CN110693935A - Garcinia entrapped transdermal patch containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and self-adhesive matrix and preparation method thereof - Google Patents
Garcinia entrapped transdermal patch containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and self-adhesive matrix and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a self-adhesive matrix transdermal patch carrying gamboge and containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and a preparation method thereof. The gamboge is coated by the oil-water amphiphilic matrix with the low-melting-point self-adhesive property, and the patch has the advantages of excellent drug transdermal performance, good adhesive performance, high drug loading capacity, good air permeability, no residue after being stripped from skin and the like. The self-adhesive matrix transdermal patch containing the compound obtained by fermenting the Chinese medicinal starch and the fatty oleic acid, which entraps the gamboges, has the characteristics of simple preparation process, no environmental pollution and organic matter residue, good medicament dispersibility, good stability, no skin irritation, high production efficiency, low cost and the like.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a gamboge-loaded transdermal patch containing a self-adhesive matrix of a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and a preparation method thereof.
Background
Gamboge is a common traditional Chinese medicine with the effects of diminishing swelling, counteracting toxic substances, removing putrefaction and healing sores, has small toxicity, is commonly used for treating diseases such as abdominal mass accumulation, tumors and the like, has poor water solubility and stability of main active ingredients of gambogic acid and neogambogic acid, is clinically commonly used as tablets, capsules, oral liquid and granules, particularly gambogic acid injection prepared by dissolving borax solution, and is still difficult to overcome the problems of stability, safety and the like. Topical administration is a good choice for attenuation, and the development focus is on finding a suitable matrix to improve its stability and dispersibility.
The traditional Chinese medicines such as the kudzuvine root, the Mongolian snakegourd root, the turmeric root-tuber and the like contain abundant starch, however, modern researches are more focused on small molecules such as puerarin, volatile oil and the like, and the starch is usually discarded after the small molecules are extracted as the main component of the medicinal materials, so that the waste of resources is caused. Similarly, seed herbs such as nux vomica and toosendan fruit are rich in fatty oleic acid, but more attention is paid to components such as strychnine and strychnine, and fatty oleic acid components are often discarded. Therefore, the traditional Chinese medicine starch and the traditional Chinese medicine fatty oleic acid are used as matrixes of external preparations for research and development, and the method has important significance for effective utilization of traditional Chinese medicine resources.
According to the research, an internal hydrophobic group and an external hydrophilic group in the traditional Chinese medicine starch are utilized to form a starch-fatty oleic acid compound with a hydrophobic group of traditional Chinese medicine fatty oleic acid under special process conditions. The compound has a larger hydrophobic cavity and stronger hydrophilic property, is a self-adhesive amphiphilic component, and has the characteristics of higher dissociation temperature and higher enzymolysis resistance. Therefore, the compound can be used for preparing a gamboge-loaded transdermal patch, so as to solve the existing problems, and research results show that the patch has good drug-forming property no matter analyzed from multiple angles of adhesiveness, dispersity, irritation, stability and the like. The research is original innovation, and no similar research report exists at present.
Disclosure of Invention
The invention aims to provide a self-adhesive matrix transdermal patch which is wrapped with gamboge and contains a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and a preparation method thereof, so as to overcome the defects in the prior art.
Specifically, the invention provides a drug-loaded self-adhesive matrix containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid, and the matrix has self-adhesion and amphipathy.
The self-adhesive matrix of the compound containing traditional Chinese medicine starch and fatty oleic acid for loading medicine is composed of the following components in percentage by weight:
1-10% of gamboge;
90-99% of amphiphilic matrix with self-adhesive property;
preferably, the self-adhesive matrix of the drug-loaded compound obtained by fermenting starch containing traditional Chinese medicines and fatty oleic acid comprises the following components in percentage by weight:
2-6% of gamboge;
94-98% of self-adhesive amphiphilic matrix;
the drug-loaded self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid is prepared by fermenting the following components in parts by weight:
preferably, the drug-loaded self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid is prepared by fermenting the following components in parts by weight:
the melting point of the matrix is 80-100 ℃, the matrix is semisolid at normal temperature and liquid at high temperature.
The Chinese medicinal starch is selected from one or more of radix Puerariae starch, Trichosanthis radix, radix Isatidis starch, radix Curcumae starch, and rhizoma Alpiniae Officinarum starch;
preferably, the traditional Chinese medicine starch is kudzu root starch and turmeric starch, and the weight ratio of the kudzu root starch: tulip starch 1:1-1:3
The traditional Chinese medicine starch is a key component influencing initial adhesion and hydrophilicity of the matrix, provides adhesion to skin, is insoluble in water, is gelatinized, swelled and thickened after fermentation, and can form a compound with prototype hydroxyl and organic acid to form a cross-linked network structure, so that the internal space of a hydrophobic group is increased, the matrix has higher drug loading capacity, and initial adhesion and peel strength are generated.
The traditional Chinese medicine fatty oleic acid is selected from one or more of chinaberry fruit, sophora alopecuroide, fructus broussonetiae, stramonium seed, cocklebur fruit, szechwan chinaberry fruit or nux vomica and the like; compared with the chinaberry fruit fatty oleic acid and the sophora alopecuroide fatty oleic acid, the chinaberry fruit fatty oleic acid has the advantages of high acid value and good forming rate; the nux vomica fatty oleic acid has the advantages of high acid value, high oil content and the like, has good compatibility with traditional Chinese medicine starch, provides adhesion and simultaneously increases drug-loading capacity, and therefore, the nux vomica fatty oleic acid and the toosendan fruit fatty oleic acid are preferably used in combination, and the preferable weight ratio is 1:1-1: 3;
the dosage of the traditional Chinese medicine fatty oleic acid is 7-15 parts, preferably 9-12 parts, if the dosage is too small, the viscosity of the matrix is too large, the plaster is difficult to tear off during the medication period, and the gamboge is difficult to release; if the amount is too large, the viscosity of the matrix is insufficient and the prepared transdermal patch cannot adhere to the skin.
The liquid solvent is low-viscosity liquid at normal temperature, can reduce cohesive strength of traditional Chinese medicine starch, thicken traditional Chinese medicine polysaccharide, provide fermentation reaction environment, facilitate formation of cross-linked network structure, and improve softness and initial viscosity of matrix, thereby facilitating coating. The main liquid solvents which can be selected comprise honey, yellow wine, rice vinegar, starch slurry, water and the like, the cost of the honey and the water is low, and the skin irritation is small, so the honey and the water are preferably used as the main liquid solvents, and the preferred weight ratio is that the honey: water is 1:0.5-1:1, the dosage of the main liquid solvent is 40-100 parts, preferably 60-100 parts, if the dosage of the main liquid solvent is too small, the adhesion of the patch is poor; if the dosage of the main liquid solvent is too much, the polymerization force of the matrix layer is obviously reduced, and the moldability is seriously influenced.
The dry yeast mainly provides matrix swelling degree, and has the effect of promoting chemical reaction between traditional Chinese medicine starch and traditional Chinese medicine fatty oleic acid. The dry yeast may be used in an amount of 2 to 5 parts, preferably 3 to 4 parts. The use amount of a plurality of yeasts is too small, the consistency of the substrate is poor, and the semi-solid state of the substrate cannot be ensured; the use amount of a plurality of yeasts is too much, the acidity of the substrate is too strong, the irritation is strong, and the comfort is poor when the patch is applied.
The invention also aims to provide a preparation method of the medicine-carrying self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid, which comprises the following steps:
(1) extracting root or rhizome of Chinese medicinal materials rich in starch, drying the extract residue insoluble in 60% ethanol under reduced pressure, and pulverizing to obtain Chinese medicinal starch;
(2) drying seed traditional Chinese medicines, crushing, and cold pressing to obtain traditional Chinese medicine fatty oleic acid;
(3) mixing Chinese medicinal starch, Chinese medicinal fatty acid, liquid solvent and dry yeast, sealing at 30 deg.C for 2-5 hr, adding resina Garciniae, mixing, and sealing at 30 deg.C for 1-2 hr to obtain matrix containing medicine; the substrate has lower softening point and coating temperature and good adhesion performance.
In the preparation method of the amphiphilic matrix with self-adhesion, an organic solvent is not used, so that the environmental pollution can be avoided, and the preparation method has the characteristics of energy conservation and environmental protection. In the preparation process, the formation of a compound between the traditional Chinese medicine starch and the fatty oleic acid is promoted by isolating air and fermentation reaction, so that the phase separation phenomenon is avoided.
The invention also aims to provide a self-adhesive matrix transdermal patch containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and carrying gamboges, which comprises a back lining layer, a module layer, a medicine-carrying self-adhesive matrix layer containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and a protective layer; the module layer covers one side of the self-adhesive matrix layer of the compound containing the traditional Chinese medicine starch and the fatty oleic acid obtained through fermentation of the medicine, and consists of a medical rubber ring, and the protective layer covers the other side of the self-adhesive matrix layer of the compound containing the traditional Chinese medicine starch and the fatty oleic acid obtained through fermentation of the medicine;
the material of the self-adhesive matrix layer of the drug-loaded compound obtained by fermenting the starch containing the traditional Chinese medicine and the fatty oleic acid is the self-adhesive matrix of the drug-loaded compound obtained by fermenting the starch containing the traditional Chinese medicine and the fatty oleic acid.
The invention also provides a preparation method of the self-adhesive substrate transdermal patch which is wrapped with gamboge and contains the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid, and the preparation method comprises the following steps:
(1) extracting root or rhizome of Chinese medicinal materials rich in starch, drying the extract residue insoluble in 60% ethanol under reduced pressure, and pulverizing to obtain Chinese medicinal starch;
(2) drying seed traditional Chinese medicines, crushing and cold pressing to obtain traditional Chinese medicine fatty oleic acid;
(3) mixing traditional Chinese medicine starch, traditional Chinese medicine fatty oleic acid, liquid solvent and dry yeast uniformly, sealing for 2-5h at 30 ℃, adding gamboge, mixing uniformly, sealing for 1-2h at 30 ℃ to prepare self-adhesive matrix which is wrapped with gamboge and contains a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid;
(4) heating the medicated matrix to 70-80 deg.C, pouring into a medical rubber ring with a back lining layer, drying under reduced pressure for 2-5 hr, covering with a protective layer, and packaging to obtain self-adhesive transdermal patch containing garcinia cambogia and containing compound obtained by fermenting Chinese medicinal starch and fatty oleic acid.
When the gamboge-loaded transdermal patch is used, the gamboge-loaded transdermal patch can be attached to the affected part or acupuncture point skin of a patient 1 time per day, 1 patch each time, and the area is 30-60cm2It is preferable.
As gamboge is a compound with strong lipid solubility, has toxicity and poor stability, the invention prepares the gamboge into a transdermal drug delivery preparation, so that the drug is released at the affected part, the burden of the liver and the kidney is reduced, and the safety is good. The patch can be used for 7 days, stably prolongs the release of main drug gamboge, and has long-term storage stability, excellent skin safety and suitable adhesion performance.
The invention has the advantages of
The gamboge is coated by the oil-water amphiphilic matrix with the low-melting-point self-adhesive property, and the patch has the advantages of excellent drug transdermal performance, good adhesive performance, high drug loading capacity, good air permeability and no residue after being stripped from the skin. The self-adhesive matrix transdermal patch containing the compound obtained by fermenting the Chinese medicinal starch and the fatty oleic acid, which entraps the gamboges, has the characteristics of simple preparation process, no environmental pollution and organic matter residue, good medicament dispersibility, good stability, no skin irritation, high production efficiency and low cost.
Drawings
Fig. 1 and 2: gambogic acid cumulative release profile;
FIG. 3: the unit area of gambogic acid is accumulated to pass through.
Detailed Description
Example 1
Preparation of amphiphilic matrix with self-adhesive properties:
cleaning fresh radix Puerariae, cutting, squeezing, homogenizing, filtering, standing for 1-2 hr, and removing supernatant. Washing and soaking the starch layer with 60% ethanol until the supernatant is colorless, suspending the starch layer with water, centrifuging to obtain white starch layer, drying, and pulverizing;
drying, crushing and cold-pressing semen Strychni to obtain semen Strychni fatty acid;
taking 100g of kudzu root starch, 14g of nux vomica fatty oleic acid, 380g of honey, 100g of water and 2g of dry yeast, continuously and rapidly stirring, uniformly mixing, sealing for 2-5h at 30 ℃, adding 20g of gamboge, uniformly mixing, and sealing for 1-2h at 30 ℃ until uniform yellow transparent colloid is formed, thus obtaining the composition.
The resulting amphiphilic matrix with self-adhesive properties was determined to have a melting point of 67 ℃.
Example 2
Preparation of amphiphilic matrix with self-adhesive properties:
extracting Curcuma rhizome or rhizome, drying the extract residue insoluble in 60% ethanol under reduced pressure, and pulverizing to obtain Curcuma rhizome starch;
drying fructus Toosendan, crushing, and cold pressing to obtain fructus Toosendan fatty acid;
100g of turmeric starch, 15g of szechwan chinaberry fruit fatty oleic acid, 150g of honey and 2g of dry yeast are uniformly mixed, the mixture is sealed for 2-5h at the temperature of 30 ℃, 20g of gamboge is added, the mixture is uniformly mixed, and the mixture is sealed for 1-2h at the temperature of 30 ℃ to prepare a medicine-containing matrix which has lower softening point and coating temperature and good adhesion performance.
The melting point of the prepared amphiphilic matrix with the self-adhesive property is determined to be 58 ℃.
Example 3
Preparing a common matrix without dry yeast fermentation for the traditional Chinese medicine starch and the fatty oleic acid:
cleaning fresh radix Puerariae, cutting, squeezing, homogenizing, filtering, standing for 1-2 hr, and removing supernatant. Washing and soaking the starch layer with 60% ethanol until the supernatant is colorless, suspending the starch layer with water, centrifuging to obtain white starch layer, drying, and pulverizing;
drying, crushing and cold-pressing semen strychni to obtain semen strychni fatty oleic acid for later use;
taking 100g of kudzu root starch, 14g of nux vomica fatty oleic acid, 380g of honey and 100g of water, continuously and rapidly stirring, uniformly mixing, sealing at 30 ℃ for 2-5h, adding 20g of gamboge, uniformly mixing, sealing at 30 ℃ for 1-2h to form uniform yellow transparent colloid, and thus obtaining the traditional Chinese medicine composition.
Example 4
Preparing a traditional Chinese medicine starch fermentation substrate:
cleaning fresh radix Puerariae, cutting, squeezing, homogenizing, filtering, standing for 1-2 hr, and removing supernatant. Washing and soaking the starch layer with 60% ethanol until the supernatant is colorless, suspending the starch layer with water, centrifuging to obtain white starch layer, drying, and pulverizing;
taking 100g of kudzu root starch, 380g of honey, 100g of water and 2g of dry yeast, continuously and rapidly stirring, uniformly mixing, sealing for 2-5h at 30 ℃, adding 20g of gamboge, uniformly mixing, and sealing for 1-2h at 30 ℃ until uniform light yellow transparent colloid is formed, thus obtaining the product.
Example 5
Preparing a traditional Chinese medicine fatty oleic acid fermentation substrate:
drying, crushing and cold-pressing semen strychni to obtain semen strychni fatty oleic acid for later use;
taking 14g of nux vomica fatty acid, 2g of dry yeast, 380g of honey and 100g of water, continuously and rapidly stirring, uniformly mixing, sealing at 30 ℃ for 2-5h, adding 20g of gamboge, uniformly mixing, and sealing at 30 ℃ for 1-2h to obtain the traditional Chinese medicine composition.
Example 6
The preparation of the self-adhesive matrix of the compound containing traditional Chinese medicine starch and fatty oleic acid fermentation with medicine loading comprises the following steps:
extracting Curcuma rhizome or rhizome, drying the extract residue insoluble in 60% ethanol under reduced pressure, and pulverizing to obtain Curcuma rhizome starch;
drying fructus Toosendan, crushing, and cold pressing to obtain fructus Toosendan fatty acid;
mixing 300g Curcuma rhizome starch, 45g fructus Toosendan fatty acid, 450g Mel and 6g dry yeast, sealing at 30 deg.C for 2-5 hr, adding resina Garciniae, mixing, and sealing at 30 deg.C for 1-2 hr to obtain matrix containing medicine.
Example 7: determination of the adhesive Properties
1. Measurement of initial adhesion: the initial adhesive force of the patch was measured using a probe method.
Removing the protective layer from the test patch, adhering to a clean test plate, and measuring the force with a force gauge probe at 300 mm/min-1The speed of the probe decreased and the probe was separated after 3 seconds of contact with the surface of the plaster, the maximum force of the probe when it left the surface of the plaster was recorded and measured 6 times in succession, the average was taken and the results are shown in table 1.
2. Measurement of permanent adhesion: the patch was attached to a vertically placed test plate and measured with a holding power measuring instrument.
The protective layer of the test article patch is removed, the test article patch is parallel to the longitudinal direction of the plate, the test article patch is stuck to the middle part of the clean stainless steel test plate and the stainless steel loading plate which are next to each other, and the patch is rolled back and forth once on the patch by a compression roller at the speed of (300 +/-10) mm/min, so that no bubble exists at the bonding part. Standing at room temperature for 20min, vertically fixing on a test rack, suspending a weight with a certain mass along the length direction of the patch, and recording the patch falling time. The measurements were performed 6 times in succession, and the average value was taken, and the experimental results are shown in Table 1.
3. Measurement of peel strength: the peel strength of the patch was measured using a 180 ° peel test.
Cutting the sample patch into size of 10cm × 2cm, removing the protective layer, sticking on clean stainless steel plate, adhering the adhesive layer of the patch to clean polyester film at the tail end, and rolling the patch with a press roller at 300 + -10 mm/min to ensure no bubble at the adhesive part. Standing at room temperature for 20-40min, respectively clamping the film and stainless steel plate on a peeling tester, continuously peeling at (300 + -10) mm/min, and recording peel strength of the patch. The measurements were performed 6 times in succession, and the average value was taken, and the experimental results are shown in Table 1.
TABLE 1 test results for various groups of different substrate adhesion properties
(note:. the expression has the significant effects of initial adhesion, permanent adhesion and peeling strength compared with the traditional Chinese medicine starch and fatty oleic acid unfermented substrate, p is less than 0.05
Difference in character)
Example 8: in vitro release assay
The Franz diffusion cell method was used, with the upper chamber being the diffusion chamber and the lower chamber being the receiving chamber. The prepared patch is taken off the protective layer, the module layer faces upwards, the medicine-containing surface faces downwards and is fixed on a receiving pool of a FranZ diffusion pool, and the upper half pool is covered and clamped by an iron clamp. The receiving cell was charged with a 60% ethanol solution of the release medium which had been degassed by ultrasound. Diffusion area of 3.14cm2The receiving volume is 7ml, the stirring speed is 250r/min, and the temperature of the receiving solution is controlled at (32 +/-0.5) DEG C. Taking out 5ml of release medium (simultaneously supplementing fresh release medium with the same temperature and the same amount) at 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 24h, 48h, 72h, 96h, 120h, 144h and 168h after the experiment is started, directly injecting sample to determine content of gambogic acid representing component, and calculating cumulative release rate Q%. Each set of experiments was performed in parallel 3 times. The cumulative release rate Q% of gambogic acid is shown in FIG. 1 and FIG. 2.
Example 9: in vitro transdermal test
Healthy nude mice weighing 18 +/-2 g are taken, bred for 24 hours, cleaned with normal saline on the skin surface, killed after neck breakage, stripped of the undamaged skin, carefully scraped of subcutaneous tissues and fat, cleaned with normal saline, and stored in a refrigerator at minus 20 ℃ for later use. The prepared skin is taken out during the experiment, naturally thawed and then soaked and washed for a plurality of times by using normal saline, the skin is fixed on a diffusion cell, the horny layer is upward, and 30% ethanol-normal saline is used as a receiving solution. Magnetic stirrers are arranged in the cell, the rotating speed is 300r/min, the area of the diffusion cell is 2cm2The total volume of the receiving pool is 7ml, water bath is carried out at the constant temperature of 37 +/-1 ℃, the balance is carried out for 30min, the receiving liquid is replaced, the air under the skin is exhausted, and the gauze sucks the liquid on the surface of the skin. Removing the protective layer from the prepared patch, precisely scraping 2g of the drug-containing matrix, and tightly applying on the skin of a nude mouse. 1ml of receiving liquid is sampled from the receiving pool at 24h, 48h, 72h, 96h, 120h, 144h and 168h respectively, and the receiving liquid with the same temperature and volume is supplemented. Filtering the sample with 0.45 μm microporous membrane, collecting filtrate, measuring gambogic acid content in the sample by HPLC, and calculating cumulative permeation (μ g/cm) per unit area at each time point2) The experiment was repeated 3 times, and the average value was used as the experimental result, which is shown in table 2 and fig. 3.
TABLE 2 results of different matrix patch in vitro transdermal tests with drug loaded gambogic acid
(Note: representing that when compared with the unfermented substrate of the traditional Chinese medicine starch and the fatty oleic acid, p is less than 0.05, and when the cumulative penetration per unit area is 24h, 48h, 72h, 96h, 120h, 144h and 168h, the cumulative penetration per unit area has significant difference compared with the unfermented substrate of the traditional Chinese medicine starch and the fatty oleic acid)
Example 10: stability test
1. Test method the transdermal patches carrying gamboge of examples 1-6 were stored at room temperature for 3 months and visually observed for the presence of crystal precipitation in appearance.
2. Test results the patches of examples 1-6 were observed to have crystal formation in example 3 and no crystal formation in the other groups, indicating that the fermentation process enhanced patch stability.
Example 11: skin irritation test
1. The test method comprises taking 6 healthy rabbits 2.8-3.0kg, dividing into intact skin group and damaged skin group, and depilating the back of the animal 24h before administration. The test drugs (patches of examples 1-2 and 4-6, 10cm each)2) And a control drug (patch of example 3, 10 cm)2) 5 pieces of each of the test and control drug areas (50 cm) are attached to the back of the animal2) Applied 1 time daily for 7 consecutive days. The residues were removed 24 hours after the last administration with warm water and physiological saline, and the erythema and edema at the application sites removed for 1 hour, 24 hours, 48 hours and 72 hours and the recovery of the above changes and time were observed, and the test results were evaluated for the stimulation response and the stimulation intensity.
2. Test results the patches of examples 1-2, 4-6 showed no irritation in both the intact skin group and the damaged skin group in the rabbit skin irritation test, and example 3 caused slight erythema and edema at the site of application.
Example 12: skin allergy test
1. The test method comprises the steps of taking 30 healthy guinea pigs of 250g-300g, and averagely dividing the healthy guinea pigs into three groups of 10 animals each with half of male and female animals. The guinea pigs were depilated 24h prior to dosing, either from the left (sensitized) or right (stimulated) side of the back, with hair removal ranging approximately 4X 4cm on each side. Group 1 Patch with test drug (Patches of examples 1-2, 4-6, 10 cm)2) Group 2, negative control drug patch (patch of example 3, 10 cm)2) Group 3 was pasted with 0.2ml of a 1% ethanol solution of 2, 4-dinitrochlorobenzene as a positive sensitizer on each side.
Sensitization, the test drug (Patch of examples 1-2, 4-6, 10 cm)2) Sticking on the outer layer of the left depilation region of animal, fixing with adhesive plaster, and removing the tested medicine after lasting for 6 hr. The same procedure was repeated on day 7 and day 14. Negative ofThe control (example 3) and positive control (2, 4-dinitrochlorobenzene) were performed in the same manner as the test drug group.
And (3) excitation, namely sticking the tested medicine to the outer layer of the right depilating area of the animal 14 days after the last sensitization, fixing the tested medicine by using a rubber plaster, removing the tested medicine after lasting for 6 hours, immediately observing, and then observing the skin anaphylactic reaction conditions again at 24 hours, 48 hours and 72 hours. The negative control (example 3) and the positive control (2, 4-dinitrochlorobenzene) were performed in the same manner as the test drug group.
The results of the test were evaluated for allergic response and allergic intensity.
2. As a result, the patches of examples 1 to 6 showed no significant allergic reaction in the guinea pig skin allergy test.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.
Claims (10)
1. A drug-loaded self-adhesive matrix containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid is characterized by comprising the following components in percentage by weight:
1-10% of gamboge;
the self-adhesive matrix of the compound obtained by fermenting the starch and the fatty acid of the traditional Chinese medicine is 90 to 99 percent.
2. The drug-loaded self-adhesive matrix containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid according to claim 1, which is characterized by comprising the following components in percentage by weight:
2-6% of gamboge;
94-98% of self-adhesive matrix containing a compound obtained by fermenting traditional Chinese medicine starch and fatty acid.
3. The drug-loaded self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid according to claim 1 or 2, which is characterized in that the self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid is prepared by fermenting the following components in parts by weight:
4. the drug-loaded self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid according to claim 3, which is characterized in that the self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid is prepared by fermenting the following components in parts by weight:
5. the self-adhesive matrix of the drug-loaded compound obtained by fermentation of starch and fatty oleic acid, according to claim 3, wherein the self-adhesive matrix of the drug-loaded compound obtained by fermentation of starch and fatty oleic acid has self-adhesive oil-water amphipathy, and the matrix has a melting point of 80-100 ℃, is semisolid at normal temperature and is liquid at high temperature.
6. The self-adhesive matrix of claim 3, wherein said loaded compound is selected from the group consisting of pueraria starch, trichosanthes root, isatis root starch, curcuma root starch, galangal rhizome starch;
the traditional Chinese medicine fatty oleic acid is selected from one or more of chinaberry fruit, sophora alopecuroide, fructus broussonetiae, stramonium seed, cocklebur fruit, szechwan chinaberry fruit or nux vomica;
the liquid solvent is selected from one or more of honey, yellow wine, rice vinegar, starch slurry and water.
7. The drug-loaded self-adhesive matrix containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty acid according to claim 6, wherein the traditional Chinese medicine starch is kudzu root starch and turmeric starch, and the weight ratio of the kudzu root starch: the tulip starch is 1:1-1: 3; the traditional Chinese medicine fatty oleic acid comprises nux vomica and szechwan chinaberry fruit, and the weight ratio of the nux vomica to the szechwan chinaberry fruit is as follows: fructus toosendan 1:0.5-1: 1; the liquid solvent comprises honey and water in a weight ratio of honey: water-1: 0.5-1: 1.
8. The drug-loaded self-adhesive matrix containing a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid according to claim 7, wherein the mass ratio of the traditional Chinese medicine starch to the fatty oleic acid is 2:1-3: 1.
9. A transdermal patch containing resina Garciniae self-adhesive matrix containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid is characterized by comprising a back lining layer, a module layer, a self-adhesive matrix layer carrying medicine containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid, and a protective layer; the module layer covers one side of the self-adhesive matrix layer of the compound containing the traditional Chinese medicine starch and the fatty oleic acid obtained through fermentation of the medicine, and consists of a medical rubber ring, and the protective layer covers the other side of the self-adhesive matrix layer of the compound containing the traditional Chinese medicine starch and the fatty oleic acid obtained through fermentation of the medicine;
the material of the self-adhesive matrix layer of the drug-loaded compound containing traditional Chinese medicine starch and fatty oleic acid is the self-adhesive matrix of the drug-loaded compound containing traditional Chinese medicine starch and fatty oleic acid according to any one of claims 1 to 8.
10. A method of making a self-adhesive matrix transdermal patch of gamboges entrapped in a complex obtained by fermentation of traditional Chinese medicine starch and fatty acids according to claim 9, comprising the steps of:
(1) extracting root or rhizome of Chinese medicinal materials rich in starch, drying the extract residue insoluble in 60% ethanol under reduced pressure, and pulverizing to obtain Chinese medicinal starch;
(2) drying seed traditional Chinese medicines, crushing and cold pressing to obtain traditional Chinese medicine fatty oleic acid;
(3) mixing traditional Chinese medicine starch, traditional Chinese medicine fatty oleic acid, liquid solvent and dry yeast uniformly, sealing for 2-5h at 30 ℃, adding gamboge, mixing uniformly, sealing for 1-2h at 30 ℃ to prepare self-adhesive matrix which is wrapped with gamboge and contains a compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid;
(4) heating the self-adhesive matrix carrying the medicine and containing the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid to 70-80 ℃, pouring the self-adhesive matrix into a medical rubber ring with a back lining layer while the self-adhesive matrix is hot, drying the self-adhesive matrix under reduced pressure for 2-5 hours, covering a protective layer, and packaging to obtain the gamboge-coated transdermal patch containing the self-adhesive matrix of the compound obtained by fermenting the traditional Chinese medicine starch and the fatty oleic acid.
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| CN201911041900.XA CN110693935A (en) | 2019-10-30 | 2019-10-30 | Garcinia entrapped transdermal patch containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and self-adhesive matrix and preparation method thereof |
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| CN201911041900.XA CN110693935A (en) | 2019-10-30 | 2019-10-30 | Garcinia entrapped transdermal patch containing compound obtained by fermenting traditional Chinese medicine starch and fatty oleic acid and self-adhesive matrix and preparation method thereof |
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| CN1473056A (en) * | 2000-10-02 | 2004-02-04 | ����Ī�����ɷ�����˾ | Self-adhesive wound dressing |
| CN102772417A (en) * | 2012-07-24 | 2012-11-14 | 上海现代药物制剂工程研究中心有限公司 | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof |
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- 2019-10-30 CN CN201911041900.XA patent/CN110693935A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1473056A (en) * | 2000-10-02 | 2004-02-04 | ����Ī�����ɷ�����˾ | Self-adhesive wound dressing |
| CN102772417A (en) * | 2012-07-24 | 2012-11-14 | 上海现代药物制剂工程研究中心有限公司 | Period effect percutaneous patch of self viscosity elastic body substrate containing testosterone and preparation method thereof |
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| 马建芳等: "透皮给药系统热熔压敏胶基质处方的优化与初步应用", 《中国医药工业杂志》 * |
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