CN104721234A - Periplaneta Americana extract product ion-activated in-situ gel and preparation method thereof - Google Patents
Periplaneta Americana extract product ion-activated in-situ gel and preparation method thereof Download PDFInfo
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- CN104721234A CN104721234A CN201310706268.2A CN201310706268A CN104721234A CN 104721234 A CN104721234 A CN 104721234A CN 201310706268 A CN201310706268 A CN 201310706268A CN 104721234 A CN104721234 A CN 104721234A
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- gel
- periplaneta americana
- deionized water
- cockroach
- american
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- 241000238675 Periplaneta americana Species 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 16
- 238000011065 in-situ storage Methods 0.000 title description 4
- 238000001879 gelation Methods 0.000 title description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000008367 deionised water Substances 0.000 claims description 20
- 229910021641 deionized water Inorganic materials 0.000 claims description 20
- 239000007788 liquid Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000000605 extraction Methods 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 150000002500 ions Chemical class 0.000 claims description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 10
- 229920002148 Gellan gum Polymers 0.000 claims description 10
- 235000010492 gellan gum Nutrition 0.000 claims description 10
- 239000000216 gellan gum Substances 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- 235000010410 calcium alginate Nutrition 0.000 claims description 8
- 239000000648 calcium alginate Substances 0.000 claims description 8
- 229960002681 calcium alginate Drugs 0.000 claims description 8
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 claims description 8
- 229960004063 propylene glycol Drugs 0.000 claims description 8
- 206010039083 rhinitis Diseases 0.000 claims description 8
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 8
- 230000008961 swelling Effects 0.000 claims description 7
- 230000002421 anti-septic effect Effects 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- 239000012467 final product Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 230000003204 osmotic effect Effects 0.000 claims description 6
- 230000000149 penetrating effect Effects 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 5
- 229930003427 Vitamin E Natural products 0.000 claims description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 5
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 5
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 5
- 229960002216 methylparaben Drugs 0.000 claims description 5
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 239000001509 sodium citrate Substances 0.000 claims description 5
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 5
- 239000011709 vitamin E Substances 0.000 claims description 5
- 235000019165 vitamin E Nutrition 0.000 claims description 5
- 229940046009 vitamin E Drugs 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 230000001804 emulsifying effect Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 229940001482 sodium sulfite Drugs 0.000 claims description 4
- 235000010265 sodium sulphite Nutrition 0.000 claims description 4
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 3
- 241000238660 Blattidae Species 0.000 claims description 3
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 3
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 3
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 235000010241 potassium sorbate Nutrition 0.000 claims description 3
- 239000004302 potassium sorbate Substances 0.000 claims description 3
- 229940069338 potassium sorbate Drugs 0.000 claims description 3
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 3
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 3
- 235000013772 propylene glycol Nutrition 0.000 claims description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229940100555 2-methyl-4-isothiazolin-3-one Drugs 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 235000010407 ammonium alginate Nutrition 0.000 claims description 2
- 239000000728 ammonium alginate Substances 0.000 claims description 2
- KPGABFJTMYCRHJ-YZOKENDUSA-N ammonium alginate Chemical compound [NH4+].[NH4+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O KPGABFJTMYCRHJ-YZOKENDUSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 238000005238 degreasing Methods 0.000 claims description 2
- 229960001484 edetic acid Drugs 0.000 claims description 2
- 238000002481 ethanol extraction Methods 0.000 claims description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- BEGLCMHJXHIJLR-UHFFFAOYSA-N methylisothiazolinone Chemical compound CN1SC=CC1=O BEGLCMHJXHIJLR-UHFFFAOYSA-N 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 235000010408 potassium alginate Nutrition 0.000 claims description 2
- 239000000737 potassium alginate Substances 0.000 claims description 2
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229960001790 sodium citrate Drugs 0.000 claims description 2
- 235000011083 sodium citrates Nutrition 0.000 claims description 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 2
- 239000000499 gel Substances 0.000 description 29
- 239000003814 drug Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 210000003928 nasal cavity Anatomy 0.000 description 7
- 230000000202 analgesic effect Effects 0.000 description 6
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- 210000004379 membrane Anatomy 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 210000004877 mucosa Anatomy 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 238000003304 gavage Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 210000002850 nasal mucosa Anatomy 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000015817 Infant Nutrition disease Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
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- 229940100652 nasal gel Drugs 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
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- 230000003578 releasing effect Effects 0.000 description 2
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- 201000008283 Atrophic Rhinitis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010017553 Furuncle Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
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- 208000002894 beriberi Diseases 0.000 description 1
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- 210000001124 body fluid Anatomy 0.000 description 1
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- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
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- 230000035619 diuresis Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
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- 235000019441 ethanol Nutrition 0.000 description 1
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- 150000004676 glycans Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- RQKFOGXUTRDQPB-UHFFFAOYSA-N hydron;2,3,5,6-tetramethylpyrazine;chloride Chemical compound Cl.CC1=NC(C)=C(C)N=C1C RQKFOGXUTRDQPB-UHFFFAOYSA-N 0.000 description 1
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- 239000007923 nasal drop Substances 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
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- 238000011160 research Methods 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention provides a periplaneta Americana extract product ion-activated in-situ gel and a preparation method thereof. The periplaneta Americana extract product ion-activated in-situ gel is not influenced by environmental temperature and pH value, disadvantages in prior art can be effectively avoided, patient compliance is obviously increased, the periplaneta Americana extract product ion-activated in-situ gel is used for treating chronic rhinitis, acute rhinitis, allergic rhinitis, medicamentous rhinitis and atrophic rhinitis, and has wide market prospect.
Description
Technical field
The invention belongs to medicine new technical field, relate to a kind of novel form of American-cockroach-extract.
Background technology
Periplaneta americana originates in South America, is the insecticide that in Blattidae, volume is larger.Become long 29 ~ 35 millimeters of polypide, bronzing, wing is longer than abdomen end.Feeler is very long, and have larger butterfly brown speckle in the middle of pronotary, the trailing edge of speckle has complete yellow band stricture of vagina, and feeding habits are extensive.Periplaneta americana composition energy promoting blood circulation to remove blood stasis, the infantile malnutrition that disappears of detoxifying, inducing diuresis to remove edema, can be used for lump in the abdomen, infantile malnutrition, beriberi edema, furuncle, toxic swelling and worm venom.Kangfuxin Liquid is the commercialized product of the dry polypide extract of periplaneta americana through State Food and Drug Administration's approval.
Nasal-cavity administration is traditional administering mode, very extensive in department of otorhinolaryngology application, is generally used for treating various nose and paranasal sinuses disease, also can be used for the adjuvant drug of the adjacent organs illness relevant with cacorhinia.The advantage of nasal-cavity administration is: 1. rich blood vessel in nasal mucosa, nasal mucosa permeability is high, is conducive to systemic Absorption.2. first pass effect of hepar, digestive tract intracellular metabolite and the degraded of medicine in gastric juice can be avoided.3. degree of absorption and speed sometimes can be suitable with intravenous injection.4. intranasal administration is convenient and easy.
Existing when carrying out nasal-cavity administration with solution dosage, as spray, nasal drop etc., medicinal liquid easily flows out with liquid condition or enters oral cavity from nasal cavity, and make drug wastage, and duration of efficacy is short, cause bioavailability to reduce, therapeutic effect is undesirable.
Situ-gel, also known as at body gel, flocculant in place, refer to that macromolecular material is with after solution or semi-solid state administration, irritate (temperature of agents area, pH value, ionic species and the change such as concentration, illuminance) to external world at medicine-feeding part and produce response, there is the reversible transition of dispersity or conformation, the semisolid of formation or solid preparation.The positions such as a mucosa, nasal mucosa, oral mucosa, rectal mucosa and drug administration by injection are widely used at present.Situ-gel drug-supplying system has become the study hotspot of pharmaceutics and biological technical field now.Nasal in-situ gel is compared with common nasal liquid preparation, be in a liquid state in storage period, in semi-solid state after contact agents area, it is short not only can to solve the liquid dosage form holdup time, the problem that bioavailability is not high, also overcome ordinary gel agent high viscosity and lack good spreadability, the uppity problem of dosage, the solution-gel property of transition of its uniqueness makes it have preparation concurrently simply, easy to use, especially mucous membrane tissue affinity is strong with agents area, the advantages such as the holdup time is long, extend drug treating time, thus enable medicine play drug effect better.
According to the difference of Forming Mechanism, situ-gel can be divided into responsive to temperature type, pH responsive type and ion-sensitive type etc.Thermosensitive in situ gel has higher requirements to temperature in production, use procedure, and the adjuvant concentration that general needs are higher, this may produce injury to body, and biodegradable problem is also the problem that such situ-gel faces.For pH sensitive in situ gels research, adopt the acid stronger macromolecular materials such as carbomers more at present, to body, there is comparatively strong and stimulating.
The present invention adopts modern science and technology that American-cockroach-extract is made ion-sensitive type situ-gel, do not affect by ambient temperature and pH value, effectively can avoid the shortcoming of prior art, significantly improve the compliance of patient, be used for the treatment of chronic rhinitis, acute rhinitis, allergic rhinitis, medicamentous rhinitis and atrophic rhinitis, market prospect is boundless.
Summary of the invention
The object of this invention is to provide a kind of American-cockroach-extract ion-sensitive type situ-gel for the treatment of rhinitis and preparation method thereof.This ion-sensitive type situ-gel utilizes containing different kinds of ions and albumen in body fluid, some polysaccharide derivatives can with cation complex wherein and change conformation, form gel at agents area.Ion-sensitive type situ-gel prepared by the present invention can extend drug release time, increases release amount, effectively reduces administration number of times.There is good bioadhesive simultaneously, improve medicine in the absorption of contact site, avoid first pass effect, thus improve bioavailability.Also do not affect by ambient temperature and pH value in addition, the macromolecular material of use is Biodegradable material, therefore to skin and the basic nonirritant of mucosa.
In order to reach foregoing invention object, the technical solution used in the present invention is: provide a kind of American-cockroach-extract ion-sensitive type situ-gel for the treatment of rhinitis and preparation method thereof, it is characterized in that, American-cockroach-extract ion-sensitive type situ-gel is grouped into primarily of the one-tenth of following weight proportion: American-cockroach-extract 0.1 ~ 25%, ion-sensitive type situ-gel substrate .2 ~ 10%, solubilizing agent 2 ~ 15%, penetrating agent 1 ~ 8%, osmotic pressure regulator 1 ~ 6%, antioxidant 0.01 ~ 1%, antiseptic 0.02 ~ 0.25%, odor mask 0.02 ~ 0.5%, all the other are water.
Described American-cockroach-extract is at least one in Periplaneta Americana powder, periplaneta americana thick paste and Kangfuxin Liquid.Periplaneta Americana powder is catched and killed after the Blattidae animal periplaneta americana fasting a few days with high-temperature vapor is nuisanceless, and low-temperature reduced-pressure is dry, and by special degreasing process, pulverize the micropowders obtained with high-frequency vibration mill.Periplaneta americana thick paste be the dry polypide of periplaneta americana in same source through ethanol extraction 3 times, merge extractive liquid, filters, and reclaims ethanol, the thick paste be condensed into.Kangfuxin Liquid is the commercialized product of the dry polypide extract of periplaneta americana through State Food and Drug Administration's approval.
Described ion-sensitive type situ-gel substrate is at least one in sodium alginate, potassium alginate, calcium alginate, ammonium alginate, gellan gum, deacetylated gellan gum, pectin.Preferred deacetylated gellan gum and calcium alginate coupling, ratio is 1:1 ~ 5.
Described solubilizing agent is at least one in propylene glycol, tween, HP-β-CD, poloxamer.
Described penetrating agent is at least one in ethanol, propylene glycol.
Described osmotic pressure regulator is at least one in mannitol, sodium chloride, sodium citrate.
Described antioxidant is at least one in vitamin E, Butylated hydroxyanisole, ascorbic acid, sodium sulfite, sodium sulfite, ethylenediaminetetraacetic acid, disodiumedetate.
Described antiseptic is at least one in Methylisothiazolinone, methylchloroisothiazandnone, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate, potassium sorbate.
Described odor mask is at least one in Mentholum, emulsifying essence.
A kind of American-cockroach-extract ion-sensitive type situ-gel for the treatment of rhinitis and preparation method thereof, is characterized in that, comprise the following steps:
Ion-sensitive type situ-gel substrate is added deionized water appropriate, be heated to stirring and dissolving under 60 DEG C ~ 90 DEG C conditions.Separately American-cockroach-extract is added deionized water appropriate, then add solubilizing agent, penetrating agent, osmotic pressure regulator, antioxidant, antiseptic and odor mask, be stirred to whole dissolving.Then to be added in fully swelling situ-gel matrix solution and to stir, finally adding deionized water to 100%, filtering, to obtain final product.
accompanying drawing explanation
Fig. 1 is that American-cockroach-extract ion-sensitive type situ-gel is external through film Accumulation dissolution figure
detailed description of the invention
Below in conjunction with specific embodiment, the specific embodiment of the present invention is described in detail:
Embodiment 1
1. compositing formula (percentage by weight):
2. preparation method:
Get calcium alginate and add deionized water in right amount, constantly stir under being heated to 80 DEG C of conditions and make it fully swelling.Separately Periplaneta Americana powder is added deionized water appropriate, then add Tween 80, ethanol, mannitol, disodiumedetate, potassium sorbate and emulsifying essence, be constantly stirred to whole dissolving.Then by above-mentioned solution mixing and stirring, finally add deionized water to 100%, filter, to obtain final product.
Embodiment 2
1. compositing formula (percentage by weight):
2. preparation method:
Remove acetyl-removed gellan gum and add deionized water in right amount, constantly stir under being heated to 90 DEG C of conditions and make it fully swelling.Separately Kangfuxin Liquid is added deionized water appropriate, then add Tween 80, propylene glycol, sodium chloride, Butylated hydroxyanisole, propyl p-hydroxybenzoate and emulsifying essence, be constantly stirred to whole dissolving.Then by above-mentioned solution mixing and stirring, finally add deionized water to 100%, filter, to obtain final product.
Embodiment 3
1. compositing formula (percentage by weight):
2. preparation method:
Removing acetyl-removed gellan gum and calcium alginate, to add deionized water appropriate, constantly stirs and make it fully swelling under being heated to 90 DEG C of conditions.Separately periplaneta americana thick paste is added deionized water appropriate, then add propylene glycol, sodium citrate, vitamin E, methyl parahydroxybenzoate and Mentholum, be constantly stirred to whole dissolving.Then by above-mentioned solution mixing and stirring, finally add deionized water to 100%, filter, to obtain final product.
Technique effect
Test example 1
American-cockroach-extract ion-sensitive type situ-gel sample prepared by embodiment 1,2,3 is carried out external permeable membrane contrast experiment.
(1) the preparation of in vitro Nasus Bovis seu Bubali mucosa
Get cattle nasal cavity, peel off the mucosa of superior nasal concha top and floor lever of sieve tray, put in refrigerator for subsequent use.(2) the preparation of artificial nose liquid
According to the electrolyte composition preparation artificial nose liquid of nose liquid, compound method is as follows: every 1000ml deionized water sodium chloride-containing 7.91g, potassium chloride 3.68g, calcium chloride 0.51g and sodium bicarbonate 2.56g.
(3) external permeable membrane experimental technique
Get the Nasus Bovis seu Bubali mucosa handled well, epidermal area upwards, is fixed in the Franz diffusion cell of transdermal instrument, epidermal area injects 1ml sample, the artificial nose liquid of the 0.25ml that reinjects.In reception tank, add receiving liquid (normal saline: ethanol=7:3), then diffusion cell is placed in temperature chamber (37 ± 1 DEG C), start magnetic stirrer and keep constant speed to stir (200rpm).The blank receiving liquid that 1ml(adds equivalent is simultaneously sampled respectively at 12h), use 0.45um filtering with microporous membrane, get subsequent filtrate 20ul sample introduction, measure in certain hour external through membrane permeation amount by HPLC method, calculate Accumulation dissolution.
(4) experimental result
External permeable membrane experimental result is in table 1 and Fig. 1.
Table 1 American-cockroach-extract ion-sensitive type situ-gel is external through film accumulation infiltration capacity
As can be seen from table 1 and Fig. 1, American-cockroach-extract ion-sensitive type situ-gel permeable membrane prepared by embodiment 1,2,3 is effective, and onset is rapid, long action time.The Ligustrazine hydrochloride kinetic curve of embodiment 1 and embodiment 2 can be divided into prominent releasing and two stages of slow release, and the initial stage releases the stage for prominent, and Accumulation dissolution can reach more than 50%.And the cumulative release curve of embodiment 3 more meets first _ order kinetics equation, release is more mild and even, there is obvious slowly releasing effect, dosing interval can be extended, reduce administration number of times, realize administration concentration steady, avoid peak valley phenomenon, be conducive to the constant curative effect keeping medicine, increase the stability of Drug therapy.
Test example 2 anti-inflammatory analgesic effect is evaluated
The nasal gel that embodiment 3 obtains carries out anti-inflammatory analgesic effect evaluation to Kunming mouse.
50 mices are divided into 5 groups at random, each 10.Blank group: will not dispose directly to acetum.Test group dosage is 6.5mgkg-1, and nasal cavity gives above-mentioned gel, and gavage group gavage is to 0.5mgmL-1
Drug solution, quiet note group vein is to the drug solution of 1mgmL-1; Nasal cavity, gavage and quiet note respectively at after administration 10 minutes, 1 hour and 0 minute lumbar injection 0.7% acetum (normal saline).
Observe and after recording injection acetum in 15 minutes with or without the writhing response number of times that writhing response occurs and produces.Calculate the analgesia rate of each group, computing formula is as follows:
Analgesia rate is higher shows that the analgesic effect of medicine is better.
Result shows, quiet note and nasal gel group all have analgesic effect (p < 0.05), and analgesia rate is respectively 55.08% and 52.51%, and without significant difference (p > 0.05) between two groups; Gavage group is without analgesic effect (p > 0.05), and analgesia rate is only 8.33%.
Analgesic effect is evaluated
By gel for nose repeated trials example 2 prepared by embodiment 1,2, result is similar.
The foregoing is only preferred embodiment of the present invention, and be not used to limit substantial technological context of the present invention, substantial technological content of the present invention is broadly defined in the right of application, any technology that other people complete, if with application right define identical, also or a kind of change of equivalence, be all covered by being regarded as among this right.
Claims (6)
1. treat the American-cockroach-extract ion-sensitive type situ-gel of rhinitis for one kind, it is characterized in that, American-cockroach-extract ion-sensitive type situ-gel is grouped into primarily of the one-tenth of following weight proportion: American-cockroach-extract 0.1 ~ 25%, ion-sensitive type situ-gel substrate 0.2 ~ 10%, solubilizing agent 2 ~ 15%, penetrating agent 1 ~ 8%, osmotic pressure regulator 1 ~ 6%, antioxidant 0.01 ~ 1%, antiseptic 0.02 ~ 0.25%, odor mask 0.02 ~ 0.5%, all the other are water.
2. gel according to claim 1, it is characterized in that described American-cockroach-extract is at least one in Periplaneta Americana powder, periplaneta americana thick paste and Kangfuxin Liquid, Periplaneta Americana powder is catched and killed after the Blattidae animal periplaneta americana fasting a few days with high-temperature vapor is nuisanceless, low-temperature reduced-pressure is dry, and by special degreasing process, the micropowders obtained is pulverized with high-frequency vibration mill, periplaneta americana thick paste is that the dry polypide of periplaneta americana in same source is through ethanol extraction 3 times, merge extractive liquid, filter, reclaim ethanol, the thick paste be condensed into.
3. gel according to claim 1, wherein said ion-sensitive type situ-gel substrate is at least one in sodium alginate, potassium alginate, calcium alginate, ammonium alginate, gellan gum, deacetylated gellan gum, pectin, preferred deacetylated gellan gum and calcium alginate coupling, ratio is 1:1 ~ 5.
4. gel according to claim 1, wherein said solubilizing agent is at least one in propylene glycol, tween, HP-β-CD, poloxamer; Described penetrating agent is at least one in ethanol, propylene glycol;
Described osmotic pressure regulator is at least one in mannitol, sodium chloride, sodium citrate;
Described antioxidant is at least one in vitamin E, Butylated hydroxyanisole, ascorbic acid, sodium sulfite, sodium sulfite, ethylenediaminetetraacetic acid, disodiumedetate;
Described antiseptic is at least one in Methylisothiazolinone, methylchloroisothiazandnone, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate, potassium sorbate;
Described odor mask is at least one in Mentholum, emulsifying essence.
5. American-cockroach-extract ion-sensitive type situ-gel for the treatment of rhinitis and preparation method thereof, is characterized in that, comprise the following steps:
Ion-sensitive type situ-gel substrate is added deionized water appropriate, be heated to stirring and dissolving under 60 DEG C ~ 90 DEG C conditions, separately American-cockroach-extract is added deionized water appropriate, add solubilizing agent, penetrating agent, osmotic pressure regulator, antioxidant, antiseptic and odor mask again, be stirred to whole dissolving, be then added in fully swelling situ-gel matrix solution and stir, finally adding deionized water to 100%, filter, to obtain final product.
6. gel according to claim 1, is characterized in that formula is
Periplaneta americana thick paste 2%
Deacetylated gellan gum 0.5%
Calcium alginate 1.5%
Propylene glycol 3%
Sodium citrate 1%
Vitamin E 0.05%
Methyl parahydroxybenzoate 0. 2%
Mentholum 0.1%
Deionized water adds to 100%
Preparation method:
Removing acetyl-removed gellan gum and calcium alginate, to add deionized water appropriate, constantly stirring under being heated to 90 DEG C of conditions makes it fully swelling, separately periplaneta americana thick paste is added deionized water appropriate, add propylene glycol, sodium citrate, vitamin E, methyl parahydroxybenzoate and Mentholum again, constantly be stirred to whole dissolving, then by above-mentioned solution mixing and stirring, finally add deionized water to 100%, filter, to obtain final product.
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