Hydrophilic plaster matrix for improving drug loading capacity and application of hydrophilic plaster matrix

Abstract

The invention relates to the field of emplastrum, and particularly discloses a hydrophilic emplastrum matrix capable of improving drug loading capacity and application thereof.The emplastrum matrix is prepared from vaseline, a water locking agent, a thickening agent, glycerin, purified water, polyvinyl alcohol, a volatile oil compound and a transdermal absorbent, the different components are coordinated and proportioned, and the synergistic complementary effect is achieved; wherein firstly, the plastic colloid is prepared, the medicinal thickener is added, a grid structure can be formed, homogenization and high stability are achieved, then the treated flexible component containing the volatile oil compound is added, the ductility is improved, the preparation method is simple, the traditional Chinese medicine paste has multiple advantages when being applied to preparation of the paste, the drug loading capacity of traditional Chinese medicine powder is large, and the traditional Chinese medicine paste is free of irritation to human skin and free of toxic and side effects. And no colloid remains on the skin after the adhesive tape is torn off, and the adhesive tape is easy to produce.

Description

Technical Field

[0001] The invention relates to the field of plasters, and in particular to a hydrophilic plaster matrix with increased drug loading and application thereof. Background Art

[0002] A patch is a paste prepared by mixing drug raw materials with a matrix. It is applied to the skin to slowly release the drug to achieve local or systemic effects. A specific type is a gel patch, and its commonly used added matrices include sodium carboxymethyl cellulose, gelatin, sodium polyacrylate, glycerin, etc. The matrix containing the drug is applied on the cloth. The patch should be smooth and flat, without any delamination or loss of adhesion. The various raw materials of the matrix should be easy to mix and blend, and have a uniform color without drug aggregation.

[0003] Since the patch acts on the skin, the skin will shrink and stretch when the human body moves, so the matrix used needs to be elastic, sticky and plastic, that is, it has a stable internal structure that can load the drug well and can smoothly spread and fit on the skin, and it is not easily affected by sweat, friction and other factors and does not tear the skin excessively. However, it is difficult for the current matrix to have all the above characteristics. The patch loads the drug in the matrix. Chinese medicine is generally a mixture of multiple drugs, and a certain amount of medicine is required to be effective. The drug loading of the general matrix is ​​only about 40%, which is too little. It is difficult for the insufficient amount of drug to have good medicinal properties. Summary of the invention

[0004] In view of the above problems, the object of the present invention is to provide a hydrophilic patch matrix with increased drug loading and application thereof.

[0005] The technical contents of the present invention are as follows:

[0006] The present invention provides a hydrophilic plaster matrix for increasing drug loading, the components of which include vaseline, a water-locking agent, a thickener, glycerin, purified water, polyvinyl alcohol, a volatile oil complex and a transdermal absorbent;

[0007] The thickener includes one of a pharmaceutical grade partially neutralized sodium polyacrylate and a pharmaceutical modified thickener;

[0008] The hydrophilic patch matrix is ​​composed of the following raw materials in proportion by mass: 2-4 parts of vaseline, 1-2 parts of water-locking agent, 2-4 parts of thickener, 2-4 parts of glycerin, 9-11 parts of purified water, 1-2.5 parts of polypropylene alcohol, 0.1-0.3 parts of volatile oil complex and 0.2-0.4 parts of transdermal absorbent.

[0009] The preparation of the pharmaceutical modified thickener is to decompose the polymer compound, add it into a carboxylic acid ester organic solvent and stir it for 10-18 minutes; the polymer compound includes one of PEG-150 distearate, hydroxypropyl cellulose and lauroyl polyoxyethylene (12) glyceride;

[0010] The decomposition treatment is to add alkaline salt at a mass fraction of 40-50% of the polymer compound under stirring, first heating to 60-70°C and then reacting for 20-30 minutes;

[0011] The pharmaceutical modified thickener can form a hydrophilic gel skeleton by decomposing and increasing long-chain polar organic matter, improving surface micelle aggregation through hydrophobic and hydrogen bonding, and increasing carbon-carbon single bonds through nucleophilic addition to improve stability and water solubility;

[0012] The preparation of the volatile oil complex comprises: adding 10-16wt% cyclodextrin to plants for ball milling, stirring for 30-40min with a mixed solvent with a mass concentration of 10-20wt%, heating at a temperature of 60-70°C for 80-100min, and then separating and concentrating to obtain the volatile oil complex; the plants comprise at least one of cloves, evodia rutaecarpa, camphor, holly and eucalyptus leaves; the solvent comprises ethanol and polyethylene glycol in a volume ratio of 10:2-4; the volatile oil containing a large amount of sesquiterpenoid compounds and monoterpenoid compounds in the plants has a good penetration-promoting effect, is a lipophilic substance, can be adsorbed and extracted by cyclodextrin, the solvent can promote extraction and elution separation, the cyclodextrin reacts with polyethylene glycol to introduce a flexible chain amino group, the hydrophilicity is improved, and the cyclodextrin after the reaction is added to the matrix to increase the viscosity and ductility of the material through hydrogen bond cross-linking;

[0013] The transdermal absorbent is one of laurocapram and Tween-80;

[0014] The water-locking agent is Carbomer 940.

[0015] The present invention also provides an application of a hydrophilic plaster matrix with increased drug loading in the preparation of a plaster, comprising the following steps:

[0016] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into fine powder of 120-200 mesh;

[0017] Step 2: Preparation of hydrophilic patch: Prepare the Chinese medicine powder into a plastic colloid, treat the vaseline, volatile oil compound and transdermal absorbent, add them into the plastic colloid and stir evenly, apply them on the cloth, cover with a lining, and cut into pieces to obtain the finished product.

[0018] The plastic colloid is prepared by adding carbomer 940, polyvinyl alcohol, a thickener, glycerin and purified water to the traditional Chinese medicine powder, and stirring and mixing them evenly;

[0019] The treatment comprises grinding the raw materials and then heating them with microwaves at a temperature of 90-110°C;

[0020] Vaseline, volatile oil complex and transdermal absorbent are compounded and can reduce impurities after treatment. Microwave can improve flexibility and ductility. The volatile oil complex can improve the hydrophilicity of polar raw materials, shape and soften the matrix, improve tissue conductivity, has good lipophilicity, can open the polar pores of the stratum corneum, and has a good penetration effect.

[0021] The beneficial effects of the present invention are as follows:

[0022] The hydrophilic plaster matrix with improved drug loading of the present invention is prepared by mixing vaseline, a water-locking agent, a thickener, glycerin, purified water, polyvinyl alcohol, a volatile oil complex and a transdermal absorbent, has a synergistic and complementary effect, has a large drug loading capacity for Chinese medicine powder, can reach more than 60%, and can even reach 75%, and has significantly improved drug loading capacity compared with traditional matrices, is non-irritating to human skin, has good excipient properties, and has no colloid residue on the skin after being torn off;

[0023] The hydrophilic patch matrix provided by the present invention is used in preparing a patch, wherein a plastic colloid is first prepared, and a pharmaceutical-grade thickener is added to form a grid structure, which is homogeneous and highly stable, can well load drugs and has a low initial adhesion, and then a processed flexible component containing a composite volatile oil is added to increase its ductility and other mechanical properties. The preparation method is simple, has many advantages in the preparation of the patch, and is easy to produce. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 A hydrophilic patch was prepared according to Example 1. DETAILED DESCRIPTION

[0025] The present invention is further described in detail below through specific implementation cases. It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of protection of the present invention. After reading the present invention, various equivalent forms of modifications to the present invention by those skilled in the art are all within the scope of the claims attached to this application.

[0026] Unless otherwise specified, all raw materials and reagents of the present invention are raw materials and reagents from the conventional market.

[0027] Example 1

[0028] A hydrophilic patch

[0029] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 160 mesh fine powder;

[0030] Step 2: Preparation of hydrophilic patch: add 1.5 parts of Carbomer 940, 1.8 parts of polyvinyl alcohol, 3 parts of pharmaceutical grade partially neutralized sodium polyacrylate, 3 parts of glycerol and 10 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, add 3 parts of vaseline, 0.2 parts of volatile oil complex, 0.3 parts of laurocapron, grind evenly, microwave heat at 100°C, add the plastic colloid and stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0031] The volatile oil complex is prepared by mixing cloves and evodia rutaecarpa, adding 13wt% cyclodextrin, and then ball milling, and then mixing ethanol and polyethylene glycol with a mass concentration of 15wt% and a volume ratio of 10:2-4, stirring for 35 minutes, heating at a temperature of 65°C for 90 minutes, and then separating and concentrating to obtain;

[0032] The prepared plaster is as Figure 1 As shown, it can be seen that the paste is smooth and flat, and has strong shaping properties.

[0033] Example 2

[0034] A hydrophilic patch

[0035] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 120 mesh fine powder;

[0036] Step 2: Preparation of hydrophilic patch: add 1 part of Carbomer 940, 1 part of polyvinyl alcohol, 2 parts of medicinal modified thickener, 2 parts of glycerol and 9 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, grind 2 parts of vaseline, 0.1 parts of volatile oil complex and 0.2 parts of Tween-80, and then microwave heat at 90°C, add the plastic colloid and stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0037] The volatile oil complex is prepared by mixing holly and evodia rutaecarpa, adding 10wt% cyclodextrin, and then ball milling, and then mixing ethanol and polyethylene glycol with a mass concentration of 10wt% and a volume ratio of 10:3, stirring for 30 minutes, heating at a temperature of 60°C for 80 minutes, and then separating and concentrating to obtain;

[0038] The preparation of the modified medicinal thickener is to decompose PEG-150 distearate, wherein the decomposition treatment is to add PEG-150 distearate to a sodium carbonate solution with a mass fraction of 40% under stirring, first heating to 60° C. and then reacting for 20 minutes; then adding ethyl acetate and stirring for 10 minutes.

[0039] Example 3

[0040] A hydrophilic patch

[0041] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 200 mesh fine powder;

[0042] Step 2: Preparation of hydrophilic plaster: add 2 parts of Carbomer 940, 2.5 parts of polyvinyl alcohol, 4 parts of medicinal modified thickener, 4 parts of glycerol and 11 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, grind 4 parts of vaseline, 0.3 parts of volatile oil complex and 0.4 parts of laurocapram, and then heat in a microwave at a temperature of 110°C, add the plastic colloid and stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0043] The volatile oil complex is prepared by mixing eucalyptus leaves and camphor, adding 16wt% cyclodextrin, and ball milling, then mixing ethanol and polyethylene glycol with a volume ratio of 10:2 with a mass concentration of 20wt%, stirring for 40min, heating at a temperature of 70°C for 100min, and then separating and concentrating to obtain;

[0044] The preparation of the modified medicinal thickener is to decompose hydroxypropyl cellulose, wherein the decomposition treatment is to add hydroxypropyl cellulose to sodium carbonate at a mass fraction of 50% under stirring, first heating to 70° C. and reacting for 30 minutes; then adding ethyl acetate and stirring for 18 minutes.

[0045] Example 4

[0046] A hydrophilic patch

[0047] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 150 mesh fine powder;

[0048] Step 2: Preparation of hydrophilic patch: add 1 part of Carbomer 940, 2.5 parts of polyvinyl alcohol, 2 parts of medicinal modified thickener, 4 parts of glycerol and 9 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, grind 4 parts of vaseline, 0.1 parts of volatile oil complex and 0.3 parts of laurocapram, and then heat in a microwave at 95°C, add the plastic colloid and stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0049] The volatile oil complex is prepared by mixing cloves and holly, adding 11wt% cyclodextrin, and ball milling, then mixing ethanol and polyethylene glycol with a mass concentration of 10wt% and a volume ratio of 10:4, stirring for 40 minutes, heating at a temperature of 65°C for 85 minutes, and then separating and concentrating to obtain;

[0050] The preparation of the modified medicinal thickener is to decompose lauroyl polyoxyethylene (12) glyceride, wherein the decomposition treatment is to add sodium carbonate at a mass fraction of 45% of lauroyl polyoxyethylene (12) glyceride under stirring, first heating to 60° C. and reacting for 30 minutes; then adding ethyl acetate and stirring for 10 minutes.

[0051] Example 5

[0052] A hydrophilic patch

[0053] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 130 mesh fine powder;

[0054] Step 2: Preparation of hydrophilic plaster: add 2 parts of Carbomer 940, 1 part of polyvinyl alcohol, 4 parts of medicinal modified thickener, 2 parts of glycerol and 11 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, grind 2 parts of vaseline, 0.2 parts of volatile oil complex and 0.2 parts of Tween-80, heat in a microwave at 105°C, add the plastic colloid and stir evenly, apply on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0055] The volatile oil complex is prepared by mixing Evodia rutaecarpa and eucalyptus leaves, adding 15wt% cyclodextrin, and then ball milling, and then mixing ethanol and polyethylene glycol with a mass concentration of 20wt% and a volume ratio of 10:2, stirring for 30 minutes, heating at a temperature of 60°C for 95 minutes, and then separating and concentrating to obtain the volatile oil complex;

[0056] The preparation of the modified medicinal thickener is to decompose PEG-150 distearate, wherein the decomposition treatment is to add PEG-150 distearate to sodium carbonate at a mass fraction of 40% under stirring, first heating to 70° C. and reacting for 20 minutes; then adding ethyl acetate and stirring for 18 minutes.

[0057] Example 6

[0058] A hydrophilic patch

[0059] Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into 180 mesh fine powder;

[0060] Step 2: Preparation of hydrophilic plaster: add 2 parts of Carbomer 940, 1.5 parts of polyvinyl alcohol, 2 parts of medicinal modified thickener, 2 parts of glycerol and 10 parts of purified water to the Chinese medicine powder, stir and mix evenly to prepare a plastic colloid, grind 3 parts of vaseline, 0.3 parts of volatile oil complex and 0.2 parts of Tween-80, and then microwave heat at 100°C, add the plastic colloid and stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product;

[0061] The volatile oil complex is prepared by mixing camphor and Evodia rutaecarpa and adding 14wt% cyclodextrin for ball milling, then mixing ethanol and polyethylene glycol with a volume ratio of 10:3 with a mass concentration of 12wt% and stirring for 32 minutes, heating at a temperature of 70°C for 100 minutes, and then separating and concentrating to obtain;

[0062] The preparation of the modified medicinal thickener is to decompose hydroxypropyl cellulose, wherein the decomposition treatment is to add 40% by mass of sodium carbonate to hydroxypropyl cellulose under stirring, firstly heating to 60° C. and reacting for 30 minutes; and then adding ethyl acetate and stirring for 10 minutes.

[0063] Comparative Example 1,

[0064] The difference between Comparative Example 1 and Example 1 is that the thickener in Comparative Example 1 is food-grade sodium polyacrylate, and the rest remains unchanged.

[0065] Comparative Example 2

[0066] The difference between Comparative Example 2 and Example 2 is that the medicinal modified thickener of Comparative Example 2 does not modify the polymer compound, and directly adds PEG-150 distearate, while other contents remain unchanged.

[0067] Comparative Example 3

[0068] The difference between Comparative Example 3 and Example 1 is that in the preparation of the patch of Comparative Example 3, in step 2, the vaseline, volatile oil complex, and transdermal absorbent are not subjected to microwave heating treatment, but are directly stirred evenly, and the other ingredients remain unchanged.

[0069] Comparative Example 4

[0070] The difference between Comparative Example 4 and Example 1 is that no volatile oil complex is added in Comparative Example 4, and the other contents remain unchanged.

[0071] Comparative Example 5

[0072] The difference between Comparative Example 5 and Example 1 is that the volatile oil compound of Comparative Example 5 is cinnamon volatile oil, and the other components remain unchanged.

[0073] The difference between Comparative Example 6 and Example 1 is that sodium alginate is used instead of carbomer 940 in Comparative Example 6, and the other contents remain unchanged.

[0074] Comparative Example 7

[0075] The difference between Comparative Example 7 and Example 1 is that lanolin is used instead of vaseline in Comparative Example 7, and the other contents remain unchanged.

[0076] The properties of the hydrophilic patch matrix prepared in the examples and comparative examples were tested as follows. An electronic tensile testing machine was used to test the initial adhesion and sustained adhesion of the patch. The test standard was in accordance with YY / T 0148-2006 "General Requirements for Medical Adhesive Tapes". The coating performance scoring standard is shown in Table 1. The coating was performed using a coater, and the drug loading was detected by gel permeation chromatography. The performance test results are shown in Table 2.

[0077] Table 1 Ductility evaluation criteria

[0078]

[0079] Table 2 Properties of hydrophilic plaster matrix

[0080]

[0081]

[0082] As can be seen from Table 2 and Comparative Examples 1-2, the medicinal thickener used in the present invention is a medicinal partially neutralized sodium polyacrylate, or the polymer compound is modified to have a good micellar effect and a hydrophilic gel skeleton, which can also achieve the effect described in Example 1. Compared with other thickeners such as food-grade sodium polyacrylate, the loading capacity and coating performance of the matrix can be improved; as can be seen from Comparative Example 3, after microwave heating treatment, the active pharmaceutical ingredients can be precipitated and skin absorption can be promoted, while the elastic deformation ability of the matrix is ​​enhanced to improve the coating performance; as can be seen from Comparative Examples 4-7, the added volatile oil complex contains a stable plant penetration-promoting component and an amino-modified oligosaccharide that enhances the mechanical properties of the matrix, and is synergistically compounded with vaseline and a skin penetration-promoting agent to comprehensively improve the performance of the plaster matrix.

[0083] In summary, the hydrophilic patch matrix of the present invention has good coating ductility, low initial adhesion, can be pulled without leaving marks, has high viscosity and is not easy to fall off, has a drug loading of 60-75%, high stability, a long storage period, and has better comprehensive performance than general matrices.

Claims

1. A hydrophilic plaster matrix for increasing drug loading, characterized in that: The hydrophilic patch matrix comprises vaseline, a water-locking agent, a thickener, glycerin, purified water, polyvinyl alcohol, a volatile oil complex and a transdermal absorbent; The thickener includes one of a pharmaceutical grade partially neutralized sodium polyacrylate and a pharmaceutical modified thickener.

2. A hydrophilic patch matrix for increasing drug loading according to claim 1, characterized in that: The composition is composed of the following raw materials in proportion by mass: 2-4 parts of vaseline, 1-2 parts of water-locking agent, 2-4 parts of thickener, 2-4 parts of glycerin, 9-11 parts of purified water, 1-2.5 parts of polypropylene alcohol, 0.1-0.3 parts of volatile oil complex and 0.2-0.4 parts of transdermal absorbent.

3. A hydrophilic patch matrix with increased drug loading according to claim 1, characterized in that: The preparation of the pharmaceutical modified thickener is to decompose the polymer compound, add it into a carboxylic acid ester organic solvent and stir it for 10-18 minutes; The polymer compound includes one of PEG-150 distearate, hydroxypropyl cellulose and lauroyl polyoxyethylene (12) glyceride.

4. A hydrophilic patch matrix for increasing drug loading according to claim 3, characterized in that: The decomposition treatment is to add alkaline salt at a mass fraction of 40-50% to the high molecular compound under stirring, first heating to 60-70° C. and then reacting for 20-30 minutes.

5. A hydrophilic patch matrix for increasing drug loading according to claim 1, characterized in that: The preparation of the volatile oil complex comprises: adding 10-16wt% cyclodextrin to plants for ball milling, stirring for 30-40min with a mixed solvent with a mass concentration of 10-20wt%, heating at a temperature of 60-70°C for 80-100min, and then separating and concentrating to obtain the volatile oil complex; the plants comprise at least one of cloves, evodia rutaecarpa, camphor, holly and eucalyptus leaves; and the solvent comprises ethanol and polyethylene glycol in a volume ratio of 10:2-4.

6. A hydrophilic patch matrix with increased drug loading according to claim 1, characterized in that: The transdermal absorbent is one of laurocapram and Tween-80.

7. A hydrophilic patch matrix for increasing drug loading according to claim 1, characterized in that: The water-locking agent is Carbomer 940.

8. Use of a hydrophilic patch matrix with increased drug loading according to any one of claims 1 to 7 in preparing a patch, characterized in that: The following steps are involved: Step 1: Preparation of Chinese medicine powder: Sterilize the Chinese medicine and crush it into fine powder of 120-200 mesh; Step 2: Preparation of hydrophilic patch: Prepare the Chinese medicine powder into a plastic colloid, treat the vaseline, volatile oil compound, and transdermal absorbent, add the plastic colloid, stir evenly, apply it on the cloth, cover with a lining, and cut into pieces to obtain the finished product; The content of the Chinese medicine powder is 60-75wt%.

9. The use according to claim 8, characterized in that: The plastic colloid is prepared by adding carbomer 940, polyvinyl alcohol, a thickener, glycerin and purified water into the traditional Chinese medicine powder, and stirring and mixing them uniformly.

10. The use according to claim 8, characterized in that: The treatment comprises grinding the raw materials and then heating them with microwave at a temperature of 90-110°C.

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