Modified hot melt pressure sensitive adhesive for herbal medicine patches and patches using the same

Abstract

The present invention relates to a modified hot melt pressure sensitive adhesive (HMPSA) for use in herbal medicine patches, a method for preparing the modified HMPSA, a patch using the modified HMPSA, and the use of the modified HMPSA in preparing a herbal medicine patch.

Description

[Technical Field]

[0001] The present invention relates to a modified hot-melt pressure sensitive adhesive (HMPSA) for use in herbal medicine patches, a method for preparing the modified HMPSA, patches using the modified HMPSA, and the use of the modified HMPSA in preparing herbal medicine patches. [Background technology]

[0002] Rubber patches, also known as adhesive patches or rubber plasters, are patches made by mixing a drug into a matrix such as rubber and coating it onto a substrate. Conventional matrices include natural rubber, thermoplastic rubber, rosin, rosin derivatives, petrolatum, lanolin, and zinc oxide. Currently, most commercially available patches use natural rubber as the matrix, and conventional preparation methods include the solvent method and hot press method. Natural rubber-based patches have drawbacks, such as poor breathability, low drug loading, and a tendency to cause skin allergies and irritation.

[0003] Pressure-sensitive adhesives (PSAs) achieve effective adhesion after wetting the surface and applying pressure. They have high initial adhesion, good holding power, and no damage to the surface of the substrate. They are therefore widely used in labels, hygiene products, packaging products, medical supplies, and various tapes. Among all types of PSAs, HMPSA is based on a thermoplastic polymer and possesses dual properties of hot melt and pressure sensitivity. On the one hand, patches using HMPSA reduce interactions between the matrix and the drug, facilitate drug release from the matrix, and cause less skin irritation than natural rubber. On the other hand, the lack of volatile organic solvents used in the preparation of HMPSA reduces drug loss, especially volatile oils. Therefore, HMPSA is a suitable matrix for herbal medicine patches. However, thermoplastic rubber is a nonpolar polymer with strong hydrophobicity, while most active ingredients in herbal medicines are polar. This limits the release of active ingredients from HMPSA, limiting its application in herbal medicine patches.

[0004] Therefore, it is desirable in the art to develop a HMPSA suitable for herbal medicine patches. Summary of the Invention [Problem to be solved by the invention]

[0005] SUMMARY OF THE INVENTION In order to achieve the above object, the object of the present invention is to provide a hot melt pressure sensitive adhesive suitable for herbal medicine patches, its preparation method and use. [Means for solving the problem]

[0006] This objective is achieved by adding a modified filler to HMPSA so that the modified HMPSA has good release of the hydrophilic active ingredients of herbal medicines, has suitable adhesive strength and good retention, and is therefore particularly suitable for the preparation of herbal medicine patches.

[0007] In one aspect, the present disclosure provides a modified hot melt pressure sensitive adhesive suitable for herbal medicine patches, said adhesive comprising, consisting essentially of, or consisting of, based on total weight for said adhesive: (a) 20 to 50% by weight, preferably 30 to 50% by weight, more preferably 40 to 50% by weight, of a thermoplastic polymer selected from styrene-isoprene-styrene polymers and / or styrene-butadiene-styrene polymers; (b) 20 to 60 wt. %, preferably 25 to 50 wt. %, more preferably 25 to 40 wt. % of a tackifier resin; (c) 10 to 25 wt. %, preferably 12 to 20 wt. %, more preferably 13 to 19 wt. % of a first plasticizer selected from mineral oil; (d) 1 to 15 wt. %, preferably 2 to 12 wt. %, more preferably 3 to 10 wt. % of a second plasticizer selected from liquid rosin resin, liquid petroleum resin, liquid rubber, and mixtures thereof; (e) 1 to 20% by weight, preferably 2 to 18% by weight, more preferably 3 to 16% by weight, of a modified filler selected from polyvinylpyrrolidone, butyl methacrylate-dimethylaminoethyl methacrylate-methyl methacrylate copolymer, sodium carboxymethylcellulose, and mixtures thereof; and (f) 0 to 8 wt. %, preferably 1 to 7 wt. %, more preferably 2 to 6 wt. % of an antioxidant.

[0008] In another aspect, the present disclosure provides a method for preparing a modified HMPSA of the invention, said method comprising: (i) mixing a first plasticizer, an optional antioxidant, and a portion of the tackifier resin and heating with stirring to a temperature in the range of 120-150°C until the components are melted; (ii) adding a thermoplastic polymer and heating with stirring to a temperature of 140-160°C and maintaining said temperature until said thermoplastic polymer is melted, preferably for about 50-120 minutes; (iii) adding the remaining tackifier resin and second plasticizer with stirring until the ingredients are melted and a uniform mixture is obtained; (iv) cooling the mixture to a temperature in the range of 120 to 150°C and adding a modified filler with stirring to obtain the modified hot melt pressure sensitive adhesive.

[0009] In another aspect, the present disclosure provides an herbal medicine patch comprising a modified HMPSA of the present invention and an herbal medicine.

[0010] In yet another aspect, the present disclosure provides the use of modified HMPSA in the preparation of an herbal medicine patch to enhance the release of the active ingredients of the herbal medicine. [Effects of the Invention]

[0011] The modified HMPSA of the present invention has the following advantages: 1) good release of hydrophilic active ingredients of herbal medicines; 2) adequate peel strength, adequate initial adhesive strength, and good retention; and 3) acceptable or even improved release of hydrophobic active ingredients of herbal medicines. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 shows the DSC curves of the modified HMPSA of Examples 1-2, Comparative Example 1 and Control 1. [Figure 2] FIG. 2 shows the FT-IR spectra of the modified HMPSA of Examples 1-2, Comparative Example 1 and Control 1. [Figure 3] FIG. 3 shows the rheology diagrams of the modified HMPSA of Examples 1-2, Comparative Example 1 and Control 1. [Figure 4] 4A-4C show the release of active ingredients of herbal medicines from the modified HMPSA of Examples 1-2, Comparative Example 1 and Control 1. DETAILED DESCRIPTION OF THE INVENTION

[0013] Those skilled in the art will appreciate that this discussion is a description of exemplary embodiments only and is not intended to limit the broader aspects of the present invention. Each aspect so described may be combined with any other aspect unless expressly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature indicated as being preferred or advantageous.

[0014] Unless otherwise specified, all weight percent or wt.% values ​​quoted herein are percentages by weight.

[0015] Unless otherwise specified, as used herein, the terms "a," "an," and "the" include singular and plural referents.

[0016] As used herein, the terms "comprising" and "comprises" are synonymous with "including," "includes," or "containing," and "contains," and are inclusive or open-ended and do not exclude additional, unrecited members, elements, or method steps.

[0017] As used herein, the term "consisting essentially of" means that the listed components make up the bulk of the composition, e.g., at least 80% by weight of the composition, at least 85% by weight of the composition, or at least 90% by weight of the composition.

[0018] As used herein, the term "consisting of" is closed-ended and excludes additional, unrecited, and intentionally added members, elements, or method steps.

[0019] The term "about" as used herein in connection with a numerical value refers to the numerical value ±10%, preferably ±5%. All numerical values ​​herein should be construed as being modified by the term "about."

[0020] Unless otherwise specified, the recitation of numerical endpoints includes the recited endpoints, and all numbers and fractions subsumed within the respective ranges.

[0021] Unless otherwise defined, all terms used herein, including technical and scientific terms, have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs.

[0022] <Modified HMPSA> thermoplastic polymer Suitable thermoplastic polymers for the modified HMPSA of the present invention include styrene-isoprene-styrene (SIS) polymers and / or styrene-butadiene-styrene (SBS) polymers.

[0023] SIS polymers useful herein include, but are not limited to, those conventionally used in HMPSA. Examples include linear SIS polymers, star SIS polymers, and combinations thereof. Preferably, the SIS polymer contains both linear and star structures. More preferably, the styrene unit content in the SIS polymer can be 10 to 40% by weight, e.g., 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, or 38% by weight. Alternatively, the styrene-isoprene diblock content in the SIS polymer can be 0 to 80% by weight, e.g., 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75% by weight.

[0024] SBS polymers useful herein include, but are not limited to, those conventionally used in HMPSA. Examples include linear SBS polymers, star SBS polymers, and combinations thereof. Preferably, the SBS polymer contains both linear and star structures. More preferably, the content of styrene units in the SBS polymer may be 10 to 40% by weight, for example, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, or 38% by weight, or the content of styrene-butadiene diblocks in the SBS polymer may be 0 to 80% by weight, for example, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, or 75% by weight.

[0025] The above thermoplastic polymers may be used alone or in combination of two or more.

[0026] Preferably, the thermoplastic polymer is present in the modified HMPSA of the present invention in an amount of 20-50% by weight, more preferably 30-50%, 40-50%, for example 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46% or 48% by weight, based on the total weight of the modified HMPSA. If the amount of thermoplastic polymer is too low, the cohesive strength of the HMPSA will be insufficient for a patch. If the amount of thermoplastic polymer is too high, the adhesive properties of the HMPSA will be too low to be used in a patch.

[0027] tackifier resin Suitable tackifier resins for the modified HMPSA of the present invention include, but are not limited to, those conventionally used in HMPSA, particularly preferred examples being C5 petroleum resins, C9 petroleum resins, C5 / C9 copolymer petroleum resins, hydrogenated C5 petroleum resins, hydrogenated C9 petroleum resins, rosin, terpene resins, dicyclopentadiene resins (DCPD resins), α-methylstyrene resins (AMS resins), and mixtures thereof.

[0028] The tackifier resins can be used alone or in combination of two or more.

[0029] Preferably, the tackifier resin is present in the modified HMPSA of the present invention in an amount of 20-60% by weight, more preferably 20-50%, 25-40% by weight, for example 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 42%, 44%, 46%, 48%, 50%, 52%, 54%, 56%, or 58% by weight, based on the total weight of the modified HMPSA. If the amount of tackifier resin is too low, the adhesive performance of the HMPSA will be too low to be used in a patch. If the amount of tackifier resin is too high, the pressure sensitivity and low temperature performance will be poor.

[0030] First Plasticizer Suitable first plasticisers for the modified HMPSA of the present invention include those selected from mineral oils, and although any mineral oil conventionally used in HMPSAs may be used in the present invention, preferred are naphthenic, aromatic or paraffinic oils or mixtures thereof.

[0031] Commercially available first plasticizers include KN4006, KN4008, and KN4010 manufactured by PertroChina Lubricant Company; white mineral oil LP 150, LP 350 manufactured by Kukdong Korea; Nyflex 222B manufactured by Nynas; and PS white mineral oil manufactured by PetroChina.

[0032] The first plasticizers may be used alone or in combination of two or more kinds.

[0033] The primary purpose of the first plasticizer is to impart plasticity to the HMPSA, to reduce the melt viscosity and Tg of the HMPSA, to impart flexibility, and to improve wettability to the adherend.

[0034] Preferably, the first plasticizer is present in the modified HMPSA of the invention in an amount of 10 to 25% by weight, more preferably 12 to 20%, 13 to 19% by weight, for example 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23% or 24% by weight, based on the total weight of the modified HMPSA.

[0035] Secondary Plasticizer Suitable second plasticizers for the modified HMPSA of the present invention include those selected from liquid rosin resins, liquid petroleum resins, liquid rubbers and mixtures thereof. The second plasticizer preferably has a higher molecular weight than the first plasticizer.

[0036] The secondary plasticizer, in addition to the function of the primary plasticizer, further improves the adhesive properties of the HMPSA.

[0037] The second plasticizers can be used alone or in combination of two or more.

[0038] Preferably, the second plasticizer is present in the modified HMPSA of the invention in an amount of from 1 to 15% by weight, more preferably from 2 to 12%, or from 3 to 10% by weight, for example 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13% or 14% by weight, based on the total weight of the modified HMPSA.

[0039] Modified Filler The modifying fillers are added to make the HMPSA more hydrophilic and therefore more compatible with polar active ingredients in herbal medicines, facilitating the release of the active ingredients.

[0040] Not all hydrophilic / polar compounds can achieve the above objectives. After extensive research, the present inventors have found that polyvinylpyrrolidone (PVP), butyl methacrylate-dimethylaminoethyl methacrylate-methyl methacrylate copolymer (BMA-DMAEMA-MMA copolymer), sodium carboxymethylcellulose, and mixtures thereof are suitable, and particularly PVP and / or BMA-DMAEMA-MMA copolymer are suitable.

[0041] The prior art has suggested adding ethyl acrylate-methyl methacrylate-triammonioethyl methacrylate chloride (RLPO) to HMPSA to increase the release of hydrophilic active ingredients, but RLPO is expensive. Therefore, it is desirable to find other compounds that are cost-effective yet achieve the desired technical effect equivalent to or better than RLPO.

[0042] Currently available commercially available PVP products are suitable for the modified HMPSA of the present invention, for example suitable grades of PVP include PVP K12, PVP K15, PVP K17, PVP K25, PVP K30, PVP K45, PVP K60, PVP K90, PVP K80, PVP K85, PVP K90, PVP K100, PVP K110, PVP K120, PVP K150 or mixtures thereof.

[0043] The BMA-DMAEMA-MMA copolymer suitable for the modified HMPSA of the present invention is a block copolymer obtained from butyl methacrylate (BMA), dimethylaminoethyl methacrylate (DMAEMA), and methyl methacrylate (MMA). The ratio of each monomer is not particularly limited. For example, the molar ratio of BMA, DMAEMA, and MMA units in the copolymer may be (1-5):(2-10):(1-5), preferably (1-2):(2-5):(1-2), e.g., 1:3:1, 2:5:1, 3:4:2, 2:2:1, 1:2:2, 2:7:3, 3:5:2, or 1:2:1.

[0044] There are no particular limitations on the sodium carboxymethylcellulose suitable for the modified HMPSA of the present invention, and commercially available products can be used in the present invention.

[0045] Furthermore, slightly modified PVP, slightly modified BMA-DMAEMA-MMA copolymer, and slightly modified sodium carboxymethylcellulose are also suitable for the present invention as long as the modifications to PVP, BMA-DMAEMA-MMA copolymer, and sodium carboxymethylcellulose do not change their basic properties, particularly hydrophilicity. Therefore, the terms "PVP" or "polyvinylpyrrolidone" or "BMA-DMAEMA-MMA copolymer" or "sodium carboxymethylcellulose" used herein also include slightly modified derivatives thereof that can achieve the same or similar effects as "PVP" or "BMA-DMAEMA-MMA copolymer" or "sodium carboxymethylcellulose" themselves.

[0046] The modified fillers can be used alone or in combination of two or more.

[0047] Preferably, the modified filler is present in the modified HMPSA of the present invention in an amount of 1 to 20% by weight, more preferably 2 to 18% by weight, or 3 to 16% by weight, for example 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, or 19% by weight, based on the total weight of the modified HMPSA. If the amount of modified filler is too low, the modified HMPSA will not adequately release the active ingredients of the herbal medicine. If the amount of modified filler is too high, the adhesive properties of the HMPSA will be adversely affected.

[0048] antioxidants Optionally, an antioxidant can be added to prevent degradation of the polymer in the modified HMPSA, thereby extending its shelf life. The antioxidants that can be used herein are not particularly limited, and include those conventionally used in HMPSA, such as aromatic amine antioxidants, hindered phenol antioxidants, thiol-based antioxidants, phosphorus-based antioxidants, and secondary antioxidants. Commercially available antioxidants include Evernox 10GF / 1726 from Everspring, Irganox 1010 / 1726 from BASF, and Thanox 1010G / 1726 from Rianlon; Everfos 168 from Everspring, Irgafos 168 from BASF, Thanox 168 from Rianlon, Thanox 412S / DSTP from Rianlon, ADK AO 412S from ADEKA, and Sumilizer TP-D from Sumitomo. The antioxidants can be used alone or in combination.

[0049] The antioxidant may be included in the modified HMPSA of the invention in an amount of 0 to 8% by weight, more preferably 1 to 7%, 2 to 6% by weight, for example 2%, 3%, 4%, 5%, 6% or 7% by weight, based on the total weight of the modified HMPSA.

[0050] Optionally, other additives such as diatomaceous earth, solvents for the modified filler, etc. may also be added to the modified HMPSA of the present invention, provided they do not adversely affect the desired properties of the modified HMPSA.

[0051] The above ingredients work together to achieve suitable adhesive properties and good release of the active ingredients of the herbal medicine.

[0052] Method for preparing modified HMPSA Although other preparation methods can be used to prepare modified HMPSA that can achieve the desired effects of the present application, it is preferred to use the preparation method of the present invention, which method comprises the steps of pre-mixing and pre-melting a first plasticizer and a tackifier resin, followed by incorporating and melting a thermoplastic polymer at a particular temperature for a particular time. Preferably, the method of the present invention comprises the following steps:

[0053] Step (i): Mixing the first plasticizer and a portion of the tackifier resin, for example 1 / 5 to 1 / 3 of the tackifier resin, and heating to a temperature in the range of 120 to 150°C with stirring until the components are melted; Step (ii): Add the thermoplastic polymer and heat with stirring to a temperature of 140-160°C, for example 150°C, and maintain that temperature for preferably about 50-120 minutes until all the thermoplastic polymer is melted; Step (iii): Add the remaining tackifier resin and second plasticizer and stir until the ingredients are melted and a uniform mixture is obtained; Step (iv): The mixture is cooled to a temperature in the range of 120 to 150°C, and the modified filler is added with stirring to obtain a modified HMPSA.

[0054] The time for each step is not particularly limited as long as each component is melted and particularly uniformly mixed.

[0055] Between steps (iii) and (iv), the mixture from step (iii) may be packaged and cooled to room temperature, and the packaged mixture may be melted again when mixed with the modified filler.

[0056] The antioxidant can be added in either step (i) or step (ii), or both.

[0057] Herbal medicine patches The herbal patch of the present invention comprises a modified HMPSA of the present invention and a solid or liquid extract or volatile oil of a herbal medicine such as ephedra, red peony root (radix paeoniae rubra), gardenia, chrysanthemum, milkvetch root, licorice (radix liquiritiae), Atractylodes macrocephala, pseudo-ginseng, Chinese cinnamon (Cinnamomum cassia Presl), Angelica sinensis, Angelica dahurica, myrrh, safflower (Carthamus) or Aconiti Radix.

[0058] The medicine can be used alone or in combination of two or more kinds.

[0059] The method for preparing the herbal medicine patch is not particularly limited, as long as the herbal medicine is uniformly dispersed within the patch. For example, the patch may be prepared by melting the modified HMPSA of the present invention and mixing with the herbal medicine while stirring. The herbal medicine may be in solid or liquid form, such as a crushed herbal medicine powder or an herbal medicine extract. After the herbal medicine is uniformly dispersed, the mixture is spread onto a liner sheet such as cloth or plastic to form a patch, and then cooled to room temperature (20-25°C). Alternatively, the mixture may be pressed onto another sheet without spreading it, forming a patch.

[0060] The weight ratio of the herbal medicine to the modified HMPSA of the present invention is not particularly limited, as long as it can uniformly disperse the herbal medicine and achieve the desired adhesive properties. Preferably, the weight ratio of the herbal medicine to the modified HMPSA is 1:100 to 20:100, for example, 2:100, 3:100, 4:100, 5:100, 6:100, 7:100, 8:100, 9:100, 10:100, 11:100, 12:100, 13:100, 14:100, 15:100, 16:100, 17:100, 18:100, or 19:100. [Example]

[0061] The present invention will now be illustrated by the following examples. The following examples are intended to assist those skilled in the art in better understanding and practicing the present invention. The scope of the present invention is not limited by the examples, but is defined by the appended claims. Unless otherwise specified, all parts and percentages are by weight.

[0062] Example 1 The ingredients used in Example 1 are shown in Table 1 as follows:

[0063] [Table 1]

[0064] The preparation method is as follows.

[0065] 15 parts by weight of KN4010, 5 parts by weight of Irganox 1010, and 6 parts by weight of C5 petroleum resin were added to a container and heated to 120-150°C with stirring until all of the tackifier resin was melted. 45 parts by weight of SIS polymer were then added to the container with stirring, the temperature was raised to approximately 160°C, and held for approximately 60 minutes until all of the SIS polymer was melted. 5 parts by weight of PB 950 and 24 parts by weight of C5 petroleum resin were then added to the container with stirring for approximately 60 minutes until a uniform mixture was obtained. This mixture was packaged to obtain HMPSA. The packaged HMPSA was melted in a container at approximately 120-150°C, and 18 parts by weight of PVP solution was added with stirring for approximately 60 minutes until a uniform modified HMPSA was obtained.

[0066] Example 2 The ingredients used in Example 2 are shown in Table 2 as follows:

[0067] [Table 2]

[0068] The preparation method was basically the same as in Example 1, except that the PVP solution was changed to BMA-DMAEMA-MMA copolymer.

[0069] Comparative Example 1 The components used in Comparative Example 1 are shown in Table 3 below.

[0070] [Table 3]

[0071] The preparation method was basically the same as in Example 1, except that PVP was changed to RLPO.

[0072] Comparative Example 2 The components used in Comparative Example 2 are shown in Table 4 below.

[0073] [Table 4]

[0074] The preparation method was basically the same as in Example 1, except that PVP was changed to polymethyl methacrylate (PMMA).

[0075] The adhesive properties of the modified HMPSA of Examples 1 and 2, Comparative Examples 1 and 2, and Control 1 (where Control 1 is HMPSA with no modified filler added) were evaluated in the following manner, and the results are shown in Table 5 below.

[0076] viscosity :Measured using a digital rotational viscometer in accordance with ASTM D3236-88, units are centipoise (cP).

[0077] softening point :Measured by ring and ball method in accordance with GB / T4507-2014, unit is °C.

[0078] 180° peel strength :Measured at room temperature using a tensile strength tester in accordance with GB / T2792-1998, unit N / cm.

[0079] Loop Tuck :Measured at room temperature using a loop tack tester in accordance with GB / T31125-2014, unit: N.

[0080] holding power :Measured at room temperature using a holding power tester in accordance with the adhesive strength test method described in the Chinese Pharmacopoeia (2020 edition), with units of time.

[0081] [Table 5]

[0082] Table 5 shows that the addition of modified fillers, such as PVP and BMA-DMAEMA-MMA copolymer, does not adversely affect the adhesive properties of the adhesive, and can achieve suitable adhesive properties. Specifically, a holding power of more than 48 hours is very suitable for patches, a loop tack of 20-45 N is within the range suitable for patches, and a 180° peel strength of 5-15 N / cm is within the range suitable for patches.

[0083] The DSC curves, FT-IR spectra, and rheology diagrams of HMPSA modified with PVP, BMA-DMAEMA-MMA, and RLPO are shown in Figures 1, 2, and 3. Figures 1 to 3 show that the modified fillers have good compatibility with HMPSA.

[0084] Specifically, the DSC curve, FT-IR spectrum, and rheology diagram were obtained as follows.

[0085] DSC curve Each amount of HMPSA was placed in a crucible, and the temperature was increased from room temperature to 150°C at a rate of 10°C / min. After holding at 150°C for 10 minutes, the temperature was decreased to -70°C at a rate of 10°C / min to remove the thermal history. The temperature was then increased again from room temperature to 150°C at a rate of 10°C / min under nitrogen protection with a nitrogen gas flow of 10 mL / min. The results are shown in Figure 1. As can be seen from Figure 1, unmodified HMPSA has a Tg of -60.90°C, HMPSA modified with PVP has a Tg of -62.23°C, HMPSA modified with BMA-DMAEMA-MMA copolymer has a Tg of -60.81°C, and HMPSA modified with RLPO has a Tg of -60.38°C.

[0086] FT-IR spectrum Each HMPSA was placed on a hot table at 150°C and pressed into a film with a thickness of 80µm. Analysis was performed by the film reflection method, and the FT-IR spectrum is shown in Figure 2.

[0087] Rheology DiagramThe rheology diagrams shown in Figure 3 were obtained by testing each HMPSA under the same conditions using a rheometer: Figure 3A is the rheology diagram for Control 1, Figure 3B is the rheology diagram for Example 2, Figure 3C is the rheology diagram for Comparative Example 1, and Figure 3D is the rheology diagram for Example 1.

[0088] Patch Example A 40 parts by weight of the modified HPSA of Example 1, Comparative Example 1, Comparative Example 2, or Control 1 was melted and mixed with 4 parts by weight of red peony extract (a hydrophilic solid powder) under stirring until a uniform mixture was obtained, and the mixture was roller-pressed into a patch with a thickness of approximately 100 μm.

[0089] The release of paeoniflorin (PF), the active ingredient in Red Peony Root, was tested according to the paddle-over-disk method described in the Pharmacopoeia of the People's Republic of China (2020 edition, Method 4 of Dissolution Release Test), which is described in detail below.

[0090] A mesh disk was used as the disk, and phosphate buffer solution (PB, pH = 5, 1% sodium dodecyl sulfate) was used as the absorption medium. The PB was degassed and placed in a dissolution cup at a temperature of approximately 32°C and a rotation speed of 200 rpm. The patch (36 cm 2 The patch was fixed between two mesh disks with the release surface facing up and placed on the bottom of the dissolution cup. The patch surface was parallel to the bottom of the rotating paddle. Stirring was started, and 4 mL samples were taken at 1, 2, 4, 6, 8, 12, and 24 hours, with 4 mL of blank absorption solution added at the same time. The samples were analyzed by HPLC, and the cumulative amount of the active ingredient PF of the herbal medicine was calculated as the area under the curve, as shown in Figure 4A.

[0091] As can be seen from Figure 4A, the PVP-modified HMPSA can release the active ingredient of Red Peony Root better than the control sample and the RLPO-modified HMPSA, specifically, the release amount follows the order HMPSA-PVP > HMPSA-RLPO > HMPSA.

[0092] Furthermore, the release of the active ingredient of Red Peony Root when using HMPSA modified with PMMA was lower than that of unmodified HMPSA (Control 1), indicating that not all hydrophilic / polar fillers can achieve better drug release effects.

[0093] Patch Example B 40 parts by weight of the modified HPSA of Example 1, Example 2, Comparative Example 1, or Control 1 was melted and mixed with 4 parts by weight of Ephedra extract (hydrophilic and liquid) under stirring until a uniform mixture was obtained. The mixture was roller-pressed into patches with a thickness of approximately 100 μm. The Ephedra extract was prepared by extraction with ethanol (90%).

[0094] The release of ephedrine (EH), the active ingredient in ephedra, was tested according to the paddle-over-disk method described in the Pharmacopoeia of the People's Republic of China (2020 edition, Method 4 of Dissolution Release Test), which is the same as detailed in Patch Example A. The results are shown in Figure 4B.

[0095] As can be seen from Figure 4B, the HMPSA modified with PVP or BMA-DMAEMA-MMA copolymers could release the active ingredients of Ephedra herb better than the control and the HMPSA modified with RLPO, specifically, the release order was HMPSA-BMA-DMAEMA-MMA > HMPSA-PVP > HMPSA-RLPO > HMPSA.

[0096] Patch Example C 40 parts by weight of the modified HPSA of Example 1, Example 2, Comparative Example 1, or Control 1 was melted and mixed with 2 parts by weight of cinnamon volatile oil (hydrophobic and liquid) under stirring until a uniform mixture was obtained, and the mixture was roller pressed into a patch having a thickness of approximately 100 μm.

[0097] The release of Cinnamomum oil (CA), the active ingredient in Chinese cinnamon, was tested according to the paddle-over-disk method described in the Pharmacopoeia of the People's Republic of China (2020 edition, Method 4 of Dissolution Release Test), which is the same as detailed in Patch Example A. The results are shown in Figure 4C.

[0098] As shown in Figure 4C, the modified HMPSA using PVP can release volatile oils better than the control sample. Therefore, although the mechanism is not yet clear, the modified HMPSA of the present invention can release not only hydrophilic active ingredients better than the control sample, but also hydrophobic active ingredients better than the control sample. Furthermore, the modified HMPSA using the BMA-DMAEMA-MMA copolymer of the present invention can achieve a volatile oil release comparable to that of the modified HMPSA using RLPO proposed in the prior art. Specifically, the release amount follows the order: HMPSA-PVP > HMPSA > HMPSA-BMA-DMAEMA-MMA ≒ HMPSA-RLPO.

[0099] While certain preferred embodiments have been described, many modifications and variations are possible in light of the above teachings. It is therefore to be understood that the invention may be practiced otherwise than as specifically described without departing from the scope of the appended claims.

Claims

1. 1. A modified hot melt pressure sensitive adhesive suitable for herbal medicine patches, said adhesive comprising, based on total weight for said adhesive: (a) 20 to 50 wt. %, preferably 30 to 50 wt. %, more preferably 40 to 50 wt. % of a thermoplastic polymer selected from styrene-isoprene-styrene polymers and / or styrene-butadiene-styrene polymers; (b) 20 to 60 wt. %, preferably 25 to 50 wt. %, more preferably 25 to 40 wt. % of a tackifier resin; (c) 10 to 25 wt. %, preferably 12 to 20 wt. %, more preferably 13 to 19 wt. % of a first plasticizer selected from mineral oil; (d) 1 to 15 wt. %, preferably 2 to 12 wt. %, more preferably 3 to 10 wt. % of a second plasticizer selected from liquid rosin resin, liquid petroleum resin, liquid rubber, and mixtures thereof; (e) 1 to 20 wt. %, preferably 2 to 18 wt. %, more preferably 3 to 16 wt. % of a modified filler selected from polyvinylpyrrolidone, butyl methacrylate-dimethylaminoethyl methacrylate-methyl methacrylate copolymer, sodium carboxymethyl cellulose, and mixtures thereof; and (f) 0 to 8 wt. %, preferably 1 to 7 wt. %, more preferably 2 to 6 wt. % of an antioxidant. Adhesive containing.

2. 10. The adhesive of claim 1, wherein the tackifier resin is selected from C5 petroleum resin, C9 petroleum resin, C5 / C9 copolymer petroleum resin, hydrogenated C5 petroleum resin, hydrogenated C9 petroleum resin, rosin, terpene resin, dicyclopentadiene resin, α-methylstyrene resin, and mixtures thereof.

3. 2. The adhesive of claim 1, wherein the styrene-isoprene-styrene polymer or styrene-butadiene-styrene polymer contains styrene units in an amount of 10 to 40% by weight.

4. 2. The adhesive of claim 1, wherein the styrene-isoprene-styrene polymer comprises styrene-isoprene diblock in an amount of 0 to 80% by weight.

5. The adhesive of claim 1, wherein the styrene-butadiene-styrene polymer comprises styrene-butadiene diblock in an amount of 0 to 80 weight percent.

6. 10. The adhesive of claim 1, wherein the mineral oil comprises a naphthenic oil, an aromatic oil, a paraffinic oil, or a mixture thereof.

7. 2. The adhesive of claim 1, wherein the polyvinylpyrrolidone is selected from PVP K12, PVP K15, PVP K17, PVP K25, PVP K30, PVP K45, PVP K60, PVP K90, PVP K80, PVP K85, PVP K90, PVP K100, PVP K110, PVP K120, PVP K150 or mixtures thereof.

8. 10. The adhesive of claim 1, wherein the butyl methacrylate-dimethylaminoethyl methacrylate-methyl methacrylate copolymer has a molar ratio of butyl methacrylate, dimethylaminoethyl methacrylate, and methyl methacrylate in said copolymer of (1-5):(2-10):(1-5).

9. 10. The adhesive of claim 1, wherein the antioxidant is selected from an aromatic amine antioxidant, a hindered phenol antioxidant, a thiol-based antioxidant, a phosphorus-based antioxidant, or a mixture thereof.

10. The adhesive of claim 1, wherein the hot melt pressure sensitive adhesive further comprises an additive selected from diatomaceous earth and a solvent for the modified filler.

11. 11. A method for preparing a modified hot melt pressure sensitive adhesive according to any one of claims 1 to 10, said method comprising: (i) mixing the first plasticizer, the optional antioxidant, and a portion of the tackifier resin and heating with stirring to a temperature in the range of 120-150°C until the components are melted; (ii) adding a thermoplastic polymer and heating with stirring to a temperature of 140-160°C and maintaining said temperature until said thermoplastic polymer is melted, preferably for about 50-120 minutes; (iii) adding the remaining tackifier resin and second plasticizer with stirring until the ingredients are melted and a uniform mixture is obtained; (iv) cooling the mixture to a temperature in the range of 120 to 150°C and adding a modified filler with stirring to obtain the modified hot melt pressure sensitive adhesive. A method comprising:

12. 12. The method of claim 11, wherein between steps (iii) and (iv), the mixture from step (iii) is packaged, cooled to room temperature, and re-melted when the packaged mixture is mixed with the modified filler.

13. 12. The method of claim 11, wherein an antioxidant is added in step (i) or step (ii) or both.

14. A herbal medicine patch comprising the modified hot melt pressure sensitive adhesive of any one of claims 1 to 10 and a herbal medicine.

15. Use of the modified hot melt pressure sensitive adhesive according to any one of claims 1 to 10 in preparing a herbal medicine patch for improving the release of the active ingredients of the herbal medicine.

16. 15. The patch of claim 14, wherein the herbal medicine comprises a solid or liquid extract or volatile oil of ephedra, red peony, gardenia, chrysanthemum, scutellaria, licorice, white atractylodes, Notoginseng, Chinese cinnamon, angelica, white berry, myrrh, safflower, or aconite.

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