wound repair effect on rats
| Rate of healing after 2d (%) | Post-5 d healing Rate (%) | Rate of healing after 8d (%) | |
| Example 2 | 15.9 | 56.4 | 82.7 |
| Example 6 | 13.1 | 52.0 | 77.3 |
| Example 7 | 17.8 | 61.1 | 89.1 |
| Example 9 | 18.6 | 67.0 | 94.6 |
| Example 10 | 16.2 | 62.1 | 90.3 |
| Example 12 | 20.4 | 72.1 | 97.8 |
| Example 15 | 25.4 | 73.8 | 99.9 |
| Example 16 | 21.6 | 67.1 | 97.1 |
| Example 17 | 23.1 | 59.6 | 91.9 |
| Comparative example 1 | 6.3 | 34.1 | 48.7 |
| Comparative example 2 | 2 | 13.3 | 18.5 |
| Comparative example 3 | 0 | 0.2 | 0.3 |
As can be seen from comparison of the results of Table 3 in example 2 and example 6, when no heating substance was added to the heat patch containing ginkgo leaf extract, the healing rate after 2d, the healing rate after 5d and the healing rate after 8d were all low. This is probably because, on the one hand, the exothermic material can dilate blood vessels and promote local blood circulation and drug absorption, and on the other hand, the active material ginkgo leaf extract and the compound 1 have higher activity at higher temperatures.
Comparison of the results of example 7 and example 2 in combination with Table 3 shows that when sodium alginate is added to the heat patch containing ginkgo leaf extract, the healing rate after 2d, the healing rate after 5d and the healing rate after 8d are all high. This is probably because the addition of sodium alginate can increase the transdermal effect of ginkgo leaf extract and compound 1, and more active substances can be absorbed at the trauma site, which is beneficial to promoting blood circulation to remove blood stasis and promoting the recovery of trauma.
As can be seen from a comparison of the results of example 9 and example 7 in combination with Table 3, when the hot compress patch containing ginkgo leaf extract was further added with magnesium nickel aluminum hydrotalcite, the healing rate after 2d, the healing rate after 5d and the healing rate after 8d were all higher. This is probably because the slow release effect is different when zinc aluminum magnesium hydrotalcite is added with different electropositivity from magnesium aluminum hydrotalcite.
As can be seen from comparison of the results of example 10 and example 7 in combination with table 3, when graphene is further added to the hot compress patch containing ginkgo leaf extract, the healing rate after 2d, the healing rate after 5d, and the healing rate after 8d become slightly higher.
As can be seen from comparison of the results of examples 12 and examples 7, 9 and 10 in combination with table 3, when the hot compress containing ginkgo leaf extract is simultaneously added with magnesium nickel aluminum hydrotalcite and graphene, and the mass ratio of magnesium nickel aluminum hydrotalcite to graphene is controlled within a certain range, the healing rate after 2d, the healing rate after 5d and the healing rate after 8d become significantly higher, which is probably because the magnesium nickel aluminum hydrotalcite and graphene can form a labyrinth structure with a certain degree of complexity under the action of the molecular force of the system, on one hand, the ginkgo leaf extract and the compound 1 which are active substances can have good slow release effect at the same time, the bioavailability of the active substances is improved, and on the other hand, the active molecules are orderly arranged, the accumulation is reduced, and the transdermal effect is promoted. The magnesium nickel aluminum hydrotalcite and the graphene have good synergistic effect in relieving burn.
Comparison of the results of examples 15 and 16 with the results of example 12 in combination with the results of Table 3 shows that the healing rate after 2d, the healing rate after 5d and the healing rate after 8d are significantly higher when locust bean gum is further added to the hot compress patch containing ginkgo leaf extract.
As can be seen from comparison of the results of example 17 and example 12 in combination with the results of table 3, when ginkgo leaf extract, compound 1, sodium alginate and water in a total amount of 40 to 60wt% are mixed, and the remaining raw materials are stirred, and the mixed materials are stirred, the healing rate after 2d, the healing rate after 5d and the healing rate after 8d become significantly higher, this is probably because the layering mixing is more favorable for coating the surface of the active molecule with the aqueous solution of sodium alginate, and for transdermal penetration of the active molecule, thereby enhancing the therapeutic effect.
As can be seen from the comparison of the results of example 2 and comparative examples 1-3 in combination with the results of table 3, the ginkgo leaf extract and the compound 1 have a synergistic effect in treating burns, and compared with the comparative example 1 added with only the active material compound 1 and the comparative example 2 added with only the ginkgo leaf extract, the use of the active material compound 1 and the ginkgo leaf extract simultaneously achieves technical effects of 1+1 of more than 2 in terms of reducing the burn area, improving the healing rate after 2 days, the healing rate after 5 days, and the healing rate after 8 days.
The foregoing are all preferred embodiments of the present application, and are not intended to limit the scope of the present application in any way, therefore: all equivalent changes in structure, shape and principle of this application should be covered in the protection scope of this application.
Claims (5)
1. A hot compress patch containing ginkgo leaf extract for activating blood circulation to dissipate blood stasis and treating burn is characterized by being prepared from the following raw materials in parts by weight:
8.5-10.5 parts by weight of ginkgo leaf extract;
9.5 to 11.5 parts by weight of compound 1;
2-3 parts by weight of reduced iron;
0.1 to 0.15 part by weight of sodium chloride;
0.5-1.5 parts by weight of activated carbon;
0.8-1.3 parts by weight of vermiculite powder;
0.75-1 parts by weight of water;
0.08-0.13 part by weight of sodium alginate;
0.19-0.22 parts by weight of a sustained release agent; the slow release agent is hydrotalcite and graphene, the hydrotalcite is aluminum-magnesium hydrotalcite or magnesium-nickel-aluminum hydrotalcite, and the mass ratio of the hydrotalcite to the graphene is (0.65-3) 1;
the folium Ginkgo extract contains flavone more than 24wt% and terpene lactone more than 6wt%;
the chemical formula of the compound 1 is shown as follows:
。
2. the hot compress patch containing ginkgo leaf extract according to claim 1, wherein the raw materials for preparing the hot compress patch containing ginkgo leaf extract further comprise additives, wherein the additives are selected from one or more of locust bean gum and carrageenan.
3. A method for preparing a hot compress patch containing ginkgo leaf extract as claimed in claim 1 or 2, comprising the steps of:
step 1): mixing all the raw materials, and stirring;
step 2): placing the stirred raw materials into a non-woven fabric bag, tiling, sealing, pressing, covering and bonding one side of an adhesive layer on the outer surface of one side of the non-woven fabric bag, covering an anti-bonding layer on the other side of the adhesive layer, and packaging to obtain the hot compress patch containing ginkgo leaf extract.
4. The method for preparing a hot compress patch containing ginkgo leaf extract according to claim 3, wherein in the step 1), ginkgo leaf extract, compound 1, sodium alginate and water accounting for 40-60wt% of the total amount are mixed and stirred to obtain a first mixture, other raw materials and the rest water are mixed and stirred to obtain a second mixture, and the first mixture and the second mixture are mixed and stirred.
5. Use of a hot compress patch containing ginkgo leaf extract according to claim 1 or 2 for preparing a medicament for activating blood circulation to dissipate blood stasis and burn.
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