CN1154842A - Skin-penetrating absorption prepration - Google Patents
Skin-penetrating absorption prepration Download PDFInfo
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- CN1154842A CN1154842A CN 96119473 CN96119473A CN1154842A CN 1154842 A CN1154842 A CN 1154842A CN 96119473 CN96119473 CN 96119473 CN 96119473 A CN96119473 A CN 96119473A CN 1154842 A CN1154842 A CN 1154842A
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- tanxi
- ketone
- absorption enhancer
- percutaneous absorption
- transdermal absorption
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Abstract
The present invention relates to a transdermal absorption preparation containing otamsedone. It is suitable for curing, preventing and remitting symptoms of nausea and vomitus due to radiotherapy and chemotherapy for curing cancer. The drug otamsedone and transdermal absorption accelerator are dissolved in propylene glycol, ethyl alcohol or water solvent together, then made into adhesive plaster, soft extract,g elata and film preparation according to the requirements. Said transdermal absorption accelerator can be one of poloxamer, urea, Azone, oleic acid and 2-HP-beta-CyD or mixture among them. Its unit dosage is 4-10mg.
Description
The present invention relates to a kind of novel form of chemicals, the transdermal absorption formulation of the medicine Ao Tanxi ketone of feeling sick, vomitting that specifically a kind of treatment and prophylaxis of cancer chemotherapy of patients, radiotherapy cause is as patch, gel, ointment, membrane etc.
Ao Tanxi ketone is the 5-HT of novel carbazole ketone, high selectivity
3Receptor antagonist is used for the treatment of, prevents and feeling sick of alleviating that cancer radiation or chemotherapy cause, symptoms of emesis.Existing pharmaceutical dosage form is tablet and injection, and the oral administration medicine has very strong first pass effect (40%), and patient is often because gastrointestinal reaction causes the difficulty of taking medicine; Injection need have the professional to help to use, and trouble body is had damage, and blood concentration fluctuation is big; Reported in literature there has been infiltration one release tablet of Ao Tanxi ketone (PCT Appl WO9204,012), has also had literature research with pharmacokinetics (Hsyu pH, etalpharm Res, 1994 behind the solution form rectally of hydrochloric acid Ao Tanxi ketone; 11; 156), show the feasibility of developing suppository, but the prescription research of inspection agent be not reported that comprehensive all searching documents there is no report to the research and the formulation development of Ao Tanxi ketone externally applied transdermal absorption aspect.
The drug transdermal absorption techniques is the popular research field that develops rapidly from early eighties in the pharmaceutics, and the Transdermal absorption administration is compared following advantage with other dosage form: (1) can avoid the first pass effect of medicine; (2) blood drug level is steady, and action time is permanent, does not need frequent administration; (3) be particularly suitable for the inconvenient patient of oral administration; (4) to the effect of body not damaged; (5) carry application conveniently.
The transdermal absorption formulation that the purpose of this invention is to provide a kind of Ao Tanxi of containing ketone, utilize transdermal drag delivery, medicine percutaneous skin is absorbed enter in the body, overcome the deficiency of other administration route, and can meet or exceed the curative effect of other dosage forms, improve the quality of life of cancer patient.
The key of drug transdermal absorption administration is the breakthrough of keratodermatitis barrier action, and selecting suitable Percutaneous absorption enhancer for use is the key that addresses the above problem.
The objective of the invention is to be achieved by the following scheme, medicine Ao Tanxi ketone and Percutaneous absorption enhancer are dissolved in propylene glycol, ethanol or the aqueous solvent jointly, make requiring to make dosage forms such as patch, gel, ointment, membrane again according to dosage form.Percutaneous absorption enhancer can be poloxamer, carbamide, laurocapram (Azone), oleic acid, 2-hydroxypropyl-beta-schardinger dextrin-(one of 2-HP-β-CyD) or the mixture between them.General unit dose is the 4-10 milligram.Medicine Ao Tanxi ketone can be free alkali or hydrochloride form.The prescription scope and the technology of patch are as follows: Ao Tanxi ketone is (weight ratio) below 5%, 0.1-10% such as Percutaneous absorption enhancer such as oleic acid, laurocapram, all the other are acrylate pressure-sensitive adhesive, the heating of Ao Tanxi ketone and Percutaneous absorption enhancer is dissolved in 90% ethanol, stirs and pour into down in the pressure sensitive adhesive, put and be chilled to room temperature to even, film, the heated volatile organic solvent covers the polyolefin film backing layer, the cutting divided dose.Gel prescription scope and technology are as follows: Ao Tanxi ketone 1-10%, and Percutaneous absorption enhancer 0.1-10%, propylene glycol or ethanol 1-5%, carbopol 0.5-5%, all the other are distilled water.Carbopol is water-soluble, regulates pH with sodium hydroxide solution, makes the formation gel, and medicine and Percutaneous absorption enhancer join in the gel after being dissolved in propylene glycol (or ethanol), stir packing.Ointment prescription scope and technology are as follows: Ao Tanxi ketone 1-10%, Percutaneous absorption enhancer 0.1-10%, all the other are substrate Polyethylene Glycol or glycerin gelatine etc., Ao Tanxi ketone and Percutaneous absorption enhancer are dissolved in the ethanol jointly, join in the molten matrix under stirring, be stirred to evenly, wave diffusing solvent, then packing.The prescription scope and the technology of membrane are as follows: Ao Tanxi ketone 1-15%, and plasticizer such as glycerol or propylene glycol 1-25%, Percutaneous absorption enhancer 0.1-10%, all the other are filmogen such as polyvinyl alcohol.Conventional method is filmed, and last membrane adheres to layer, polyolefin backing layer, silicon paper protective layer and medicine film by pressure sensitive adhesive and is composited.
The invention has the advantages that the mode that has adopted transdermal absorption formulation treats that cancer radiation or chemotherapy cause feel sick, the correct selection of symptoms of emesis and drug transdermal absorption enhancer, the easier skin that sees through of medicine is entered in the body, curative effect is better, patient is acceptant, use more convenient, to body also not damaged.
Fig. 1 is a test water flat Valia-Chien diffusion cell sketch map
1 is grinding port plug among the figure, and 2 is the donor pond, and 3 is Corium Mus, and 4 is stirrer, and 5 for accepting the pond.
The present invention is described in further detail below in conjunction with embodiment.We in order to confirm feasibility of the present invention, have designed following test in research process, assay device is seen Fig. 1, is called the Valia-Chien diffusion cell.Between two and half ponds Corium Mus is housed, stratum corneum side is fixed with 502 glue to the donor pond.Pack in the donor pond 10 ml physiological saline supersaturated solutions of medicine are being accepted the pond timing sampling, and sample volume is 3 milliliters, replenishes the normal saline of equal volume simultaneously, and the UV method is measured.Experimental temperature is 32 ± 0.5 ℃, and experimental result is as follows: different Percutaneous absorption enhancers see the following form to the facilitation of Ao Tanxi ketone percutaneous permeation.Mean containing of each parameter in the table: Js is a steady-state flow rate, and Ps is an infiltration coefficient, t
LBe lag time.
The osmotic engine mathematic(al) parameter of Ao Tanxi ketone under different Percutaneous absorption enhancer effects
By data in the table as can be seen, the percutaneous permeation of the equal Ke Yi Shi of Percutaneous absorption enhancer Ao Tanxi ketone increases, particularly laurocapram can improve nearly 23 times of infiltration coefficient and steady-state flow rate, make diminish lag time, thereby improved the percutaneous penetration of drugs amount greatly, in other words, the present invention has feasibility.
| Js(μg?cm -2hr -1) | ???Ps(cm?hr -1) | ??t L(hr) | |
| No Percutaneous absorption enhancer laurocapram oleic acid 2-HP-β-CyD carbamide poloxamer | ??8.87 ??208.69 ??15.60 ??12.38 ??11.25 ??17.22 | ??5.66×10 -4??1.32×10 -2??9.95×10 -4??7.89×10 -4??7.17×10 -4??1.10×10 -3 | ????2.28 ????1.36 ????1.76 ????1.28 ????2.00 ????4.10 |
Embodiment 1: the method for making that with the laurocapram is the patch that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 1.5%, laurocapram 1%, acrylate pressure-sensitive adhesive is to full dose.Medicine and laurocapram heating are dissolved in 90% ethanol, pour in the acrylate pressure-sensitive adhesive under stirring, to even, cooling is filmed, and diffusing organic solvent (60-70 ℃) is waved in heating, add a cover backing layer, be controlled at 0.05-1mg/cm according to the variation unit are content of dispersion of coating thickness
2,, cut into the patch of suitable size according to the dosage requirement.
Embodiment 2: the method for making that with the laurocapram is the patch that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 3%, laurocapram 4%, acrylate pressure-sensitive adhesive are to full dose, with embodiment 1 prepared patch.
Embodiment 3: the method for making that with oleic acid is the gel that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 1%, carbopol 941 3%, oleic acid 1%, propylene glycol 5%, water is to full dose.Carbopol is water-soluble, regulates pH with sodium hydroxide solution, makes the formation gel, after medicine and Percutaneous absorption enhancer are dissolved in propylene glycol, joins in the gel, and packing stirs.Unit dose is the 4-10 milligram.
Embodiment 4: the method for making that with the laurocapram is the gel that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 1%, carbopol 9413%, laurocapram 1%, propylene glycol 5%, water is to full dose.Prepared gel with embodiment 3.
Embodiment 5: the method for making that with the laurocapram is the ointment that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get Ao Tanxi ketone free alkali 1%, PEG4000 38%, PEG40060%, and laurocapram 1% is dissolved in an amount of ethanol with Ao Tanxi ketone and laurocapram, joins in the molten matrix, stirs, and waves diffusing solvent, packing.Unit dose is the 4-10 milligram.
Embodiment 6: the method for making that with carbamide is the ointment that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 2%, PEG400044%, PEG20051%, carbamide 3% is with the prepared ointment of embodiment 5.
Embodiment 7: be the method for making that contains Ao Tanxi ketone membrane of Percutaneous absorption enhancer with 2-HP-β-CyD; Get hydrochloric acid Ao Tanxi ketone 7%, 2-HP-β-CyD7%, glycerol 16%, PVA-1788 is to full dose.Component in the prescription is dissolved in the suitable quantity of water, films, 60-70 ℃ is drying to obtain the medicine film.Medicine film, adhesion layer, backing layer and the protective layer membrane that is composited.Unit dose is the 4-10 milligram.
Embodiment 8: the method for making that with the laurocapram is the membrane that contains Ao Tanxi ketone of Percutaneous absorption enhancer; Get hydrochloric acid Ao Tanxi ketone 5%, laurocapram 5%, glycerol 15%, PVA-0488 are to full dose, and laurocapram is dissolved in ethanol, and all the other components are water-soluble, with two solution mixings, film under stirring, and 60-70 ℃ is drying to obtain the medicine film.
Ao Tanxi ketone patch according to embodiment 1 makes has carried out Preliminary Clinical Observation, and patient is the cancer patient, in chemotherapy, radiotherapy all with serious feel sick, symptoms of emesis.Case load 29 examples.Patch can be used for positions such as patient's arm, lower limb, breast or the back of the body, and subsides in a day are equivalent to 9 milligrams of hydrochloric acid Ao Tanxi ketone.The result shows that the patient's symptoms of emesis more than 90% is controlled or eliminates that nauseating sense obviously alleviates or disappears, and can have meal in right amount.All patients all do not have anaphylaxis performances such as red and swollen pruritus.
Claims (7)
1, a kind of transdermal absorption formulation that contains Ao Tanxi ketone is characterized in that: medicine Ao Tanxi ketone and Percutaneous absorption enhancer are dissolved in propylene glycol, ethanol or the aqueous solvent jointly, make requiring to make dosage forms such as patch, gel, ointment, membrane again according to dosage form.
2, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1 is characterized in that: Percutaneous absorption enhancer can be poloxamer, carbamide, laurocapram (Azone), oleic acid, 2-hydroxypropyl-beta-schardinger dextrin-(one of 2-HP-β-CyD) or the mixture between them.
3, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1 is characterized in that: medicine Ao Tanxi ketone can be free alkali or hydrochloride form.
4, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1, it is characterized in that: the prescription scope and the technology of patch are as follows: Ao Tanxi ketone is below 5%, Percutaneous absorption enhancer such as laurocapram 0.1-10%, all the other are acrylate pressure-sensitive adhesive, Ao Tanxi ketone and Percutaneous absorption enhancer heating are dissolved in 90% ethanol, pour under stirring in the pressure sensitive adhesive to even, put and be chilled to room temperature, film, the heated volatile organic solvent, cover the polyolefin film backing layer, the cutting divided dose, general every patch is the 4-10 milligram.
5, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1, it is characterized in that: gel prescription scope and technology are as follows: Ao Tanxi ketone 1-10%, Percutaneous absorption enhancer 0.1-10%, propylene glycol or ethanol 1-5%, carbopol 0.5-5%, all the other are distilled water, carbopol is water-soluble, regulate pH with sodium hydroxide solution, make the formation gel, after medicine and Percutaneous absorption enhancer are dissolved in propylene glycol (or ethanol), join in the gel, stir, packing, unit dose is the 4-10 milligram.
6, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1, it is characterized in that: ointment prescription scope and technology are as follows: Ao Tanxi ketone 1-10%, Percutaneous absorption enhancer 0.1-10%, all the other are substrate Polyethylene Glycol or glycerin gelatine etc., and Ao Tanxi ketone and Percutaneous absorption enhancer are dissolved in the ethanol jointly, join in the molten matrix under stirring, be stirred to evenly, wave diffusing solvent, packing then, unit dose is the 4-10 milligram.
7, a kind of transdermal absorption formulation that contains Ao Tanxi ketone according to claim 1; it is characterized in that: the prescription of membrane is as follows: Ao Tanxi ketone 1-15%; plasticizer such as glycerol or propylene glycol 1-25%; Percutaneous absorption enhancer 0.1-10%; all the other are filmogen such as polyvinyl alcohol; conventional method is filmed, and last membrane adheres to layer, polyolefin backing layer, silicon paper protective layer and medicine film by pressure sensitive adhesive and is composited, and unit dose is the 4-10 milligram.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96119473A CN1078465C (en) | 1996-10-10 | 1996-10-10 | Skin-penetrating absorption prepration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96119473A CN1078465C (en) | 1996-10-10 | 1996-10-10 | Skin-penetrating absorption prepration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1154842A true CN1154842A (en) | 1997-07-23 |
| CN1078465C CN1078465C (en) | 2002-01-30 |
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ID=5125726
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN96119473A Expired - Lifetime CN1078465C (en) | 1996-10-10 | 1996-10-10 | Skin-penetrating absorption prepration |
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| Country | Link |
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| CN (1) | CN1078465C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100441179C (en) * | 2003-04-08 | 2008-12-10 | 施瓦茨制药有限公司 | Transdermal administration of (r)-3,3-diphenylpropylamine monoesters. |
| CN101077340B (en) * | 2006-05-22 | 2010-07-21 | 天津宝康科技发展有限公司 | Penetration-promoting type catablasm matrix |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06509073A (en) * | 1991-06-26 | 1994-10-13 | セプラコア，インコーポレーテッド | Methods and compositions for the treatment of emesis, nausea and other disorders using optically pure S(-)ondansetron |
-
1996
- 1996-10-10 CN CN96119473A patent/CN1078465C/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100441179C (en) * | 2003-04-08 | 2008-12-10 | 施瓦茨制药有限公司 | Transdermal administration of (r)-3,3-diphenylpropylamine monoesters. |
| CN101077340B (en) * | 2006-05-22 | 2010-07-21 | 天津宝康科技发展有限公司 | Penetration-promoting type catablasm matrix |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1078465C (en) | 2002-01-30 |
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Owner name: CHANGZHOU SIYAO PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHENYANG PHARMACEUTICAL UNIVERSITY Effective date: 20040806 |
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Effective date of registration: 20040806 Address after: 213003 Mei long dam, Jiangsu, Changzhou, China Patentee after: Pharmaceutical Co., Ltd., Changzhou Pharmaceutical Factory No.4 Address before: 110015 scientific research office, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe, Liaoning, Shenyang Patentee before: Shenyang Pharmaceutical University |
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