CN1895311A - Hydrophilic gel pleximetric paste and its preparation - Google Patents
Hydrophilic gel pleximetric paste and its preparation Download PDFInfo
- Publication number
- CN1895311A CN1895311A CNA2006100192327A CN200610019232A CN1895311A CN 1895311 A CN1895311 A CN 1895311A CN A2006100192327 A CNA2006100192327 A CN A2006100192327A CN 200610019232 A CN200610019232 A CN 200610019232A CN 1895311 A CN1895311 A CN 1895311A
- Authority
- CN
- China
- Prior art keywords
- hydrophilic gel
- pleximetric
- gel
- volatile oil
- radix bupleuri
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims description 11
- 239000000499 gel Substances 0.000 claims abstract description 72
- 239000000341 volatile oil Substances 0.000 claims abstract description 47
- 239000000853 adhesive Substances 0.000 claims abstract description 17
- 230000001070 adhesive effect Effects 0.000 claims abstract description 17
- 239000002904 solvent Substances 0.000 claims abstract description 17
- 239000004094 surface-active agent Substances 0.000 claims abstract description 16
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 15
- 239000000945 filler Substances 0.000 claims abstract description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 27
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 230000000149 penetrating effect Effects 0.000 claims description 16
- 239000000080 wetting agent Substances 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 7
- 239000004745 nonwoven fabric Substances 0.000 claims description 7
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000470 constituent Substances 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 4
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 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 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 2
- HXFCUMCLVYNZDM-UHFFFAOYSA-N 2-aminoacetic acid;sodium Chemical compound [Na].NCC(O)=O HXFCUMCLVYNZDM-UHFFFAOYSA-N 0.000 claims description 2
- 239000005995 Aluminium silicate Substances 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 2
- 229910021502 aluminium hydroxide Inorganic materials 0.000 claims description 2
- 235000012211 aluminium silicate Nutrition 0.000 claims description 2
- 239000000440 bentonite Substances 0.000 claims description 2
- 229910000278 bentonite Inorganic materials 0.000 claims description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 229940025250 camphora Drugs 0.000 claims description 2
- 239000010238 camphora Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 239000010642 eucalyptus oil Substances 0.000 claims description 2
- 229940044949 eucalyptus oil Drugs 0.000 claims description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003921 oil Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 239000004408 titanium dioxide Substances 0.000 claims description 2
- 239000011787 zinc oxide Substances 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 229960003511 macrogol Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 6
- 241000202726 Bupleurum Species 0.000 abstract description 3
- 239000003906 humectant Substances 0.000 abstract 1
- 230000036760 body temperature Effects 0.000 description 16
- 238000002347 injection Methods 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 238000011160 research Methods 0.000 description 7
- 206010002198 Anaphylactic reaction Diseases 0.000 description 6
- 208000003455 anaphylaxis Diseases 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 230000036783 anaphylactic response Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 210000000436 anus Anatomy 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 206010022000 influenza Diseases 0.000 description 4
- 239000002510 pyrogen Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 241000510654 Bupleurum chinense Species 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000002951 depilatory effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003746 feather Anatomy 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 210000003314 quadriceps muscle Anatomy 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
Abstract
A percutaneous paster of hydrophilic gel for medicine features that its gel layer contains the volatile oil of bupleurum root, hydrophilic gel, cross-linking agent, humectant, surfactant, filler, adhesive, osmosis promoter and solvent. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to medical technical field, particularly relate to hydrophilic gel pleximetric paste that a kind of drug transdermal controlled release treatment uses and preparation method thereof.
Background technology
Hydrophilic gel pleximetric paste (crust cloth cream) is to be substrate with water-soluble high-molecular compound or hydroaropic substance, after medicine or Chinese medicine extract mix, coats the external paster of making on the non-woven fabrics.To biocompatibility, affinity, breathability, the sweat proof of skin with to repeat to take off pulling property all better, and be difficult for irritated.At the seventies initial stage, states such as Japan, Europe have begun to develop medical cataplasma, and along with the continuous development of medical industry, this novel form develops to some extent in China in recent years.According to World Health Organization's prediction, in the coming years, there is the medicine more than 30% will make percutaneous drug administration preparation into, will start the new upsurge of an inner disease outer treat.
But with the hydrophilic gel pleximetric paste complicated component of prior art development, and active constituent content is low, and portioned product has certain zest, easy sensitization, and come off easily.
Radix Bupleuri volatile oil is the volatile oil that has extracted the bupleurum Chinese of extensive use from clinically, main component is volatile oil in the injection of Radix Bupleuri that wherein uses clinically, it is clearing away heat and expelling pathogen in the exterior that the injection of Radix Bupleuri function cures mainly, the heating that is used for the treatment of flu, influenza, malaria etc. truly has curative effect (the accurate word Z41020926 of traditional Chinese medicines), Radix Bupleuri volatile oil is applied on the hydrophilic gel pleximetric paste was also meeting at present.
Summary of the invention
Problem to be solved by this invention is to propose a kind of hydrophilic gel pleximetric paste at above-mentioned prior art, its nonirritant, no anaphylaxis, no peeling phenomenon, sheet drug loading are far above the drug administration by injection amount, and the energy slow releasing pharmaceutical, make the medicine long action time, and reach the antipyretic purpose.
Another object of the present invention provides a kind of method for preparing hydrophilic gel pleximetric paste.
The present invention is adopted solution to be by the problem of the above-mentioned proposition of solution: hydrophilic gel pleximetric paste; include backing layer, gel layer and protecting film; its difference is that gel layer includes following component; Radix Bupleuri volatile oil, hydrophilic gel, cross-linking agent, wetting agent, surfactant, filler, adhesive, penetrating agent, solvent, described constituent content is by weight percentage
Radix Bupleuri volatile oil 1.0～20% hydrophilic gels 2.5%～10% cross-linking agent 0～1%
Wetting agent 20～40% surfactants 0～5% filler 0～0.1%
Adhesive 1～3% penetrating agent 1～12% solvent 40～74%
Press such scheme, described hydrophilic gel is a sodium polyacrylate.
Press such scheme, described cross-linking agent is an organic acid, as any one or multiple mixing among tartaric acid, citric acid etc. and aluminium hydroxide, Glycine sodium, aluminum glycinate, the EDTA-4Na (tetrasodium ethylenediamine tetraacetate).
Press such scheme, described wetting agent is any one or the multiple mixing in glycerol, propylene glycol, sorbitol, the Polyethylene Glycol.
Press such scheme, described surfactant is a tween.
Press such scheme, described filler is any one in Kaolin, zinc oxide, micropowder silica gel, calcium carbonate, Bentonite, the titanium dioxide.
Press such scheme, described adhesive is any one among gelatin, CMC-Na (sodium carboxymethyl cellulose), the PVP-90 (polyvinyl pyrrolidone);
Press such scheme, described penetrating agent is two or more the mixing in ethanol, propylene glycol, glycerol, oleic acid, PEG300 (Polyethylene Glycol), PEG400, low mass molecule alcohol class, azone, carbamide, Herba Menthae, Camphora, Borneolum Syntheticum, eucalyptus oil, the Fructus Cnidii oil.
Press such scheme, described solvent is a water.
The preparation method of hydrophilic gel pleximetric paste is with hydrophilic gel; adhesive; Radix Bupleuri volatile oil; surfactant; penetrating agent; filler is dispersed under stirring condition and forms the A phase in the wetting agent; cross-linking agent is dispersed in formation B phase in the solvent under stirring condition; again B is stirred under the certain vacuum condition and be scattered in A and form gel layer in mutually; then gel layer is coated on the non-woven fabrics; be covered with protecting film; cut to certain specification; produce the hydrophilic gel paster that contains Radix Bupleuri volatile oil through cold curing, described each constituent content is by weight percentage
Radix Bupleuri volatile oil 1.0～20% hydrophilic gels 2.5%～10% cross-linking agent 0～1%
Wetting agent 20～40% surfactants 0～5% filler 0～0.1%
Adhesive 1～3% penetrating agent 1～12% solvent 40～74%.
Can produce the main component of separating thermal effect among the present invention is Radix Bupleuri volatile oil, Radix Bupleuri volatile oil is the main component in the analgesic injection bupleurum Chinese injection of life-time service clinically, contain in the hydrophilic gel pleximetric paste of Radix Bupleuri volatile oil in the present invention, the consumption of Radix Bupleuri volatile oil is 1.0～20%.
In the present invention, the hydrophilic gel pleximetric paste employing hydrophilic gel that contains Radix Bupleuri volatile oil is a substrate, hydrophilic gel is a kind of substrate that has been widely used in the externally applied transdermal administration at present abroad, it is to nontoxic, non-stimulated, the no anaphylaxis of human body, be a kind of safe and reliable pharmaceutic adjuvant, the hydrophilic gel consumption is suitable with 4～10% among the present invention.
Radix Bupleuri volatile oil is volatile oils and fats material, the barrier action and the paster forming degree of skin is good when making the principal agent composition see through skin, so in percutaneous plaster of the present invention, based on hydrophilic gel substrate, solvent is water, add surfactant, wetting agent, cross-linking agent, adhesive, filler and penetrating agent, behind abundant mix homogeneously, coat mounting on the backing material of base non-woven fabrics, produce the hydrophilic gel pleximetric paste that contains Radix Bupleuri volatile oil.
The present invention is embodied in the following aspects in the effect aspect pharmacodynamic study and zest research and the anaphylaxis research:
1) pharmacodynamic study result:
A) Radix Bupleuri volatile oil hydrophilic gel transdermal (crust cloth cream) paster is to the therapeutical effect of bacterial heating
Method by volumes such as Xu Shuyun " pharmacological testing methodology " (third edition) P935 record is tested: it is a collection of to get Japan's kind large ear rabbit, every zoometry body temperature secondary before the experiment, twice temperature difference must not surpass 0.2 ℃ as animal for research, get 24 of qualified animals, body weight 1.5 ± 0.5kg, male and female half and half.Be divided into three groups at random, 8 every group, male and female half and half; The 1st group is blank paster negative control group, the 2nd group is the injection of Radix Bupleuri positive controls, intravenously administrable, dosage is 1ml/kg, the 3rd group is that (tested preceding 24 hours, and lost hair or feathers with depilatory at the back, area is 10cm * 10cm) for the hydrophilic gel pleximetric paste group that contains Radix Bupleuri volatile oil, the external application administration, dosage 1 pastes (containing Radix Bupleuri volatile oil in the paster is 1%); Get cultured Bacillus paratyphosus B culture fluid 0.2ml (1 * 10
6), give the injection down of every rabbit: survey the anus temperature per half an hour one time, when treating that body temperature reaches 40 ℃ of left and right sides, 2nd, 3 treated animals begin administration by above-mentioned route of administration, after the administration, every animal per of each treated animal is surveyed the anus temperature once every half an hour, writes down every animal heat changing value.Poor according to regular using warming therapy before body temperature and the pyrogenicity after every animal pyrogenicity of each group, use the variance statistical disposition, judge significant difference, it the results are shown in table 1.
Table 1 Radix Bupleuri volatile oil hydrophilic gel transdermal (crust cloth cream) paster is to the therapeutical effect (n=8 only) of bacterial heating
| Matched group | The paster group | The injection group | |
| BBT | 39.6±0.1 | 39.7±0.1 | 39.7±0.1 |
| 3.5h body temperature after the modeling | 40.6±0.2 | 40.7±0.1 | 40.7±0.2 |
| Body temperature after the administration | |||
| 0.5h | 40.6±0.3 | 40.7±0.1 | 40.8±0.2 |
| 1.0h | 40.9±0.3 | 40.7±0.3 | 40.7±0.3 |
| 1.5h | 41.0±0.3 | 40.6±0.3 | 40.7±0.3 |
| 2.0h | 41.1±0.3 | 40.5±0.3 | 40.7±0.4 |
| 2.5h | 41.0±0.2 | 40.4±0.3 | 40.6±0.4 |
| 3.0h | 40.9±0.3 | 40.3±0.3 | 40.5±0.4 |
| 3.5h | 40.8±0.3 | 40.1±0.2 | 40.4±0.3 |
| 4.0h | 40.7±0.3 | 40.0±0.2 | 40.4±0.4 |
| 4.5h | 40.5±0.3 | 39.8±0.3 | 40.1±0.5 |
| 5.0h | 40.3±0.2 | 39.7±0.3 | 40.0±0.4 |
| 5.5h | 40.2±0.3 | 39.8±0.3 | 39.9±0.3 |
| Matched group | The paster group | The injection group |
| BBT | 39.6±0.1 | 39.7±0.1 | 39.7±0.1 |
| 5h body temperature after the modeling | 1.0±0.2 | 1.0±0.1 | 1.0±0.3 |
| The body temperature of different time and basal body temperature is poor after the administration | |||
| 0.5h | 1.0±0.1 | 1.1±0.2 | 1.1±0.2 |
| 1h | 1.3±0.1 | 1.0±0.4 | 1.0±0.3 |
| 1.5h | 1.4±0.1 | 0.9±0.3** | 1.0±0.3* |
| 2h | 1.4±0.1 | 0.8±0.3*** | 1.0±0.3** |
| 2.5h | 1.3±0.2 | 0.7±0.3*** | 0.9±0.4* |
| 3h | 1.2±0.3 | 0.6±0.3*** | 0.8±0.4* |
| 3.5h | 1.1±0.2 | 0.4±0.1***Δ | 0.7±0.3* |
| 4h | 1.1±0.1 | 0.3±0.2***Δ | 0.7±0.4* |
| 4.5h | 0.9±0.1 | 0.1±0.2*** | 0.4±0.5* |
| 0.7±0.1 | 0.1±0.2*** | 0.3±0.4* | |
| 0.6±0.1 | 0.1±0.2*** | 0.2±0.3* | |
* P＜0.05, * * P＜0.01, * * * P＜0.001 and blank group are relatively;
Compare with the injection group Δ P＜0.05;
B) bupleurum Chinense volatile oil percutaneous hydrophilic gel paster is to the therapeutical effect of the bacterial heating of yeast
Method by volumes such as Xu Shuyun " pharmacological testing methodology " (third edition) P935 record is tested: it is a collection of to get Japan's kind large ear rabbit, every zoometry body temperature secondary before the experiment, twice temperature difference must not surpass 0.2 ℃ as animal for research, get 24 of qualified animals, body weight 1.5 ± 0.5kg, male and female half and half.Be divided into three groups at random, 8 every group, male and female half and half; The 1st group is blank paster negative control group, the 2nd group is the injection of Radix Bupleuri positive controls, intravenously administrable, dosage is 1ml/kg, the 3rd group is that (tested preceding 24 hours, and lost hair or feathers with depilatory at the back, area is 10cm * 10cm) to Radix Bupleuri volatile oil hydrophilic gel percutaneous controlled-release paster group, the external application administration, dosage 1 pastes (containing Radix Bupleuri volatile oil in the paster is 1%); Get 10% yeast suspension, inject 2ml/kg in every rabbit quadriceps femoris meat: anus temperature of survey in per 1 hour, when treating that body temperature reaches 40 ℃ of left and right sides, 2nd, 3 treated animals begin administration by above-mentioned route of administration, after the administration, every animal per of each treated animal is surveyed the anus temperature once every half an hour, writes down every animal heat changing value.Poor according to regular using warming therapy before body temperature and the pyrogenicity after every animal pyrogenicity of each group, use the variance statistical disposition, judge significant difference, it the results are shown in table 2.
The bupleurum Chinense volatile oil percutaneous hydrophilic gel of table 2 (crust cloth cream) paster is to the therapeutical effect of the microbial heating of yeast
| Matched group | The paster group | The injection group | |
| BBT | 39.7±0.1 | 39.7±0.1 | 39.7±0.1 |
| 5h body temperature after the modeling | 40.9±0.1 | 40.8±0.1 | 40.7±0.1 |
| Body temperature after the administration | |||
| 0.5h | 40.9±0.1 | 40.7±0.1 | 40.6±0.1 |
| 1.0h | 40.8±0.2 | 40.5±0.1 | 40.5±0.1 |
| 1.5h | 40.8±0.2 | 40.4±0.1 | 40.4±0.2 |
| 2.0h | 40.7±0.1 | 40.2±0.2 | 40.4±0.2 |
| 2.5h | 40.7±0.1 | 40.0±0.1 | 40.3±0.2 |
| 3.0h | 40.6±0.3 | 39.9±0.1 | 40.1±0.1 |
| 3.5h | 40.5±0.2 | 39.8±0.1 | 40.1±0.1 |
| 4.0h | 40.4±0.2 | 39.7±0.1 | 39.9±0.2 |
| 4.5h | 40.3±0.2 | 39.7±0.1 | 39.8±0.1 |
| Matched group | The paster group | The injection group | |
| BBT | 39.6±0.1 | 39.7±0.1 | 39.7±0.1 |
| 5h body temperature after the modeling | 1.3±0.1 | 1.2±0.1 | 1.0±0.1 |
| The body temperature of different time and basal body temperature is poor after the administration | |||
| 0.5h | 1.3±0.1 | 1.1±0.1* | 0.9±0.1* |
| 1.0h | 1.1±0.1 | 0.9±0.1* | 0.8±0.2* |
| 1.5h | 1.1±0.1 | 0.7±0.1* | 0.7±0.2* |
| 2.0h | 1.1±0.1 | 0.5±0.1**Δ | 0.7±0.2* |
| 2.5h | 1.0±0.2 | 0.3±0.2***Δ | 0.6±0.2** |
| 3.0h | 1.0±0.3 | 0.2±0.1***ΔΔ | 0.5±0.2** |
| 3.5h | 0.9±0.2 | 0.1±0.1***ΔΔ | 0.4±0.2*** |
| 4.0h | 0.8±0.1 | 0.1±0.1*** | 0.2±0.2*** |
| 4.5h | 0.7±0.1 | 0.0±0.1*** | 0.1±0.2*** |
* P＜0.05, * * P＜0.01, * * * P＜0.001 and blank group are relatively;
Δ P＜0.05, compare with the injection group Δ Δ P＜0.01;
2) safety research result
A) zest research: 1% Radix Bupleuri volatile oil hydrophilic gel pleximetric paste once and repeatedly external application does not see after 24 hours that any toxicity, side effect takes place.
B) anaphylaxis research: 1% Radix Bupleuri volatile oil hydrophilic gel pleximetric paste external application, anaphylactic reaction does not take place, the visible heatings such as hydrophilic gel pleximetric paste external curing flu, influenza and malaria that contain Radix Bupleuri volatile oil of the present invention be safety, reliably, have no side effect.
Beneficial effect of the present invention:
Hydrophilic gel pleximetric paste nonirritant of the present invention as can be seen from the above results, no anaphylaxis, nothing are peeled off reaction, the sheet drug loading is far above the drug administration by injection amount, and the energy slow releasing pharmaceutical, makes the medicine long action time, and reach the antipyretic purpose, and there is not any toxicity, side effect generation.
The specific embodiment
The invention will be further described below in conjunction with implementing.
The concrete prescription of implementing: (following all be weight percentage)
Radix Bupleuri volatile oil 1～20%
Hydrophilic gel 2.5～10%
Surfactant 0～5%
Cross-linking agent 0～1%
Wetting agent 20～40%
Filler 0～0.1%
Adhesive 1～3.0%
Penetrating agent 1～12%
Solvent 40～74%
The concrete preparation method of implementing is:
Hydrophilic gel, adhesive, Radix Bupleuri volatile oil, surfactant, penetrating agent, filler are dispersed in formation A phase in the wetting agent under stirring condition; cross-linking agent is dispersed in formation B phase in the solvent under stirring condition; again B is stirred under the certain vacuum condition and be scattered in A and form gel layer in mutually; then gel layer is coated on the non-woven fabrics; be covered with protecting film, cut, produce the hydrophilic gel paster that contains Radix Bupleuri volatile oil through cold curing to certain specification.
Embodiment 1
Following prescription:
(Radix Bupleuri volatile oil) Radix Bupleuri volatile oil 1.0%
(penetrating agent) oleic acid 4.0%, azone 3.0%, PEG 4.0%
(surfactant) tween 1.0%
(adhesive) gelatin 1.0%
(wetting agent) propylene glycol 5.0% glycerol 24%
(hydrophilic gel) sodium polyacrylate 4.0%
(solvent) water 53.0%
Preparation method is: sodium polyacrylate, gelatin, Radix Bupleuri volatile oil, tween, oleic acid, azone, PEG are dispersed in (A phase) in propylene glycol, the glycerol under stirring condition; aqueous solvent is the B phase; again B is stirred under the certain vacuum condition and be scattered in A and form gel layer in mutually; then gel layer is coated on the non-woven fabrics; be covered with protecting film, cut, produce the hydrophilic gel paster that contains Radix Bupleuri volatile oil through cold curing to certain specification.
Embodiment 2
(Radix Bupleuri volatile oil) Radix Bupleuri volatile oil 5.0%
(penetrating agent) oleic acid 1.0%, azone 3.0%, PEG 1.0%
(surfactant) tween 2.0%
(adhesive) gelatin 1.0%
(wetting agent) propylene glycol 5.0% glycerol 25%
(hydrophilic gel) sodium polyacrylate 4.0%
(solvent) water 53%
Preparation method is with embodiment 1
Embodiment 3
(Radix Bupleuri volatile oil) Radix Bupleuri volatile oil 5.0%
(cross-linking agent) aluminum glycinate 0.1%, EDTA-4Na (tetrasodium ethylenediamine tetraacetate) 0.025%, tartaric acid 0.25%
(wetting agent) propylene glycol 7.5%, glycerol 15%
(penetrating agent) azone 3.0%, carbamide 3.0%, Herba Menthae 0.6%, PEG2.5%
(adhesive) CMC-Na 1%
(hydrophilic gel) sodium polyacrylate 2.5%
(solvent) water 59.525%
Preparation method is: sodium polyacrylate, Radix Bupleuri volatile oil, CMC-Na, azone, carbamide, Herba Menthae, PEG are dispersed under stirring condition form the A phase in propylene glycol, the glycerol; aluminum glycinate, EDTA-4Na, tartaric acid are dispersed in formation B phase in the aqueous solvent under stirring condition; again B is stirred under the certain vacuum condition and be scattered in A and form gel layer in mutually; then gel layer is coated on the non-woven fabrics; be covered with protecting film, cut, produce the hydrophilic gel paster that contains Radix Bupleuri volatile oil through cold curing to certain specification.
Claims (10)
1, hydrophilic gel pleximetric paste; include backing layer, gel layer and protecting film; it is characterized in that gel layer includes following component; Radix Bupleuri volatile oil, hydrophilic gel, cross-linking agent, wetting agent, surfactant, filler, adhesive, penetrating agent, solvent, described constituent content is by weight percentage
Radix Bupleuri volatile oil 1.0～20% hydrophilic gels 2.5%～10% cross-linking agent 0～1%
Wetting agent 20～40% surfactants 0～5% filler 0～0.1%
Adhesive 1～3% penetrating agent 1～12% solvent 40～74%.
2, by the described hydrophilic gel pleximetric paste of claim 1, it is characterized in that described hydrophilic gel is a sodium polyacrylate.
3, by claim 1 or 2 described hydrophilic gel pleximetric pastes, it is characterized in that described cross-linking agent be organic acid with aluminium hydroxide, Glycine sodium, aluminum glycinate, tetrasodium ethylenediamine tetraacetate in any one or multiple mixing.
4,, it is characterized in that described wetting agent is any one or the multiple mixing in glycerol, propylene glycol, sorbitol, the Polyethylene Glycol by claim 1 or 2 described hydrophilic gel pleximetric pastes.
5, by claim 1 or 2 described hydrophilic gel pleximetric pastes, it is characterized in that described surfactant is a tween.
6, by claim 1 or 2 described hydrophilic gel pleximetric pastes, it is characterized in that described filler is any one in Kaolin, zinc oxide, micropowder silica gel, calcium carbonate, Bentonite, the titanium dioxide.
7, by claim 1 or 2 described hydrophilic gel pleximetric pastes, it is characterized in that described adhesive is any one in gelatin, sodium carboxymethyl cellulose, the polyvinyl pyrrolidone;
8,, it is characterized in that described penetrating agent is two or more the mixing in ethanol, propylene glycol, glycerol, oleic acid, Liquid Macrogol, PEG400, low mass molecule alcohol class, azone, carbamide, Herba Menthae, Camphora, Borneolum Syntheticum, eucalyptus oil, the Fructus Cnidii oil by claim 1 or 2 described hydrophilic gel pleximetric pastes.
9, by claim 1 or 2 described hydrophilic gel pleximetric pastes, it is characterized in that described solvent is a water.
10, the preparation method of the described hydrophilic gel pleximetric paste of claim 1 is characterized in that may further comprise the steps:
1) preparation gel layer:
Hydrophilic gel, adhesive, Radix Bupleuri volatile oil, surfactant, penetrating agent, filler are dispersed in formation A phase in the wetting agent under stirring condition;
Cross-linking agent is dispersed in formation B phase in the solvent under stirring condition;
Again B is stirred under the certain vacuum condition and be scattered in A and form gel layer in mutually;
Described each constituent content is by weight percentage
Radix Bupleuri volatile oil 1.0～20% hydrophilic gels 2.5%～10% cross-linking agent 0～1%
Wetting agent 20～40% surfactants 0～5% filler 0～0.1%
Adhesive 1～3% penetrating agent 1～12% solvent 40～74%
2) gel layer is coated on the non-woven fabrics, be covered with protecting film, cut, produce the hydrophilic gel paster that contains Radix Bupleuri volatile oil through cold curing to certain specification.
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| CN112957265A (en) * | 2021-02-25 | 2021-06-15 | 郑州依莱恩生物科技有限公司 | Hydrophilic gel with good permeability and controllable permeation time and preparation method thereof |
| CN114886981A (en) * | 2022-05-12 | 2022-08-12 | 杭州市萧山区中医院 | Traditional Chinese medicine composition and application thereof in preparation of medicine for treating neck, shoulder, waist and leg pain |
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