CN114732843A - Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof - Google Patents
Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof Download PDFInfo
- Publication number
- CN114732843A CN114732843A CN202210234228.1A CN202210234228A CN114732843A CN 114732843 A CN114732843 A CN 114732843A CN 202210234228 A CN202210234228 A CN 202210234228A CN 114732843 A CN114732843 A CN 114732843A
- Authority
- CN
- China
- Prior art keywords
- traditional chinese
- chinese medicine
- dpn
- parts
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 181
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 230000035515 penetration Effects 0.000 title abstract description 17
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 title 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 title 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 39
- 239000000843 powder Substances 0.000 claims abstract description 28
- 230000000694 effects Effects 0.000 claims abstract description 22
- 239000011159 matrix material Substances 0.000 claims abstract description 18
- 244000020518 Carthamus tinctorius Species 0.000 claims abstract description 16
- 241000112528 Ligusticum striatum Species 0.000 claims abstract description 15
- 235000003255 Carthamus tinctorius Nutrition 0.000 claims abstract description 14
- 235000006533 astragalus Nutrition 0.000 claims abstract description 13
- 235000001287 Guettarda speciosa Nutrition 0.000 claims abstract description 8
- 241001061264 Astragalus Species 0.000 claims abstract description 6
- 210000004233 talus Anatomy 0.000 claims abstract description 6
- 240000007164 Salvia officinalis Species 0.000 claims abstract description 4
- 244000061520 Angelica archangelica Species 0.000 claims abstract 4
- 235000005412 red sage Nutrition 0.000 claims abstract 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- 238000002156 mixing Methods 0.000 claims description 25
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 21
- 229920002125 Sokalan® Polymers 0.000 claims description 19
- 229960001631 carbomer Drugs 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 16
- 239000006254 rheological additive Substances 0.000 claims description 16
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 15
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 claims description 15
- 229940116229 borneol Drugs 0.000 claims description 15
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 claims description 15
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 claims description 15
- 229910000278 bentonite Inorganic materials 0.000 claims description 14
- 239000000440 bentonite Substances 0.000 claims description 14
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 14
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 14
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 14
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 210000003141 lower extremity Anatomy 0.000 claims description 13
- 239000002994 raw material Substances 0.000 claims description 13
- 235000011135 Salvia miltiorrhiza Nutrition 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 239000003381 stabilizer Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 10
- 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 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 239000003961 penetration enhancing agent Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- 239000000835 fiber Substances 0.000 claims description 8
- 238000007873 sieving Methods 0.000 claims description 7
- 239000003906 humectant Substances 0.000 claims description 6
- 239000002985 plastic film Substances 0.000 claims description 6
- 229920006255 plastic film Polymers 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- 229940049638 carbomer homopolymer type c Drugs 0.000 claims description 5
- 229940043234 carbomer-940 Drugs 0.000 claims description 5
- 238000000643 oven drying Methods 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 208000005392 Spasm Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000003020 moisturizing effect Effects 0.000 claims description 3
- 231100000862 numbness Toxicity 0.000 claims description 3
- 208000035824 paresthesia Diseases 0.000 claims description 3
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- 235000017276 Salvia Nutrition 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims 1
- 244000132619 red sage Species 0.000 claims 1
- 238000002791 soaking Methods 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 abstract description 5
- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 96
- 210000003491 skin Anatomy 0.000 description 25
- 238000002474 experimental method Methods 0.000 description 16
- 238000012360 testing method Methods 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 241000283973 Oryctolagus cuniculus Species 0.000 description 12
- 206010070834 Sensitisation Diseases 0.000 description 12
- 230000008313 sensitization Effects 0.000 description 12
- 241000304195 Salvia miltiorrhiza Species 0.000 description 11
- 235000011187 glycerol Nutrition 0.000 description 11
- 238000001467 acupuncture Methods 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 229910000831 Steel Inorganic materials 0.000 description 9
- 239000010959 steel Substances 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 8
- IAVUBSCVWHLRGE-UXEKTNMQSA-N (6e)-2,5-dihydroxy-6-[(e)-1-hydroxy-3-(4-hydroxyphenyl)prop-2-enylidene]-2,4-bis[(2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]cyclohex-4-ene-1,3-dione Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C(C(C(O)([C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)C1=O)=O)=C(O)\C1=C(/O)\C=C\C1=CC=C(O)C=C1 IAVUBSCVWHLRGE-UXEKTNMQSA-N 0.000 description 7
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 7
- 241000382455 Angelica sinensis Species 0.000 description 7
- 241000045403 Astragalus propinquus Species 0.000 description 7
- 206010015150 Erythema Diseases 0.000 description 7
- HYXITZLLTYIPOF-UHFFFAOYSA-N Tanshinone II Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)=CO2 HYXITZLLTYIPOF-UHFFFAOYSA-N 0.000 description 7
- QMNWISYXSJWHRY-YLNUDOOFSA-N astragaloside IV Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)[C@H]4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)C[C@H]3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-YLNUDOOFSA-N 0.000 description 7
- 231100000321 erythema Toxicity 0.000 description 7
- 229940114124 ferulic acid Drugs 0.000 description 7
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 7
- 235000001785 ferulic acid Nutrition 0.000 description 7
- 230000007830 nerve conduction Effects 0.000 description 7
- AZEZEAABTDXEHR-UHFFFAOYSA-M sodium;1,6,6-trimethyl-10,11-dioxo-8,9-dihydro-7h-naphtho[1,2-g][1]benzofuran-2-sulfonate Chemical compound [Na+].C12=CC=C(C(CCC3)(C)C)C3=C2C(=O)C(=O)C2=C1OC(S([O-])(=O)=O)=C2C AZEZEAABTDXEHR-UHFFFAOYSA-M 0.000 description 7
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N tanshinone IIA Natural products C1=CC2=C(C)C=CC=C2C(C(=O)C2=O)=C1C1=C2C(C)=CO1 AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 description 7
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- QMNWISYXSJWHRY-BCBPIKMJSA-N astragaloside IV Natural products CC(C)(O)[C@@H]1CC[C@@](C)(O1)[C@H]2[C@@H](O)C[C@@]3(C)[C@@H]4C[C@H](O[C@@H]5O[C@H](CO)[C@H](O)[C@@H](O)[C@H]5O)[C@H]6C(C)(C)[C@H](CC[C@@]67C[C@@]47CC[C@]23C)O[C@@H]8OC[C@@H](O)[C@H](O)[C@H]8O QMNWISYXSJWHRY-BCBPIKMJSA-N 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- PFKIBRPYVNVMRU-UHFFFAOYSA-N cyclosieversioside F Natural products CC(C)(O)C1COC(C)(C1)C2C(O)CC3(C)C4CC(OC5OC(CO)C(O)C(O)C5O)C6C(C)(C)C(CCC67CC47CCC23C)OC8OCC(O)C(O)C8O PFKIBRPYVNVMRU-UHFFFAOYSA-N 0.000 description 6
- ZZMASNSDVDSYKO-UHFFFAOYSA-N hydroxysafflor yellow A Natural products OCC1OC(C(O)C(O)C1O)C2=C(O)C(O)(C3OC(CO)C(O)C(O)C3O)C(=O)C(=C2O)C(=O)C=Cc4ccc(O)cc4 ZZMASNSDVDSYKO-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 206010030113 Oedema Diseases 0.000 description 5
- 239000000017 hydrogel Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000010298 pulverizing process Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000000007 visual effect Effects 0.000 description 5
- 241000125175 Angelica Species 0.000 description 4
- 206010040880 Skin irritation Diseases 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000001186 cumulative effect Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 231100000475 skin irritation Toxicity 0.000 description 4
- 230000036556 skin irritation Effects 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007794 irritation Effects 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- -1 purity 98%) Chemical compound 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 2
- 241000628997 Flos Species 0.000 description 2
- 239000009636 Huang Qi Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 208000030961 allergic reaction Diseases 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000004745 nonwoven fabric Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000013441 quality evaluation Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229940126680 traditional chinese medicines Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 description 1
- 235000003717 Boswellia sacra Nutrition 0.000 description 1
- 240000007551 Boswellia serrata Species 0.000 description 1
- 235000012035 Boswellia serrata Nutrition 0.000 description 1
- 101100134058 Caenorhabditis elegans nth-1 gene Proteins 0.000 description 1
- 240000007311 Commiphora myrrha Species 0.000 description 1
- 235000006965 Commiphora myrrha Nutrition 0.000 description 1
- 241000510667 Conioselinum Species 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 1
- 239000004863 Frankincense Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- 235000007265 Myrrhis odorata Nutrition 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010070835 Skin sensitisation Diseases 0.000 description 1
- 241000913745 Spatholobus Species 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 description 1
- 229940107666 astragalus root Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003958 fumigation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229930195259 hydroxysafflor yellow Natural products 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical group O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 231100000370 skin sensitisation Toxicity 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- 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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- 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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
-
- 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
- A61K36/286—Carthamus (distaff thistle)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/16—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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the field of external traditional Chinese medicine preparations, and particularly relates to a traditional Chinese medicine gel patch for treating Diabetic Peripheral Neuropathy (DPN) through medicine permeation, and a preparation method and application thereof. The traditional Chinese medicine gel patch for treating DPN through medicine penetration comprises traditional Chinese medicine powder and a gel matrix, wherein the traditional Chinese medicine powder comprises astragalus, red sage root, safflower, angelica and ligusticum wallichii. The traditional Chinese medicine gel patch for thoroughly treating DPN is a new traditional Chinese medicine external preparation formulation used by matching with a traditional Chinese medicine directional medicine permeation therapeutic apparatus, improves the original rough operation method, is simpler, more convenient and more efficient in use and operation, realizes the stability and controllability of the medicine dosage concentration in the treatment process, is beneficial to developing clinical scientific research work, and shows that the curative effect of the traditional Chinese medicine gel patch for thoroughly treating DPN is better than that of the traditional operation of gauze medicine soaking.
Description
Technical Field
The invention relates to the technical field of external traditional Chinese medicine preparations, in particular to a traditional Chinese medicine gel patch for treating DPN through medicine penetration, and a preparation method and application thereof.
Background
Diabetes is one of the most common chronic non-infectious diseases at present, has the characteristics of high morbidity, high disability rate, high mortality and high medical expense, and the number of patients is increased year by year at present, and is expected to exceed 6.42 hundred million people worldwide by 2040 years. Various complications caused by the rise of blood sugar are the main causes of diabetes death, and the incidence rate of diabetic peripheral neuropathy is the highest among a plurality of complications, especially the incidence rate of painful diabetic peripheral neuropathy (diabetes peripheral neuropathy DPN) of a type 2 diabetes patient is far over 60 percent, the life quality of the diabetes patient is seriously influenced, and the family and the society of the patient are heavily burdened with economic burden. At present, the pathogenic treatment aiming at DPN only comprises the control of blood sugar and blood fat, and also comprises treatment methods such as blood vessel expansion, nerve nutrition supplement, antioxidation, symptomatic pain relief and the like, but the treatment methods can only be alleviated for a short time and cannot achieve the effect of effective reversion or even effective treatment.
The pathogenesis of DPN is very complex, so that western medicine cannot obtain good curative effect through a treatment method of a single mechanism way, Chinese medicine treatment has the advantage of multiple targets, and the optimal curative effect can be expected by combining conventional western medicine treatment and adopting an optimized comprehensive treatment method combining traditional Chinese medicine and western medicine and internal and external combined treatment, so that the method is particularly important for further researching and exploring a new, simpler, more convenient and cheaper-effective treatment method to supplement the deficiency of the current treatment. The external treatment method of the traditional Chinese medicine comprises acupuncture, massage, medicinal application, fumigation and washing and the like, wherein acupuncture point medicine is taken as a novel external treatment method generated under the modern background of the traditional Chinese medicine in recent years, the external treatment method is characterized in that the utilization rate of the external medicine is greatly improved through medicine ion introduction, and the medicine introduction and the acupuncture point stimulation are organically combined to achieve double treatment effects. The inventor adopts an acupoint medicine penetration therapy to treat patients with painful diabetic peripheral neuropathy, the symptoms of the patients are obviously relieved after the treatment, the nerve conduction is improved, and the total effective rate reaches more than 90%.
The existing medicine permeation operation method has more problems that firstly, the stability of the dosage form of the traditional Chinese medicine decoction is poor, secondly, the whole technology is complex to operate, in addition, the individual operation curative effect difference is large, the quality control is difficult, and the technical operation specification is difficult to realize, so the treatment technology needs to be further optimized, and the medicine electrode with controllable quality, better performance and curative effect and simple and convenient operation is manufactured.
Disclosure of Invention
In order to overcome the problems in the prior art, the invention aims to provide a traditional Chinese medicine gel patch for treating DPN through medicine penetration, and a preparation method and application thereof.
In order to achieve the above objects and other related objects, the present invention adopts the following technical solutions:
the invention provides a traditional Chinese medicine gel patch for treating DPN through medicine penetration, which comprises traditional Chinese medicine powder and a gel matrix, wherein the traditional Chinese medicine powder comprises astragalus, salvia miltiorrhiza, safflower, angelica and ligusticum wallichii.
In some embodiments, the traditional Chinese medicine powder comprises the following components in parts by weight: 0.6 to 1.6 parts of astragalus, 0.6 to 1.6 parts of salvia miltiorrhiza, 0.3 to 0.8 part of angelica, 0.3 to 0.8 part of safflower and 0.3 to 0.8 part of ligusticum wallichii.
In some embodiments, the gel matrix comprises a gel stock, a rheology modifier, a pH modifier, a humectant, a stabilizer, a solvent, a penetration enhancer.
In some preferred embodiments, the gel material comprises sodium polyacrylate, bentonite.
In some preferred embodiments, the rheology modifier is carbomer 940.
In some preferred embodiments, the pH adjusting agent is AlCl3。
In some preferred embodiments, the humectant is glycerin.
In some preferred embodiments, the stabilizer is EDTA-2 Na.
In some preferred embodiments, the solvent is absolute ethanol.
In some preferred embodiments, the penetration enhancer comprises azone and borneol.
In some preferred embodiments, the gel matrix comprises the following raw materials in parts by weight: 4-10 parts of glycerol, 6-10 parts of absolute ethyl alcohol, 6-6 parts of sodium polyacrylate NP-7002, 0.5-1.5 parts of bentonite, 1.5-3 parts of azone, 1.5-3 parts of borneol, 94024-32 parts of carbomer, 0.05-0.2 part of EDTA-2Na, and AlCl30.05-0.2 part of water and 8-20 parts of water.
In some preferred embodiments, the gel matrix comprises the following raw materials in parts by weight: 4 parts of glycerol, 8 parts of absolute ethyl alcohol, 8 parts of sodium polyacrylate NP-7005 parts, 1 part of bentonite, 2 parts of azone, 2 parts of borneol, 94028 parts of carbomer, 0.1 part of ethylene diamine tetraacetic acid (EDTA-2Na), and AlCl30.1 part and 20 parts of water.
In a second aspect of the present invention, a preparation method of the traditional Chinese medicine gel patch for the transdermal DPN treatment is provided, which comprises the following steps:
s1, uniformly mixing the moisturizing agent, the solvent, the gel raw material and the penetration enhancer to obtain a phase I;
s2, preparing a rheology modifier into a rheology modifier aqueous solution;
s3, adding a solvent into the Chinese medicinal powder, and then adding the aqueous solution of the rheology modifier prepared in the step S2 and uniformly mixing to obtain a phase II;
s4, adding water into the stabilizer and the pH regulator to dissolve the stabilizer and the pH regulator to obtain a phase III;
s5, adding phase I into phase III, mixing, adding phase II, stirring, coating on the substrate, making into medicinal cake, and oven drying to obtain the final product.
In some preferred embodiments, the aqueous rheology modifier solution in step S2 is a 3 wt% aqueous carbomer solution.
In some preferred embodiments, the method for preparing the Chinese medicinal powder in step S3 is: mixing and pulverizing radix astragali, Saviae Miltiorrhizae radix, Carthami flos, radix Angelicae sinensis and rhizoma Ligustici Chuanxiong according to weight parts, sieving for more than three times until no crude fiber is visible to naked eyes.
In some preferred embodiments, the base layer in step S5 is a plastic film.
In some preferred embodiments, the drying condition in step S5 is drying at 60 ℃ for 1-3 h.
In a third aspect of the invention, the application of the traditional Chinese medicine gel patch for thoroughly treating the DPN is provided for treating painful diabetic peripheral neuropathy.
In a fourth aspect of the invention, the application of the traditional Chinese medicine gel patch for thoroughly treating the DPN is provided for preparing a product for treating painful diabetic peripheral neuropathy.
In a fifth aspect of the present invention, there is provided a use of the traditional Chinese medicine gel patch for DPN transdermal therapy for preparing a product for treating painful diabetic peripheral neuropathy, wherein the product has any one of the following effects: 1) relieve pain in both lower extremities of DPN patients; 2) relieving numbness of both lower limbs of DPN patients; 3) relieving spasm of both lower limbs of DPN patients; (4) reduce the paraesthesia of the lower limbs of the DPN patients.
Compared with the prior art, the invention has the following beneficial effects:
1. the traditional Chinese medicine gel patch is a new traditional Chinese medicine external application formulation matched with a traditional Chinese medicine directional medicine permeation therapeutic apparatus, the used traditional Chinese medicine powder has the effects of tonifying qi, activating blood circulation, dredging collaterals and relieving pain under the synergistic effect of all components, the used gel matrix has the advantages of good biocompatibility, high water absorption, high water retention, soft texture, large medicine carrying capacity and difficulty in bacterial contamination in the using process, the original rough operation method is improved, the use and the operation of the patch are simpler, more convenient and more efficient, the stability and the controllability of the medicine dosage concentration in the treatment process are realized, and the development of clinical scientific research work is facilitated.
2. Animal safety experiments, including rabbit skin irritation experiments and guinea pig allergy experiments, prove that the traditional Chinese medicine gel patch for treating DPN through medicine penetration has good safety, and the transdermal experiment result shows that the traditional Chinese medicine gel patch has a penetration promoting effect on percutaneous absorption of effective ingredients of the medicine which is obviously better than that of medicine-soaked gauze, so that the traditional Chinese medicine gel patch can relieve pain of patients and improve nerve conduction speed when being applied to clinical treatment of DPN, has a curative effect which is better than that of a conventional treatment group and a traditional gauze medicine-soaked group, and has good clinical application value.
Drawings
Fig. 1 is a picture of gauze soaked with medicine and oriented medicine permeation.
FIG. 2 is a photograph of the directional penetration of a Chinese medicinal hydrogel patch of the present invention.
Detailed Description
Before the present embodiments are further described, it is to be understood that the scope of the invention is not limited to the particular embodiments described below; it is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the respective manufacturers.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition to the specific methods, devices, and materials used in the examples, any methods, devices, and materials similar or equivalent to those described in the examples may be used in the practice of the invention in addition to the specific methods, devices, and materials used in the examples, in keeping with the knowledge of one skilled in the art and with the description of the invention.
Unless otherwise indicated, the experimental methods, detection methods and preparation methods disclosed in the present invention all employ conventional techniques in the art.
The invention provides a traditional Chinese medicine gel patch for treating DPN through medicine penetration, which comprises traditional Chinese medicine powder and a gel matrix, wherein the traditional Chinese medicine powder comprises astragalus mongholicus, salvia miltiorrhiza, safflower carthamus, angelica sinensis and ligusticum wallichii. Preferably, the traditional Chinese medicine powder comprises the following components in parts by weight: 0.6-1.6 parts of astragalus membranaceus, 0.6-1.6 parts of salvia miltiorrhiza, 0.3-0.8 parts of angelica sinensis, 0.3-0.8 parts of safflower and 0.3-0.8 parts of ligusticum wallichii, and more preferably, the traditional Chinese medicine powder consists of the astragalus membranaceus, the salvia miltiorrhiza, the safflower, the angelica sinensis and the ligusticum wallichii according to the weight part ratio of 2:2:1:1: 1.
The traditional Chinese medicine powder used by the invention has the same medicinal ingredients and compatibility proportion as the traditional Chinese medicine and the compatibility proportion in the earlier clinical test of the inventor. The traditional Chinese medicine considers that the compound has the acupuncture point medicine penetration formula with the effects of tonifying qi, activating blood circulation, dredging collaterals and relieving pain. The formula takes the astragalus root as a monarch and the angelica as a minister, supplements qi and nourishes blood, and adds the salvia miltiorrhiza, the safflower, the ligusticum wallichii and the borneol as an assistant and a guide, wherein the salvia miltiorrhiza, the safflower and the ligusticum wallichii are common blood-activating traditional Chinese medicines, and the borneol is added to promote blood circulation, so that the effect of dredging collaterals and relieving pain can be enhanced, and the effect of guiding channels can be achieved directly. The blood circulation promoting and collateral dredging medicine of the present invention, such as angelica, salvia miltiorrhiza, safflower and hemlock parsley, can also be replaced by the traditional Chinese medicines with the same efficacy, such as frankincense, myrrh, sapanwood, suberect spatholobus stem, etc.
In some preferred embodiments, the gel material comprises sodium polyacrylate, bentonite. The sodium polyacrylate is colorless and transparent water-soluble resin, is preferably medical sodium polyacrylate NP-700, and generates strong adhesion effect after undergoing a crosslinking reaction and forms a hydrogel high molecular compound; the bentonite is hydrated aluminum silicate of natural colloid, has strong hygroscopicity, can absorb water with volume 8-20 times of the bentonite itself and expand to 30 times, can be dispersed in a water medium to form colloidal suspension, and has certain viscosity, thixotropy and lubricity. The hydrogel which has good adhesive force and stability and can be repeatedly pasted is obtained by reasonably proportioning the three components.
In some preferred embodiments, the rheology modifier is carbomer 940. The carbomer used in the invention is acrylic acid crosslinked resin obtained by crosslinking pentaerythritol and the like with acrylic acid, is a main gel matrix raw material commonly used in the pharmaceutical industry, is used as a rheological regulator of the gel matrix, and regulates the hardness of the gel by regulating the concentration of the carbomer.
In some preferred embodiments, the pH adjusting agent is AlCl3. AlCl used in the invention3Is a pH value regulator of matrix by adding AlCl3The pH of the substrate is adjusted to between 5 and 6 to optimize substrate spreadability and uniformity.
In some preferred embodiments, the humectant is glycerol, and the humectant is matched with the rest components, so that the gel matrix has good water retention performance, is soft, promotes skin hydration and improves the transdermal effect of the medicine.
In some preferred embodiments, the stabilizer is EDTA-2 Na. EDTA-2Na is a commonly used complex that acts as a stabilizer in the gel matrix.
In some preferred embodiments, the solvent is absolute ethanol. The anhydrous ethanol is used as solvent of the Chinese medicinal powder, and can promote dissolution of effective substances in the Chinese medicinal powder.
In some preferred embodiments, the penetration enhancer comprises azone and borneol. The borneol is not only a traditional Chinese medicine, is used for enhancing the effects of dredging collaterals and relieving pain by cooperating with other components in the traditional Chinese medicine powder, but also is used as a penetration enhancer by cooperating with azone so as to enhance the transdermal effect of the medicinal components in the gel patch.
In some preferred embodiments, the gel matrix comprises the following raw materials in parts by weight: 4-10 parts of glycerol, 6-10 parts of absolute ethyl alcohol, 6-6 parts of sodium polyacrylate NP-7002, 0.5-1.5 parts of bentonite, 1.5-3 parts of azone, 1.5-3 parts of borneol, 94024-32 parts of carbomer, 0.05-0.2 part of EDTA-2Na, and AlCl30.05-0.2 part of water and 8-20 parts of water.
In some preferred embodiments, the gel matrix comprises the following raw materials in parts by weight: 4 parts of glycerol, 8 parts of absolute ethyl alcohol, 8 parts of sodium polyacrylate NP-7005 parts, 1 part of bentonite, 2 parts of azone, 2 parts of borneol, 94028 parts of carbomer and disodium ethylene diamine tetraacetate (ED)TA-2Na)0.1 part, AlCl30.1 part and 20 parts of water. Further, the concentration of carbomer 940 was 7 wt%.
The quality of the Chinese medicinal gel patch was evaluated by scoring the initial adhesive force, bubble number, uniformity, coating property, skin-following property and residual amount of the medicinal gel according to the patch evaluation index and score criteria table (table 1), and the results are shown in the following table (table 2).
TABLE 1 evaluation index and score criteria table for patch
Note: determination of initial adhesion: the initial adhesion of the gel patch was measured using an initial adhesion tester. The inclination number of the inclined plate of the tester is adjusted to 30 degrees, the anti-sticking layer is uncovered before the experiment, and the inclined plate is placed at room temperature for more than 2 hours. Cleaning the surfaces of the inclined plate and the stainless steel ball by using a wiping material dipped with absolute ethyl alcohol until the surfaces are clean, taking a sample, placing the sample in the center of the inclined plate, enabling the paste surface to face upwards, covering the upper part 10cm and the lower part 15cm of the inclined plane by using a polyester film, reserving the paste surface of 5cm in the middle, and freely rolling down the steel ball from the top end of the inclined plane. The steel ball can be stuck on the test section after repeated determination for 3 times, and the steel ball can be stuck on the test section after 2 or more than 2 times if 1 time exists, and the steel ball can be stuck after a small first steel ball experiment. If only 1 time can stick the steel ball, and the other 2 times can stick only a smaller steel ball, 1 piece of the steel ball should be taken again for retesting, and the steel ball can be stuck for 3 times, which is in accordance with the regulations.
TABLE 2 quality evaluation score chart for Chinese medicinal gel patch
The gel matrix has uniform and soft texture, large drug loading rate, good stability and biocompatibility and good skin viscosity, overcomes the defects of small absorption amount of the traditional gauze medicine soaking liquid medicine, unstable drug loading rate and the like, and is matched with a traditional Chinese medicine oriented medicine permeation therapeutic apparatus for use.
In a second aspect of the present invention, a preparation method of the traditional Chinese medicine gel patch for the transdermal DPN treatment is provided, which comprises the following steps:
s1, uniformly mixing the moisturizing agent, the solvent, the gel raw material and the penetration enhancer to obtain a phase I;
s2, preparing a rheology modifier solution from the rheology modifier;
s3, adding a solvent into the Chinese medicinal powder, and then adding the rheological regulator solution prepared in the step S2 and uniformly mixing to obtain a phase II;
s4, adding water into the stabilizer and the pH regulator to dissolve the stabilizer and the pH regulator to obtain a phase III;
and S5, adding phase I into phase III, mixing, adding phase II, stirring, coating on the substrate, making into medicated cake, and oven drying to obtain Chinese medicinal gel patch.
In some preferred embodiments, the rheology modifier solution in step S2 is a 3 wt% mass fraction aqueous carbomer solution.
In some preferred embodiments, the method for preparing the Chinese medicinal powder in step S3 is: mixing and pulverizing radix astragali, Saviae Miltiorrhizae radix, Carthami flos, radix Angelicae sinensis, and rhizoma Ligustici Chuanxiong according to weight parts, sieving for more than three times until no coarse fiber is visible to naked eyes.
In some preferred embodiments, the substrate in step S5 is a plastic film, a fiber filter paper, or a stainless steel tray.
In some preferred embodiments, the drying condition in step S5 is drying at 60 ℃ for 1-3 h.
The application method of the traditional Chinese medicine gel patch for treating DPN through medicine penetration provided by the invention specifically comprises the following steps:
step one, turning on the traditional Chinese medicine directional medicine permeation therapeutic apparatus, connecting a power line, switching on a power supply, and inserting a plug of a lead electrode into an output jack of a selected channel;
flatly attaching the traditional Chinese medicine gel patch to the electrode plate, attaching the traditional Chinese medicine gel patch to a corresponding treatment acupuncture point, and pressurizing, binding and fixing the traditional Chinese medicine gel patch with an external bandage;
setting initial temperature, intensity and treatment time;
step four, pressing a 'start' key to start the treatment. Pressing the increase key "+" to gradually adjust the dosage, stopping increasing when the patient has just the feeling of pulse and slight irritation, and pressing the decrease key "-" to decrease the dosage until the patient hardly feels;
and step five, the treatment ending instrument automatically cuts off the output current, takes down the electrode and the patch and finishes shutdown.
The application method of the invention adopts the acupuncture points of Weizhong acupuncture point and Zusanli acupuncture point of double lower limbs.
In a third aspect of the invention, the application of the traditional Chinese medicine gel patch for the transdermal DPN treatment in the aspect of treating painful diabetic peripheral neuropathy is provided.
In a fourth aspect of the invention, the application of the traditional Chinese medicine gel patch for the thorough drug therapy of DPN in preparing a product for treating painful diabetic peripheral neuropathy is provided.
In a fifth aspect of the invention, the application of the traditional Chinese medicine gel patch for the transdermal DPN treatment is provided for preparing a product for treating painful diabetic peripheral neuropathy, wherein the product has any one of the following effects: 1) relieve pain in both lower extremities of DPN patients; 2) relieving numbness of both lower limbs of DPN patients; 3) relieving spasm of both lower limbs of DPN patients; (4) reduce the paraesthesia of the lower limbs of the DPN patients.
Example 1
The preparation method of the traditional Chinese medicine gel patch for thoroughly treating DPN comprises the following steps:
s1, mixing 1.00g of glycerol, 1.00g of absolute ethyl alcohol, 1.00g of sodium polyacrylate NP-7001.25 g, 0.25g of bentonite, 0.50g of azone and 0.50g of borneol in parts by weight, and adding the mixture into a test tube to serve as a phase I;
s2, adding 9407.00 g of carbomer into purified water, and stirring uniformly to prepare a 7 wt% carbomer aqueous solution;
s3, weighing 0.20g of astragalus membranaceus, 0.20g of salvia miltiorrhiza, 0.10g of safflower carthamus, 0.10g of angelica sinensis and 0.10g of ligusticum wallichii according to the weight ratio of 2:2:1:1:1, uniformly mixing, then pulverizing and sieving, sieving for four times without coarse fibers visible to naked eyes, adding 1.00g of absolute ethyl alcohol into the medicinal powder, adding the carbomer aqueous solution prepared in the step S2, and uniformly mixing to obtain a phase II;
s4, taking EDTA-2Na and AlCl3Adding 25mg of each into 5mL of water, and fully dissolving to obtain a phase III;
s5, adding phase I into phase III, mixing, adding phase II, stirring, coating on plastic film to obtain medicinal cake with thickness of 2mm and length of 4cm × 6cm, and oven drying in 60 ° oven for 2 hr to obtain the final product.
The traditional Chinese medicine gel patch prepared by the embodiment is as shown in fig. 2, the traditional Chinese medicine gel patch is fine in texture, the traditional Chinese medicine powder is uniformly dispersed, no medicine residue or spots exist, the extensibility is good, and no crack or wrinkle phenomenon occurs in the using process.
Example 2
The preparation method of the traditional Chinese medicine gel patch for treating DPN by medicine penetration comprises the following steps:
s1, mixing 2.00g of glycerol, 1.00g of absolute ethyl alcohol, 7001.25 g of sodium polyacrylate NP-7001.25 g, 0.25g of bentonite, 0.50g of azone and 0.50g of borneol in parts by weight, and adding the mixture into a test tube to serve as a phase I;
s2, adding 9407.00 g of carbomer into purified water, and stirring uniformly to prepare a 7 wt% carbomer aqueous solution;
s3, weighing 0.30g of astragalus membranaceus, 0.30g of salvia miltiorrhiza, 0.15g of safflower, 0.15g of angelica sinensis and 0.15g of ligusticum wallichii which are traditional Chinese medicine raw materials, uniformly mixing, then pulverizing, sieving for four times without coarse fibers visible to naked eyes, adding 1.00g of absolute ethyl alcohol into the medicinal powder, adding the carbomer aqueous solution prepared in the step S2, and uniformly mixing to obtain a phase II;
s4, taking EDTA-2Na and AlCl3Adding 25mg of each into 2mL of water, and fully dissolving to obtain a phase III;
s5, adding the phase I into the phase III, mixing uniformly, adding the phase II, stirring uniformly, coating on a plastic film to prepare a medicine cake with the thickness of 2mm and the length multiplied by the width of 4cm multiplied by 6cm, and drying the medicine cake in a 60-degree oven for 2 hours to obtain the traditional Chinese medicine gel patch.
Example 3
The preparation method of the traditional Chinese medicine gel patch for thoroughly treating DPN comprises the following steps:
s1, mixing 2.00g of glycerol, 1.00g of absolute ethyl alcohol, 7001.20 g of sodium polyacrylate NP-7001.20 g, 0.25g of bentonite, 0.50g of azone and 0.50g of borneol in parts by weight, and adding the mixture into a test tube to serve as a phase I;
s2, adding 9407.00 g of carbomer into purified water, and stirring uniformly to prepare a 5 wt% carbomer aqueous solution;
s3, weighing 0.20g of astragalus membranaceus, 0.20g of salvia miltiorrhiza, 0.10g of safflower, 0.10g of angelica sinensis and 0.10g of ligusticum wallichii which are traditional Chinese medicine raw materials, uniformly mixing, then pulverizing, sieving for four times without coarse fibers visible to naked eyes, adding 1.00g of absolute ethyl alcohol into the medicinal powder, adding the carbomer aqueous solution prepared in the step S2, and uniformly mixing to obtain a phase II;
s4, taking EDTA-2Na and AlCl3Adding 25mg of each into 5mL of water, and fully dissolving to obtain a phase III;
s5, adding the phase I into the phase III, mixing uniformly, adding the phase II, stirring uniformly, coating on a plastic film to prepare a medicine cake with the thickness of 2mm and the length multiplied by the width of 4cm multiplied by 6cm, and drying the medicine cake in a 60-degree oven for 2 hours to obtain the traditional Chinese medicine gel patch.
The thickness of each sample of the gel patch prepared in the embodiment 1-3 is 2mm, and the size is 4cm multiplied by 6 cm; the content of each component of each tablet is as follows: 1.079-2.490g of glycerol, 1.968-2.153g of absolute ethyl alcohol, 1.8978-1.263 g of sodium polyacrylate NP-7000.623-1.263 g, 0.245-0.256g of bentonite, 0.494-0.509g of azone, 0.497-0.512g of borneol, 6.996-7.603g of carbomer 940 (5-7%), 0.020-0.025g of disodium ethylene diamine tetraacetate (EDTA-2Na), and AlCl30.024-0.025g, 2-5ml water; chinese medicine powder: 0.626-1.269 g. Wherein the quality evaluation score of the Chinese medicinal gel patch prepared in the embodiment 1 is highest, and the property is optimal. The traditional Chinese medicine gel patch adopted in the subsequent test is prepared by the method of the embodiment 1.
Comparative example 1: preparation of gauze soaked with medicine
The preparation method of the medicine-soaked gauze comprises the following steps:
the preparation method comprises the steps of uniformly mixing 20g of the traditional Chinese medicine astragalus membranaceus, 20g of the root of red-rooted salvia, 10g of safflower, 10g of angelica sinensis and 10g of ligusticum wallichii, adding water, decocting to obtain a liquid, concentrating to 200mL, spraying the liquid on medical gauze to enable the gauze to be completely soaked by the liquid, and lifting the gauze until no liquid is dripped to obtain the liquid medicine soaked gauze.
Chinese medicinal gel patch for testing skin irritation of rabbit
1 purpose of experiment: observing the stimulation reaction condition of the traditional Chinese medicine gel patch on the skin contact part of the rabbit after multiple times of administration, and investigating whether the skin contact part of the animal causes local reactions such as red swelling, exudation, degeneration or necrosis.
2 experimental materials:
traditional Chinese medicine gel paster: the source is as follows: the preparation method of the pharmacological laboratory (third-level laboratory of national institute of traditional Chinese medicine) of Shanghai medical university is as in example 1; the storage method comprises the following steps: storing in a refrigerator at 4 ℃.
Animals: big ear white rabbit, half male and female, each group is 6, weight: 1.8-2.2 kg.
3 Experimental methods
Preparing animal skin: the two sides of the spinal column of the back of the animal are unhaired 24 hours before administration, the area is about 10 percent of the body surface area, whether the skin is damaged or not is detected before administration, and the damaged animal is removed in a complete skin experiment.
Grouping and dose setting: the preparation method comprises the following steps of (1) pasting the traditional Chinese medicine gel patch on the back skin of the rabbit for 4 hours by using 6 Chinese medicine gel patches in each group, each group is half of a male and female group, and the traditional Chinese medicine gel patch is applied to the back skin of the rabbit for 1 week continuously according to the same time point and the same administration time of the same part, which is consistent with the clinical use times.
The administration method comprises the following steps: adopting the left side and the right side of the same rabbit to control, evenly smearing the medicine cake of the tested traditional Chinese medicine gel patch on one side, and smearing excipient or menstruum on the other side.
And (3) observation period: the condition of erythema and edema is observed and recorded 1 hour after removing the test object and before coating again, and if the erythema or erythema needs to be graded, the condition of erythema or edema at the coating part is observed and recorded by naked eyes after the last administration.
Result processing and analysis
Multiple dosing skin irritation test: calculating the average value of the reaction of the Chinese medicinal gel patch and the excipient on the rabbit skin and the stimulation intensity. The irritation of the traditional Chinese medicine gel patch to the skin of the rabbit is analyzed by adopting a t test.
4 results of the experiment
The experimental results are shown in table 3 below, and the conditions such as erythema and edema are not found after 1 hour after the traditional Chinese medicine gel patch cake is removed each time and before the traditional Chinese medicine gel patch is applied again, and after the traditional Chinese medicine gel patch is administered last time, the conditions such as no obvious erythema or edema on the rabbit glue application part of the traditional Chinese medicine gel patch are observed by naked eyes, which indicates that the traditional Chinese medicine gel patch prepared in the embodiment 1 of the invention has no obvious irritation on the rabbit skin.
TABLE 3 Scoring Standard of Chinese medicine gel Patch for Rabbit skin irritation reaction
Test of skin allergy of traditional Chinese medicine gel patch to guinea pig
1 purpose of experiment: observing the expression of the traditional Chinese medicine gel patch on the skin of the immune system of the guinea pig body after multiple administrations, and investigating whether the traditional Chinese medicine gel patch has sensitization on the skin.
2 experimental materials:
(1) traditional Chinese medicine gel paster: the source is as follows: the preparation method of the pharmacological laboratory (third-level laboratory of national institute of traditional Chinese medicine) of Shanghai medical university is as in example 1; the storage method comprises the following steps: storing in a refrigerator at 4 ℃.
(2) Test animals: animals with high sensitivity are selected, guinea pigs are generally selected, and the animals are male and female, and each group comprises 10 animals.
3 Experimental methods
Grouping and dose setting: guinea pigs were divided into 4 groups by weight: low-dose group (0.125g drug/tablet) of traditional Chinese medicine gel patch, high-dose group (0.25 g/tablet) of traditional Chinese medicine gel patch, excipient group, positive drug group (sensitization group, sensitization drug: 2, 4-dinitrochlorobenzene), and negative control group (normal control group), wherein each group contains 10 drugs, and each group is half male and half female.
Preparing animal skin: both sides of the spinal column of the animal were dehaired 24 hours before dosing, with a dehairing range of 3cm x 3 cm.
The administration method comprises the following steps:
sensitization and contact: respectively applying appropriate amount of Chinese medicinal gel patch, excipient and positive medicine on the left depilated area of guinea pig, fixing by appropriate method, continuously contacting the ointment for 6 hr, and repeating the same method on 7 th and 14 th days.
And (3) observation period:
after the last application is finished, residues are removed by warm water, observation can be carried out, then the skin anaphylactic reaction condition is observed again at 24, 48 and 72 hours, and the administration method of the blank group and the positive control method is the same as that of the drug-containing hydrogel test group.
Result processing and analysis
Evaluation of skin allergy: the skin allergic reaction condition is scored according to the table 1, the incidence rate is calculated according to the table 2, and whether the animals have systemic anaphylaxis such as asthma, unstable standing or shock and the like should be observed.
4 results of the experiment
The experimental results are shown in table 4 below, no obvious sensitization was found after removing the traditional Chinese medicine gel patch each time and before re-application, and no obvious sensitization was observed on the applied part of the guinea pig gelatin by naked eyes after the last administration, which indicates that the traditional Chinese medicine gel patch prepared in example 1 of the present invention has no obvious sensitization on the skin.
TABLE 4 score of skin allergic reaction degree of guinea pig for each group
| Group of | Erythema status score | Edema status scoring | Incidence of sensitization (%) | Evaluation of skin sensitization |
| Negative control group | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 | No sensitization |
| Traditional Chinese medicine gel patch group | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 | No sensitization |
| Positive drug group | 0.0±0.0 | 0.0±0.0 | 70.2±3.2 | Moderate sensitization |
| Excipient group | 0.0±0.0 | 0.0±0.0 | 0.0±0.0 | No sensitization |
Transdermal absorption test of Chinese medicinal gel patch
1 Instrument and Material
(1) Instrument for measuring the position of a moving object
AB204-E microbalance, Mettler Toledo, Switzerland; HH-ZK4 constant temperature water bath, chongqing dongyue instruments ltd; CS101-2ABN electric heat blast air drying cabinet, the perpetual experimental instrument factory of Chongqing city; agilent 1260Infinity ii hplc, 1260VWD (Agilent corporation); agilent 1260Infinity II evaporative light Detector (Agilent Corp.); sartorius electronic analytical balance model BSA224S (beijing Sartorius scientific instruments ltd).
(2) Material
ViscomateTM NP-700, Showa Denko K.K.; glycerin, Chongqing Chuandong chemical Co., Ltd; aluminum glycollate, shanghai sen ltd; astragaloside IV as reference (lot number: 84687-43-4, purity 98%), tanshinone IIA (lot number: 20958-15-0, purity 98%), hydroxysafflor yellow A (lot number: 78281-02-4, purity 98%), ferulic acid (lot number: 1135-24-6, purity 98%) were obtained from Shanghai leaf biology, Inc.; acetonitrile (chromatographically pure, Fisher corporation); phosphoric acid (chromatographically pure, TED corporation); child-haha purified water (Hangzhou child-haha group ltd); the other reagents are analytically pure traditional Chinese medicine extracts, and are self-made in laboratories; and (5) purifying the water. The clean-grade Kunming mouse, male, has a weight of 18-22 g, is provided by Beijing Wintonlika company, is bred in the laboratory animal center of Shanghai university of medicine, and has a qualification number of SCXK (Shanghai) 2017-0002. Chinese medicine gel patches (batch number: 20210701) and drug-impregnated gauze were prepared by the laboratory.
2 methods and results
2.1 method for measuring content
2.1.1 chromatographic conditions
Gradient elution (0-25 min, 5% A → 30% A; 25-50 min, 30% A → 35% A; 50-65 min, 35% A → 45% A; 65-95 min, 45% A → 95% A; 95-105 min, 95% A) with methanol as mobile phase A and 0.1% acetic acid aqueous solution as mobile phase B by using Waters Symmetry C18 chromatographic column (250mm × 4.6mm, 5 μm), and flow rate of 1.0 mL/min-1The column temperature was 30 ℃ and the amount of sample was 5. mu.L. Adopting VWD and ELSD detectors, the drift tube temperature is 70 ℃, and the carrier gas flow rate is 2.0 L.min-1. Under the chromatographic conditions, the retention time of the astragaloside IV, the tanshinone IIA, the hydroxysafflor yellow A and the ferulic acid in the sample is kept consistent with that of a reference substance, chromatographic peaks of 4 components can be well separated, and the purity check meets the requirement.
2.1.2 preparation of reference stock solutions
Taking appropriate amount of astragaloside IV, tanshinone IIA, hydroxysafflor yellow A, and ferulic acid reference, precisely weighing, adding methanol, and making into reference stock solutions containing astragaloside IV 784.97 μ g, tanshinone IIA 294.33 μ g, hydroxysafflor yellow A612.537 μ g and ferulic acid 194.184 μ g per 1mL respectively.
2.2 Ex vivo mouse skin preparation
With 8% Na2And removing hair on the abdomen of the mouse by using the S solution, killing the mouse after 24 hours, peeling the skin on the abdomen, removing subcutaneous fat and mucus tissues, washing the mouse by using normal saline, placing the mouse in the normal saline, refrigerating and storing the mouse in a refrigerator, and naturally thawing the mouse before the experiment.
2.3 transdermal test
Fixing the 2.2 skin between a supply pool and a receiving pool of a diffusion pool, facing the stratum corneum to the supply pool, discharging bubbles, adhering the Chinese medicinal gel patch to the mouse skin, collecting physiological saline water, and stirring at 32 deg.C and 200r/min with magnetic force. Taking out 2mL of receiving medium respectively at 2,4, 6, 8, 12 and 24h, simultaneously adding fresh receiving medium with the same isothermal volume into the receiving pool, filtering the taken-out receiving solution by using a 0.45 mu m microporous filter membrane to obtain a sample solution, measuring the contents of astragaloside IV, ferulic acid, tanshinone IIA and hydroxysafflor yellow A in the receiving solution for 24h by using a method under 4.2.2.1, calculating the cumulative permeation amount Qn of each component at different time points, and calculating the cumulative permeation amount (Qn) in a unit area by using a formula Qn (V total Cn + Cn-1V is taken)/A (V total is the volume of a receiving chamber of a diffusion pool, Cn is the mass concentration of the medicine in the receiving solution measured at the nth sampling point, Cn-1 is the mass concentration of the medicine in the receiving solution measured at the nth-1 sampling point, V is the sampling volume, and A is the permeation area). QEF is Qi-24 h/Q0-24 h, ER is Jsi/JS 0. QEF (μ g cm)-2) The representation represents the penetration enhancing properties.
2.4 results of the experiment
Regression analysis of the in vitro transdermal absorption curves of 3 components in the Chinese medicinal gel patch and the drug-impregnated gauze was performed by using a zero-order model, a first-order model and a Higuchi model, and the results are shown in Table 5, and the skin of the mouse passing through the Chinese medicinal gel patch was determined from the cumulative transdermal amount and the steady transdermal rateAfter treatment, the total transdermal absorption penetration amount of astragaloside IV, ferulic acid, tanshinone IIA and hydroxysafflor yellow A is 10.270, 11.074, 9.493 and 1.399 microgram cm-2(ii) a After the skin of the mouse is treated by the drug-soaked gauze, the cumulative penetration of the astragaloside, the ferulic acid, the tanshinone IIA and the hydroxysafflor yellow A are 3.351, 3.496, 2.160 and 0.275 mu g/cm respectively-2The transdermal absorption of chemical components of the skin of the mouse treated by the traditional Chinese medicine gel patch has a remarkable promoting effect compared with that of medicine-soaked gauze; QEF and ER represent permeation-promoting properties, and as can be seen from the results of QEF and ER, the permeation-promoting effect of the traditional Chinese medicine gel patch is obviously higher than that of the gauze soaked with the medicine.
TABLE 5 pharmacokinetic parameters of transdermal absorption of chemical components of Chinese medicinal gel patch and drug-impregnated gauze (n ═ 3)
Clinical application
1. The research method comprises the following steps: 96 patients who are diagnosed as painful Diabetic Peripheral Neuropathy (DPN) are admitted, the patients are randomly divided into a conventional treatment group (group A), a gauze medicine-soaking medicine-permeating group (group B) and a traditional Chinese medicine gel patch medicine-permeating group (group C) within the age of 30-70 years, all the patients are treated by a conventional blood sugar lowering scheme, under the condition of good blood sugar control, the patients are treated by thioctic acid injection with intravenous drip, the traditional Chinese medicine directional medicine-permeating technology is used in a combined manner, the gauze medicine-soaking medicine-permeating group patients are treated by the gauze medicine-soaking treatment mode prepared in the comparative example 1, and the traditional Chinese medicine gel patch medicine-permeating group patients are treated by the traditional Chinese medicine gel patch treatment mode prepared in the example 1 for 14 days. Specifically, the gauze-soaked medicine-permeable group therapy mode is as shown in fig. 1, a traditional Chinese medicine water decoction is soaked on gauze or non-woven fabric, then the gauze or non-woven fabric is applied on a traditional Chinese medicine directional medicine-permeable therapy apparatus conductive plate and is pasted on corresponding acupuncture points of a patient, a bandage is bound and fixed, and corresponding parameters are adjusted by electrifying to perform therapy; the Chinese medicinal hydrogel patch is applied on the conductive plate of the traditional Chinese medicinal directional medicine permeation therapeutic apparatus, and is attached to the corresponding acupuncture point of a patient, the bandage is bound and fixed, and the corresponding parameters are adjusted by electrifying to be consistent with those of the gauze medicine-soaked medicine permeation set for treatment. The clinical efficacy of DPN was evaluated A, B, C in three groups of patients, comparing the change in pain Visual Analogue Score (VAS), Nerve Conduction Velocity (NCV), and Toronto Clinical Scoring System (TCSS) scores before and after treatment in the three groups of patients.
2. The research results are as follows: the baseline data of each group of patients, including age, sex, course of disease, etc., have no statistical difference and are comparable, and the curative effect comparison of each group is shown in table 6; a comparison of pain Visual Analogue Scores (VAS) for each group of patients is shown in table 7; a comparison of Nerve Conduction Velocity (NCV) for each group of patients is shown in table 8; changes in the Toronto Clinical Scoring System (TCSS) scores for each group of patients are shown in Table 9.
TABLE 6 comparison of clinical efficacy of two groups of patients
As can be seen from table 4, the effective rate of the patients in the traditional Chinese medicine gel patch medicine permeation group is higher than that in the conventional treatment group and the gauze medicine soaking medicine permeation group.
TABLE 7 comparison of pain Visual Analog Score (VAS) for two groups of patients
Note: comparing the P value with that before treatment, wherein the P value is less than 0.05; ② compared with group A, P is less than 0.05; (iii) and B
For group comparison, P is less than 0.05.
As can be seen from Table 5, the pain Visual Analogue Score (VAS) of the patients in the transdermal Chinese medicinal patch group after treatment was statistically different from that in the other two groups.
TABLE 8 comparison of Nerve Conduction Velocity (NCV) in two groups of patients
Note: comparing the P value with that before treatment, wherein the P value is less than 0.05; ② comparing with A group, P is less than 0.05; and comparing the P with the B group, wherein the P is less than 0.05.
As can be seen from Table 6, the Nerve Conduction Velocity (NCV) of the treated patients in the transdermal Chinese medicinal patch group was statistically different from that of the other two groups.
TABLE 9 Lorentuon clinical Scoring System (TCSS) score comparison for two groups of patients
Note: comparing with the pretreatment, P is less than 0.05; ② compared with group A, P is less than 0.05; and comparing the P with the B group, wherein the P is less than 0.05.
As can be seen from Table 9, the change in Toronto Clinical Scoring System (TCSS) scores of patients after the treatment of the Chinese medicinal gel patch transdermal drug delivery group was statistically different from that of the other two groups.
In conclusion, the changes of pain visual simulation score (VAS), Nerve Conduction Velocity (NCV) and Toronto Clinical Scoring System (TCSS) score of patients in the traditional Chinese medicine gel patch transdermal drug treatment group after treatment are all statistically different from those in the other two groups, which shows that the overall curative effect of traditional Chinese medicine gel patch transdermal drug treatment is better than that of the other two groups.
While the invention has been described with respect to a preferred embodiment, it will be understood by those skilled in the art that the foregoing and other changes, omissions and deviations in the form and detail thereof may be made without departing from the scope of this invention. Those skilled in the art can make various changes, modifications and equivalent arrangements, which are equivalent to the embodiments of the present invention, without departing from the spirit and scope of the present invention, and which may be made by utilizing the techniques disclosed above; meanwhile, any changes, modifications and variations of the above-described embodiments, which are equivalent to those of the technical spirit of the present invention, are within the scope of the technical solution of the present invention.
Claims (10)
1. A traditional Chinese medicine gel paster for thoroughly treating DPN is characterized by comprising traditional Chinese medicine powder and a gel matrix, wherein the traditional Chinese medicine powder comprises astragalus, red sage root, safflower, angelica and ligusticum wallichii.
2. The traditional Chinese medicine gel patch for the transdermal treatment of DPN according to claim 1, wherein the traditional Chinese medicine powder comprises the following components in parts by weight: 0.6 to 1.6 parts of astragalus, 0.6 to 1.6 parts of salvia miltiorrhiza, 0.3 to 0.8 part of angelica, 0.3 to 0.8 part of safflower and 0.3 to 0.8 part of ligusticum wallichii.
3. The traditional Chinese medicine gel patch for the transdermal treatment of DPN according to claim 1 or 2, wherein the gel matrix comprises a gel raw material, a rheology modifier, a pH modifier, a humectant, a stabilizer, a solvent, and a penetration enhancer.
4. The transdermal DPN patch of claim 3, further comprising one or more of the following features:
1) the gel raw materials comprise sodium polyacrylate and bentonite;
2) the rheology modifier is carbomer 940;
3) the pH regulator is AlCl3；
4) The humectant is glycerol;
5) the stabilizer is EDTA-2 Na;
6) the solvent is absolute ethyl alcohol;
7) the penetration enhancer comprises azone and borneol.
5. The traditional Chinese medicine gel patch for the transdermal treatment of DPN according to claim 4, wherein the gel matrix comprises the following raw materials in parts by weight: 4-10 parts of glycerol, 6-10 parts of absolute ethyl alcohol, 6-6 parts of sodium polyacrylate NP-7002, 0.5-1.5 parts of bentonite, 1.5-3 parts of azone, 1.5-3 parts of borneol, 94024-32 parts of carbomer, 0.05-0.2 part of EDTA-2Na, and AlCl30.05-0.2 part of water and 8-20 parts of water.
6. A method for preparing a Chinese medicinal gel patch for the transdermal treatment of DPN according to any one of claims 3 to 5, comprising the steps of:
s1, uniformly mixing the moisturizing agent, the solvent, the gel raw material and the penetration enhancer to obtain a phase I;
s2, preparing a rheology modifier into a rheology modifier aqueous solution;
s3, adding a solvent into the Chinese medicine powder, and then adding the aqueous solution of the rheology modifier prepared in the step S2 and uniformly mixing to obtain a phase II;
s4, adding water into the stabilizer and the pH regulator to dissolve the stabilizer and the pH regulator to obtain a phase III;
and S5, adding phase I into phase III, mixing, adding phase II, stirring, coating on the substrate, making into medicated cake, and oven drying to obtain Chinese medicinal gel patch.
7. The method of claim 6, further comprising one or more of the following features:
(1) in the step S2, the aqueous solution of the rheology modifier is a carbomer aqueous solution with the mass fraction of 3%;
(2) the preparation method of the traditional Chinese medicine powder in the step S3 comprises the following steps: mixing and powdering the astragalus, the salvia, the safflower, the angelica and the ligusticum wallichii according to the weight part ratio, and sieving for more than three times until no obvious coarse fiber can be seen by naked eyes;
(3) in the step S5, the base layer is a plastic film, fiber filter paper or a stainless steel tray;
(4) and in the step S5, the drying condition is drying for 1-3 h at 60 ℃.
8. The traditional Chinese medicine gel patch for the transdermal DPN treatment according to any one of claims 1 to 5, for use in the treatment of painful diabetic peripheral neuropathy.
9. Use of the traditional Chinese medicine gel patch for the transdermal DPN treatment of any one of claims 1 to 5 in the preparation of products for treating painful diabetic peripheral neuropathy.
10. The use of the traditional Chinese medicine gel patch for the transdermal DPN treatment of any one of claims 1 to 5 for preparing a product for treating painful diabetic peripheral neuropathy, wherein the product has any one of the following effects: 1) relieve pain in both lower extremities of DPN patients; 2) relieving numbness of both lower limbs of DPN patients; 3) relieving spasm of both lower limbs of DPN patients; (4) reduce the paraesthesia of the lower limbs of the DPN patients.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210234228.1A CN114732843A (en) | 2022-03-10 | 2022-03-10 | Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210234228.1A CN114732843A (en) | 2022-03-10 | 2022-03-10 | Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114732843A true CN114732843A (en) | 2022-07-12 |
Family
ID=82275236
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210234228.1A Pending CN114732843A (en) | 2022-03-10 | 2022-03-10 | Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114732843A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108057077A (en) * | 2018-02-09 | 2018-05-22 | 马飞 | Treat Chinese medicine composition of diabete peripheral herve pathology and preparation method thereof |
| CN108210484A (en) * | 2016-12-11 | 2018-06-29 | 复旦大学 | Tamoxifen gel emplastrum and preparation method thereof |
| CN112022929A (en) * | 2019-06-03 | 2020-12-04 | 鲁南制药集团股份有限公司 | Traditional Chinese medicine composition for treating diabetic peripheral neuropathy and preparation method thereof |
-
2022
- 2022-03-10 CN CN202210234228.1A patent/CN114732843A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108210484A (en) * | 2016-12-11 | 2018-06-29 | 复旦大学 | Tamoxifen gel emplastrum and preparation method thereof |
| CN108057077A (en) * | 2018-02-09 | 2018-05-22 | 马飞 | Treat Chinese medicine composition of diabete peripheral herve pathology and preparation method thereof |
| CN112022929A (en) * | 2019-06-03 | 2020-12-04 | 鲁南制药集团股份有限公司 | Traditional Chinese medicine composition for treating diabetic peripheral neuropathy and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 李影;: "通脉胶囊治疗糖尿病周围神经病变临床观察" * |
| 苏凯毅;吕雄;: "糖尿病周围神经病变中医药内外治疗探讨" * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107854367B (en) | Essence for repairing sensitive skin | |
| CN109125107B (en) | Polypeptide composition for effectively improving and repairing facial hormone-dependent dermatitis | |
| CN103919967B (en) | Sanguis Draxonis compound recipe and the application in preparation treatment more wound medicine thereof | |
| CN105055768A (en) | Traditional Chinese medicine compound external-application preparation for treating cicatrix and preparation method and application thereof | |
| CN104274546B (en) | A kind of external medicine composition, traditional Chinese medicine for outer use and its preparation method and application | |
| CN103735765B (en) | Plaster for activating collaterals and relieving pain and preparation method thereof | |
| CN105726366A (en) | Skin lipid membrane repairing composition | |
| CN105497261A (en) | Matrix of patch for external use and patch and sleeping-aid patch made from matrix | |
| CN108392512B (en) | Mongolian medicinal bath powder for treating arthritis and preparation method thereof | |
| CN108078868B (en) | Antiallergic composition for skin care products | |
| CN114732843A (en) | Traditional Chinese medicine gel patch for treating DPN (dipeptidyl peptidase-IV) through medicine penetration and preparation method and application thereof | |
| CN110974861A (en) | Blumea balsamifera oil liposome | |
| CN110339256A (en) | A kind of pain cold compress gel | |
| CN108403932A (en) | A kind of Chinese medicine compound prescription external preparation and its preparation method and application for treating steroid dependent dermatitis | |
| CN107823260A (en) | A kind of compound skin cream for treating chloasma, preparation method and application | |
| KR101605711B1 (en) | Microneedle coated by oriental medicine compositions and method for manufacturing thereof | |
| CN100525751C (en) | Meridian point therapeutic plaster of high polymer multi hole energy gathering ion and its preparation method and application | |
| KR20120009183A (en) | Composition for promoting the differentiation of human mesenchymal stem cell | |
| CN111643606B (en) | Gel plaster for treating insomnia and preparation method thereof | |
| CN106377583B (en) | A kind of processing procedure and its quality determining method of Gansu genunie medicinal materials Aconitum Szechenyianum Gay | |
| CN104784627A (en) | Traditional Chinese medicine externally used film agent used for treatment surgical open or closed injury and preparation method thereof | |
| CN114796196B (en) | External medicine composition for treating vascular vertigo and application thereof | |
| CN109316516A (en) | A kind of plaster and preparation method thereof for treating rheumatism, rheumatoid arthritis, scapulohumeral periarthritis, osteoproliferation, cervical spondylosis | |
| CN113171400B (en) | Transdermal absorbent for treating diabetic peripheral neuropathy, preparation method and application thereof | |
| CN103705903B (en) | A kind of hyperosteogeny adhesive plaster and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220712 |
|
| RJ01 | Rejection of invention patent application after publication |