CN102631400A - Compound minoxidil nano-emulsion antihypertensive medicament - Google Patents
Compound minoxidil nano-emulsion antihypertensive medicament Download PDFInfo
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- CN102631400A CN102631400A CN2012101427734A CN201210142773A CN102631400A CN 102631400 A CN102631400 A CN 102631400A CN 2012101427734 A CN2012101427734 A CN 2012101427734A CN 201210142773 A CN201210142773 A CN 201210142773A CN 102631400 A CN102631400 A CN 102631400A
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Abstract
The invention discloses a compound minoxidil nano-emulsion antihypertensive medicament. Based on 100 mass percent, the compound minoxidil nano-emulsion antihypertensive medicament comprises the following raw materials in percentage by mass: 1 to 20 percent of minoxidil, 15 to 40 percent of surfactant, 1 to 25 percent of cosurfactant, 1 to 25 percent of oil, 5 to 40 percent of cosolvent, 1 to 15 percent of aqueous extract of kudzuvine root, 1 to 15 percent of aqueous extract of pine needle and the balance distilled water. The nano-emulsion antihypertensive medicament is small in emulsion droplet granularity, uniform in distribution, low in viscosity and high in fluidity. By the nano-emulsion antihypertensive medicament, the medicament dissolution and permeation capability of the minoxidil can be improved, and the stability of the minoxidil can be improved. After the minoxidil is prepared into a nano-emulsion form, the antihypertensive effect of the minoxidil is remarkably improved, the half-life period of the nano-emulsion antihypertensive medicament is prolonged, the number of times of drug administration is reduced, and the nano-emulsion antihypertensive medicament is conveniently taken, and has broad market prospect.
Description
Technical field
The invention belongs to field of medicaments, relate to a kind of novel form of antihypertensive drug minoxidil, particularly a kind of compound recipe minoxidil nano-emulsion antihypertensive drug.
Background technology
Minoxidil (Minoxidil) is potassium channel openers, and the vascular smooth muscle that can directly relax has powerful small artery dilating effect, and Peripheral resistance is descended, blood pressure drops, and capacitance vessel is not had influence, so can promote venous return.Simultaneously, because reflexive regulating action and positivity frequency effect can make cardiac output and heart rate increase, but not cause postural hypotension.Can be used for intractable hypertension, renal hypertension.Its hypotensive effect is stronger than Aiselazine.Mechanism of action is K
+Channel opener makes the vascular smooth muscle diastole.Belong to and expand the blood vessel hypotensor.Do not cause postural hypotension, long-term prescription does not see that drug effect reduces.
The interaction property of minoxidil is similar with hydralazine, but effect is strong and lasting.It directly acts on vascular smooth muscle, and the diastole small artery reduces Peripheral resistance, thereby makes blood pressure drops, and capacitance vessel is not had obvious effect.Also can the reflex excitation sympathetic nerve when blood pressure lowering and make that heart rate is accelerated, cardiac output increases, plasma renin activity increases and water-sodium retention.Heart rate accelerates also have direct positive inotropic action relevant with these article to heart.Its water-sodium retention agency part is that part makes renal tubules to Na owing to directly act on renal tubules because renin secretion increases
+Due to increasing with the absorption again of water.Its mechanism of action maybe be owing to be metabolized to minoxidil N-O sulfate in vivo, and the latter increases the VSMC film to K
+Permeability, promote K in the cell
+Outflow causes VSMC film hyperpolarization, thereby makes vascular smooth muscle relaxation and blood pressure drops.
Have antihypertensive drugs on the market now like the minoxidil tablet; Though can be after oral from gastrointestinal absorption; But absorb not exclusively, the dissolution rate of tablet Chinese traditional medicine is slow in addition, and bioavailability is poor; Add minoxidil effect itself slowly, make the drug effect of minoxidil can't obtain rapidly utilizing.
Summary of the invention
To the shortcomings and deficiencies that exist in the prior art, the object of the present invention is to provide a kind of being evenly distributed, good stability, the compound recipe minoxidil nano-emulsion antihypertensive drug that permeability is high, dissolubility is good, bioavailability is high.
The technical scheme that realizes the foregoing invention purpose is: a kind of compound recipe minoxidil nano-emulsion antihypertensive drug, and the particle diameter that it is characterized in that this medicine is between 67.1～102.4nm, and mean diameter is 88.4nm, and its raw material and mass percent thereof are:
Surfactant 15%～30%
Cosolvent 5%～30%
Radix Puerariae water extract 0.1%～10%
Folium Pini water extract 0.1%～10%
All the other compositions are distilled water, and the mass percent sum of above-mentioned raw materials is 100%.
Described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or the poloxamer 188 any one or with the mixture of span80, these surfactants are to human body low toxicity, safe, non-stimulated.
The oil that the oil that the present invention selects for use is is any one or a few the mixture in isopropyl myristate, ethyl acetate or the oleic acid, and is safe, nontoxic.
Described cosurfactant is a dehydrated alcohol, 1, the mixture of any one or a few in 2-propylene glycol, PEG400 or the glycerin.
The main carbohydrate containing of Radix Puerariae; Vegetable protein; Multivitamin and mineral; Contain Flavonoid substances in addition: contain multiple flavones ingredient, main active is big legumin (daidzein), daidzin (daidzin), puerarin (puerarin), puerarin-7-xyloside (puerarin-7-xyloside) etc.
The flavone that proposes in the Radix Puerariae can increase brain and crown vascular flow amount.Behind the anesthesia Canis familiaris L. internal carotid artery injection Radix Puerariae flavone, cerebral blood flow increases, the corresponding reduction of vascular resistance; Effect was kept 2～20 minutes; Like intravenous injection, then the cerebral blood flow increase is lighter, can not remove epinephrine and norepinephrine and shrink cerebrovascular effect; But then can improve cerebral circulation to the hypertensive arteriosclerosis patient, its action temperature with.Radix Puerariae flavone and kudzuvine root wine extractum are injected in coronary artery and the vein of Canis familiaris L., and the coronary vasodilator blood flow is increased, and vascular resistance reduces.To the crystallization that proposes in rat abdominal cavity and subcutaneous injection kudzuvine root wine extractum and its water decoction of lumbar injection and the Radix Puerariae, caused heart ischemia reaction all has protective effect to pituitrin, and the Radix Puerariae water decoction is oral not to have tangible hypotensive effect to the hypertension Canis familiaris L..
Specifically; Radix Puerariae has a lot of outstanding effects to cardiovascular: (1) is to the influence of cerebral circulation: the anesthesia Canis familiaris L. is with the direct measure cerebral blood flow volume of electromagnetic flowmeter; Through carotid artery injection Radix Puerariae total flavones 0.1～0.5mg/kg; Cerebral blood flow increases by 87.7%～134%, and like vena femoralis injection total flavones 10～30mg/kg, the cerebral blood flow flow increases about 20%; Hypertensive patient's intramuscular injection total flavones 200mg, patient's cerebral blood flow of about 53% has improvement, and vascular resistance and inlet time reduce.(2) to the influence of coronary circulation: insert anesthesia Canis familiaris L. rami circumflexus arteriae coronariae sinistrae to measure CF with ductus arteriosus; Through intra-arterial injection total flavones 1～2mg/kg; Blood flow increases by 102%～120%, and vascular resistance descends 50%, and intravenous injection also has effect is necessarily arranged; The effect of ethanol extract is similar with total flavones, and Radix Puerariae can be treated angina pectoris maybe be relevant therewith.(3) to the protective effect of acute myocardial ischemia: the side shoot blood flow when giving rat abdominal cavity or subcutaneous injection Radix Puerariae ethanol preserved material 10g/kg myocardial ischemia to causing because of the vein pituitrin; And the minimizing hemodynamic parameter relevant with myocardial oxygen consumption, this all is of value to the treatment myocardial ischemia.(4) to the influence of cardiac contractile force and frequency: puerarin 0.1,3 μ mol/L can block positivity chronotropic and the negative inotropic property effect of isoproterenol to isolated rabbit atrium flesh and GPT, and the selectivity of heart muscle β 1 receptor is better than the beta 2 receptor to tracheal strip.But have the puerarin of thinking that α, beta receptor are not all had effect, its mechanism of action is not through adrenoceptor yet.(5) to microcirculatory influence: mouse mainline puerarin 52mg/kg can alleviate the microcirculation disturbance that the mesentery arteriole shrinks, velocity of blood flow slows down and flow reduces due to the local instillation epinephrine.
α-aminobutyric acid that Folium Pini contains can promote the decomposition of glucose, the blood ammonia of reduction is arranged and promote the brain metabolism, makes brain function active, has the effect of blood pressure lowering.Folium Pini contains rich nutrient contents, carotenoid (comprising beta-carotene), vitamin E, C, B1, B2, H, K, calcium, ferrum, manganese, magnesium, copper, selenium etc.; Contained natural anti-oxidation (defying age) material of Folium Pini is the strongest in all plants of finding at present.Be Folium Camelliae sinensis etc. can not than.All there is medical value at each position of pinaster.Antioxidant in the Folium Pini can dissolve fat and gallbladder in the blood vessel because of alcohol, can untie erythrocyte and hematoblastic gathering, lets erythrocyte carry more oxygen, nutrient to whole body everywhere.Therefore, it can make diseases such as hypertension, hyperlipidemia, hyperglycemia take a turn for the better.Because patient takes Folium Pini, has reduced the absorption of chemicals and vitamin.Abundant vitamin and the aminoacid of Folium Pini is again good tonic undoubtedly, has changed people's nutriture and mental status, so Folium Pini more can treating both the principal and secondary aspects of a disease on treatment mechanism.
Because the dissolubility of minoxidil in water and oil is all little, be cosolvent among the present invention so added acetic acid, phosphoric acid or glycerol formal.
The present invention adds the bland surface that helps like ethanol, 1 in medicine; 2-propylene glycol, glycerin or PEG400; Except the hydrotropy effect; Cosurfactant mainly is in order to adjust HLB VALUE OF SURFACTANTS (HLB), to make oil water interfacial tension further reduce, increasing the profit property and the rigidity of limitans.Cosurfactant is incorporated in the interfacial film, promotes the very formation of membranelle of radius of curvature, enlarges the breast district area of compound recipe minoxidil nano-emulsion.
Compound recipe minoxidil nano-emulsion administered through oral of the present invention administration has improved the dissolubility of medicine greatly, reduces medicine first pass effect in vivo, promotes the gastrointestinal absorption of medicine.Minoxidil utmost point indissoluble in water is separated; Make the transhipment and the absorption of medicine become difficult; Nano-emulsion substrate is that minoxidil provides good dissolving environment, and through compound kudzu root water extract and Folium Pini water extract, makes that the antihypertensive effect of this compound nanometer emulsion is better remarkable and lasting.Can absorb the barrier when overcoming first pass effect and molecule when oral through lymph through gastrointestinal tract.
Compound recipe minoxidil nano-emulsion of the present invention compared with prior art has the following advantages:
1. the diameter of aspirin particle of minoxidil resisting hypertension nano-emulsion of the present invention is between 67.1～102.4nm; Mean diameter is 88.4nm; Be that minoxidil is dissolved in the cosolvent; Dissolve each other with oil phase again, add surfactant (or and cosurfactant), be titrated to even, transparent nano-emulsion system with distilled water.The compound recipe minoxidil nano-emulsion that forms contains minoxidil and reaches more than 7%.
2. minoxidil resisting hypertension nano-emulsion of the present invention is evenly distributed, and transparent, the good stability of system has lower surface tension, and water-in-oil type nanoemulsion has good flowability.
3. engulfed by reticuloendothelial cell rapidly after the minoxidil resisting hypertension nano-emulsion of the present invention administration, make the rapid onset of medicine, and keep constant blood drug level and pharmacodynamics effect, improve bioavailability of medicament, reduce amount of drug and access times.
4. this compound nanometer emulsion makes that through adding Radix Puerariae water extract and Folium Pini water extract the antihypertensive effect of this compound nanometer emulsion is better remarkable and lasting.
5. minoxidil resisting hypertension nano-emulsion method for preparing of the present invention is simple, efficacy stability, and living power consumption is low.
6. the present invention processes and can be made into oral liquid after the nanometer and directly take, also can seal or through processing such as lyophilized powder technology through capsule.
Description of drawings
Fig. 1 is a compound recipe minoxidil nano-emulsion electromicroscopic photograph of the present invention.
Fig. 2 is a compound recipe minoxidil nano-emulsion granularmetric analysis curve chart of the present invention.
The specific embodiment
The inventor provides concrete method for preparing embodiment and uses the test of pesticide effectiveness to further specify the effect of medicine of the present invention.
Test Example 1 compound recipe minoxidil nano-emulsion antihypertensive drug size of the present invention is analyzed
The present invention detects (Fig. 1) through transmission electron microscope, and drop type of being is spherical, good dispersion, no adhesion.Detect (Fig. 2) its diameter Distribution between 67.1～102.4nm through the Ma Erwen Particle Size Analyzer, mean diameter is 88.4nm.
Test Example 2 compound recipe minoxidil nano-emulsion antihypertensive drug of the present invention stability analyses
Whether through the stability that compound recipe minoxidil nano-emulsion antihypertensive drug of the present invention is observed in following centrifugal test, light stability test, temperature stability test etc., observing the present invention has layering, muddiness or crystal wild effect such as to separate out.
1. high speed centrifugation test
Get the compound recipe minoxidil nano-emulsion antihypertensive drug of the present invention for preparing in right amount in centrifuge tube; With centrifugal 15 min of the rotating speed of 10 000r/min; After the centrifugal test; Compound recipe minoxidil nano-emulsion antihypertensive drug of the present invention still keeps the clear before centrifugal, wild effect such as do not see that layering, muddiness or crystal are separated out.
2. light stability test
The compound recipe minoxidil nano-emulsion antihypertensive drug for preparing is in right amount packed in transparent good colourless, the transparent vial, and sealing is positioned over 10d under the normal illumination condition, respectively at 1d, 2d, 4d, 6d, 8d, the 10d observation of taking a sample.The result shows that the every duplicate samples of compound recipe minoxidil nano-emulsion antihypertensive drug all keeps clear, wild effect such as do not see that layering, muddiness or crystal are separated out.
3. temperature stability test
The compound recipe minoxidil nano-emulsion antihypertensive drug for preparing is in right amount packed in transparent good colourless, the Clear glass bottles and jars, sealing, be positioned over 4 ℃, room temperature (25 ℃) with 40 ℃ three in keep sample under the temperature conditions and investigate each 30d, every at a distance from 5d sampling observation.The result shows that compound recipe minoxidil nano-emulsion antihypertensive drug all keeps clear under these three kinds of temperature conditions, wild effect such as do not see that layering, muddiness or crystal are separated out.
4. long-term stable experiment
3 batches of nano-emulsions are sealed in the Brown Glass Brown glass bottles and jars only; Placed (25 ± 2) ℃, relative humidity (60 ± 5) % condition following 12 months; Respectively at 0,3,6,9 and time sampling in 12 months; Investigate the character and the changes of contents of nano-emulsion, and the list of references statistical analysis technique, the effect duration of calculating compound recipe minoxidil nano-emulsion antihypertensive drug.Result of the test is illustrated under the long term test condition, and the outward appearance of compound recipe minoxidil nano-emulsion antihypertensive drug keeps clear and bright, homogeneous always, does not see phenomenons such as layering, complexion changed, flocculation and breakdown of emulsion; Minoxidil content in the system prolongs in time and reduces gradually, the equation of linear regression that its content-time changing curve provides, and the effect duration that calculates compound recipe minoxidil nano-emulsion antihypertensive drug is 25.22 months.
Test Example 3 rat tails manometrys are measured the drug effect (with commercially available minoxidil sheet contrast) of compound recipe minoxidil nano-emulsion antihypertensive drug
20 of SHR rats are divided into 2 groups at random, 10 every group, are made as minoxidil sheet intervention group and compound recipe minoxidil nano-emulsion group respectively; Give minoxidil sheet suspension and each 15mg/kgd of compound recipe minoxidil nano-emulsion respectively, be dissolved in the drinking-water, all administration from drinking-water; 1 time/d, continuous 14 weeks.10 of WKY rats are the normal control group, and 10 positive matched groups of SHR rat, matched group are not given medicine, normal drinking-water.
Measure and respectively organize rat arteria caudalis blood pressure.(before the medication) pressure measurement was 1 time when Mus was 6 weeks age, and Mus 7 weeks of age (1 week after the medication) pressure measurement 1 time is whenever later on surveyed 1 blood pressure at a distance from two weeks, up to the experiment end.The result sees table 1.
Table 1 respectively organize rat SBP comparison (x ± s, n=10)
| Group | Systolic pressure (mmHg) |
| Positive control | 198.0±10.3 |
| The minoxidil sheet | 136.4±9.3 |
| Compound recipe minoxidil nano-emulsion | 131.6±10.1 |
| WKY normal control group | 126.8±7.4 |
The result shows that compound recipe minoxidil nano-emulsion and positive controls and minoxidil sheet compare, and difference is all extremely remarkable, show that minoxidil not only can significantly reduce the blood pressure of positive rat, and antihypertensive effect is compared better effects if with the minoxidil tablet.
Test Example 4 toxicity tests
1. toxicological study project and conclusion:
Product of the present invention is in strict accordance with non-clinical safety evaluation methodology of new drug and commercially available minoxidil tablet contrast having carried out acute toxicity test; Repeat administration toxicity test, genetic toxicity test (comprising Ames test, mouse bone marrow cells micronucleus test, the test of In vitro culture mammalian cell chromosome mutation), reproductive toxicity test (general reproductive toxicity test, sensitive period to teratogenic agent toxicity test, perinatal toxicity test), carcinogenic test, immunotoxicity test and local irritation test, result of the test is following.
These article are to chmice acute toxicity test conclusion: with commercially available minoxidil tablet contrast, untoward reaction and death in measuring does not appear in compound recipe minoxidil nano-emulsion.
The result of genetic toxicity tests such as the Salmonella reversion test of product of the present invention, mouse sperm deformity test and testicular chromosome aberration test is all negative.
The result that rat 30d feeds product of the present invention shows: with commercially available minoxidil tablet contrast; In experimental period; Each experimental group animal growth is good in the metering of compound recipe minoxidil nano-emulsion; All in normal range, histopathologic examination is no abnormality seen also for indexs such as body weight, food ration, routine blood test, blood biochemistry, organ coefficient.
These article long term toxicity test conclusion: with commercially available minoxidil tablet contrast; In experimental period; In the metering of compound recipe minoxidil nano-emulsion; This medicine was not seen the rat untoward reaction in three months at continuous gastric infusion, and all in normal range, its main organs of pathologic finding and target organ do not see that all the toxic pathology that this guiding drug rises changes to each item inspection index.
Test Example 5 pharmacokinetics
Result of the test shows, compound recipe minoxidil nano-emulsion antihypertensive drug oral absorption good (can reach 93%).These article do not combine with plasma protein.After this 1 hour blood Chinese medicine concentration peaking after the administration descends rapidly.Blood plasma t1/2 is 2.8～4.2 hours, and is constant during renal dysfunction.But minoxidil concentration does not have corresponding relation in hypotensive effect and the blood.Behind the oral potion in 1.2 hours hypotensive effect begin, maximum reducing acts on after the administration and sustainable 70 hours of hypotensive effect to occur in 2 hours.It is at intrahepatic metabolism, and the metabolite glucuronide conjugate can be discharged with urine.
Accurately take by weighing 14g cosolvent ethanol, dissolving in the minoxidil as much as possible, obtaining its meltage is 6.2g, dissolves each other with 6gIPM again; The oil that accurately takes by weighing surfactant EL40 28g and cosurfactant ethanol 4g and dissolved minoxidil stirs under room temperature (25 ℃) condition, then to the distilled water that wherein slowly splashes into dissolving Radix Puerariae water extract and Folium Pini water extract.Increase along with the distillation water yield; The system stickiness increases, and when the amount that adds distilled water made system become the oil-in-water type nano-emulsion by Water-In-Oil, the system viscosity was thinning from the most heavy-gravity state; What produced this moment promptly is the compound recipe minoxidil nano-emulsion of clear; The amount that add distilled water this moment is 31.7g, and the Radix Puerariae water extract is 5.2g, and the Folium Pini water extract is 4.9g.This ratio is the optimal proportion of minoxidil resisting hypertension nano-emulsion.
Following examples step is with embodiment 1:
Embodiment 2
Dehydrated alcohol 10g, minoxidil 5.7g, IPM 6.5g, EL40 24g, 1,2-propylene glycol 8g, Radix Puerariae water extract are 5.2g, the Folium Pini water extract is 6g, distilled water 34.6 g.
Embodiment 3
Dehydrated alcohol 10g, minoxidil 5.1g, ethyl oleate 6g, RH40 24g, ethanol 4g, Radix Puerariae water extract are 5.8g, the Folium Pini water extract is 6.4g, distilled water 38.7 g.
Embodiment 4
Dehydrated alcohol 14g, minoxidil 8.1g, ethyl acetate 9.5g, poloxamer 188 24g, ethanol 12g, Radix Puerariae water extract are 1.8g, the Folium Pini water extract is 2.7g, distilled water 27.9 g.
Embodiment 5
Dehydrated alcohol 9g, minoxidil 7.3g, ethyl oleate 5.5g, Tween 80 22g, PEG400 11g, Radix Puerariae water extract are 6g, the Folium Pini water extract is 4.8g, distilled water 34.4 g.
Embodiment 6
Acetic acid 11g, minoxidil 6.7g, ethyl oleate 7g, Tween 80 20g, ethanol 12g, Radix Puerariae water extract are 4.4g, the Folium Pini water extract is 5.8g, distilled water 33.1 g.
Embodiment 7
Acetic acid 5g, minoxidil 1g, IPM 15g, EL40 30g, 1,2-propylene glycol 1g, Radix Puerariae water extract are 5g, the Folium Pini water extract is 6g, distilled water 37 g.
Embodiment 8
Acetic acid 5g, minoxidil 1g, ethyl acetate 10g, span80 10, poloxamer 188 20g, ethanol 5g, Radix Puerariae water extract are 10g, the Folium Pini water extract is 9g, distilled water 30 g.
Embodiment 9
Acetic acid 10g, minoxidil 3g, ethyl oleate 10g, RH40 25g, glycerin 8g, 1,2-propylene glycol 2g, Radix Puerariae water extract are 9g, the Folium Pini water extract is 10g, distilled water 23 g.
Phosphatase 11 5g, minoxidil 5g, oleic acid 8g, ethyl acetate 5g, Tween 80 15g, glycerin 13g, Radix Puerariae water extract are 5g, the Folium Pini water extract is 6g, distilled water 28 g.
Embodiment 11
Phosphoric acid 20g, minoxidil 8g, IPM 7g, Tween 80 15g, PEG400 6g, Radix Puerariae water extract are 4g, the Folium Pini water extract is 1g, distilled water 39g.
Embodiment 12
Phosphoric acid 25g, minoxidil 8g, ethyl oleate 5g, Tween 80 10g, ethanol 5g, Radix Puerariae water extract are 1g, the Folium Pini water extract is 4g, distilled water 42g.
Embodiment 13
Phosphoric acid 30g, minoxidil 10g, IPM 1g, Tween 80 5g, PEG400 1g, Radix Puerariae water extract are 0.1g, the Folium Pini water extract is 0.1g, distilled water 52.3g.
Claims (2)
1. compound recipe minoxidil nano-emulsion antihypertensive drug is characterized in that its raw material and mass percent thereof are:
Minoxidil 1%～10%
Surfactant 15%～30%
Cosurfactant 1%～15%
Oil 1%～15%
Cosolvent 5%～30%
Radix Puerariae water extract 0.1%～10%
Folium Pini water extract 0.1%～10%
All the other compositions are distilled water, and the mass percent sum of above-mentioned raw materials is 100%;
Described surfactant be in polyoxyl 40 hydrogenated castor oil, castor oil polyoxyethylene ether 40, Tween 80 or the poloxamer 188 any one or with the mixture of span80;
Described oil is any one or a few the mixture in isopropyl myristate, ethyl acetate or the oleic acid;
Described cosurfactant is a dehydrated alcohol, 1, the mixture of any one or a few in 2-propylene glycol, PEG400 or the glycerin.
2. compound recipe minoxidil nano-emulsion antihypertensive drug according to claim 2, the particle diameter that it is characterized in that this medicine is between 67.1～102.4nm.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105943539A (en) * | 2016-05-24 | 2016-09-21 | 成都市斯贝佳科技有限公司 | Pharmaceutical compound preparation with effective and safe blood pressure lowering function |
| CN115089594A (en) * | 2022-06-20 | 2022-09-23 | 苏州大学 | Nano emulsion and preparation method and application thereof |
| CN116350584A (en) * | 2023-03-30 | 2023-06-30 | 上海应用技术大学 | Minoxidil microemulsion and preparation and application thereof |
-
2012
- 2012-05-10 CN CN2012101427734A patent/CN102631400A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105943539A (en) * | 2016-05-24 | 2016-09-21 | 成都市斯贝佳科技有限公司 | Pharmaceutical compound preparation with effective and safe blood pressure lowering function |
| CN115089594A (en) * | 2022-06-20 | 2022-09-23 | 苏州大学 | Nano emulsion and preparation method and application thereof |
| CN116350584A (en) * | 2023-03-30 | 2023-06-30 | 上海应用技术大学 | Minoxidil microemulsion and preparation and application thereof |
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Application publication date: 20120815 |