CN102284012A - Gel plaster containing curcumin and bletilla hyacinthina gum and preparation method thereof - Google Patents
Gel plaster containing curcumin and bletilla hyacinthina gum and preparation method thereof Download PDFInfo
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- CN102284012A CN102284012A CN201110227364XA CN201110227364A CN102284012A CN 102284012 A CN102284012 A CN 102284012A CN 201110227364X A CN201110227364X A CN 201110227364XA CN 201110227364 A CN201110227364 A CN 201110227364A CN 102284012 A CN102284012 A CN 102284012A
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Abstract
The invention provides a gel plaster containing curcumin and bletilla hyacinthina gum, which comprises the following components in parts by weight: 0.2-0.5 part of curcumin, 1.0-2.5 parts of bletilla hyacinthina gum, 2.0-5.0 parts of polyacrylic acid, 0.4-1.4 parts of adhesive, 25.0-65.0 parts of humectant, 0.1-0.2 part of aluminum hydroxide, 0-5.0 parts of solid dispersion material, 0-1.5 parts of permeation promoter and 35.0-58.0 parts of water. The adhesive is selected from polyvinylpyrrolidone, hydroxypropyl methylcellulose, polyvinyl alcohol and the like; the humectant is selected from glycerol, propylene glycol, polyethylene glycol and the like; the solid dispersion material is selected from polyvinylpyrrolidone, mannitol, polyethylene glycol, poloxamer and the like; and the permeation promoter is selected from hydroxypropyl-beta-cyclodextrin, borneol, pennyroyal, olive oil and the like. The curcumin in the gel plaster can be transdermally absorbed and slowly and continuously released, and can stably be taken for a long time; and the bletilla hyacinthina gum can protect the skin, and reduce the irritation of the drugs to the skin.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of gel adhesive that contains curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue and preparation method thereof.
Background technology
Curcumin is a kind of natural pigment, is mainly derived from zingiberaceous plant Rhizoma Curcumae Longae Curcuma longa L. rhizome, is the main active in the Rhizoma Curcumae Longae.Modern pharmacological research shows, curcumin has physiological function and effects such as function of gallbladder promoting, blood fat reducing, antiinflammatory, rheumatism, antibiotic, anticancer, antioxidation, removing free radical, can be widely used in medical science, food, cosmetic field (Mei Quanxi etc., modern Chinese medicine pharmacology handbook, China Traditional Chinese Medicine Publishing House, 1998,490-491).Yet, curcumin has unstability and water-insoluble, in air, be easy to fade, existing pharmaceutical dosage form is mainly ejection preparation, microemulsion formulation and soft capsule preparation (Cui Jing etc., the development of curcumin microemulsion and property research thereof, Chinese Pharmaceutical Journal, 2005,40 (24): 1877-1880), bioavailability is also unsatisfactory, has limited its applying in food industry and pharmaceutical preparation.
Transdermal delivery system has been obtained remarkable progress adhering to the short aspect such as means and methods of oozing of controlled-release material and percutaneous in recent years, and some of them have been used for clinical and have formed commodity, have shown gratifying prospect.Percutaneous dosing is for the whole body therapeutic of local skin treatment of diseases and some disease all significant (Liang Wenquan etc., percutaneous dosing product development present situation, external treatment with Chinese medicine magazine, 2005,14 (1): 3).And the curcumin percutaneous drug administration preparation, the key issue of existence is how to guarantee stability of drug, the percutaneous rate of medicine and the adhesion property of patch.In addition, medicine is discharged from substrate and promote drug transdermal to absorb, be still the person that needs the preparation work further problem (Cui Fude, pharmaceutics, People's Health Publisher, the 2005:425-433 of research; Pan Weisan, the new drug preparation technique, Chemical Industry Press, 2004:201-202).And the application success of curcumin in transdermal delivery system is to the development and use of Chinese medicine significant (Liu Qiang etc., the progress of Chinese medicine percutaneous drug administration preparation and development trend, external treatment with Chinese medicine magazine, 2004,13 (1): 31-33).
The Pseudobulbus Bletillae (Rhizoma Bletillae) is the dry tuber of the orchid Pseudobulbus Bletillae (Rhizoma Bletillae) (Bletilla striata (Thunb) Reichb.f); has astringing to arrest bleeding; effects such as detumescence and promoting granulation can be treated hemorrhage, pneumonopathy, burn etc., also can be used for having in the cosmetics effect of protection skin, slow down aging.Pseudobulbus Bletillae (Rhizoma Bletillae) glue is the water-soluble polysaccharide that is rich in the Pseudobulbus Bletillae (Rhizoma Bletillae), and the glucose that it is made up of 4 molecule mannose and 1 molecule glucose is joined mannan, and relative molecular mass is about 100,000-200,000.Pseudobulbus Bletillae (Rhizoma Bletillae) glue has multiple biological activity, clinically is used for effects such as antiinflammatory coagulant blood, antitumor, anticomplementary activity, immunosuppressant, can be used as pharmaceutical adjunct; as filmogen, suspending agent, emulsifying agent etc.; also can be used in the daily chemical products, the instead of chemical thickening agent, and have functions such as the zest of minimizing, protection skin, slow down aging; be extremely promising biomedical material (Wang Jun etc.; the clinical practice of Pseudobulbus Bletillae (Rhizoma Bletillae) glue, Chinese Hospitals pharmaceutical journal, 2004; 24 (9), 556-557).
Summary of the invention
The object of the present invention is to provide a kind ofly to be distributed in skin surface the gel adhesive that contains curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue that good stability, dissolubility height, bioavailability be good, improve patient's medication compliance with higher concentration.
Another object of the present invention provides the above-mentioned preparation method that contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue.
For achieving the above object, the technical solution used in the present invention is:
A kind of gel adhesive that contains curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue comprises the component of following weight proportion:
Curcumin 0.2～0.5 Pseudobulbus Bletillae (Rhizoma Bletillae) glue 1.0～2.5 framework materials 2.0～5.0
Adhesive 0.4～1.4 wetting agent 25.0～65.0 cross-linking agent 0.1～0.2
Wherein said framework material is a polyacrylic acid.Described adhesive is for being selected from polyvinylpyrrolidone (PVP), hypromellose (HPMC), starch, polyvinyl alcohol (PVA), gelatin, arabic gum, the Polyethylene Glycol one or more; Described wetting agent is to be selected from glycerol, propylene glycol, sorbitol, Polyethylene Glycol, ethylene glycol, the 1,3 butylene glycol one or more.Described cross-linking agent is an aluminium hydroxide.Described solid dispersion material is to be selected from polyvinylpyrrolidone, hypromellose, chitosan, mannitol, Polyethylene Glycol, the poloxamer one or more, preferably polyethylene ketopyrrolidine or mannitol.Described penetrating agent is to be selected from HP-, Borneolum Syntheticum, Oleum menthae, olive oil, the carbamide one or more.The weight proportion of above-mentioned solid dispersion material is preferably 1.0～5.0, penetrating agent preferred 0.5～1.5.
In a kind of preferred implementation, described gel adhesive comprises the component of following weight proportion:
Wherein the weight proportion of solid dispersion material more preferably 1.0～5.0, and penetrating agent is 0.5～1.5.
Pseudobulbus Bletillae (Rhizoma Bletillae) glue of the present invention can prepare by the following method: will add in the distilled water of 10～12 times of volumes (in ml) after 1 weight portion (in the g) Pseudobulbus Bletillae (Rhizoma Bletillae) pulverizing medicinal materials, be heated to 50 ℃ and stirred 1 hour, filter, collect extracting solution; The medicinal residues distilled water that adds 5～6 times of volumes (in ml) respectively repeats to extract 1～3 time then; Merge extractive liquid, is concentrated into half volume, adds 95% ethanol and regulates ethanol mass concentration to 70%, separates out precipitation, and centrifugal, collecting precipitation is used washing with alcohol, in 80 ℃ of dryings, obtains Pseudobulbus Bletillae (Rhizoma Bletillae) glue.
The present invention also provides the above-mentioned preparation method that contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue, comprises step:
1) preparation of curcumin solid dispersion: according to the prescription consumption proportion, curcumin is dissolved in an amount of organic solvent, with the solid dispersion material mixing, fully stir under 60 ℃ of condition of water bath heating, organic solvent is removed in evaporation, puts and is chilled to room temperature, dry 5h in 45～55 ℃ of vacuum drying ovens again, pulverize, sieve, promptly;
2) preparation of substrate: according to the prescription consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, wetting agent, cross-linking agent are stirred under 25 ℃～35 ℃ water bath condition, add framework material, adhesive, penetrating agent then, fully stir, promptly;
3) preparation of pastille glue: according to the prescription consumption proportion, the curcumin solid dispersion of curcumin or step 1) preparation is added in the substrate after with an amount of solvent (water or glycerol) dissolving dispersion, adds remaining water, stir, de-bubbled, promptly;
4) preparation of gel adhesive: pastille glue is applied on the backing layer, and in 40～60 ℃ of down dry 0.5～3.5h, the loam cake protective layer cuts, promptly.
In one embodiment, curcumin can be dissolved in volatile organic solvents such as dehydrated alcohol, acetone in the step 1), and vacuum drying normally carried out about 5 hours at about 50 ℃, and sieving can be the sieve in 80 orders, 100 orders or other different apertures.
In one embodiment, step 2) the aqueous solution form of 0.5～10wt% that adhesive can be prepared in advance in is added, and by its dilution is gluey aqueous solution, helps each component and mixes quickly and evenly.For example, preferably, polyvinylpyrrolidone is to add with the aqueous solution form of 1.5～8.5wt%, and polyvinyl alcohol is to add with the aqueous solution form of 1.5～9.5wt%, and hypromellose is to add with the aqueous solution form of 0.5～3.5wt%.
In one embodiment, Pseudobulbus Bletillae (Rhizoma Bletillae) glue also can directly add in the described gel adhesive with the form of Pseudobulbus Bletillae (Rhizoma Bletillae) medicinal powder without extraction step 2).When using with the form of common bletilla, its consumption is about as much as 3～4 times of Pseudobulbus Bletillae (Rhizoma Bletillae) glue consumption.
In one embodiment, in the step 3) de-bubbled can adopt ultrasonic, leave standstill or method such as centrifugal is carried out.
In one embodiment, backing layer can be cellulose acetate, spun rayon cloth or medical adhesive-bonded fabric etc. in the step 4), and protective layer can be polypropylene film, polyethylene film, cellophane or mylar etc.
Beneficial effect of the present invention is, mechanism such as matrix type and adhesive decentralized are combined, and promotes the Transdermal absorption of medicine and continues to discharge.As active component, synergism strengthens drug effect with curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue, and Pseudobulbus Bletillae (Rhizoma Bletillae) glue can be protected skin simultaneously, and reducing stimulates; Gelatinous Pseudobulbus Bletillae (Rhizoma Bletillae) glue also can be used as adhesion material, adheres on the skin with the framework material polyacrylic acid and as drug depot sustained release medicine, makes the active component effect of described gel adhesive lasting, can stablize administration for a long time.In addition, can also add solid dispersion material and penetrating agent by selectivity.The solid dispersion material makes medicine that higher dissolubility be arranged in the substrate when guaranteeing to make medicine stability, is discharged into skin surface by substrate smoothly; Penetrating agent makes medicine see through horny layer from skin surface, diffuses into corium.The use in conjunction of above-mentioned each component, the purpose that makes the curcumin in the gel adhesive reach Transdermal absorption and slowly continue to discharge, and reduce the zest of medicine to skin, reach the purpose of protection skin.
The gel adhesive that contains curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue of the present invention can be used for the treatment of multiple disease, comprises the auxiliary treatment of arthroncus, arthritis, skin carcinoma or the auxiliary treatment of breast carcinoma etc.The in-vitro evaluation experimental result shows that preparation of the present invention reaches more than 93% at the 2h medicine realeasing rate; Drug accumulation transdermal amount reaches 40 μ gcm
-2More than, accumulation transdermal amount reached 347 μ gcm after medication preparation became solid dispersion
-2, significantly improve the accumulation transdermal amount of medicine.Said preparation can be stablized administration in 32h.
Description of drawings
Fig. 1 is the cumulative release percentage rate Q-t curve of gel adhesive sample of the present invention.
Fig. 2 is the accumulation transdermal amount Q-time t curve of gel adhesive sample of the present invention.
Fig. 3 is the accumulation transdermal amount Q-t of gel adhesive sample of the present invention
1/2Curve.
The specific embodiment
Following preferred embodiment only is provided for further understanding characteristics of the present invention and advantage, and should not be construed as limitation of the present invention.Wherein curcumin is provided by Tianjin recovery fine chemistry industry institute, lot number CBO346-5G-N, available from branch, pharmacy of Tongrentang Linyi, Beijing, other materials and reagent are common commercially available prod to the Pseudobulbus Bletillae (Rhizoma Bletillae) (Bletilla striata (Thunb) Reichb.f) unless otherwise specified.
[embodiment 1] preparation Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Take by weighing the about 20g of common bletilla, adding distil water 240mL, heating in water bath to 50 ℃ insulation dipping stirs and extracted 1 hour, through four layers of filtered through gauze, gets extracting solution.The medicinal residues about 80～120ml of adding distil water again repeat to extract twice as stated above, merge three times filtrate, be concentrated into half volume, add 95% ethanol and make the alcohol amount of containing reach 70wt%, separate out a large amount of white precipitates this moment rapidly, centrifugal, reclaim ethanol, the collecting precipitation thing, with small amount of ethanol washing 3 times, volatilize ethanol, and dry about 80 ℃, obtain the about 5.6g of Pseudobulbus Bletillae (Rhizoma Bletillae) glue.
[embodiment 2] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.4 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?2.5 | Active component, adhesive |
| Polyacrylic acid | ?3.0 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.8 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.3 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.2 | Substrate, adhesive |
| Glycerol | ?15.0 | Substrate, wetting agent |
| Propylene glycol | ?15.0 | Substrate, wetting agent |
| Polyethylene Glycol | ?5.0 | Substrate, wetting agent |
| Aluminium hydroxide (Al (OH) 3) | ?0.1 | Substrate, cross-linking agent |
| Water | ?57.7 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of substrate: according to above-mentioned prescription consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol (can stay the solvent of a little glycerol as step 3), propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 35 ℃ of water bath condition, add polyacrylic acid again, PVP (can be formulated as the PVP aqueous solution form of about 5wt% in advance, also claim " glue "), PVA (can be formulated as the PVA aqueous solution form of about 5wt% in advance), HPMC (can be formulated as the HPMC aqueous solution form of about 2wt% in advance), stir, obtain substrate.
2) preparation of pastille glue: after curcumin disperseed with an amount of solvent (dehydrated alcohol, water or glycerol) dissolving, be added in the substrate, add remaining water, stir, ultrasonic or leave standstill de-bubbled, obtain pastille glue.
3) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 60 ℃ of dry about 0.5h, loam cake cellophane protective layer cuts promptly.
[embodiment 3] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.4 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?2.0 | Active component, adhesive |
| ?PVP?k-30 | ?4.0 | The solid dispersion material |
| Polyacrylic acid | ?4.0 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.6 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.1 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.3 | Substrate, adhesive |
| Glycerol | ?25.0 | Substrate, wetting agent |
| Propylene glycol | ?15.0 | Substrate, wetting agent |
| Polyethylene Glycol | ?10.0 | Substrate, wetting agent |
| Aluminium hydroxide | ?0.2 | Substrate, cross-linking agent |
| Water | ?38.4 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of curcumin solid dispersion: according to above-mentioned prescription consumption proportion, curcumin is dissolved in an amount of dehydrated alcohol, add PVPk-30 and mix, ultrasonic 5min makes dissolving, fully stirs under 60 ℃ of condition of water bath heating, dehydrated alcohol is removed in evaporation, put and be chilled to room temperature, dry 5h in 50 ℃ of vacuum drying ovens takes out and pulverizes again, cross 80 mesh sieves, be stored in the exsiccator standby.
2) preparation of substrate: according to above-mentioned prescription consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol (can stay the solvent of a little glycerol as step 3), propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 25 ℃ of water bath condition, the HPMC of glue form of PVA, 2wt% of glue form that adds glue form PVP, the 5wt% of polyacrylic acid, 5wt% again, stir, obtain substrate.
3) preparation of pastille glue: after curcumin solid dispersion disperseed with an amount of solvent (water or glycerol) dissolving, be added in the substrate, add remaining water, stir, the ultrasonic degas bubble obtains pastille glue.
4) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 60 ℃ of dry about 0.5h, loam cake cellophane protective layer cuts promptly.
[embodiment 4] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.4 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?1.0 | Active component |
| Mannitol | ?3.0 | The solid dispersion material |
| Polyacrylic acid | ?5.0 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.3 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.1 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.1 | Substrate, adhesive |
| Glycerol | ?35 | Substrate, wetting agent |
| Propylene glycol | ?10 | Substrate, wetting agent |
| Polyethylene Glycol | ?10 | Substrate, wetting agent |
| Aluminium hydroxide | ?0.1 | Substrate, cross-linking agent |
| Water | ?35.0 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of curcumin solid dispersion: according to above-mentioned consumption proportion, curcumin is dissolved in an amount of dehydrated alcohol, add mannitol, fully stir under 60 ℃ of condition of water bath heating, dehydrated alcohol is removed in evaporation, puts and is chilled to room temperature, dry 5h in 50 ℃ of vacuum drying ovens again, take out and pulverize, cross 80 mesh sieves, be stored in the exsiccator standby.
2) preparation of substrate: according to above-mentioned consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol, propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 30 ℃ of water bath condition, the HPMC of glue form of PVA, 1wt% of glue form of PVP, 6wt% that adds the glue form of polyacrylic acid, 5wt% again, stir, obtain substrate.
3) preparation of pastille glue: after curcumin solid dispersion disperseed with an amount of solvent (water or glycerol) dissolving, be added in the substrate, add remaining water, stir, the ultrasonic degas bubble obtains pastille glue.
4) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 40 ℃ of down dry about 3.0h, loam cake cellophane protective layer cuts promptly.
[embodiment 5] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.2 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?1.5 | Active component |
| Polyethylene glycol 6000 | ?2.0 | The solid dispersion material |
| Polyacrylic acid | ?3.5 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.1 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.3 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.3 | Substrate, adhesive |
| Glycerol | ?20 | Substrate, wetting agent |
| Propylene glycol | ?5 | Substrate, wetting agent |
| Polyethylene Glycol | ?15 | Substrate, wetting agent |
| Oleum menthae | ?1.0 | Substrate, penetrating agent |
| Borneolum Syntheticum | ?0.5 | Substrate, penetrating agent |
| Aluminium hydroxide | ?0.1 | Substrate, cross-linking agent |
| Water | ?50.5 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of curcumin solid dispersion: according to above-mentioned consumption proportion, curcumin is dissolved in an amount of dehydrated alcohol, add polyethylene glycol 6000, fully stir under 60 ℃ of condition of water bath heating, dehydrated alcohol is removed in evaporation, puts and is chilled to room temperature, dry 5h in 50 ℃ of vacuum drying ovens again, take out and pulverize, cross 80 mesh sieves, be stored in the exsiccator standby.
2) preparation of substrate: according to above-mentioned consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol, propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 30 ℃ of water bath condition, the HPMC of glue form of PVA, 3.5wt% of glue form of PVP, 8wt% that adds the glue form of polyacrylic acid, 5wt% again, Oleum menthae, Borneolum Syntheticum, stir, obtain substrate.
3) preparation of pastille glue: after curcumin solid dispersion disperseed with an amount of solvent (water or glycerol) dissolving, be added in the substrate, add remaining water, stir, the ultrasonic degas bubble obtains pastille glue.
4) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 40 ℃ of down dry about 3.0h, loam cake cellophane protective layer cuts promptly.
[embodiment 6] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.5 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?2.0 | Active component |
| Poloxamer 188 | ?5.0 | The solid dispersion material |
| Polyacrylic acid | ?4.5 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.2 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.2 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.2 | Substrate, adhesive |
| Glycerol | ?30.0 | Substrate, wetting agent |
| Propylene glycol | ?5.0 | Substrate, wetting agent |
| Polyethylene Glycol | ?5.0 | Substrate, wetting agent |
| HP- | ?0.5 | Substrate, penetrating agent |
| Olive oil | ?0.5 | Substrate, penetrating agent |
| Aluminium hydroxide | ?0.2 | Substrate, cross-linking agent |
| Water | ?46.2 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of curcumin solid dispersion: according to above-mentioned consumption proportion, curcumin is dissolved in an amount of dehydrated alcohol, add polyethylene glycol 6000, fully stir under 60 ℃ of condition of water bath heating, dehydrated alcohol is removed in evaporation, puts and is chilled to room temperature, dry 5h in 50 ℃ of vacuum drying ovens again, take out and pulverize, cross 80 mesh sieves, be stored in the exsiccator standby.
2) preparation of substrate: according to above-mentioned consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol, propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 25 ℃ of water bath condition, HPMC, HP-, the olive oil of glue form of PVA, 1wt% of glue form of PVP, 6wt% that adds the glue form of polyacrylic acid, 5wt% again, stir, obtain substrate.
3) preparation of pastille glue: after curcumin solid dispersion disperseed with an amount of solvent (water or glycerol) dissolving, be added in the substrate, add remaining water, stir, the ultrasonic degas bubble obtains pastille glue.
4) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 50 ℃ of down dry about 2.0h, loam cake cellophane protective layer cuts promptly.
[embodiment 7] preparation contains the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Prescription:
| Component | Consumption (g) | Effect |
| Curcumin | ?0.3 | Active component |
| Pseudobulbus Bletillae (Rhizoma Bletillae) glue | ?1.5 | Active component, adhesive |
| Polyacrylic acid | ?3.0 | Framework material, adhesive |
| Polyvinylpyrrolidone (PVP) | ?0.6 | Substrate, adhesive |
| Polyvinyl alcohol (PVA) | ?0.3 | Substrate, adhesive |
| Hypromellose (HPMC) | ?0.3 | Substrate, adhesive |
| Glycerol | ?20.0 | Substrate, wetting agent |
| Propylene glycol | ?10.0 | Substrate, wetting agent |
| Polyethylene Glycol | ?10.0 | Substrate, wetting agent |
| Oleum menthae | ?1.0 | Substrate, penetrating agent |
| Aluminium hydroxide | ?0.2 | Substrate, cross-linking agent |
| Water | ?52.8 | Substrate |
| Amount to | ?100 |
Preparation method:
1) preparation of substrate: according to above-mentioned consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, glycerol, propylene glycol, Polyethylene Glycol, aluminium hydroxide are stirred under 30 ℃ of water bath condition, the HPMC of glue form of PVA, 1wt% of glue form of PVP, 6wt% that adds the glue form of polyacrylic acid, Oleum menthae, 5wt% again, stir, obtain substrate.
2) preparation of pastille glue: after curcumin disperseed with the dissolving of suitable quantity of water or glycerol, be added in the substrate, add remaining water, stir, the ultrasonic degas bubble obtains pastille glue.
3) preparation of gel adhesive: pastille glue is applied on the medical adhesive-bonded fabric, and in 50 ℃ of down dry about 2.0h, loam cake cellophane protective layer cuts promptly.
The recruitment evaluation of [embodiment 8] gel adhesive
1, extracorporeal releasing experiment (Chinese Pharmacopoeia 2005 editions, two appendix XD, the three therapeutic methods of traditional Chinese medicine)
The gel adhesive of getting embodiment 1,2,3 is denoted as sample A, B and C, throws off protective layer and is fixed between the two-layer video disc, and emission surface up.As accepting medium, accepting medium temperature is 32 ± 0.5 ℃ with 30% ethanol-normal saline solution, and accepting the medium volume is 200mL, and mixing speed is 100rmin
-1In experiment beginning back sampling, behind 0.45 μ m filtering with microporous membrane, after each sampling, add the blank acceptable solution of isothermal.Calculate the cumulative release amount of each time period by the analysis result of each sample point.Each time point drug accumulation discharges percentage rate Q and is listed in the table below 1.With time t each point cumulative release percentage rate Q is figure, obtains the release in vitro curve, as shown in Figure 1.
Table 1 contains the extracorporeal releasing experiment result (n=6) of the gel adhesive of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
2, the transdermal performance is investigated
The gel adhesive of getting embodiment 1,2,3 is denoted as sample A, B and C, carries out the transdermal test.
Adopt the Franze diffusion cell of improvement, device transdermal area is 1.766cm
2, the volume of accepting the pond is 17mL, ON cycle water-bath, 32 ± 1 ℃ of constant temperature.Get mouse skin and be fixed on and accept between pond and the supply pool, patch is cut into suitable size, be affixed on the above-mentioned synthetic membrane, accept the pond with the normal saline of 30% dehydrated alcohol for accepting medium, make itself and contact skin.It is closely fixing to accept pond and supply chamber, drains bubble, adds stirrer with 150rmin
-1Speed stir, respectively at 1,2,4,6,8,12,20, the 32h 3mL that take a sample from accept the pond places test tube, need further dilute with constant temperature (32 ℃) acceptable solution by the patch of solid dispersion making, add 32 ℃ of acceptable solution 3mL simultaneously.Measure absorbance in the 425nm place, substitution regression equation calculation concentration, and try to achieve unit are accumulative total infiltration capacity according to following formula, Q=(CnVn+ ∑ CiVi)/S, wherein Cn is the concentration of n sub-sampling, and Vn is the volume of n sub-sampling, and Ci is the concentration of i sub-sampling, Vi is the volume of i sub-sampling, and S is the transdermal area.To time (t) mapping, obtain equation with unit are accumulative total infiltration capacity (Qr), calculate percutaneous rate Js.
The accumulation transdermal amount Q of each time point t is as shown in table 2 below in each gel adhesive.With the time (t) to the accumulation transdermal amount (Qr) mapping, obtain the release in vitro curve, see Fig. 2.With time t
1/2To each point accumulation transdermal amount Q mapping, see Fig. 3.Unit are accumulative total infiltration capacity (Qr)-t curve is pressed zero level Q-t and Higuchi equation Q-t respectively
1/2Carry out the model match, calculate infiltration rate, the results are shown in Table 3.
Table 2 contains the gel adhesive transdermal test in vitro experimental result (n=6) of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
Table 3 contains the gel adhesive model The regression equation of curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue
| Prescription | The zero level equation | R 2 | Js/μg.cm -2.h -1 | The Higuchi equation | R 2 | Js/μg.cm -2.h -1 |
| A | Q＝1.189t+1.819 | 0.9828 | 1.189 | ?Q＝66.269t 1/2-0.444 | 0.9697 | 66.269 |
| B | Q＝3.999t+31.391 | 0.8813 | 3.999 | ?Q＝28.33t 1/2-8.638 | 0.9721 | 28.33 |
| C | Q＝9.075t+96.907 | 0.7898 | 9.075 | ?Q＝7.978t 1/2-8.769 | 0.9231 | 7.987 |
From The above results as can be seen, gel adhesive of the present invention can reach more than 93% at the 2h medicine realeasing rate; Drug accumulation transdermal amount reaches 40 μ gcm
-2More than, accumulation transdermal amount reached 347 μ gcm after medication preparation became solid dispersion
-2, significantly improve the accumulation transdermal amount of medicine.Said preparation can be stablized administration in 32h.
Gel adhesive of the present invention can be cut into suitable size in clinical practice, every subsides contain different sizes such as curcumin 10mg, 20mg, and each one pastes the external application affected part.
More than be that description to preferred embodiment of the present invention does not limit the present invention, those skilled in the art can make various changes and distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the category of claims of the present invention.
Claims (9)
1. a gel adhesive that contains curcumin and Pseudobulbus Bletillae (Rhizoma Bletillae) glue is characterized in that, comprises the component of following weight proportion:
Curcumin 0.2～0.5 Pseudobulbus Bletillae (Rhizoma Bletillae) glue 1.0～2.5 framework materials 2.0～5.0
Adhesive 0.4～1.4 wetting agent 25.0～65.0 cross-linking agent 0.1～0.2
Solid dispersion material 0～5.0 penetrating agent 0～1.5 water 35.0～58.0
Wherein said framework material is a polyacrylic acid; Described adhesive is to be selected from polyvinylpyrrolidone, hypromellose, starch, polyvinyl alcohol, gelatin, arabic gum, the Polyethylene Glycol one or more; Described wetting agent is to be selected from glycerol, propylene glycol, sorbitol, Polyethylene Glycol, ethylene glycol, the 1,3 butylene glycol one or more; Described cross-linking agent is an aluminium hydroxide; Described solid dispersion material is to be selected from polyvinylpyrrolidone, hypromellose, chitosan, mannitol, Polyethylene Glycol, the poloxamer one or more; Described penetrating agent is to be selected from HP-, Borneolum Syntheticum, Oleum menthae, olive oil, the carbamide one or more.
2. gel adhesive as claimed in claim 1 is characterized in that, described gel adhesive comprises the component of following weight proportion:
3. gel adhesive as claimed in claim 1 is characterized in that, described Pseudobulbus Bletillae (Rhizoma Bletillae) glue is to prepare by the following method: will add in the distilled water of 10～12 times of volumes after the 1 weight portion Pseudobulbus Bletillae (Rhizoma Bletillae) pulverizing medicinal materials, be heated to 50 ℃ and stirred 1 hour, filter, collect extracting solution; The medicinal residues distilled water that adds 5～6 times of volumes respectively repeats to extract 1～3 time then; Merge extractive liquid, is concentrated into half volume, adds 95% ethanol and regulates ethanol mass concentration to 70%, separates out precipitation, and centrifugal, collecting precipitation is used washing with alcohol, in 80 ℃ of dryings, obtains Pseudobulbus Bletillae (Rhizoma Bletillae) glue.
4. gel adhesive as claimed in claim 1 is characterized in that, described gel adhesive comprises the component of following weight proportion:
Curcumin 0.4, Pseudobulbus Bletillae (Rhizoma Bletillae) glue 2.5, polyacrylic acid 3.0, polyvinylpyrrolidone 0.8, polyvinyl alcohol 0.3 hypromellose 0.2, glycerol 15.0, propylene glycol 15.0, Polyethylene Glycol 5.0, aluminium hydroxide 0.1, water 57.7.
5. gel adhesive as claimed in claim 1 is characterized in that, described gel adhesive comprises the component of following weight proportion:
Curcumin 0.4, Pseudobulbus Bletillae (Rhizoma Bletillae) glue 2.0, polyacrylic acid 4.0, polyvinylpyrrolidone 0.6, polyvinyl alcohol 0.1, hypromellose 0.3, glycerol 25.0, propylene glycol 15.0, Polyethylene Glycol 10.0, aluminium hydroxide 0.2, polyvinylpyrrolidone k-304.0, water 38.4.
6. gel adhesive as claimed in claim 1 is characterized in that, described gel adhesive comprises the component of following weight proportion:
Curcumin 0.4, Pseudobulbus Bletillae (Rhizoma Bletillae) glue 1.0, polyacrylic acid 5.0, polyvinylpyrrolidone 0.3, polyvinyl alcohol 0.1, hypromellose 0.1, glycerol 35.0, propylene glycol 10.0, Polyethylene Glycol 10.0, aluminium hydroxide 0.1, mannitol 3.0, water 35.0.
7. method for preparing the described gel adhesive of claim 1 comprises step:
1) preparation of curcumin solid dispersion: according to the prescription consumption proportion, curcumin is dissolved in an amount of organic solvent dehydrated alcohol or the acetone, with the solid dispersion material mixing, fully stir under 60 ℃ of condition of water bath heating, organic solvent is removed in evaporation, puts and is chilled to room temperature, dry 5h in 45～55 ℃ of vacuum drying ovens again, take out and pulverize, sieve, promptly;
2) preparation of substrate: according to the prescription consumption proportion, Pseudobulbus Bletillae (Rhizoma Bletillae) glue, wetting agent, cross-linking agent are stirred under 25 ℃～35 ℃ water bath condition, add framework material, adhesive, penetrating agent then, fully stir, promptly;
3) preparation of pastille glue: according to the prescription consumption proportion, be added in the substrate after the curcumin solid dispersion of curcumin or step 1) preparation disperseed with suitable quantity of water or glycerol dissolving, add remaining water, stir, de-bubbled, promptly;
4) preparation of gel adhesive: pastille glue is applied on the backing layer, and in 40～60 ℃ of down dry 0.5～3.5h, the loam cake protective layer cuts, promptly.
8. method as claimed in claim 7 is characterized in that, described step 2) in adhesive be to add with the aqueous solution form of 0.5～10wt%.
9. method as claimed in claim 8, it is characterized in that, described step 2) adhesive is selected from polyvinylpyrrolidone, polyvinyl alcohol and hypromellose in, and polyvinylpyrrolidone is to add with the aqueous solution form of 1.5～8.5wt%, polyvinyl alcohol is to add with the aqueous solution form of 1.5～9.5wt%, and hypromellose is to add with the aqueous solution form of 0.5～3.5wt%.
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