CN114796164B - Preparation method of emplastrum matrix for rapidly releasing volatile medicines - Google Patents

Preparation method of emplastrum matrix for rapidly releasing volatile medicines Download PDF

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CN114796164B
CN114796164B CN202210567617.6A CN202210567617A CN114796164B CN 114796164 B CN114796164 B CN 114796164B CN 202210567617 A CN202210567617 A CN 202210567617A CN 114796164 B CN114796164 B CN 114796164B
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block polymerization
reaction kettle
matrix
emplastrum
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CN114796164A (en
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熊伟
郭立
李磊
卢玉斌
张春霞
高锡意
杨春光
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Henan Lingrui Pharmaceutical Co ltd
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
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Abstract

A preparation method of a plaster matrix for rapidly releasing volatile medicines is characterized in that the plaster matrix is prepared by compounding SIS framework material with liquid paraffin, antioxidant BHT and hydrogenated rosin glyceride, and comprises the following steps: (1) synthesis of linear SIS block copolymer; b. after the first block polymerization is finished, initiating a second block polymerization reaction; c. after the second block polymerization is finished, initiating a third block polymerization reaction; d. after the third block polymerization reaction is finished, adding 900-1100ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying at 48-52 ℃ for 10-14h to obtain a dried SIS elastomer; and (2) preparing a plaster matrix. The preparation method is simple, can realize the quick release of the medicine, has the accumulated release rate obviously higher than that of the original process sample, reduces the resource waste, provides a feasible method for improving the potential curative effect of the product, and has remarkable social and economic benefits.

Description

Preparation method of emplastrum matrix for rapidly releasing volatile medicines
Technical Field
The invention relates to the field of medicinal preparations, in particular to a preparation method of a plaster matrix for rapidly releasing volatile medicines.
Background
The pain-relieving body-building paste is a well-known product sold in the market (such as an original external plaster preparation of Henan Ling Rui pharmaceutical GmbH), and mainly treats rheumatic arthralgia, lumbago and skelalgia and swelling and pain caused by traumatic injury and contusion, namely the aim of relieving pain is fulfilled. The medicine formula is as follows: 90 to 120g of salvia miltiorrhiza, 90 to 120g of safflower, 90 to 120g of suberect spatholobus stem, 90 to 120g of gardenia, 45 to 65g of clematis root, 45 to 65g of pubescent angelica root, 45 to 65g of pepper, 130 to 165g of borneol, 90 to 120g of camphor and 90 to 120g of menthol. The formula is prepared according to monarch, minister, assistant and guide requirements under the guidance of the traditional Chinese medicine theory: the camphor is pungent and cool, can activate blood, reduce swelling and relieve pain, and is fragrant and avoids dirt; the salvia miltiorrhiza is specially used in blood, and has the effects of activating blood and promoting qi flow … … to promote joint movement and dredge collaterals, so that the waist and the knees are healthy and have impediment movement; safflower promotes blood circulation and dredges the menstrual flow, removes stasis and relieves pain; the three medicines are all used for activating blood and dissolving stasis to dredge channels, and are used as monarch medicines together; the pricklyash peel warms middle energizer to dispel cold and remove dampness, the caulis spatholobi activates blood circulation to relax muscles and tendons, the radix clematidis dispels wind and dampness and unblocks channels and collaterals, and the radix angelicae pubescentis dispels wind and dampness and dispels cold and stops pain, the four medicines are all suitable to be used commonly and are ministerial medicines together; borneol is pungent, bitter and cool, can dredge orifices, dispel depression fire, relieve swelling and pain, gardenia is bitter and cold, clears heat and purges fire, treats sprain gall, has both cold and cool properties, can clear heat evil in channels and can purge stagnated heat of blood of channels and collaterals, and is used as adjuvant drug together; menthol is a pungent and fragrant herb moving away and can induce the action of herbs to reach the disease site, and has the actions of relieving swelling and pain.
The pain-relieving body-building plaster medicine is used as a substance basis for exerting curative effect, medicine molecules need to firstly diffuse through a matrix formed by combining an SIS framework, a softening agent, a tackifier and the like to reach the surface of human skin, SIS used as a framework material is a triblock high molecular copolymer generated by polymerization reaction of styrene and isoprene monomers, the technical parameters mainly comprise the configuration, the block ratio (S/I), the molecular mass and the 2-block SI content of the SIS, and the SIS has excellent medicine wrapping and framework supporting capacity and is a key material for determining the diffusion speed of the medicine. By changing index parameters in the SIS and adjusting corresponding physicochemical properties of the elastomer, the pressure-sensitive adhesive matrix meeting different use requirements can be prepared.
The pain-relieving body-building paste is mainly used for local pain relief, the pain relief effect of the pain-relieving body-building paste has a great relation with the dosage of a medicine acting body part, more than half of dosage still remains in the paste by analyzing the residual dosage of the existing process product after use and taking a volatile medicine as a test index through a daily use period, so that not only is the resource waste caused, but also the medicine can not fully play a role; in addition, some patients are applied for a long time in order to save energy, and the skin of the applied part is easy to cause adverse reactions such as skin irritation, allergy and the like because the skin is in a closed state for a long time. The reason is that the preparation of the plaster substrate has problems, so how to improve and innovate the production process of the plaster substrate, so that the technical problem to be solved is to improve the drug release amount of the plaster and reduce the overdue application of the product in practical application.
Disclosure of Invention
In view of the above situation, the present invention aims to provide a method for preparing a plaster matrix capable of rapidly releasing volatile drugs, which can effectively solve the problem of resource waste caused by insufficient release of drug amount when the existing plaster is used.
In order to achieve the aim, the technical scheme of the invention is that the preparation method of the emplastrum matrix for rapidly releasing the volatile medicine is characterized in that the emplastrum matrix is prepared by mixing SIS framework material with liquid paraffin, antioxidant BHT and hydrogenated rosin glyceride, and comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until the reaction kettle is anhydrous and anaerobic, cooling to room temperature, adding 1900-2100mL of cyclohexane into the reaction kettle, sequentially adding 23-26g of styrene, 1-1.4mL of tetrahydrofuran and 5-7mL of 1.5 multiplied by 10 -5 Heating the reaction kettle to 40-45 ℃ with mol/L n-butyllithium to initiate the first block polymerization reaction, wherein the temperature is 200-25%Reacting for 30-35min under the condition of 0 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, under the protection of nitrogen, adding 440-460g of isoprene monomer into the reaction kettle, heating to 45-50 ℃, initiating a second block polymerization reaction, and stirring and reacting for 35-40min under the condition of 200-250 rpm; c. after the second block polymerization is finished, controlling the temperature to be 50-52 ℃, adding 23-27g of styrene monomer into the reaction kettle under the protection of nitrogen, heating to 55-60 ℃, initiating a third block polymerization reaction, and stirring and reacting for 30-35min under the condition of 150-200 rpm; d. after the third block polymerization reaction is finished, adding 900-1100ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying at 48-52 ℃ for 10-14h to obtain a dried SIS elastomer;
(2) Preparing a plaster matrix: putting 180-210g of SIS elastomer, 45-55g of liquid paraffin and 2-4g of antioxidant BHT into a closed oil bath stirring tank, stirring for 50-60min at 95-100 ℃ and 60-80rpm, adding 90-110g of hydrogenated rosin glyceride into the oil bath stirring tank, stirring for 20-30min at 85-90 ℃ and 60-80rpm, and obtaining the emplastrum substrate.
The preparation method of the emplastrum matrix for rapidly releasing the volatile medicine comprises the following steps:
(1) Placing the medicinal paste and the emplastrum matrix into a stirring tank, and stirring for 20-30min at 65-70 ℃ and 60-70rpm, wherein the emplastrum matrix is as follows: the content ratio of the medicine paste is 3-10 to obtain a mixture colloid, and the mixture colloid passes through a 80-mesh screen;
(2) Uniformly coating the sieved mixture colloid by a transfer method, controlling the temperature of a coating head of a glue spreader to be 85-90 ℃, the coating speed to be 5m/min and the paste content to be 1.5g/100cm 2 Cutting the composite elastic cloth into required size.
The preparation method is simple, can realize the rapid release of the medicine, has the accumulated release rate obviously higher than that of the original formula process sample, reduces the resource waste, provides a feasible method for improving the potential curative effect of the product, and has remarkable social and economic benefits.
Drawings
FIG. 1 is an NMR spectrum of a control group of the present invention.
FIG. 2 is an NMR spectrum of an experimental group of the present invention.
Detailed Description
The following examples and specific examples will explain the present invention in detail.
Example 1
A preparation method of a plaster matrix for rapidly releasing volatile medicines comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until the reaction kettle is anhydrous and anaerobic, cooling to room temperature, adding 1900mL of cyclohexane into the reaction kettle, sequentially adding 23g of styrene, 1mL of tetrahydrofuran and 5mL of 1.5 multiplied by 10 -5 Heating the reaction kettle to 40 ℃ by using mol/L n-butyllithium, initiating a first block polymerization reaction, and reacting for 35min under the condition of 200 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, adding 440g of isoprene monomer into the reaction kettle under the protection of nitrogen, heating to 45 ℃, initiating a second block polymerization reaction, and stirring and reacting for 40min under the condition of 200 rpm;
c. after the second block polymerization is finished, controlling the temperature at 50 ℃, under the protection of nitrogen, adding 23g of styrene monomer into the reaction kettle, heating to 55 ℃, initiating a third block polymerization reaction, and stirring and reacting for 35min under the condition of 150 rpm;
d. after the third block polymerization reaction is finished, adding 900ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying for 14h at 48 ℃ to obtain a dried SIS elastomer;
(2) And preparing a plaster matrix: putting 180g of SIS elastomer, 45g of liquid paraffin and 2g of antioxidant BHT into a closed oil bath stirring tank, stirring for 60min at 95 ℃ and 60rpm, adding 90g of hydrogenated rosin glycerol ester into the oil bath stirring tank, and stirring for 30min at 85 ℃ and 60rpm to obtain the emplastrum matrix.
Example 2
A preparation method of a plaster matrix for rapidly releasing volatile medicines comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until the reaction kettle is anhydrous and anaerobic, cooling to room temperature, adding 2000mL of cyclohexane into the reaction kettle, and sequentially adding 25g of styrene, 1.2mL of tetrahydrofuran and 6mL of 1.5 multiplied by 10 -5 Heating the reaction kettle to 43 ℃ by mol/L n-butyllithium, initiating a first block polymerization reaction, and reacting for 32min at 230 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, adding 450g of isoprene monomer into the reaction kettle under the protection of nitrogen, heating to 48 ℃, initiating a second block polymerization reaction, and stirring at 230rpm for 38min;
c. after the second block polymerization is finished, controlling the temperature at 52 ℃, adding 25g of styrene monomer into the reaction kettle under the protection of nitrogen, heating to 57 ℃, initiating a third block polymerization reaction, and stirring and reacting for 32min at 180 rpm;
d. after the third block polymerization reaction is finished, adding 1000ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying for 12 hours at 50 ℃ to obtain a dried SIS elastomer;
(2) And preparing a plaster matrix: putting 200g of SIS elastomer, 50g of liquid paraffin and 3g of antioxidant BHT into a sealed oil bath stirring tank, stirring for 55min at 97 ℃ and 70rpm, adding 100g of hydrogenated rosin glyceride into the oil bath stirring tank, and stirring for 25min at 87 ℃ and 70rpm to obtain the emplastrum matrix.
Example 3
A preparation method of a plaster matrix for rapidly releasing volatile medicines comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until no water and no oxygen exist, cooling the reaction kettle to room temperature, adding 2100mL of cyclohexane into the reaction kettle, and sequentially adding 26g of benzeneEthylene, 1.4mL of tetrahydrofuran and 7mL of 1.5X 10 -5 Heating the reaction kettle to 45 ℃ with mol/L n-butyllithium, initiating a first block polymerization reaction, and reacting for 30min at 250 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, under the protection of nitrogen, adding 460g of isoprene monomer into the reaction kettle, heating to 50 ℃, initiating a second block polymerization reaction, and stirring and reacting for 35min at 250 rpm;
c. after the second block polymerization is finished, controlling the temperature to be 50-52 ℃, adding 27g of styrene monomer into the reaction kettle under the protection of nitrogen, heating to 60 ℃, initiating a third block polymerization reaction, and stirring and reacting for 30min under the condition of 200 rpm;
d. after the third block polymerization reaction is finished, adding 1100ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying at 52 ℃ for 10 hours to obtain a dried SIS elastomer;
(2) And preparing a plaster matrix: placing 210g of SIS elastomer, 55g of liquid paraffin and 4g of antioxidant BHT together in a closed oil bath stirring tank, stirring for 50min at 100 ℃ and 80rpm, adding 110g of hydrogenated rosin glyceride into the oil bath stirring tank, and stirring for 20min at 90 ℃ and 80rpm to obtain the emplastrum substrate.
Example 4
A preparation method of a plaster matrix for rapidly releasing volatile medicines comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until the reaction kettle is anhydrous and anaerobic, cooling to room temperature, adding 2000mL of cyclohexane into the reaction kettle, sequentially adding 24g of styrene, 1.3mL of tetrahydrofuran and 6mL of 1.5 multiplied by 10 -5 Heating the reaction kettle to 41 ℃ by using mol/L n-butyllithium, initiating a first block polymerization reaction, and reacting for 32min under the condition of 210 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, adding 445g of isoprene monomer into the reaction kettle under the protection of nitrogen, heating to 46 ℃, initiating a second block polymerization reaction, and stirring at 245rpm for 36min;
c. after the second block polymerization is finished, controlling the temperature at 50 ℃, adding 24g of styrene monomer into the reaction kettle under the protection of nitrogen, heating to 56 ℃, initiating a third block polymerization reaction, and stirring and reacting for 31min at 180 rpm;
d. after the third block polymerization reaction is finished, adding 1000ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying for 11 hours at 50 ℃ to obtain a dried SIS elastomer;
(2) Preparing a plaster matrix: 185g of SIS elastomer, 47g of liquid paraffin and 2g of antioxidant BHT are placed in a closed oil bath stirring tank together, stirred for 52min at 96 ℃ and 65rpm, 96g of hydrogenated rosin glyceride is added into the oil bath stirring tank, and stirred for 28min at 86 ℃ and 65rpm, so that the emplastrum substrate is obtained.
The emplastrum substrate prepared by the method in any one of the embodiments 1-4 of the invention can effectively realize the rapid and full release of the medicine, and the same or similar results are obtained through a plurality of repeated tests, taking the embodiment 2 as an example, the related data are as follows:
1. preparation of control and experimental groups:
the pain-relieving and body-building ointment originally invented by the Henan Ling Sha pharmaceutical Co., ltd is used as a control group (patent No. CN 201210358615.2), and the experimental group takes the emplastrum base prepared in example 2 as an example to prepare a plaster containing medicines.
The preparation method of the control group comprises the following steps: firstly, 92g of salvia miltiorrhiza, 92g of safflower, 92g of suberect spatholobus stem, 92g of gardenia, 46g of clematis root, 46g of pubescent angelica root and 46g of pepper are crushed into coarse powder, ethanol with the volume concentration of 90 percent is used for soaking for 24 hours and then is percolated according to the percolation method under the general rule of 0189 fluid extract and extract item of the four departments of 2020 version of Chinese pharmacopoeia, 900ml of primary percolate is collected, the medicine residue is added with solvent gasoline for extraction for 3 times, 450ml is added for the first time, 220ml is added for the second time and the third time, extract oil is obtained, the medicine residue after the oil is extracted is continuously percolated by ethanol with the volume concentration of 70 percent, 1250ml of medicine residue percolate of salvia miltiorrhiza, safflower, suberect spatholobus stem, gardenia, clematis root, pubescent angelica root and pepper is collected and is combined with 900ml of primary percolate, and is decompressed and concentrated to the relative density measured at 70 ℃ which is not lowerExtracting the extract in the amount of 1.25 for later use; preparing thermoplastic elastomer SIS605g, liquid paraffin 160g, rosin glyceride 605g, antioxidant 2,6-ditert-butyl-p-cresol 15g into matrix, adding the above extract, extract oil, borneolum 135g, camphora 92g, and Mentholum 92g, mixing, spreading on base fabric with an ointment content of 1.5g/100cm 2 Covering with anti-sticking layer, and slicing to obtain control group unguent.
The preparation method of the experimental group comprises the following steps: firstly, crushing 92g of salvia miltiorrhiza, 92g of safflower, 92g of suberect spatholobus stem, 92g of gardenia, 46g of clematis root, 46g of pubescent angelica root and 46g of pepper into coarse powder, soaking the coarse powder for 24 hours by using 90% ethanol according to a percolation method under the general rule 0189 fluid extract and extract item of the four ministerial of China pharmacopoeia 2020, percolating the coarse powder after collecting 900ml of primary percolate, adding a solvent gasoline into the dregs of a decoction for extraction for 3 times, adding 450ml into the first time, and obtaining an extract oil by using 220ml of both the second time and the third time, continuously percolating the dregs of the extract oil by using 70% ethanol, collecting 1250ml of dregs of salvia miltiorrhiza, safflower, suberect spatholobus stem, gardenia, clematis root, pubescent angelica root and pepper, merging with 900ml of primary percolate, and concentrating the mixture under reduced pressure to obtain an extract with a relative density of not less than 1.25 for later use; placing the extract, the extract oil, 135g of borneol, 92g of camphor and 92g of menthol and the emplastrum substrate prepared in the embodiment 2 into a stirring tank, and stirring for 25min at 67 ℃ and 65rpm, wherein the emplastrum substrate is as follows: the mass ratio of the extract is 3.3; uniformly coating the mixture colloid by transfer method, controlling the coating head temperature of the coater at 85 deg.C, coating speed at 5m/min, and paste content of 1.5g/100cm 2 And cutting the composite elastic cloth into specified sizes to obtain the experimental ointment.
2. SIS elastomer index determination
The number average molecular weight, the weight average molecular weight and the diblock content of the SIS of the control group and the SIS of the experimental group are measured by a gel permeation chromatograph. Mn is the number average molecular weight, mw is the weight average molecular weight, and Mw/Mn is the molecular weight distribution of SIS. As can be seen from Table 1, the molecular weights of the experimental groups were significantly lower than those of the control group, and the molecular weight distributions of the SIS were not significantly different.
TABLE 1 molecular weight, SI content of SIS
Figure BDA0003658800830000061
And (3) testing the styrene content in the SIS by using NMR, and according to the NMR spectrum analysis data, calculating to obtain that the styrene content in the SIS before optimization is 32%, and the styrene content in the SIS after optimization is 14%, so that the styrene content is obviously reduced. The NMR spectrum is shown in FIG. 1 and FIG. 2:
from the above, it can be seen that the number average molecular weight of the SIS triblock copolymer was reduced from 13 to 10 ten thousand, the styrene content was reduced from 32 to 14%, and the diblock SI content was all 0, as determined by gel permeation chromatography.
3. Evaluation method
Representative volatile substances of camphor, menthol, borneol and limonene are selected, an in-vitro release experiment is adopted to carry out in-vitro release on the plaster, and the condition that the medicine is released through a matrix can be visually compared.
4. Preparation of control solutions
Accurately weighing Camphora control, mentholum control, borneolum Syntheticum control and limonene control, and adding ethyl acetate to obtain solutions containing 1.0mg, 1.0mg and 0.2mg per 1ml as mixed control stock solutions.
5. Determination of correction factors
Naphthalene was precisely weighed and added with ethyl acetate to prepare a solution containing 0.05mg per 1mL as an internal standard solution. And measuring 1mL of the mixed reference substance stock solution and 2mL of the internal standard solution, placing the mixed reference substance stock solution and the internal standard solution into a 50mL volumetric flask, adding ethyl acetate to a constant volume to a scale, shaking up, precisely sucking 1 mu L, injecting into a gas chromatograph, and measuring. The correction factors f of camphor, menthol, borneol and limonene are respectively calculated as follows: 1.01, 1.05, 1.08, 1.03.
6. Preparation of test solution
Respectively sticking the samples of the experimental group and the control group on a vertical Franz diffusion cell tightly, with the drug-containing side facing the receiving cell, and the release solution of 20% PEG400 normal saline at 300 r.min -1 Diffusion area of 3.14cm 2 The total volume of the receiving pool is 18mL,32 ± -2Water bath circulation at 0.5 ℃. Sampling is carried out for 0.5, 1, 2, 4, 6, 8, 12 and 24 hours respectively, 5ml of the sample is taken each time, and release liquid with equal volume and equal temperature is added simultaneously. The released liquid is taken out and placed in a centrifuge tube, 4ml of ethyl acetate and 1ml of naphthalene internal standard solution are added, shaking is carried out evenly, centrifugation is carried out for 5min (centrifugal force 2414.88 Xg), and supernatant is taken to be used as a test solution.
7. Chromatographic conditions
A capillary column (column length of 30cm, column inner diameter of 0.32mm, membrane thickness of 0.25 μ M) using polyethylene glycol 20000 (PEG-20M) as stationary phase, column temperature of 140 deg.C, injection port temperature of 180 deg.C, detector FID of 230 deg.C. The carrier gas is nitrogen, the flow rate is 2 ml/min -1 And the flow ratio of the hydrogen to the water is 20 -1 Air flow rate of 400 ml/min -1 (ii) a The sample amount is 1 mul, the theoretical plate number is not less than 10000 calculated according to the naphthalene peak, the separation degree of each peak and the adjacent chromatographic peak is more than 1.5, and the tailing factor of each peak is between 0.95 and 1.05.
8. Sink conditions
Respectively measuring 20mL of normal saline, 20mL of 20% ethanol normal saline and 20mL of 20% PEG400 normal saline, placing the solution in a vial with a cover, respectively adding 3 parts of camphor, menthol, borneol and limonene, and continuously oscillating in a 32 ℃ water bath for 72 hours to achieve dissolution balance. Centrifuging the sample solution (centrifugal force 2414.88 Xg) for 10min, separating the measuring solution in a leak groove, extracting with ethyl acetate for 3 times, 5ml each time, filtering the extract with anhydrous sodium sulfate to 20ml volumetric flask, adding ethyl acetate to constant volume to scale, injecting into a gas chromatograph, and measuring.
9. In vitro release
The test solutions of the experimental group and the control group were measured under the above-mentioned chromatographic conditions, and the cumulative release amount per unit area (Q) at each time point of the components was calculated by the following formula n )：
Figure BDA0003658800830000071
In the formula, "C n "is the drug concentration (μ g. ML) measured at the nth sampling point -1 )；“C i ' isThe drug concentration (mu g/mL) measured at the ith (i is more than or equal to 1 and less than or equal to n-1) sampling point -1 )；“V 0 "receiving pool volume (18 mL)," V i "is the sample volume (5 mL)," A "is the area of release (3.14 cm) 2 )，“Q n "cumulative permeation quantity per unit area (μ g. Cm) -2 ). SPSS22.0 software is adopted to carry out t-test statistical analysis on independent samples, and whether the release rates of the index components in the control group and the experimental group are significantly different or not is compared.
At 3.14cm 2 The amounts of camphor, menthol, borneol and limonene in the experimental group and the control group were equal for the release area, the average values of the groups were 5.642mg, 5.642mg, 7.899mg and 0.020mg, respectively, and the volume of the release solution was 18ml, calculated, 20% of PEG400 physiological saline was used as the release solution, and the sink conditions were satisfied that the volume of the release solution was at least 5 times the volume of the saturated solution of each substance.
The saturated concentrations of camphor, menthol, borneol and limonene in the three release solutions are shown in table 2:
TABLE 2 saturated concentration mg/ml of the components
Figure BDA0003658800830000072
The accumulative release rate of representative index components of borneol, camphor, menthol and limonene in an experimental group for 24 hours is obviously higher than that of a control group, and is respectively improved by 2.1, 2.3, 2.5 and 2.3 times (P is less than 0.05), and the comparison results are shown in a table 3:
table 3 24h cumulative release (%) (x ± s, n = 6)
Figure BDA0003658800830000073
And (3) fitting a kinetic equation to the time (t) according to the cumulative release percentage of each index component at different time points, wherein the fitting equation selects the zero-order, first-order and Higuchi. The results show that the cumulative release percentage-time curves of the index components in the experimental group have higher fitting degree by taking the Higuchi equation as a mathematical model, and the in vitro release rules of the index drugs are consistent.
From the above, it is clear that the invention enables the in vitro release of the index drug to be effectively accelerated by optimizing and modifying the performance index in the framework material SIS, which provides the premise for improving the curative effect of the product in the application process. Novel SIS were prepared by reducing the number average molecular weight of SIS triblock copolymers from 13 to 10 ten thousand, the styrene content from 32 to 14%, and neither containing a diblock. In addition, according to the characteristics of multiple Chinese herbal compound medicines, complex components, various active ingredients and low content, the principle of effectiveness, specificity, testability, traceability and transmission and traditional Chinese medicine theory compatibility is combined, representative index components are selected, and in-vitro release experiments prove that the pain-relieving body-building ointment prepared by the emplastrum matrix prepared by the method can realize the rapid release of volatile medicines, and the cumulative release rate is obviously higher than that of the original formula process samples.
The above experiments are repeated three times, the results are consistent, the same experiments are also performed on the examples 1, 3 and 4 while the experiment is performed on the example 2, the same results similar to the example 2 are obtained, and the experiments do not list one by one, so that the preparation method is stable and reliable, has good effect, and has good use and popularization values.
The preparation method is simple, can realize the rapid and sufficient release of the medicine, has the accumulated release rate obviously higher than that of the original prescription process sample, reduces the resource waste, improves the potential curative effect of the product, and has remarkable social and economic benefits.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.

Claims (3)

1. A preparation method of a emplastrum for rapidly releasing volatile medicines is characterized by comprising the following steps:
1. preparation of emplastrum base
The emplastrum matrix is prepared by mixing SIS framework material with liquid paraffin, antioxidant BHT and hydrogenated rosin glyceride, and comprises the following steps:
(1) Synthesis of linear SIS block copolymers:
a. heating and baking the reaction kettle, repeatedly replacing the reaction kettle with nitrogen until the reaction kettle is anhydrous and oxygen-free, cooling the reaction kettle to room temperature, adding 2000mL of cyclohexane into the reaction kettle, and sequentially adding 25g of styrene, 1.2mL of tetrahydrofuran and 6mL of 1.5 multiplied by 10 -5 Heating the reaction kettle to 43 ℃ by mol/L n-butyllithium, initiating a first block polymerization reaction, and reacting for 32min at 230 rpm;
b. after the first block polymerization is finished, cooling to 25 ℃, under the protection of nitrogen, adding 450g of isoprene monomer into the reaction kettle, heating to 48 ℃, initiating a second block polymerization reaction, and stirring at 230rpm for 38min;
c. after the second block polymerization is finished, controlling the temperature at 52 ℃, adding 25g of styrene monomer into the reaction kettle under the protection of nitrogen, heating to 57 ℃, initiating a third block polymerization reaction, and stirring and reacting for 32min at 180 rpm;
d. after the third block polymerization reaction is finished, adding 1000ml of anhydrous methanol to terminate the reaction to obtain an SIS elastomer, placing the SIS elastomer in a vacuum oven, and drying for 12 hours at 50 ℃ to obtain a dried SIS elastomer;
(2) Preparing a plaster matrix: putting 200g of SIS elastomer, 50g of liquid paraffin and 3g of antioxidant BHT together into a closed oil bath stirring tank, stirring for 55min at 97 ℃ and 70rpm, adding 100g of hydrogenated rosin glyceride into the oil bath stirring tank, and stirring for 25min at 87 ℃ and 70rpm to obtain a plaster matrix;
2. preparing the medicine-containing emplastrum
(1) Placing the medicinal paste and the emplastrum matrix into a stirring tank, and stirring for 25min at 67 ℃ and 65rpm, wherein the emplastrum matrix is as follows: the content ratio of the medicine paste is 3.3;
(2) Uniformly coating the sieved mixture colloid by a transfer method, controlling the temperature of a coating head of a glue spreader to be 85 ℃, the coating speed to be 5m/min and the paste content to be 1.5g/100cm 2 Cutting the composite elastic cloth into a specified size to obtain the composite elastic cloth;
the medicinal ointment is prepared from 92g of salvia miltiorrhiza, 92g of safflower, 92g of suberect spatholobus stem, 92g of cape jasmine fruit, 46g of clematis chinensis, 46g of radix angelicae pubescentis, 46g of pepper, 135g of borneol, 92g of camphor and 92g of menthol.
2. The method of claim 1, wherein said patch matrix SIS has a number average molecular weight of 10 ten thousand, a styrene content of 14%, and a diblock SI content of 0.
3. A medicated patch prepared by the process of claim 1.
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010006761A (en) * 2008-06-27 2010-01-14 Yutoku Yakuhin Kogyo Kk Percutaneous absorption patch containing fentanyl or its salt and method for producing the same
CN101745088A (en) * 2009-12-02 2010-06-23 甘肃奇正藏药有限公司 Damp pain-relieving rubber paste and making method thereof
CN102558466A (en) * 2012-01-10 2012-07-11 宁波科元塑胶有限公司 Synthesis method of transparent block copolymer
CN105218766A (en) * 2015-11-10 2016-01-06 宁波科元特种橡胶有限公司 A kind of synthetic method of styrene isoprene styrene block copolymer (SIS)
CN106822326A (en) * 2015-12-07 2017-06-13 北京乳凝创智生物技术研发中心（有限合伙） New medicine patch cervicodynia emplastrum and preparation method thereof
CN107828000A (en) * 2017-09-30 2018-03-23 山东玉皇化工有限公司 A kind of method of styrene-isoprene-styrene triblock copolymer homogeneous catalytic hydrogenation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102573843B (en) * 2009-10-21 2014-09-24 帝国制药株式会社 Transdermally absorbable donepezil-containing preparation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010006761A (en) * 2008-06-27 2010-01-14 Yutoku Yakuhin Kogyo Kk Percutaneous absorption patch containing fentanyl or its salt and method for producing the same
CN101745088A (en) * 2009-12-02 2010-06-23 甘肃奇正藏药有限公司 Damp pain-relieving rubber paste and making method thereof
CN102558466A (en) * 2012-01-10 2012-07-11 宁波科元塑胶有限公司 Synthesis method of transparent block copolymer
CN105218766A (en) * 2015-11-10 2016-01-06 宁波科元特种橡胶有限公司 A kind of synthetic method of styrene isoprene styrene block copolymer (SIS)
CN106822326A (en) * 2015-12-07 2017-06-13 北京乳凝创智生物技术研发中心（有限合伙） New medicine patch cervicodynia emplastrum and preparation method thereof
CN107828000A (en) * 2017-09-30 2018-03-23 山东玉皇化工有限公司 A kind of method of styrene-isoprene-styrene triblock copolymer homogeneous catalytic hydrogenation

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