CN105998463A - Micro needle transdermal patch for treating osteoarthritis and preparation method thereof - Google Patents
Micro needle transdermal patch for treating osteoarthritis and preparation method thereof Download PDFInfo
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- CN105998463A CN105998463A CN201610478678.XA CN201610478678A CN105998463A CN 105998463 A CN105998463 A CN 105998463A CN 201610478678 A CN201610478678 A CN 201610478678A CN 105998463 A CN105998463 A CN 105998463A
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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Abstract
The invention discloses a micro needle transdermal patch for treating osteoarthritis and a preparation method thereof. The micro needle transdermal patch is prepared from bark of oriental variegated coralbean, radix achyranthis bidentatae, tinospora sinensis(Lour.)Merr., caulis spatholobi, radix clematidis, rhizoma homalomenae, herba lycopodii, lignum sappan, raw folium artemisiae argyi, herbs of tuberculate speranskia, rhizoma corydalis, seeds of peppertree pricklyash and tacrolimus. The patch is composed of a base plate, medicament, an ointment blank patch body and an ointment back patch body, the front face of the base plate is provided with a plurality of micro needles, micro needle gaps are formed among the micro needles, the medicament is stored in the micro needle gaps and a porous structure, the back face of the base plate is a plane and is pasted to the inner surface of the ointment blank patch body, the inner surface of the ointment back patch body is arranged on the front face of the base plate in a covering mode, and the inner surface of the ointment blank patch body and the inner surface of the ointment back patch body are fixedly connected in a pasting mode. The invention further discloses preparation steps of the micro needle transdermal patch. The micro needle transdermal patch has the advantages of being good in curative effect, quick in effect initiating, nearly free of damage to human skin and free of toxic or side effect.
Description
Technical field
The present invention relates to tcm field, particularly relate to a kind of microneedle cutaneous patch of herbal mixture treating osteoarthritis and system thereof
Preparation Method.
Background technology
Osteoarthritis, also known as osteoarthritis, osteoarthritis, senile arthritis, hypertrophiarthritis etc., is owing to constituting
Soft tissue degeneration, the degenerations such as the cartilage in joint, intervertebral disc, ligament, joint margins synovial membrane etc. changes, and causes insecondary bone to close
Joint inflammation, osteoarthritis belongs to the category of ' rheumatism involving the bone ' of the traditional Chinese medical science.Rheumatism involving the bone is not enough by human righteousness or liver and kidney deficiency, muscles and bones lose in
Moisten foster, invaded meridians by exopathogen such as wind, cold, wets, cause meridians inaccessible, block joint, qi stagnation hemagglutination, with the passing of time cause pass
Joint deformation, enlargement, joint stuffiness, numb pain.The treatment of osteoarthritis, doctor trained in Western medicine is mainly to relieve the pain medicine or play closing
Pin, as with medicines such as indometacin, ibuprofen, big to gastric irritation, side effect is big, and life-time service patient can not accept, and plays closing
Pin mainly uses procaine hydrochloride, meticortelone, although treatment is effectively, but effect is undesirable, and have then takes operation.In
Doctor has medication treatment, medicament, unguentum, patch etc.；Physiotherapy has therapies such as massage, acupuncture, cup, existing in
Medication effect is respectively arranged with feature.
A kind of microneedle cutaneous patch treating osteoarthritis that the present invention relates to is a kind of to optimize the new of existing microneedle transdermal patch
Preparation.On the least area, with micron-sized porous microneedle keratodermatitis, make to be stored in micropin loose structure Chinese medicine
Thing penetrates infiltration epidermal area.Avoid the chemical permeation enhancers overstimulation to skin, simplify percutaneous importing process simultaneously,
Said preparation is coated filling liquid using solid lipid nanoparticle suspension as the micropin of ingredient, it is possible to achieve ingredient accurately,
Painless, slow release, efficiently, be advantageously administered.
Summary of the invention
It is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of microneedle cutaneous patch treating osteoarthritis and
Its preparation method, to solve common Chinese liniment, liniment, patch and the micropin patch medicament storage when preparation or actual application
Measure the technical problem such as little, the sustained release time is short and propose.
The present invention is achieved by the following technical solutions: a kind of microneedle cutaneous patch treating osteoarthritis, including following former
Material and content: Cortex erythrinae 30～50 grams, Radix Achyranthis Bidentatae 40～60 grams, Herba Lycopodii 30～50 grams, Caulis Spatholobi 20～40 grams, Wheeling
30～40 grams, Rhizoma Homalomenae 30～50 grams, Herba Lycopodii 30～40 grams, Lignum Sappan 30～40 grams, raw Folium Artemisiae Argyi 30～50 grams, deep
Grass 30～50 grams, Rhizoma Corydalis 40～50 grams, Semen zanthoxyli 20～30 grams, Herba Menthae 40～60g and adjuvant Tween-80 10～50
Milliliter, mass ratio are the soybean phospholipid of 1:1～3:1 and glyceryl monostearate mixture 10～30 grams, tacrolimus 0.5～1
Gram.
A kind of microneedle cutaneous patch treating osteoarthritis disclosed by the invention, including substrate, medicament, ointment blank patch and medicine
Cream back of the body patch, substrate is positioned at the centre of ointment blank patch and ointment back of the body patch, and substrate uses the material with loose structure, and substrate is just
Face is provided with more than one micropin, and the top of micropin is provided with sharp portion, and micropin is vertically fixed on substrate, has micro-between micropin
Pin gap, medicament is stored among micropin gap and loose structure, and the back side of substrate is plane, and the back side of substrate is pasted onto ointment
On the inner surface of blank patch, the inner surface of ointment back of the body patch covers on the front of substrate, and the inner surface of ointment blank patch is carried on the back with ointment
The inner surface of patch is fixedly connected by the way of pasting.In use, can directly open backing layer will be containing medicament for patient
Adhesive layer be attached to affected part, thus realize the purpose for the treatment of.
In order to ensure the convenience of the microneedle cutaneous patch of herbal mixture and improve therapeutic efficiency, microneedle array is multiple, micropin
The length of array and width are all for being designed as 0.5cm, and the spacing between microneedle array is adjacent is 0.1cm, in actual production, it is also possible to
According to market demand be designed as all size and shape to plaster.
Wherein, in order to ensure can to store more medicine component and the time of increase medicament sustained release to plaster, substrate is selected
Material be the one in porous silicon, POROUS TITANIUM or expanded polystyrene or other composites.The selection of substrate to possess
Loose structure skin to human body simultaneously will not produce the material of secondary injury.
The preparation method of a kind of microneedle cutaneous patch treating osteoarthritis disclosed by the invention, including following preparation process:
1) Cortex erythrinae 30～50 grams, Radix Achyranthis Bidentatae 40～60 grams, Herba Lycopodii 30～50 grams, Caulis Spatholobi 20～40 grams, prestige are weighed
Spirit 30～40 grams, Rhizoma Homalomenae 30～50 grams, Herba Lycopodii 30～40 grams, Lignum Sappan 30～40 grams, raw Folium Artemisiae Argyi 30～50 grams, saturating
GUCAO 30～50 grams, Rhizoma Corydalis 40～50 grams, Semen zanthoxyli 20～30 grams, join the concentration of 2000～3000 grams after being pulverized and mixed
Be 50～80% ethanol solution in soak, filter, collect filtrate and to described filtrate solvent evaporate after, obtain herbal mixture dense
Contracting thing I；
2) weigh Herba Menthae 40～60 grams put in there-necked flask, distillation, to distillate centrifugal treating, centrifugal after stand, take
Upper strata fluid, obtains active Chinese drug component compositions II；
3) by step 1) described in herbal mixture concentrate I, with 200～1000ml purified water and 10～50ml poly-Pyrusussuriensiss
The mixed liquor of ester-80 dissolves, ultrasonic disperse after three's mixing, and stirring is incubated under the conditions of 65～75 DEG C, obtains mixed liquor A；
4), after mass ratio being 1:1～3:1 soybean phospholipid and glyceryl monostearate mixing, 10～30 grams of mixture are obtained
B, dissolves described mixture B with the ethanol/dichloromethane mixed liquor that 200～500ml volume ratios are 4:1, obtains solution
C, by step 2) in the active Chinese drug component compositions II of gained be stirred with described solution C and tacrolimus crude drug, ultrasonic molten
After solving dispersion, prepare mixed liquor D；
5) by mixed liquor D implantation step 3) in described mixed liquor A in stir, obtain milky suspension E, by described
After milky suspension E ultrasonic disperse, obtain lipid nanoparticle suspension crude product F；
6) by step 5) described in lipid nanoparticle suspension crude product F inject in high pressure homogenizer, at cold water (2-6 DEG C)
Carrying out high pressure homogenize under circulator bath, the operating pressure that described high pressure homogenizer sets as 2000Bar, after concentration, obtains in compound recipe
Medicine solid lipid nanoparticle G.
7) use laser-etching method that the one side of porous silicon substrate is cut into microneedle array, make many with 0.5*0.5cm size
Hole microneedle unit；Described microneedle unit is placed in described herbal mixture solid lipid nanoparticle G, through being coated, filling,
After taking-up is dried, described microneedle unit is fixed on described adhesive layer, then is covered with described backing layer and i.e. obtains herbal mixture micropin transdermal
To plaster.Wherein microneedle array is the arrangement of square formation formula, and unit interval 0.1cm, scope of structuring the formation 2*2cm to 4*4cm are producing
Time can give quantitative flexible selection by different size.
Wherein, the front of substrate forms many micropins after laser-etching method in its surface, and these micropins are formed on substrate
One group of rectangular-shaped microneedle array, microneedle array is multiple, and the length of microneedle array and width are all 0.5cm, between adjacent microneedle array
Spacing be 0.1cm.
Wherein, step 1) in soak time be decided according to the actual requirements, step 3) in 200～2000ml purified water steps 4)
In weigh the weight ratio of soybean phospholipid and glyceryl monostearate between 1:1～1:3, the two mixed weight 10～30g it
Between, measure ethanol/dichloromethane mixed liquor that volume ratio is 4:1 200～500ml, can be by mixture as long as realizing mixed liquor
It is completely dissolved.Step 5) in order to realize stirring, mixing speed should control 1500～2000rpm.Step 7) in base
Panel material can be selected for the composite of one or more in porous silicon, POROUS TITANIUM or expanded polystyrene.
The present invention by solid lipid nanoparticle technology and micropin percutaneous technique R. concomitans in percutaneous administration patch, by by slightly solubility
Composition makes solid lipid nanoparticle, improves medicine carrying efficiency, homogeneous with water soluble ingredient mixes, by permeating, inlay, filling,
The mode such as it is coated, effective ingredient is carried on (interior) on the micropin that porous polymer materials is made, medicine is penetrated horny layer and goes directly
It is delivered to epidermal area effective site.This porous micropin is also equipped with the slow release effect of similar porous microsphere, can avoid patient repeat to
Medicine, extends drug effect.
Accompanying drawing explanation
Fig. 1 is substrate back structural representation；
Fig. 2 is microneedle array structural representation；
Fig. 3 is the product structure schematic diagram of the present invention；
Fig. 4 is the scanning electron microscope (SEM) photograph of substrate loose structure.
Detailed description of the invention
Elaborating embodiments of the invention below, the present embodiment is implemented under premised on technical solution of the present invention,
Give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.This
Bright include: ointment blank patch inner surface 1, substrate 2, ointment back of the body patch 3, medicament, microneedle array gap 4, sharp portion 5, micro-
Pin 6 and micropin gap 7；
Embodiment 1
As shown in figures 1-4, substrate 2 is positioned at the centre of ointment blank patch and ointment back of the body patch, and the front of substrate is through laser-etching method
After form many micropins 6 in its surface, these micropins 6 form one group of rectangular-shaped microneedle array on a substrate 2.Substrate 2 is adopted
With having the porous silica material of loose structure, the top of micropin 6 is provided with sharp portion 5, and micropin 6 is vertically fixed on substrate 2,
Having micropin gap 7 between micropin 6, medicament is stored among micropin gap 7 and loose structure, and the back side of substrate 2 is plane,
The back side of substrate 2 is pasted onto on the inner surface 1 of ointment blank patch, and the inner surface of ointment back of the body patch 3 covers on the front of substrate 2,
The inner surface 1 of ointment blank patch is fixedly connected by the way of pasting with the inner surface of ointment back of the body patch, sets between microneedle array
Having microneedle array gap 4, the spacing of adjacent microneedle array is 0.1cm, and the size of microneedle array is 0.5*0.5cm, scope of structuring the formation
2*2cm。
Embodiment 2
In the present embodiment, the material that substrate 2 uses is expanded polystyrene, and substrate 2 has loose structure, the front warp of substrate
Forming many micropins 6 after crossing laser-etching method in its surface, these micropins 6 form one group of rectangular-shaped micropin battle array on a substrate 2
Row, microneedle array is to be arranged in order by multiple micropins 6 to form, and the top of micropin 6 is provided with sharp portion 5, and microneedle array is vertical
Fixing have micropin gap 7 on a substrate 2 between micropin 6, medicament is stored among micropin gap 7 and loose structure, base
The back side of plate 2 is plane, and the back side of substrate 2 is pasted onto on ointment blank patch inner surface 1, and ointment back of the body patch 3 covering is at substrate 2
Front on, ointment blank patch inner surface 1 and ointment the back of the body patch 3 size and shape adapt and opposing parallel setting, micropin
Being provided with microneedle array gap 4 between array, the spacing of adjacent microneedle array is 0.1cm, and the size of microneedle array is 0.5*0.5cm,
The scope of structuring the formation is 4*4cm, in order to paste closely by plaster, can leave 1cm size in the surrounding of ointment blank patch inner surface 1
Paste district, so can improve the sealing effectiveness of plaster, prevent because surrounding covered with dust causes stickup property the strongest.
Embodiment 3
In embodiment 3, the material that substrate 2 uses is porous titanium material, and substrate 2 has loose structure, and the front of substrate 2 sets
Having microneedle array, microneedle array is to be arranged in order by multiple micropins 6 to form, and the top of micropin 6 is provided with sharp portion 5, spine
The big I in portion 5 adjusts the precision of laser-etching according to actual needs and is realized, and microneedle array is vertically fixed on substrate 2, micro-
Having micropin gap 7 between pin 6, medicament is stored among micropin gap 7 and loose structure, and the back side of substrate 2 is plane,
The back side of substrate 2 is pasted onto on the inner surface 1 of ointment blank patch, and the inner surface of ointment back of the body patch 3 covers on the front of substrate 2,
The inner surface 1 of ointment blank patch is fixedly connected by the way of pasting with the inner surface of ointment back of the body patch, sets between microneedle array
Having microneedle array gap 4, the spacing of adjacent microneedle array is 0.1cm, and the size of microneedle array is 0.5*0.5cm, scope of structuring the formation
For 4*4cm.
Embodiment 4
Medicament in above-described embodiment is obtained through the following steps:
1) weigh Cortex erythrinae 30g, Radix Achyranthis Bidentatae 40g, Herba Lycopodii 30g, Caulis Spatholobi 20g, Wheeling 30g, Rhizoma Homalomenae 30g, stretch
Muscle grass 30g, Lignum Sappan 30g, raw Folium Artemisiae Argyi 30g, Herba speranskiae tuberculatae 30g, Rhizoma Corydalis 40g and Semen zanthoxyli 20g, pulverize after mixing, with
Concentration is that mixture is carried out soaking 72h by the ethanol solution of 50%, filters soak, collects filtrate and to described filtrate
Evaporation and concentration, i.e. obtains herbal mixture concentrate I after removing solvent；
2) weigh Herba Menthae 40g and put in there-necked flask, distillation, to distillate centrifugal treating, stand after being centrifuged, take upper strata oil
Liquid, obtains active Chinese drug component compositions II；
3) by step 1) described in herbal mixture concentrate I, dissolve with the mixed liquor of purified water and Tween-80,
Ultrasonic disperse after three's mixing, stirring, it is incubated under the conditions of 65～75 DEG C, obtains mixed liquor A；
4) by after soybean phospholipid that mass ratio is 2:1 and glyceryl monostearate 20 grams mixing, mixture B is obtained, with 400
Milliliter volume ratio is that described mixture B is dissolved by the ethanol/dichloromethane mixed liquor of 4:1, obtains solution C, by step 2)
The active Chinese drug component compositions II of middle gained is stirred with described solution C and tacrolimus crude drug, after ultrasonic dissolution dispersion, and system
Obtain mixed liquor D；
5) by mixed liquor D implantation step 3) in described mixed liquor A in stir, mixing speed 1500rpm, obtain milky white
Color contamination suspension E, after described milky suspension E ultrasonic disperse, continues insulated and stirred, after evaporation of organic solvent, ultrasonic point
Dissipate 30 minutes, obtain lipid nanoparticle suspension crude product F；
6) by step 5) described in lipid nanoparticle suspension crude product F inject in high pressure homogenizer, follow at cold water (2 DEG C)
Carrying out high pressure homogenize under ring water-bath, the operating pressure that described high pressure homogenizer sets as 2000Bar, after concentration, obtains herbal mixture
Solid lipid nanoparticle G.
7) laser-etching method is used the one side of expanded polystyrene substrate to be cut into microneedle array, with 0.5*0.5cm size system
Become porous microneedle unit；Described microneedle unit is placed in described herbal mixture solid lipid nanoparticle G, through being coated, filling out
Fill, take out after drying, described microneedle unit is fixed on described adhesive layer, then be covered with described backing layer and i.e. obtain treatment osteoarthritis
Microneedle cutaneous patch.
Embodiment 5
The medicament mentioned in invention, is extracted by following medical herbs, weighs Cortex erythrinae 50g, Radix Achyranthis Bidentatae 60g, Herba Lycopodii
50g, Caulis Spatholobi 40g, Wheeling 40g, Rhizoma Homalomenae 50g, Herba Lycopodii 40g, Lignum Sappan 40g, raw Folium Artemisiae Argyi 50g, Herba speranskiae tuberculatae 50g,
Rhizoma Corydalis 50g, Semen zanthoxyli 30g, Herba Menthae 60g and tacrolimus 1g preparation process are as follows:
1) weigh Cortex erythrinae 50g, Radix Achyranthis Bidentatae 60g, Herba Lycopodii 50g, Caulis Spatholobi 40g, Wheeling 40g, Rhizoma Homalomenae 50g, stretch
Muscle grass 40g, Lignum Sappan 40g, raw Folium Artemisiae Argyi 50g, Herba speranskiae tuberculatae 50g, Rhizoma Corydalis 50g and Semen zanthoxyli 30g, pulverize after mixing, with
Concentration is that mixture is carried out soaking 72h by the ethanol solution of 60%, filters soak, collects filtrate and to described filtrate
Evaporation and concentration, i.e. obtains herbal mixture concentrate I after removing solvent；
2) weigh Herba Menthae 60g and put in there-necked flask, use steam distillation it is carried out distillation procedure, to distillate from
The heart processes, and stands ten minutes, take upper strata fluid, obtain active Chinese drug component compositions II after being centrifuged；
3) by step 1) described in herbal mixture concentrate I, with 200ml purified water and the mixing of 10ml Tween-80
Liquid dissolves, ultrasonic disperse 30 minutes after three's mixing, stirs, is heated to 65 DEG C and carries out being incubated standby, obtains mixed liquor A；
4) weighing soybean phospholipid and each 5g of glyceryl monostearate, obtain mixture B, measuring 200ml volume ratio is 4:1's
Described mixture B is dissolved by ethanol/dichloromethane mixed liquor, obtains solution C, adds step the most again in described solution C
Rapid 2) active Chinese drug component compositions II described in and 1g tacrolimus crude drug are stirred, and ultrasonic dissolution disperses 15 minutes, prepare
Mixed liquor D；
5) by step 4) described in mixed liquor D implantation step 3) in stirring and in the described mixed liquor A of water bath heat preservation,
Mixing speed 1500rpm, forms milky suspension E, continues insulated and stirred, after evaporation of organic solvent, ultrasonic disperse 30 points
Clock, obtains lipid nanoparticle suspension crude product F；
6) by step 5) described in lipid nanoparticle suspension crude product F inject in high pressure homogenizer, follow at cold water (4 DEG C)
Carrying out high pressure homogenize under ring water-bath, the operating pressure that described high pressure homogenizer sets as 2000Bar, after concentration, obtains herbal mixture
Solid lipid nanoparticle G.
7) use laser-etching method that the one side of POROUS TITANIUM substrate is cut into microneedle array, make porous with 0.5*0.5cm size
Microneedle unit；Described microneedle unit is placed in described herbal mixture solid lipid nanoparticle G, through being coated, filling, takes
Go out after drying, described microneedle unit is fixed on described adhesive layer, then being covered with described backing layer, i.e. to obtain treatment osteoarthritis micropin saturating
Skin is to plaster.
Embodiment 6
Weigh Cortex erythrinae 40g, Radix Achyranthis Bidentatae 50g, Herba Lycopodii 40g, Caulis Spatholobi 30g, Wheeling 35g, Rhizoma Homalomenae 40g, Herba Lycopodii
30g, Lignum Sappan 35g, raw Folium Artemisiae Argyi 40g, Herba speranskiae tuberculatae 40g, Rhizoma Corydalis 40g, Semen zanthoxyli 30g, Herba Menthae 50g and tacrolimus 1g examination
Test step as follows:
1) weigh Cortex erythrinae 40g, Radix Achyranthis Bidentatae 50g, Herba Lycopodii 40g, Caulis Spatholobi 30g, Wheeling 35g, Rhizoma Homalomenae 40g, stretch
Muscle grass 30g, Lignum Sappan 35g, raw Folium Artemisiae Argyi 40g, Herba speranskiae tuberculatae 40g, Rhizoma Corydalis 40g and Semen zanthoxyli 30g, pulverize after mixing, with
Concentration is that mixture is carried out soaking 48h by the ethanol solution of 80%, filters soak, collects filtrate and to described filtrate
Evaporation and concentration, i.e. obtains herbal mixture concentrate I after removing solvent；
2) weigh Herba Menthae 50g and put in there-necked flask, use steam distillation it is carried out distillation procedure, to distillate from
The heart processes, and stands ten minutes, take upper strata fluid, obtain active Chinese drug component compositions II after being centrifuged；
3) by step 1) described in compound Chinese medicine extract I, mixed with 2000ml purified water and 50ml Tween-80
Close liquid to dissolve, ultrasonic disperse 30 minutes after three's mixing, stir, be heated to 75 DEG C and carry out being incubated standby, mixed
Liquid A；
4) weigh soybean phospholipid and glyceryl monostearate 30g for the ratio of 3:1 in mass ratio, obtain mixture B, measure
500ml volume ratio is that described mixture B is dissolved by the ethanol/dichloromethane mixed liquor of 4:1, obtains solution C, the most again
In described solution C, add step 2) described in active Chinese drug component compositions II and 1g tacrolimus crude drug be stirred, ultrasonic
Dissolve dispersion 15 minutes, prepare mixed liquor D；
5) by step 4) described in mixed liquor D implantation step 3) in stirring and in the described mixed liquor A of water bath heat preservation,
Mixing speed 2000rpm, forms milky suspension E, continues insulated and stirred, after evaporation of organic solvent, ultrasonic disperse 30 points
Clock, obtains lipid nanoparticle suspension crude product F；
6) by step 5) described in lipid nanoparticle suspension crude product F inject in high pressure homogenizer, follow at cold water (6 DEG C)
Carrying out high pressure homogenize under ring water-bath, the operating pressure that described high pressure homogenizer sets as 2000Bar, after concentration, obtains herbal mixture
Solid lipid nanoparticle G.
7) use laser-etching method that the one side of porous silicon substrate is cut into microneedle array, make porous with 0.5*0.5cm size
Microneedle unit；Described microneedle unit is placed in described herbal mixture solid lipid nanoparticle G, through being coated, filling, takes
Go out after drying, described microneedle unit is fixed on described adhesive layer, then be covered with described backing layer and i.e. obtain the micropin for the treatment of osteoarthritis
Transdermal administration pastes.
Claims (7)
1. the preparation method of the microneedle cutaneous patch treating osteoarthritis, it is characterised in that include following preparation process:
1) Cortex erythrinae, Radix Achyranthis Bidentatae, Herba Lycopodii, Caulis Spatholobi, Wheeling, Rhizoma Homalomenae, Herba Lycopodii, Lignum Sappan, raw Folium Artemisiae Argyi, Herba speranskiae tuberculatae, Rhizoma Corydalis and Semen zanthoxyli are weighed, join after being pulverized and mixed in organic solvent and soak, filter, after collecting filtrate and described filtrate solvent being evaporated, obtain herbal mixture concentrate I；
2) weigh Herba Menthae and put in there-necked flask, distillation, to distillate centrifugal treating, stand after being centrifuged, take upper strata fluid, obtain active Chinese drug component compositions II；
3) by step 1) described in herbal mixture concentrate I dissolve with the mixed liquor of purified water and Tween-80, three mixing after ultrasonic disperse, stirring, under the conditions of 65～75 DEG C be incubated, obtain mixed liquor A；
4) by after soybean phospholipid that mass ratio is 1:1～3:1 and glyceryl monostearate mixing, obtain mixture B, with the ethanol/dichloromethane mixed liquor that volume ratio is 4:1, described mixture B is dissolved, obtain solution C, by step 2) in the active Chinese drug component compositions II of gained be stirred with described solution C and tacrolimus crude drug three, after ultrasonic dissolution dispersion, prepare mixed liquor D；
5) by mixed liquor D implantation step 3) in described mixed liquor A in stir, obtain milky suspension E, after described milky suspension E ultrasonic disperse, obtain lipid nanoparticle suspension crude product F；
6) by step 5) described in lipid nanoparticle suspension crude product F inject in high pressure homogenizer and carry out high pressure homogenize, after concentration, obtain herbal mixture solid lipid nanoparticle G.
7) use laser-etching method that the front of substrate is cut into microneedle unit；Described microneedle unit is placed in described herbal mixture solid lipid nanoparticle G, through being coated, filling, after taking-up is dried, the back side of the substrate after etch processes is pasted on ointment blank patch and has the sticking side, covering with ointment back of the body exchange premium row of described microneedle unit, it is middle with described ointment back of the body patch that described substrate is positioned at described ointment blank patch, and three is fixedly connected by the way of pasting, and must treat the microneedle cutaneous patch of osteoarthritis.
A kind of preparation method of the microneedle cutaneous patch treating osteoarthritis, it is characterized in that, the component content of described Cortex erythrinae, Radix Achyranthis Bidentatae, Herba Lycopodii, Caulis Spatholobi, Wheeling, Rhizoma Homalomenae, Herba Lycopodii, Lignum Sappan, raw Folium Artemisiae Argyi, Herba speranskiae tuberculatae, soybean phospholipid/glyceryl monostearate mixture, Tween-80, Rhizoma Corydalis, Semen zanthoxyli and tacrolimus is:
Cortex erythrinae 30～50g
Radix Achyranthis Bidentatae 40～60g
Herba Lycopodii 30～50g
Caulis Spatholobi 20～40g
Wheeling 30～40g
Rhizoma Homalomenae 30～50g
Herba Lycopodii 30～40g
Lignum Sappan 30～40g
Raw Folium Artemisiae Argyi 30～50g
Herba speranskiae tuberculatae 30～50g
Soybean phospholipid/glyceryl monostearate mixture 10～30g
Tween-80 10～50ml
Rhizoma Corydalis 40～50g
Semen zanthoxyli 20～30g
Tacrolimus 0.5～1g.
3. require the preparation method of a kind of microneedle cutaneous patch treating osteoarthritis as described in 1 such as power, it is characterized in that, the component content of described Cortex erythrinae, Radix Achyranthis Bidentatae, Herba Lycopodii, Caulis Spatholobi, Wheeling, Rhizoma Homalomenae, Herba Lycopodii, Lignum Sappan, raw Folium Artemisiae Argyi, Herba speranskiae tuberculatae, soybean phospholipid/glyceryl monostearate mixture, Tween-80, Rhizoma Corydalis, Semen zanthoxyli and tacrolimus is:
Cortex erythrinae 30g
Radix Achyranthis Bidentatae 40g
Herba Lycopodii 30g
Caulis Spatholobi 20g
Wheeling 30g
Rhizoma Homalomenae 30g
Herba Lycopodii 30g
Lignum Sappan 30g
Raw Folium Artemisiae Argyi 30g
Herba speranskiae tuberculatae 40g
Soybean phospholipid/glyceryl monostearate mixture 20g
Tween-80 30ml
Rhizoma Corydalis 50g
Semen zanthoxyli 30g
Tacrolimus 1g.
4. the microneedle cutaneous patch treating osteoarthritis, it is characterized in that, the microneedle cutaneous patch of described treatment osteoarthritis is to be prepared by either method in the preparation method of a kind of microneedle cutaneous patch treating osteoarthritis described in claims 1 to 3.
nullA kind of microneedle cutaneous patch treating osteoarthritis，It is characterized in that，Including substrate、Medicament、Ointment blank patch and ointment back of the body patch，Described substrate is positioned at the centre of described ointment blank patch and described ointment back of the body patch，Described substrate uses the material with loose structure，The front of described substrate is provided with more than one micropin，The top of described micropin is provided with sharp portion，Described micropin is vertically fixed on described substrate，There is between described micropin micropin gap，Described medicament is stored among described micropin gap and described loose structure，The back side of described substrate is plane，The back side of described substrate is pasted onto on the inner surface of described ointment blank patch，The inner surface of described ointment back of the body patch covers on the front of described substrate，The inner surface of described ointment blank patch is fixedly connected by the way of pasting with the inner surface of described ointment back of the body patch.
A kind of microneedle cutaneous patch treating osteoarthritis, it is characterized in that, the arrangement of described micropin forms a rectangular-shaped microneedle array, described microneedle array is more than one, the length of described microneedle array and width are all 0.5cm, and the spacing between adjacent described microneedle array is 0.1cm.
A kind of microneedle cutaneous patch treating osteoarthritis, it is characterised in that the material that described substrate is selected is porous silicon, POROUS TITANIUM or expanded polystyrene.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114452270A (en) * | 2022-01-19 | 2022-05-10 | 广东省第二中医院（广东省中医药工程技术研究院） | Microneedle patch for treating osteoarthritis and preparation method thereof |
| WO2023085363A1 (en) * | 2021-11-12 | 2023-05-19 | 国立大学法人長崎大学 | Transdermal absorption-type patch |
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| CN104367940A (en) * | 2014-10-28 | 2015-02-25 | 无锡济民可信山禾药业股份有限公司 | Microneedle transdermal drug delivery system of Chinese herbal medicine compound preparation |
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| WO2023085363A1 (en) * | 2021-11-12 | 2023-05-19 | 国立大学法人長崎大学 | Transdermal absorption-type patch |
| CN114452270A (en) * | 2022-01-19 | 2022-05-10 | 广东省第二中医院（广东省中医药工程技术研究院） | Microneedle patch for treating osteoarthritis and preparation method thereof |
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