CN116603005A - Pharmaceutical composition for adjuvant therapy of senile hypertension and preparation method thereof - Google Patents

Pharmaceutical composition for adjuvant therapy of senile hypertension and preparation method thereof Download PDF

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Publication number
CN116603005A
CN116603005A CN202310703542.4A CN202310703542A CN116603005A CN 116603005 A CN116603005 A CN 116603005A CN 202310703542 A CN202310703542 A CN 202310703542A CN 116603005 A CN116603005 A CN 116603005A
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microneedle
traditional chinese
chinese medicine
matrix
pharmaceutical composition
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马英哲
赵华龙
王胜业
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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)
    • A61K36/46—Eucommiaceae (Eucommia family), e.g. hardy rubber tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
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    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
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    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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    • A61M2037/0053—Methods for producing microneedles
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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Abstract

The invention relates to a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof, belonging to the technical field of pharmaceutical compositions. The invention provides an external soluble microneedle patch formulation for combining traditional Chinese medicine and western medicine, which aims at solving the problem that the traditional Chinese medicine and western medicine combined product aiming at senile hypertension is easy to cause liver and kidney burden of the aged. The microneedle patch of the invention adopts the administration mode to enable the medicine to enter the systemic circulation through the dermal layer capillary vessel to realize the whole body treatment, avoid the first pass effect and relieve the liver and kidney burden of the old. The microneedle patch does not produce pain when in use, is convenient to administer, and improves the medication compliance of the aged patients. The microneedle patch is used for assisting in treating senile hypertension, can relieve the burden of the aged on the body caused by long-term combined administration, and can maintain stable blood pressure through slow drug release.

Description

Pharmaceutical composition for adjuvant therapy of senile hypertension and preparation method thereof
Technical Field
The invention belongs to the technical field of pharmaceutical compositions, and particularly relates to a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
Background
Senile hypertension refers to a condition with an age of over 65 years, and blood pressure values which are over 3 times or not on the same day exceed standard blood pressure diagnosis standards. Senile hypertension has high prevalence, about 50%, and most of them are simple systolic hypertension. This indicates that a significant number of elderly people need to take antihypertensive drugs each day to regulate blood pressure. With age and decline of physiological functions, the elderly are prone to various diseases, and often need to take multiple drugs for different conditions. Due to the decline of organism organ and tissue functions, the pharmacokinetics of the aged is necessarily changed correspondingly when the aged is dosed, and the dosing risk of the aged is increased by long-term dosing or combined dosing. The liver volume of the old is reduced, the tissue blood flow is reduced, the metabolism and detoxification functions are also reduced, and the drug metabolism is easy to become slow, even drug liver injury occurs. Taking the medicine for a long time inevitably causes a large burden on the liver of the elderly. In addition, with the decrease of renal function of the elderly, the clearance of the kidney drug decreases, the blood flow becomes smaller, and various adverse reactions are easily caused by the increase of the concentration of the drug in the body.
The combination of traditional Chinese medicine and western medicine refers to a comprehensive medical mode combining traditional Chinese medicine with western medicine to achieve better diagnosis and treatment effects. In recent years, the medical community in China actively explores the application of the combination of traditional Chinese medicine and western medicine, and remarkable achievement is achieved. Traditional Chinese medicine has gained increasing attention over the last decades as part of traditional medicine. It is known that the traditional Chinese medicine has different side effects from western medicines, and the use safety of the traditional Chinese medicine is higher. Meanwhile, the compound of the traditional Chinese medicine can also enhance the curative effect. Therefore, the research of traditional Chinese medicine is an important component for combining traditional Chinese medicine and western medicine. In the research of recent years, researchers explore the anticancer, antiviral and anti-inflammatory equivalent of Chinese herbal medicines, and remarkable results are achieved.
Compared with the single use of traditional Chinese medicines or western medicines, the combination of the traditional Chinese medicines and the western medicines has the characteristics of enhancing the curative effect, expanding the indications and the like, and the advantages of combining the traditional Chinese medicines and the western medicines are reflected. The multi-component and multi-target point of the traditional Chinese medicine can be integrated from multiple angles, the disadvantage of chemical medicine on organism function regulation is overcome, the specificity and pertinence of the chemical medicine action target point have the characteristics of quick effect, definite curative effect and the like, the defect of slow effect of the traditional Chinese medicine is avoided, and the combination of the traditional Chinese medicine and the chemical medicine can enhance the curative effect.
However, the existing traditional Chinese and western medicine combination product for senile hypertension still cannot solve the problem that liver and kidney burden of the aged is easily caused by long-term medicine taking.
Disclosure of Invention
The invention provides a pharmaceutical composition for auxiliary treatment of senile hypertension and a preparation method thereof, aiming at solving the problem that the current combined product of traditional Chinese medicine and western medicine aiming at senile hypertension is easy to cause liver and kidney burden of the elderly.
The technical scheme of the invention is as follows:
the pharmaceutical composition for adjuvant treatment of senile hypertension is in a soluble microneedle patch form and comprises a microneedle part and a bottom backing, wherein the micrometer needlepoints of the microneedle part are arranged on the bottom backing in an array; the microneedle part comprises sartan antihypertensive drugs and a needlepoint matrix, and the mass ratio of the sartan antihypertensive drugs to the needlepoint matrix is 1:5-50; the needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material; the volume mass ratio of the traditional Chinese medicine water extract to the water-soluble matrix material is 100 mL:35-45 g; the traditional Chinese medicine water extract is prepared from folium cortex eucommiae, folium ginkgo, radix puerariae, radix astragali, liquorice and lotus leaves.
Further, the sartan antihypertensive drug is valsartan, irbesartan, telmisartan, losartan potassium, candesartan, tasosartan, eprosartan or olmesartan medoxomil.
Further, the traditional Chinese medicine liquid extract is an aqueous extract prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 5-25:1-15:1-10:1-12:1-10:1-8:1-5.
Further, the water-soluble matrix material is one or two of medical sodium carboxymethyl cellulose, medical sodium alginate, medical hyaluronic acid or medical polyvinyl alcohol.
Further, the preparation materials of the bottom backing are hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1.
Further, the height of the micrometer needlepoints of the microneedle part is 500-2000 mu m, the distance between the needlepoints is 0.7-0.8 mm, and 144-256 micrometer needlepoints are arranged on the single patch.
A preparation method of a pharmaceutical composition for adjuvant therapy of senile hypertension, comprising the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 8-10 hours, then carrying out water extraction, heating the traditional Chinese medicine mixed powder to boiling, keeping micro-boiling for 30-40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving a water-soluble matrix material in the traditional Chinese medicine liquid obtained in the first step, uniformly stirring to obtain a needle point matrix, uniformly stirring a sartan antihypertensive medicine and the needle point matrix to obtain a medicine carrying matrix, pouring the medicine carrying matrix into a needle point cavity at the lower part of a microneedle mould, centrifuging to fully fill the medicine carrying matrix into the needle point cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and dissolving the bottom backing material in a solvent, pouring the obtained bottom backing material solution onto the cured microneedle part of the microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom backing material solution, fully drying, and demoulding to obtain the soluble microneedle patch.
Furthermore, the traditional Chinese medicine mixed powder in the first step is subjected to freezing treatment before water extraction.
Further, in the second step, the microneedle mould is a female mould, the lower part is a needle tip cavity, the upper part of the needle tip cavity is a communicated bottom cavity, the needle tip cavity is in a quadrangular pyramid, a triangular pyramid or a cone, and the outline of the bottom cavity is square, rectangular, circular or elliptical.
Further, in the second step, the micro needle mold is placed at a rotating speed of 3000rpm for 5min.
The invention has the beneficial effects that:
the pharmaceutical composition for assisting in treating senile hypertension provided by the invention is an external medicament combining traditional Chinese medicine and western medicine, adopts a soluble microneedle patch formulation, and simultaneously carries sartan antihypertensive drugs and traditional Chinese medicine aqueous extracts in a micrometer needlepoint. In the treatment process, the micrometer needle tip can directionally penetrate through the stratum corneum to generate a micrometer-sized mechanical channel, the medicine is directly released into the upper dermis layer, and the medicine can participate in microcirculation without penetrating through the stratum corneum to play a pharmacological role.
The microneedle patch of the invention adopts the administration mode to enable the medicine to enter the systemic circulation through the dermal layer capillary vessel so as to realize the systemic treatment, thereby avoiding the reduction of the medicine effect due to the first pass effect when the oral medicine passes through the alimentary canal and the liver, relieving the burden of long-term combined medication on the gastrointestinal tract and the liver and kidney of the old, avoiding the stimulation of the medicine to the gastrointestinal tract and the liver, reducing the probability of medicine enzymolysis, keeping the high activity of the medicine and fully utilizing the medicine resource. Meanwhile, the medicine can be slowly released into the body along with degradation of the needle point matrix, so that stable transdermal absorption rate is realized, stable blood concentration can be maintained for a long time, stable blood pressure reducing effect is ensured, pressure of kidney metabolism medicine is relieved, and good medication safety is realized. The invention prevents the micrometer needle tip from touching the capillary vessel and the nerve ending by controlling the length of the micrometer needle tip, does not generate pain, is convenient to administer, and improves the medication compliance of the aged patients.
According to the combination theory of traditional Chinese medicine and modern Chinese and Western medicine, the medicine is scientifically selected, the selected western medicine sartan antihypertensive medicine is a clinically common antihypertensive medicine, and the selected Chinese medicines including eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves are compounded to achieve the effects of reducing blood pressure and restoring vascular elasticity, so that the problems of arteriosclerosis and rigidity of old people are improved while the stability of blood pressure is maintained, and the symptoms of hypertension are radically relieved. The microneedle patch is used for assisting in treating senile hypertension, and can relieve the burden on the body caused by taking various antihypertensive drugs for the elderly simultaneously by slowly releasing the drugs to maintain stable blood pressure.
The invention takes the traditional Chinese medicine liquid extract as the raw material to participate in the preparation of the microneedle part, avoids the reduction of the medicine concentration while increasing the traditional Chinese medicine components, has simple and feasible preparation process of the microneedle patch, low cost and obvious clinical application curative effect, and is suitable for wide popularization and application.
Detailed Description
The following embodiments are used for further illustrating the technical scheme of the present invention, but not limited thereto, and all modifications and equivalents of the technical scheme of the present invention are included in the scope of the present invention without departing from the spirit and scope of the technical scheme of the present invention. The process equipment or apparatus not specifically noted in the following examples are all conventional equipment or apparatus in the art, and the raw materials and the like used in the examples of the present invention are commercially available unless otherwise specified; unless specifically indicated, the technical means used in the embodiments of the present invention are conventional means well known to those skilled in the art.
Example 1
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 500 mu m, the needlepoint distance is 0.75mm, and 144 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises a valsartan antihypertensive agent and a needlepoint matrix, wherein the mass ratio of the valsartan to the needlepoint matrix is 1:5.
The needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical sodium carboxymethylcellulose and medical sodium alginate with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL:35g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 25:15:10:12:10:8:5.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 10 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical sodium carboxymethyl cellulose and medical sodium alginate in the traditional Chinese medicine liquid obtained in the step one, stirring uniformly to obtain a needlepoint matrix, mixing valsartan and the needlepoint matrix, stirring uniformly to obtain a medicine carrying matrix, pouring the medicine carrying matrix into a needlepoint cavity at the lower part of a microneedle mould, wherein the shape of the needlepoint cavity is a cone, centrifuging at a rotating speed of 3000rpm for 5min to fully fill the medicine carrying matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom cavity, wherein the thickness of the bottom cavity is 5mm, the outline shape is square, and demoulding after full drying to obtain the soluble microneedle patch.
Example 2
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 500 mu m, the needlepoint distance is 0.75mm, and 144 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises sartan antihypertensive agent irbesartan and a needlepoint matrix, and the mass ratio of the irbesartan to the needlepoint matrix is 1:10.
The needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical sodium carboxymethylcellulose and medical hyaluronic acid with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL:40g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 22:15:8:10:10:8:5.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 10 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical sodium carboxymethyl cellulose and medical hyaluronic acid in the traditional Chinese medicine liquid obtained in the first step, uniformly stirring to obtain a needle point matrix, uniformly stirring to obtain a medicine carrying matrix after mixing irbesartan and the needle point matrix, pouring the medicine carrying matrix into a needle point cavity at the lower part of a microneedle mould, wherein the shape of the needle point cavity is a triangular pyramid, and centrifuging for 5min at a rotating speed of 3000rpm to fully fill the medicine carrying matrix into the needle point cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom backing material solution, wherein the thickness of the bottom cavity is 5mm, the outline shape is rectangular, and demoulding after being fully dried to obtain the soluble microneedle patch.
Example 3
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 1000 mu m, the needlepoint distance is 0.75mm, and 196 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises telmisartan which is a sartan antihypertensive drug and a needlepoint matrix, and the mass ratio of the telmisartan to the needlepoint matrix is 1:20.
The needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical sodium alginate and medical hyaluronic acid with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL:45g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 20:14:10:8:8:6:4.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 8 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical sodium alginate and medical hyaluronic acid in the traditional Chinese medicine extract obtained in the step one, uniformly stirring to obtain a needle point matrix, uniformly stirring to obtain a medicine carrying matrix after mixing telmisartan and the needle point matrix, pouring the medicine carrying matrix into a needle point cavity at the lower part of a microneedle mould, wherein the shape of the needle point cavity is a quadrangular pyramid, and centrifuging at a rotating speed of 3000rpm for 5min to fully fill the medicine carrying matrix into the needle point cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom backing material solution, wherein the thickness of the bottom cavity is 5mm, the outline shape is round, and demoulding after full drying to obtain the soluble microneedle patch.
Example 4
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 1000 mu m, the needlepoint distance is 0.75mm, and 196 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises losartan potassium and a needlepoint matrix of a sartan antihypertensive drug, and the mass ratio of the losartan potassium to the needlepoint matrix is 1:30.
The needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical polyvinyl alcohol and medical sodium alginate with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL:38g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 20:15:9:10:8:8:4.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 8 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical polyvinyl alcohol and medical sodium alginate in the traditional Chinese medicine extract obtained in the step one, uniformly stirring to obtain a needlepoint matrix, uniformly stirring to obtain a medicine carrying matrix after mixing losartan potassium and the needlepoint matrix, pouring the medicine carrying matrix into a needlepoint cavity at the lower part of a microneedle mould, wherein the shape of the needlepoint cavity is a cone, centrifuging at a rotating speed of 3000rpm for 5min to fully fill the medicine carrying matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom backing material solution, wherein the thickness of the bottom cavity is 5mm, the outline shape is elliptical, and demoulding after full drying to obtain the soluble microneedle patch.
Example 5
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 1500 mu m, the needlepoint distance is 0.75mm, and 225 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises candesartan and a needlepoint matrix of a sartan antihypertensive drug, and the mass ratio of the candesartan to the needlepoint matrix is 1:40.
The needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical polyvinyl alcohol and medical hyaluronic acid with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL and 40g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 18:15:10:10:8:6:2.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 10 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical polyvinyl alcohol and medical hyaluronic acid in the traditional Chinese medicine extracting solution obtained in the step one, uniformly stirring to obtain a needlepoint matrix, uniformly stirring to obtain a medicine carrying matrix after candesartan and the needlepoint matrix are mixed, pouring the medicine carrying matrix into a needlepoint cavity at the lower part of a microneedle mould, wherein the shape of the needlepoint cavity is a cone, and centrifuging at a rotating speed of 3000rpm for 5min to fully fill the medicine carrying matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom cavity, wherein the thickness of the bottom cavity is 5mm, the outline shape is square, and demoulding after full drying to obtain the soluble microneedle patch.
Example 6
The embodiment provides a pharmaceutical composition for adjuvant therapy of senile hypertension and a preparation method thereof.
The pharmaceutical composition of this example is a soluble microneedle patch dosage form comprising a microneedle portion and an underlying backing.
The micrometer needlepoints of the microneedle part are arranged on the backing of the bottom layer in an array manner, the height of the micrometer needlepoints is 2000 mu m, the needlepoint distance is 0.75mm, and 256 micrometer needlepoints are arranged on the single patch.
The microneedle part of the embodiment comprises a sartan antihypertensive drug, namely, tasosartan and a needlepoint matrix, wherein the mass ratio of the tasosartan to the needlepoint matrix is 1:50;
the needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material, the water-soluble matrix material of the embodiment is medical sodium carboxymethylcellulose and medical polyvinyl alcohol with equal mass, and the volume mass ratio of the traditional Chinese medicine aqueous extract to the water-soluble matrix material is 100mL:45g.
The traditional Chinese medicine liquid extract is prepared from eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves in a mass ratio of 15:14:6:8:6:5:1.
The preparation materials of the bottom backing of the microneedle patch of the embodiment are hydroxypropyl cellulose and soluble chitosan with the mass ratio of 5:1.
The preparation method of the pharmaceutical composition for adjuvant therapy of senile hypertension comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 10 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical sodium carboxymethyl cellulose and medical polyvinyl alcohol in the traditional Chinese medicine liquid obtained in the first step, uniformly stirring to obtain a needlepoint matrix, uniformly stirring to obtain a medicine carrying matrix after the mixture of the tasosartan and the needlepoint matrix, pouring the medicine carrying matrix into a needlepoint cavity at the lower part of a microneedle mould, wherein the shape of the needlepoint cavity is a cone, and centrifuging at a rotating speed of 3000rpm for 5min to fully fill the medicine carrying matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom cavity, wherein the thickness of the bottom cavity is 5mm, the outline shape is square, and demoulding after full drying to obtain the soluble microneedle patch.
Comparative example 1
The present example provides a pharmaceutical composition and a method for preparing the same, and the comparative example differs from example 1 only in that the needle tip matrix in the comparative example contains distilled water and a water-soluble matrix material, and the volume mass ratio of the distilled water to the water-soluble matrix material is 100mL:35g.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps:
step one, preparing a microneedle part:
dissolving medical sodium carboxymethyl cellulose and medical sodium alginate in distilled water, uniformly stirring to obtain a needlepoint matrix, mixing valsartan and the needlepoint matrix, uniformly stirring to obtain a medicine carrying matrix, pouring the medicine carrying matrix into a needlepoint cavity at the lower part of a microneedle mould, centrifuging at 3000rpm for 5min to fully fill the medicine carrying matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom cavity, wherein the thickness of the bottom cavity is 5mm, the outline shape is square, and demoulding after full drying to obtain the soluble microneedle patch.
Comparative example 2
The present example provides a pharmaceutical composition and a method for preparing the same, and the difference between the present comparative example and example 1 is that the microneedle part in the present comparative example does not contain sartan antihypertensive agent and only contains a needlepoint matrix.
The preparation method of the pharmaceutical composition of the comparative example comprises the following steps:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 10 hours, carrying out water extraction after freezing treatment, heating to boiling, keeping micro-boiling for 40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving medical sodium carboxymethyl cellulose and medical sodium alginate into the traditional Chinese medicine liquid obtained in the step one, stirring uniformly to obtain a needlepoint matrix, pouring the needlepoint matrix into a needlepoint cavity at the lower part of a microneedle mould, wherein the needlepoint cavity is conical, centrifuging for 5min at a rotating speed of 3000rpm to fully fill the needlepoint matrix into the needlepoint cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and (3) dissolving hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1 in distilled water to obtain a bottom backing material solution with the concentration of the hydroxypropyl cellulose being 50mg/mL and the concentration of the soluble chitosan being 10mg/mL, pouring the obtained bottom backing material solution onto a microneedle part solidified by a microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom cavity, wherein the thickness of the bottom cavity is 5mm, the outline shape is square, and demoulding after full drying to obtain the soluble microneedle patch.
Microneedle patch effect validation test:
1. microneedle morphology:
the microneedle tips were consistently long and firmly attached to the underlying backing without defects or breaks as observed by the naked eye.
2. Microneedle penetration rate:
the skin of the abdomen of the rat was taken, the microneedle patches prepared in example 1, example 3 and example 5 were placed on the skin of the abdomen of the rat, the backing of the bottom layer was peeled off after pressing for 3min, the skin of the rat was stained with methylene blue, and the number of microneedle pinholes of the skin of the rat was recorded, and the microneedle penetration rate= (number of voids/total number of microneedle tips) ×100.
The microneedle penetration rate of the microneedle patch of example 1 was calculated to be 97.2%, the microneedle penetration rate of the microneedle patch of example 3 was calculated to be 97.95%, and the microneedle penetration rate of the microneedle patch of example 5 was calculated to be 93.3%.
3. In vitro transdermal sustained release assay:
the skin of the separated pig ear is taken as a transdermal material, and an in-vitro transdermal penetration test is carried out by adopting a full-automatic transdermal instrument, so that the accumulated release rate of the sartan antihypertensive drugs of the microneedle patches prepared in the example 1 and the example 3 is detected. The test temperature is controlled at 37 ℃, the receiving solution is 0.01M phosphate buffer solution with pH=7.4, the sampling mode is full sampling, the receiving solution with the same volume is added after each sampling, the sampling time is 0h, 1h, 4h, 8h, 12h, 24h,36h, 48h and 60h, and the accumulated release rate=the amount of the sartan antihypertensive drug in the receiving solution sample/the amount of the sartan antihypertensive drug in the microneedle patch is multiplied by 100%. The results are shown in Table 1:
TABLE 1
As can be seen from the data in table 1, the microneedle patch prepared by the invention can continuously and stably release the sartan antihypertensive drug within 60 hours.
4. Blood pressure lowering drug effect test of rats:
primary hypertension model rats were used as subjects.
30 male SHR mice (weight 250+ -50 g) were randomly divided into 5 groups,
group 1: blank control group, lavage equivalent physiological saline;
group 2: the oral valsartan group is filled with the gastric valsartan, and the dosage is 10mg/kg;
group 3: example 1 group the microneedle patch prepared in example 1 was used on rat abdominal skin and the underlying backing was peeled off after 1min,24h of pressure;
group 4: comparative example 1 group the microneedle patch prepared in comparative example 1 was used on the abdominal skin of rats and after 1min,24h was pressed the underlying backing was peeled off;
group 5: comparative example 2 group the microneedle patch prepared in comparative example 2 was used on the abdominal skin of rats and the underlying backing was peeled off after 1min,24h of pressure.
Blood pressure was measured in each group of rats at 0h, 4h, 8h, 12h, 24h,36h and 48h, respectively, and the rat blood pressure, including systolic and diastolic blood pressure, was measured by the rat tail artery noninvasive blood pressure measurement method, and the results are shown in table 2.
TABLE 2
From the comparison of the data in table 2, it can be seen that the microneedle patch prepared in group 3 using example 1 has a more durable and stable blood pressure lowering effect compared with the oral valsartan in group 2. The microneedle patch prepared by the invention has good drug slow release capability, can maintain stable blood pressure within 48 hours, is suitable for assisting in treating senile hypertension, reduces the types and times of oral hypertension drugs for the elderly, improves the drug compliance of the elderly, relieves the burden of long-term combined drug administration of the elderly on gastrointestinal tracts and livers, avoids the irritation of the drugs on the gastrointestinal tracts and livers, can relieve the pressure of kidney metabolism drugs, and has good drug administration safety.
Compared with the microneedle patch containing only valsartan in the 4 th group and the microneedle patch containing only Chinese medicinal liquid extract in the 5 th group, the microneedle patch prepared by the 3 rd group and the embodiment 1 has more remarkable blood pressure reducing effect, and particularly can keep good and stable blood pressure reducing effect after 12 hours. The invention combines the western medicine sartan antihypertensive drug with the Chinese medicine aqueous extract by the combination theory of the Chinese medicine and the western medicine, and the technical effect of 1+1 & gt2 is obtained. The traditional Chinese medicine eucommia ulmoides leaves have the effect of nourishing liver and kidney, and can reduce blood pressure and relieve liver and kidney injury caused by long-term oral administration of various medicines to old patients; the ginkgo leaf is used for improving microcirculation and promoting medicine absorption and utilization; the corn silk is used for promoting urination and reducing blood pressure, and the kudzuvine root, the astragalus root, the liquorice and the lotus leaf are used for softening blood vessels, restoring the elasticity of the blood vessels and reducing the viscosity of blood. The sartan antihypertensive drug has a synergistic effect with the drug effects of the traditional Chinese medicines, the sartan antihypertensive drug can maintain the blood pressure stable for a long time through slow release, and the traditional Chinese medicine aqueous extract not only plays a role in assisting blood pressure reduction, but also can improve microcirculation and further promote absorption and utilization of the drugs, so that the drug effect of the western medicine sartan antihypertensive drug is enhanced, meanwhile, the traditional Chinese medicine aqueous extract can improve the problems of arteriosclerosis and rigidity of the old human blood vessels, thereby radically relieving the symptoms of the hypertension and further stabilizing the blood pressure reducing effect.
The invention takes the traditional Chinese medicine liquid extract as the raw material to participate in the preparation of the microneedle part, increases the traditional Chinese medicine components, avoids the reduction of the medicine concentration, and realizes the efficient combination of the traditional Chinese medicine and western medicine. The microneedle patch is used for assisting in treating senile hypertension, and can relieve the burden on the body caused by taking various antihypertensive drugs for the elderly simultaneously by slowly releasing the drugs to maintain stable blood pressure.

Claims (10)

1. The pharmaceutical composition for adjuvant treatment of senile hypertension is characterized by being in a soluble microneedle patch form and comprising a microneedle part and a bottom backing, wherein the micrometer needlepoints of the microneedle part are arranged on the bottom backing in an array; the microneedle part comprises sartan antihypertensive drugs and a needlepoint matrix, and the mass ratio of the sartan antihypertensive drugs to the needlepoint matrix is 1:5-50; the needle tip matrix contains a traditional Chinese medicine aqueous extract and a water-soluble matrix material; the volume mass ratio of the traditional Chinese medicine water extract to the water-soluble matrix material is 100 mL:35-45 g; the traditional Chinese medicine water extract is prepared from folium cortex eucommiae, folium ginkgo, radix puerariae, radix astragali, liquorice and lotus leaves.
2. A pharmaceutical composition for the adjuvant treatment of senile hypertension according to claim 1, characterized in that the said sartan antihypertensive drug is valsartan, irbesartan, telmisartan, losartan potassium, candesartan, tasosartan, eprosartan or olmesartan medoxomil.
3. The pharmaceutical composition for adjuvant therapy of senile hypertension according to claim 1 or 2, wherein the Chinese medicinal liquid extract is prepared from eucommia ulmoides leaf, corn silk, ginkgo leaf, kudzuvine root, astragalus root, liquorice and lotus leaf in a mass ratio of 5-25:1-15:1-10:1-12:1-10:1-8:1-5.
4. A pharmaceutical composition for the adjuvant treatment of senile hypertension according to claim 3, wherein the water-soluble matrix material is one or two of medical sodium carboxymethyl cellulose, medical sodium alginate, medical hyaluronic acid or medical polyvinyl alcohol.
5. The pharmaceutical composition for the adjuvant therapy of senile hypertension according to claim 4, wherein the preparation materials of the bottom backing are hydroxypropyl cellulose and soluble chitosan in a mass ratio of 5:1.
6. The pharmaceutical composition for adjuvant therapy of senile hypertension according to claim 5, wherein the height of the micrometer needlepoints of the microneedle part is 500-2000 μm, the distance between the needlepoints is 0.7-0.8 mm, and 144-256 micrometer needlepoints are arranged on the single patch.
7. A method for preparing a pharmaceutical composition for the adjuvant treatment of senile hypertension according to any one of claims 1 to 6, comprising the steps of:
step one, preparing a traditional Chinese medicine aqueous extract:
sequentially weighing eucommia ulmoides leaves, corn silk, ginkgo leaves, kudzuvine roots, astragalus roots, liquorice and lotus leaves according to a mass ratio, mixing and crushing the materials to 100 meshes to obtain traditional Chinese medicine mixed powder, soaking the traditional Chinese medicine mixed powder in distilled water with the mass of 10 times for 8-10 hours, then carrying out water extraction, heating the traditional Chinese medicine mixed powder to boiling, keeping micro-boiling for 30-40 minutes, filtering and collecting filtrate, adding distilled water with the mass of 5 times into the obtained residue to boiling, keeping micro-boiling for 30 minutes, filtering and collecting filtrate, and combining the two filtrates to obtain traditional Chinese medicine liquid extract;
step two, preparing a microneedle part:
dissolving a water-soluble matrix material in the traditional Chinese medicine liquid obtained in the first step, uniformly stirring to obtain a needle point matrix, uniformly stirring a sartan antihypertensive medicine and the needle point matrix to obtain a medicine carrying matrix, pouring the medicine carrying matrix into a needle point cavity at the lower part of a microneedle mould, centrifuging to fully fill the medicine carrying matrix into the needle point cavity of the mould, and fully drying to obtain a solidified microneedle part;
preparing a bottom backing layer:
and dissolving the bottom backing material in a solvent, pouring the obtained bottom backing material solution onto the cured microneedle part of the microneedle mould, fully filling the bottom cavity of the microneedle mould with the bottom backing material solution, fully drying, and demoulding to obtain the soluble microneedle patch.
8. The method for preparing a pharmaceutical composition for adjuvant therapy of senile hypertension according to claim 7, wherein the powder mixture of the traditional Chinese medicinal materials is frozen before the water extraction.
9. The method of preparing a pharmaceutical composition for adjuvant therapy of senile hypertension according to claim 8, wherein the shape of the needle tip cavity in the second step is a quadrangular pyramid, a triangular pyramid or a cone, and the outline shape of the bottom layer cavity is square, rectangle, circle or ellipse.
10. The method of preparing a pharmaceutical composition for adjuvant therapy of senile hypertension according to claim 9, wherein the centrifugation in step two is to centrifuge the microneedle mould at 3000rpm for 5min.
CN202310703542.4A 2023-06-14 2023-06-14 Pharmaceutical composition for adjuvant therapy of senile hypertension and preparation method thereof Pending CN116603005A (en)

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