CN114366707A - Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof - Google Patents

Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof Download PDF

Info

Publication number
CN114366707A
CN114366707A CN202210166059.2A CN202210166059A CN114366707A CN 114366707 A CN114366707 A CN 114366707A CN 202210166059 A CN202210166059 A CN 202210166059A CN 114366707 A CN114366707 A CN 114366707A
Authority
CN
China
Prior art keywords
chinese herbal
herbal medicine
vesicle
salt
peo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202210166059.2A
Other languages
Chinese (zh)
Inventor
杜娜
陈楠
王春省
侯万国
骆兴伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shandong University
Original Assignee
Shandong University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shandong University filed Critical Shandong University
Priority to CN202210166059.2A priority Critical patent/CN114366707A/en
Publication of CN114366707A publication Critical patent/CN114366707A/en
Priority to CN202211195633.3A priority patent/CN115350136B/en
Priority to PCT/CN2023/076491 priority patent/WO2023160458A1/en
Pending legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9789Magnoliopsida [dicotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14Liposomes; Vesicles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37Esters of carboxylic acids
    • A61K8/375Esters of carboxylic acids the alcohol moiety containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • A61K8/673Vitamin B group
    • A61K8/675Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9755Gymnosperms [Coniferophyta]
    • A61K8/9761Cupressaceae [Cypress family], e.g. juniper or cypress
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9794Liliopsida [monocotyledons]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/985Skin or skin outgrowth, e.g. hair, nails
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00Preparations for care of the hair
    • A61Q5/12Preparations containing hair conditioners
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00Preparations for affecting hair growth
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Emergency Medicine (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention relates to a Chinese herbal medicine active substance @ vesicle compound with hair nourishing and hair growing effects, and a preparation method and application thereof. The Chinese herbal medicine active matter is coated in the vesicle: the hydrophilic substance is coated in the hydrophilic micro-area, namely the water core; the hydrophobic substance is solubilized between the bilayer membranes of the vesicles. The Chinese herbal medicine active substance @ vesicle compound integrates the Chinese herbal medicine active substance and the vesicle, the core-shell double-layer membrane structure of the vesicle can solubilize the hydrophilic and hydrophobic active ingredients in the Chinese herbal medicine extract at the same time, and a stable Chinese herbal medicine active substance @ vesicle micro-ecological environment is formed around the scalp and hair follicles by virtue of the permselectivity and the slow release performance of the core-shell double-layer membrane structure, so that the optimal utilization of the medicine effect is obtained, and the effects of nourishing and developing the hair are achieved. The invention has better permeability, dispersibility and sustained-release performance, simple process and good application in the fields of cosmetics and drug delivery and controlled release.

Description

Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof
Technical Field
The invention relates to a Chinese herbal medicine active substance @ vesicle compound with hair nourishing and hair growing effects and a preparation method thereof, and belongs to the technical field of cosmetics.
Background
The hair is one of the components of the human body, and the change of the hair has close relation with the physiological and pathological changes of the human body. Modern people have fast pace of life, long working time, great mental stress and irregular work and rest, and the alopecia has gradually become a trouble of more and more modern people and shows a trend of youthfulness. In china, the number of people suffering from alopecia has increased in recent years, and 1 person suffers from alopecia in every 6 persons. According to statistics, the alopecia rate of the population worldwide reaches 32.13%, and the number of alopecia patients is increased year by year. There is an increasing demand for hair-growing cosmetic products that aid in hair growth, reduce hair loss and break hair, and the efficacy requirements are also increasing.
The problems of hair oil, dryness and alopecia are not only the problems of hair but also the problems of scalp and hair follicle by tracing the root. The scalp and hair are the relationship between soil and vegetation, good soil grows good vegetation, and good scalp can have good hair similarly. Scalp care is therefore the key to solving the problem of hair loss. At present, the products for treating alopecia in the market are various, wherein western medicines are abundant in hormones, certain side effects can be brought to the body after long-term use, and the alopecia is easy to relapse after stopping the medicines. Since 2015, the number of traditional Chinese medicine cosmetics increases year by year with the deepening of the supporting strength of traditional Chinese medicines in national policies. Actually, the history of treating hair diseases by traditional Chinese medicine is long, and good hair nourishing formulas are recorded in a plurality of medical classics and are transmitted to the present. The Chinese herbal medicine extract contains a plurality of natural components such as flavonoid, tannin, cordycepic acid, tartaric acid, saponin, amino acid, trace elements and the like, has the functions of expanding blood vessels, diminishing inflammation, resisting bacteria, resisting oxidation, regulating immunity and the like, and can effectively treat alopecia and promote hair growth. However, since the active ingredients in the herbal extracts are various and complex, and their physicochemical properties are very different, it is difficult to dissolve them in the same solvent at the same time, which affects the dispersion and absorption of the active ingredients and prevents the efficacy from being exerted.
The vesicle is a closed bilayer with a core-shell structure formed by the aggregation of amphiphilic molecules, can contain various substances, and solubilizes the substances at different positions according to the polarity of the substances. The hydrophilic substance is contained in the hydrophilic micro-area, namely the water core; the hydrophobic substance is solubilized in the hydrocarbon chain interlayer of the amphiphilic molecule. Therefore, the hydrophilic and hydrophobic active ingredients in the Chinese herbal medicine extract can be solubilized and loaded by the vesicles at the same time, the solubility and the dispersibility of the indissolvable active substances are improved, and the selective permeability and the slow release performance brought by the bilayer membrane structure of the vesicles can ensure that the active substances are stably and durably released on the scalp. The active substance generates micro-ecological environment on the surface of scalp and around hair follicle under the holding of vesicle system, reduces the damage of ion introduction to hair follicle, and effectively stimulates the vitality of hair follicle from the root, thereby obtaining the best utilization of drug effect and achieving the effects of nourishing and growing hair.
Indian patent document IN1764MUM2014A IN order to improve bioavailability or absorption of poorly fat-soluble drugs, the solubility of the active ingredient is increased by combining the herbal active ingredient with phosphatidylcholine. However, liposomes formed from phosphatidylcholine have poor permeability and are detrimental to the release of the active ingredient. Moreover, the Chinese herbal medicine components disclosed in the patent document are mainly used for oral administration, and the solubility and bioabsorbability of the Chinese herbal medicine extract for external use cannot be determined.
Korean patent document KR1020090059445A discloses a hair care composition for depilation prevention and hair growth, and more particularly, to a depilation prevention hair care composition that promotes adsorption to the scalp and hair by containing cationic/anionic surfactant mixed vesicles. However, when the cationic/anionic surfactant is mixed, precipitation is likely to occur due to electrostatic interaction, and a vesicle structure is formed only in a narrow range of the compounding ratio. And the vesicle structure is easily damaged and precipitation occurs under the influence of strong electrolytes such as acid, alkali, salt and the like, even charged Chinese herbal medicine extracts.
Disclosure of Invention
The active ingredients of the traditional Chinese herbal medicines, especially fat-soluble active ingredients, are difficult to solubilize in a molecular state and enter products to act on scalp and hair follicles, and the optimal drug effect cannot be exerted, so that the hair loss preventing and growing effect is greatly reduced. Most of active ingredients in the existing products have high concentration action on the scalp only at the moment of use, lack of slow and sustained release environment of active substances and cannot be maintained at a certain dynamic effective concentration, so the absorption effect is poor. Aiming at the defects of the prior art and the defects of the prior product, the invention provides a safe and effective Chinese herbal medicine active substance @ vesicle compound with the effects of preventing alopecia, nourishing hair and promoting hair growth and a preparation method thereof. The core-shell double-layer membrane structure of the vesicle can solubilize hydrophilic and hydrophobic active ingredients in the Chinese herbal medicine extract at the same time, and a stable Chinese herbal medicine active substance @ vesicle micro-ecological environment is formed around the scalp and hair follicles by virtue of the selective permeability and the slow release performance of the vesicle, so that the optimal utilization of the drug effect is obtained, and the effects of nourishing and developing the hair are achieved.
The Chinese herbal medicine active matter @ vesicle compound with the hair nourishing and hair growing effects is characterized by comprising the following two components in parts by weight: the first is a complex formed by coexistence of Chinese herbal medicine active substances and vesicles; secondly, the Chinese herbal medicine active substance @ vesicle compound has the effects of nourishing hair and growing hair.
The invention aims to provide a Chinese herbal medicine active substance @ vesicle compound, wherein the Chinese herbal medicine active substance is coated in vesicles and coexists with the vesicles. The compound has a specific core-shell structure, controllable size and good stability.
The invention also aims to provide a preparation method of the Chinese herbal medicine active substance @ vesicle compound, which is prepared while vesicles are spontaneously formed under the induction of the Chinese herbal medicine active substance.
The third purpose of the invention is to provide an application of the Chinese herbal medicine active substance @ vesicle compound, wherein the Chinese herbal medicine active substance @ vesicle compound has the effects of nourishing hair and nourishing hair, and can be applied to the field of cosmetics.
The technical scheme of the invention is as follows:
a Chinese herbal medicine active substance @ vesicle compound with the effects of nourishing and growing hair comprises a Chinese herbal medicine active substance and vesicles, wherein the Chinese herbal medicine active substance is coated in the vesicles: the hydrophilic substance is coated in the hydrophilic micro-area, namely the water core; the hydrophobic substance is solubilized between the bilayer membranes of the vesicles.
According to the invention, preferably, the particle size of the compound is 80 nm-5 μm; the particle size of most of the particles is between 80 and 900nm, the particle size is further preferably between 200 and 800nm, and the particle size of the compound in a small amount of system can reach 1 to 5 mu m.
According to the invention, preferably, the vesicle is a bilayer membrane vesicle, and the thickness of the bilayer membrane is between 3 nm and 7 nm.
According to the invention, preferably, the content of the Chinese herbal medicine active substance in the Chinese herbal medicine active substance @ vesicle compound is in a range of 30-100 g/L.
According to the invention, preferably, the vesicle is formed by an amphiphilic molecule system, and the concentration range of amphiphilic molecules is 0.1-20 g/L, and more preferably 0.2-10 g/L. The amphiphilic molecules are called vesicle precursors in the invention.
According to the invention, preferably, the Chinese herbal medicine active substances are extracted from the following raw material medicines:
polygoni Multiflori radix, Concha Haliotidis, Ecliptae herba, radix Adenophorae, Atractylodis rhizoma, Alismatis rhizoma, radix Paeoniae Rubra, pericarpium Citri Reticulatae viride, cortex Phellodendri, rhizoma Polygonati, radix Polygoni Multiflori Preparata, herba Gynostemmatis, folium Platycladi, rhizoma Ligustici Chuanxiong, rhizoma Gastrodiae, mume fructus charcoal, Kochiae fructus, herba Trifolii Pratentis, and colla Corii Asini;
further preferably, the Chinese herbal medicine extract comprises the following raw materials in parts by weight:
5-15 parts of polygonum multiflorum, 5-15 parts of groundsel, 5-15 parts of eclipta, 20-50 parts of adenophora stricta, 20-50 parts of bighead atractylodes rhizome, 5-15 parts of rhizoma alismatis, 20-50 parts of red paeony root, 5-15 parts of green tangerine peel, 5-15 parts of golden cypress, 20-50 parts of rhizoma polygonati, 20-50 parts of prepared polygonum multiflorum, 20-50 parts of gynostemma pentaphylla, 20-50 parts of cacumen biotae, 5-15 parts of ligusticum wallichii, 5-15 parts of gastrodia elata, 5-15 parts of dark plum carbon, 5-15 parts of fructus kochiae, 20-50 parts of red clover and 20-50 parts of donkey-hide gelatin;
more preferably: 10 parts of tuber fleeceflower root, 10 parts of groundsel, 10 parts of yerbadetajo herba ecliptae, 30 parts of root of straight ladybell, 30 parts of largehead atractylodes rhizome, 12 parts of oriental waterplantain rhizome, 30 parts of red paeony root, 12 parts of green tangerine peel, 15 parts of amur corktree bark, 30 parts of rhizoma polygonati, 30 parts of prepared tuber of multiflower knotweed, 30 parts of fiveleaf gynostemma herb, 30 parts of cacumen biotae, 12 parts of szechuan lovage rhizome, 12 parts of tall gastrodia tuber, 10 parts of dark plum fruit charcoal, 10 parts of broom cypress fruit, 25 parts of red clover and 35 parts of donkey-hide gelatin.
According to the present invention, preferably, the vesicle precursor can be selected from one or a combination of the following: fatty acid monoglyceride, monoalkyl phosphate ester and salt thereof, 2-hydroxy fatty acid and salt thereof, nicotinic acid and derivative thereof, and triblock copolymer.
According to the present invention, preferably, the fatty acid monoglyceride is a linear fatty acid monoglyceride; more preferably C8-C18A linear chain mono-fatty acid glyceride; more preferably: caprylin, caprin, lauric glyceride, myristic glyceride, pentadecanoic glyceride, and palmitic glyceride.
According to the present invention, preferably, the monoalkyl phosphate ester and the salt thereof are linear alkyl phosphate ester and the salt thereof; more preferably C8-C16A linear monoalkyl phosphate ester of chain length or a salt thereof; more preferably: octyl phosphate and its sodium salt, potassium salt, magnesium salt, zinc salt, decyl phosphate and its sodium salt, potassium salt, magnesium salt, zinc salt, lauryl phosphate and its sodium salt, potassium salt, magnesium salt, zinc salt, myristyl phosphate and its sodium salt, potassium salt, magnesium salt, zinc salt, palmityl phosphate and its sodium salt, potassium salt, magnesium salt, zinc salt.
According to the inventionOptionally, the 2-hydroxy fatty acid and salt thereof is 2-hydroxy straight chain fatty acid and salt thereof; more preferably C8-C162-hydroxy straight chain fatty acids of chain length and salts thereof; more preferably: 2-hydroxyoctanoic acid and sodium salt, potassium salt, magnesium salt and zinc salt thereof, 2-hydroxydecanoic acid and sodium salt, potassium salt, magnesium salt and zinc salt thereof, 2-hydroxylauric acid and sodium salt, potassium salt, magnesium salt and zinc salt thereof, 2-hydroxymyristic acid and sodium salt, potassium salt, magnesium salt and zinc salt thereof, and 2-hydroxypalmitic acid and sodium salt, potassium salt, magnesium salt and zinc salt thereof.
According to the invention, the nicotinic acid and the derivatives thereof are preferably nicotinic acid, benzyl nicotinate and tocopherol nicotinate.
According to the present invention, it is preferred that the triblock copolymer has the general chemical composition formula: PEO (polyethylene oxide)x-PPOy-PEOxX is more than or equal to 13 and less than or equal to 133, and y is more than or equal to 29 and less than or equal to 65; (ii) a More preferably: PEO (polyethylene oxide)77-PPO29-PEO77、PEO13-PPO30-PEO13、PEO24-PPO35-PEO24、 PEO133-PPO50-PEO133、PEO19-PPO30-PEO19、PEO100-PPO65-PEO100、PEO26-PPO40-PEO26
The Chinese herbal medicine active substance @ vesicle compound is a uniform and stable system and can be stably placed for more than 1 year at normal temperature.
The preparation method of the Chinese herbal medicine active substance @ vesicle compound comprises the following steps:
adding a mixed solvent into the raw material medicines for extraction, collecting the extract, adding the vesicle precursor, uniformly mixing, precipitating with ethanol, centrifuging, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ vesicle compound.
According to the present invention, preferably, the mixed solvent is an ethanol-water mixed solution. According to the present invention, the ethanol-water mixed solution preferably has a concentration of ethanol of 40% to 80% by volume, and more preferably 55% to 70% by volume.
According to the invention, preferably, the extraction times are 1-5 times, and the extraction time is 1-5 hours each time; the extraction temperature is 55-80 ℃.
Most preferably, the number of extractions is 4, each of said extractions being for 4 hours, the temperature of extraction being 70 ℃.
According to the invention, the Chinese herbal medicine active substance @ vesicle compound is prepared while vesicles are spontaneously formed under the induction of the Chinese herbal medicine active substance.
According to the invention, the Chinese herbal medicine active substance @ vesicle compound is applied to the field of cosmetics.
The invention has the following technical characteristics and beneficial effects:
the active ingredients of the traditional Chinese herbal medicines, especially fat-soluble active ingredients, are difficult to solubilize in a molecular state and enter products to act on scalp and hair follicles, and the optimal drug effect cannot be exerted, so that the hair loss preventing and growing effect is greatly reduced. Most of active ingredients in the existing products have high concentration action on the scalp only at the moment of use, lack of slow and sustained release environment of active substances and cannot be maintained at a certain dynamic effective concentration, so the absorption effect is poor. Aiming at the defects of the prior art and the defects of the prior product, the invention provides a safe and effective Chinese herbal medicine active substance @ vesicle compound with the effects of preventing alopecia, nourishing hair and promoting hair growth and a preparation method thereof. The core-shell double-layer membrane structure of the vesicle can solubilize hydrophilic and hydrophobic active ingredients in the Chinese herbal medicine extract at the same time, and a stable Chinese herbal medicine active substance @ vesicle micro-ecological environment is formed around the scalp and hair follicles by virtue of the selective permeability and the slow release performance of the vesicle, so that the optimal utilization of the drug effect is obtained, and the effects of nourishing and developing the hair are achieved.
1. The invention provides a Chinese herbal medicine active substance @ vesicle compound, wherein the active substance is coated in vesicles, so that the solubility and the dispersibility of an insoluble active substance are improved. The hydrophilic substance is coated in the hydrophilic micro-area, namely the water core; the hydrophobic substance is solubilized between the bilayer membranes of the vesicles.
2. The Chinese herbal medicine active substance @ vesicle microenvironment technology enables the active substance to be stably and durably released, improves the stability of the active ingredient extract, achieves better hair nourishing and hair growing effects, and has important application prospects in the fields of drug delivery, controlled release, cosmetics and the like.
3. The dispersion solvent of the Chinese herbal medicine active substance @ vesicle compound is ethanol-water mixed liquor, and has better permeability and sterilization capability compared with solvents such as pure water and the like.
4. The Chinese herbal medicine active substance @ vesicle compound is simple in preparation method, mild in reaction and suitable for large-scale production.
5. The Chinese herbal medicine active substance @ vesicle compound is a uniform and stable system, the content range of the Chinese herbal medicine active substance is 30-100 g/L, the particle size of the compound is preferably nano (200-800 nm), the particle size of a compound particle of a small amount of system can reach 1-5 mu m, and the compound can be stably placed for more than 1 year at normal temperature.
6. The pH value of the Chinese herbal medicine extracting solution is 5-6, and the Zete potential is about-15 +/-5.0 mV, so that a nonionic surfactant or an anionic surfactant is selected as a vesicle precursor, and the inactivation or precipitation of active substances extracted from the Chinese herbal medicine is avoided. In particular, the vesicle precursor of nonionic surfactant has good solubility in water or alcohol, is not in an ionic state, and thus has high stability and is not easily affected by acid, alkali or strong electrolyte inorganic salt. In addition, the surfactant has good compatibility with other types of surfactants, and can be used in a complex way.
7. The complex adopts tincture solvent (ethanol-water mixed solution), wherein short-chain alcohol is a common vesicle disrupter, so that most of phase vesicle systems cannot exist stably in the tincture solution. The vesicular complex of the present invention can be spontaneously formed in a tincture solvent, and stably exists, so that the transdermal capacity is superior, which is also an advantage of the dosage form of the present invention.
Drawings
Figure 1 is a dynamic light scattering particle size distribution plot and transmission electron micrograph of the herbal active @ glyceryl laurate vesicle complex of example 1.
FIG. 2 is a graph of the dynamic light scattering particle size distribution and light micrographs of the vesicular complex of the herbal active @ mono-sodium dodecyl phosphate of example 2.
FIG. 3 is a dynamic light scattering particle size distribution diagram and transmission electron micrograph of the vesicular complex of the herbal active @ nicotinic acid (0.5g/L) of example 3.
FIG. 4 is a dynamic light scattering particle size distribution diagram and transmission electron micrograph of the vesicular complex of the herbal active @ nicotinic acid (1g/L) of example 4.
FIG. 5 is a graph of the dynamic light scattering particle size distribution and transmission electron micrograph of the vesicular complex of herbal active @ 2-hydroxyoctanoate sodium of example 5.
FIG. 6 is the active-uncoated PEO of example 677-PPO29-PEO77(5g/L) dynamic light scattering particle size distribution and transmission electron micrographs of vesicles.
FIG. 7 is the Chinese herbal active @ PEO of example 677-PPO29-PEO77(5g/L) dynamic light scattering particle size distribution and transmission electron micrographs of vesicle complexes.
FIG. 8 is the Chinese herbal active @ PEO of example 777-PPO29-PEO77(10g/L) dynamic light scattering particle size distribution diagram and transmission electron micrograph of vesicle complex.
FIG. 9 is the Chinese herbal active @ PEO of example 813-PPO30-PEO13Dynamic light scattering particle size distribution plots and optical micrographs of vesicular complexes.
FIG. 10 is a photograph showing the appearance of the Chinese herbal medicine active @ vesicle complex in experimental example 1 in a mouse hair growth experiment.
Figure 11 is a light microscope photograph of hair follicles on the back of mice of the herbal active @ vesicle complex of test example 1.
FIG. 12 is a fluorescent staining pattern of inflammatory factor in the back of mice of the herbal active @ vesicle complex of test example 1.
FIG. 13 is a transmission electron micrograph of an extract of Chinese herbal medicine to which a vesicle precursor was not added in comparative example 1.
FIG. 14 is a transmission electron micrograph of a mixture of glyceryl laurate and an extract solution of chinese herbal medicines in which the addition order was changed in comparative example 2.
FIG. 15 is a transmission electron micrograph of the herbal active mixed with Tween 80 of comparative example 3.
FIG. 16 is a transmission electron micrograph of a mixture of herbal actives and glyceryl stearate of comparative example 4.
FIG. 17 is a graph of the herbal actives and PEO of comparative example 577-PPO29-PEO77(1g/L) Transmission Electron micrograph of the mixture.
FIG. 18 is a graph of comparative example 6 herbal actives and PEO13-PPO30-PEO13(25g/L) Transmission Electron micrograph of the mixture.
Detailed Description
The present invention is further illustrated by the following examples, which are, however, to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
The medicinal materials used in the examples were as follows:
radix Polygoni Multiflori, Concha Haliotidis, herba Ecliptae, radix Adenophorae, rhizoma Atractylodis Macrocephalae, rhizoma Alismatis, radix Paeoniae Rubra, pericarpium Citri Reticulatae viride, cortex Phellodendri, rhizoma Polygonati, radix Polygoni Multiflori Preparata, gynostemma pentaphyllum, cacumen Platycladi, rhizoma Chuanxiong, rhizoma Gastrodiae, charred fructus mume, fructus Kochiae, herba Trifolii Pratentis, and colla Corii Asini.
The extraction process of the active ingredients is as follows:
adding a mixed solvent into the raw material medicines for extraction, collecting the extract, adding the vesicle precursor, uniformly mixing, precipitating with ethanol, centrifuging, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ vesicle compound.
Example 1:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 0.3g of lauric glyceride into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ lauric glyceride vesicle compound.
The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the Chinese herbal medicine active @ glyceryl laurate vesicle compound obtained in the example are shown in fig. 1. As can be seen from fig. 1, a large number of vesicles exist in the product of this example, the vesicle size distribution was about 700nm, and a large number of aggregates having a particle size of about 200nm were observed in the negative-staining transmission electron micrograph.
Example 2:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 1.5g of mono-sodium dodecyl phosphate into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ mono-sodium dodecyl phosphate vesicle compound.
The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the Chinese herbal medicine active substance @ mono-sodium dodecyl phosphate vesicle compound obtained in the example are shown in fig. 2. As shown in FIG. 2, the product of this embodiment contains a large amount of nano-sized vesicles and micro-sized vesicles, and the particle size distribution is between 10-100 nm and 1-5 μm, respectively.
Example 3:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 0.5g of nicotinic acid into the Chinese herbal medicine extract obtained in the operation (2), stirring by vortex, centrifuging, standing for 24 hours, filtering and concentrating to obtain the Chinese herbal medicine active substance @ nicotinic acid (0.5g/L) vesicle compound.
The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the Chinese herbal medicine active @ nicotinic acid (0.5g/L) vesicle complex obtained in the example are shown in FIG. 3. As is clear from FIG. 3, the product of this example contains a large amount of vesicles having a particle size of about 200nm, and is uniformly dispersed.
Example 4:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 1g of nicotinic acid into the Chinese herbal medicine extract obtained in the operation (2), stirring by vortex, centrifuging, standing for 24 hours, filtering and concentrating to obtain the Chinese herbal medicine active substance @ nicotinic acid (1g/L) vesicle compound.
The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the Chinese herbal medicine active substance @ nicotinic acid (1g/L) vesicle compound obtained in the example are shown in FIG. 4. As can be seen from FIG. 4, the product of this example contains a large amount of vesicles having a particle size of about 200 to 400nm, and is uniformly dispersed.
Example 5:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 3.6g of 2-sodium hydroxyoctanoate into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ 2-sodium hydroxyoctanoate vesicle compound.
The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the Chinese herbal medicine active substance @ 2-sodium hydroxyoctanoate vesicle compound obtained in the example are shown in FIG. 5. As can be seen from fig. 5, a large number of vesicles exist in the product of this example, the vesicle size distribution was about 600nm, and a large number of aggregates having a particle size of about 200nm were observed in the negative-staining transmission electron micrograph.
Example 6:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 5g PEO into the Chinese herbal medicine extract obtained in the operation (2)77-PPO29-PEO77Vortex stirring, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ PEO77-PPO29-PEO77(5g/L) vesicle complexes.
PEO without Chinese herbal medicine active matter coating77-PPO29-PEO77(5g/L) vesicles and herbal actives obtained in this example @ PEO77-PPO29-PEO77The dynamic light scattering particle size distribution diagram and the transmission electron micrograph of the (5g/L) vesicle complex are shown in FIGS. 6 and 7, respectively. The vesicles before being coated with the active substance are uniformly dispersed, and the particle size is 200-400 nm (figure 6); the particle size of the Chinese herbal medicine active substance @ vesicle coated with the active substance is remarkably increased to about 700-800nm, and the membrane wall is thickened (figure 7).
Example 7:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 10g of PEO into the Chinese herbal medicine extract obtained in the operation (2)77-PPO29-PEO77Vortex stirring, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ PEO77-PPO29-PEO77(10g/L) vesicle complexes.
Chinese herbal medicine active @ PEO obtained in this example77-PPO29-PEO77The dynamic light scattering particle size distribution diagram and transmission electron micrograph of the (10g/L) vesicle complex are shown in FIG. 8. As is clear from FIG. 8, the product of this example contains a large number of vesicles, and the size of the vesicles is about 200nm and the vesicles are uniformly dispersed.
Example 8:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 5g PEO into the Chinese herbal medicine extract obtained in the operation (2)13-PPO30-PEO13Vortex stirring, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ PEO13-PPO30-PEO13A vesicular complex.
The herbal active obtained in this example @ PEO13-PPO30-PEO13The dynamic light scattering particle size distribution diagram and the optical micrograph of the vesicular complex are shown in fig. 9. As can be seen from FIG. 9, the product of this example contains a large number of vesicular micro-scale vesicles, and the particle size distribution is wide, about 2-4 μm.
Example 9:
(1) weighing 15g of polygonum multiflorum, 10g of groundsel, 5g of eclipta, 20g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 40g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 35g of prepared polygonum multiflorum, 25g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of gastrodia elata, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing, and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 0.3g of lauric glyceride into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ lauric glyceride vesicle compound II.
Example 10:
(1) weighing 5g of polygonum multiflorum, 5g of groundsel, 5g of eclipta, 35g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 35g of red paeony root, 12g of green tangerine peel, 10g of golden cypress, 40g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of gastrodia elata, 5g of carbonized dark plum fruit, 15g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing, and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 1.5g of mono-sodium dodecyl phosphate into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ mono-sodium dodecyl phosphate vesicle compound II.
Example 11:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 20g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 20g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 20g of rhizoma polygonati, 35g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 35g of cacumen biotae, 12g of ligusticum wallichii, 10g of gastrodia elata, 15g of carbonized dark plum fruit, 12g of fructus kochiae, 20g of red clover and 35g of donkey-hide gelatin, mixing, and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 10g of PEO into the Chinese herbal medicine extract obtained in the operation (2)77-PPO29-PEO77Vortex stirring, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ PEO77-PPO29-PEO77(10g/L) vesicular complexes II.
Example 12:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 2 hours each time, and the extraction temperature is 80 ℃.
(3) And (3) adding 0.3g of lauric glyceride into the Chinese herbal medicine extract obtained in the operation (2), stirring in a vortex mode, centrifuging, standing for 24 hours, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ lauric glyceride vesicle compound III.
Example 13:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 5 hours each time, and the extraction temperature is 60 ℃.
(3) And (3) adding 0.3g of lauric glyceride into the Chinese herbal medicine extract obtained in the operation (2), carrying out vortex stirring, centrifuging, standing for 24 hours, filtering and concentrating to obtain the Chinese herbal medicine active substance @ lauric glyceride vesicle compound IV.
Test example 1 mouse Hair growth test of Chinese herbal medicine active substance @ vesicle Complex
According to literature research, C57BL/6 mice were selected as the subject for hair loss modeling in this experiment. The black hair of the mouse can show unique hair cycle synchronicity. And the melanocytes of the skin of the trunk of the mouse exist only in hair follicles, and only synthesize melanin in the anagen phase. During the hair growth phase, the skin appears black due to the constant production of melanin by the hair bulb melanocytes, which is transferred to the hair follicle keratinocytes. During the catagen phase, melanin production is reduced and the skin is grayish black. In telogen, the hair follicle ceases to produce melanin and the skin turns pink as the hair bulb disappears. After the hair in the resting period is pulled out, a new hair cycle with high synchronization can be induced locally, and the histology is consistent with the natural cycle change of the rat, so the change of the hair cycle can be deduced from the change of the skin color.
Animal molding: c57BL/6 mice, female, 7 weeks old, weight 18-20 g. The animal shaver is used for shaving hair simply and then depilating hair with depilatory cream, and the depilatory area is 2 × 3cm2And the successful molding is determined when the skin is pink.
The administration method comprises the following steps: the mice successfully molded are randomly divided into 6 groups, each group comprises 5 mice, the corresponding medicine is given for treatment 2 times (morning and evening) each day according to the group, the smearing time is the same, the smearing amount is 0.4mL each time, and the medicine is continuously given for 21 days. The blank group was treated with 55% tincture solvent, the positive control group was treated with 3% minoxidil tincture, and the drug treatment group was treated with the sample prepared in the example of the present invention.
Wherein:
the administration group A is treated by Chinese herbal medicine active substance extracting solution;
administration group B was treated with the compound of example 2;
administration group C was treated with the compound of example 7;
the smearing mode is that cotton swabs are dipped and evenly smeared on the unhairing area.
Evaluation indexes are as follows: the skin color change in the depilated area of the mice was observed daily after dosing (fixed time per day) and a set of photographs were taken every 7 days, the time for the skin color to change from pink to grey and from grey to full hair for each depilated area of the mice was recorded, the average hair length for each group of mice was recorded, and the average change in body weight of the mice was recorded.
Mice given 21 days of continuous dosing were sacrificed by cervical dislocation, briefly shaved using an animal shaver, and the dorsal skin was trimmed to 2X 2cm with scissors2The shape of the tissue is that surface hair is washed by normal saline, then the tissue is soaked in 4 percent paraformaldehyde for 24 to 36 hours, the cut skin tissue section and HE are dyed, the number of hair follicles on the cross section and the longitudinal section of the tissue section and the shape of the hair follicles are observed under an optical microscope, the number of the hair follicles under the (multiplied by 10) visual field of each group of mice is taken, SPSS.26 software is used for statistical analysis and processing, and data are stored to
Figure BDA0003515978780000134
The results are shown, the comparison among groups is carried out by using one-way variance analysis, and P is less than 0.05, which has statistical significance.
After the cut skin tissue is sliced, inflammatory factors IL-6 and TNF-alpha are selected for marking and staining, and the inflammation condition of the mouse skin tissue under a visual field (multiplied by 200) is observed under a fluorescence confocal microscope (the positive area is green).
The results of the mouse hair growth experiments with the herbal actives @ vesicle complex are shown in figure 10, table 1 and table 2. The skin color blackening time of the hair removal area of the mice in the administration group is obviously shorter than that of the blank group; the new hair length of the mice in the administration group is obviously better than that in the blank group; the Chinese herbal medicine active substance @ vesicle compound has better hair growth effect on mice than a Chinese herbal medicine extract system without vesicle precursors. In conclusion, both example 2 and example 7 showed good hair growth promoting properties in the mouse hair model.
TABLE 1 mouse depilatory area skin color change
Figure BDA0003515978780000131
TABLE 2 average mouse Hair growth after 21 days of dosing
Figure BDA0003515978780000132
TABLE 3 average number of hair follicles in mice after 21 days of drug administration
Figure BDA0003515978780000133
Figure BDA0003515978780000141
“**”Represents a very significant difference from the control group, P < 0.01
The results of the light microscopy experiments on the hair follicles on the back of mice with the Chinese herbal medicine active @ vesicle compound are shown in fig. 11 and table 3. The number of hair follicles in the blank group is small, the color of the hair follicles is light, the lower end is degenerated and is in a catagen phase, the number of the hair follicles in the positive control group and the administration group A, B, C is large, the hair follicles are distributed more closely, the hair papilla is large, melanin in hair bulbs is obvious, and the hair follicles are still in a growth phase. The administered group B, C showed a slightly larger number of hair follicles than the administered group a, and showed a better hair growth promoting property in the mouse hair model.
The results of the mouse dorsal inflammatory factor fluorescent staining experiments with the Chinese herbal medicine active @ vesicle complex are shown in fig. 12. The inflammation condition of the mice in each group is not obviously different, which indicates that the inflammatory factors in the skin tissues of the mice are normally secreted, and the A, B, C in the administration group does not show toxic effect on the growth of the mice within 21 days of administration.
Test example 2 human Hair growth experiment of Chinese herbal medicine active substance @ vesicle Complex
(1) Human hair growth experiments were performed for examples 1, 2, 4, 5, 7, and 8.
(2) Total 120 subjects, 60 men, 60 women, age: 26-60 years old, and meets the inclusion criteria of the subjects. Subjects were randomized into 6 groups of 20 people each.
(3) Treatment was performed using the herbal active @ vesicle complexes prepared in examples 1, 2, 4, 5, 7, 8.
(4) 5mL of the Chinese herbal medicine active substance @ vesicle compound is smeared on the scalp for 2 times every day, the existence of systemic and local adverse reactions is observed, the result is recorded in detail, the detection is carried out for 1 time every week, the observation is carried out for 4 weeks, and the result is shown in Table 4.
(5) The therapeutic effect standard is divided into (a) significant effect: no obvious alopecia and a large amount of new hair generation; (b) the method has the following advantages: alopecia is controlled, and a small amount of new hair is generated; (c) and (4) invalidation: no obvious change before and after treatment; (d) is harmful: adverse reactions occur systemically or locally.
(6) The results of the human trials of the Chinese herbal medicine active @ vesicle complex are shown in table 1.
Table 4 human trial experimental results of Chinese herbal medicine active @ vesicle complexes
Figure BDA0003515978780000142
As can be seen from table 4, examples 1, 2, 4, 5, 7 and 8 all showed good hair growth promoting properties.
Comparative example 1:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 75g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) carrying out vortex stirring on the Chinese herbal medicine extract obtained in the operation (2), centrifuging, standing for 24 hours, filtering, concentrating, layering a sample, precipitating at the bottom, and forming a uniform and stable solution at normal temperature.
In comparative example 1, no vesicle precursor was added, and a transmission electron micrograph of the herbal extract is shown in FIG. 13. The active substances in the extract have poor dispersibility and serious aggregation. This demonstrates that the vesicle precursor plays an important role in the dispersibility, homogeneity and stability of the active substances in the Chinese herbal medicine extract.
Comparative example 2:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the traditional Chinese medicine powder obtained in the operation (1) into an extraction tank, adding 0.3g of lauric glyceride, 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, extracting, centrifuging, standing for 24 hours, filtering, concentrating, layering a sample, separating out a large amount of oil drops, and forming a uniform and stable traditional Chinese medicine active substance @ vesicle compound at normal temperature.
The order of addition of vesicle precursors was changed in comparative example 2. A transmission electron micrograph of a mixture of the lauric acid glyceride and the Chinese herbal medicine extract is shown in FIG. 14, the dispersibility of the extract in a sample is poor, and the aggregation is serious, which indicates that the addition sequence of the vesicle precursors influences the solubility and the dispersibility of the Chinese herbal medicine extract.
Comparative example 3:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 5g of Tween 80 into the Chinese herbal medicine extract obtained in the operation (2), carrying out vortex stirring, centrifuging, standing for 24 hours, filtering, concentrating, wherein a spherical vesicle structure is not found in a sample, the aggregation is serious, layering occurs after 48 hours, and a uniform and stable Chinese herbal medicine active substance @ vesicle compound cannot be formed at normal temperature.
The vesicle precursor in comparative example 3 was Tween 80, and a transmission electron micrograph of a mixture with herbal actives is shown in FIG. 15. Tween 80 can not form a vesicle structure in the Chinese herbal medicine extract, the extract is seriously aggregated and has poor dispersibility, and the active ingredients can not be encapsulated and released.
Comparative example 4:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) And (3) adding 0.4g of glyceryl stearate into the Chinese herbal medicine extract obtained in the operation (2), carrying out vortex stirring, centrifuging, standing for 24 hours, filtering, concentrating, wherein the sample has poor dispersibility, no vesicle structure is found, aggregation is serious, layering occurs after 30 minutes, and a uniform and stable Chinese herbal medicine active substance @ vesicle compound cannot be formed at normal temperature.
Comparative example 4a transmission electron micrograph of a mixture of herbal actives and glyceryl stearate is shown in fig. 16. Only oil drops are observed in the mixed sample, which indicates that the stearin cannot form a vesicle structure in the Chinese herbal medicine extract, the system solubility and dispersibility are poor, and the active ingredients cannot be encapsulated and released.
Comparative example 5:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(3) Adding 1g PEO into the Chinese herbal medicine extract obtained in the operation (2)77-PPO29-PEO77Vortex stirring, centrifuging, standing for 24 hours, filtering, concentrating, and obtaining a sample with poor dispersibility, wherein a spherical vesicle structure is not found, layering occurs after 24 hours, and a uniform and stable Chinese herbal medicine active substance @ vesicle compound cannot be formed at normal temperature.
Comparative example 5 herbal actives and PEO77-PPO29-PEO77(1g/L) Transmission electron micrograph of the mixture is shown in FIG. 17. Vesicle precursor PEO77-PPO29-PEO77At too low a concentration, vesicles cannot form in the herbal extract system, the solubility and dispersibility of the sample are poor, and the active ingredients cannot be encapsulated and released.
Comparative example 6:
(1) weighing 10g of polygonum multiflorum, 10g of climbing groundsel herb, 10g of eclipta, 30g of adenophora stricta, 30g of bighead atractylodes rhizome, 12g of rhizoma alismatis, 30g of red paeony root, 12g of green tangerine peel, 15g of golden cypress, 30g of rhizoma polygonati, 30g of prepared polygonum multiflorum, 30g of gynostemma pentaphylla, 30g of cacumen biotae, 12g of ligusticum wallichii, 12g of rhizoma gastrodiae, 10g of carbonized dark plum fruit, 10g of fructus kochiae, 25g of red clover and 35g of donkey-hide gelatin, mixing and crushing into powder.
(2) Putting the Chinese herbal medicine powder obtained in the operation (1) into an extraction tank, adding 650mL of tertiary water and 800mL of ethanol, soaking for 30 minutes, precipitating with ethanol, concentrating, and extracting to obtain the Chinese herbal medicine extract. Wherein the extraction times are 4 times, the extraction time is 4 hours each time, and the extraction temperature is 70 ℃.
(4) Adding 25g of PEO into the Chinese herbal medicine extract obtained in the operation (2)13-PPO30-PEO13Vortex stirring, centrifuging, standing for 24 hours, filtering, concentrating, and obtaining a sample with poor dispersibility, wherein a spherical vesicle structure is not found, and a uniform and stable Chinese herbal medicine active substance @ vesicle compound cannot be formed at normal temperature.
Comparative example 6 herbal actives and PEO13-PPO30-PEO13A transmission electron micrograph of the (25g/L) mixture is shown in FIG. 18. When vesicle precursor PEO13-PPO30-PEO13At too high a concentration, no vesicles can form in the system, the solubility and dispersibility of the mixed sample are poor, the coalescence is severe, and the active ingredient cannot be encapsulated and released.

Claims (10)

1. The Chinese herbal medicine active substance @ vesicle compound is characterized by comprising Chinese herbal medicine active substances and vesicles, wherein the Chinese herbal medicine active substances are coated in the vesicles: the hydrophilic substance is coated in the hydrophilic micro-area, namely the water core; the hydrophobic substance is solubilized between the bilayer membranes of the vesicles.
2. The Chinese herbal medicine active @ vesicle complex having hair nourishing effect as claimed in claim 1, wherein the particle size of the complex is 80nm to 5 μm;
preferably, the vesicle is a double-layer membrane vesicle, and the thickness of the double-layer membrane is between 3 nm and 7 nm.
3. The Chinese herbal medicine active substance @ vesicle compound having the hair nourishing effect as claimed in claim 1, wherein the content of the Chinese herbal medicine active substance @ vesicle compound is in the range of 30-100 g/L.
4. The Chinese herbal medicine active ingredient @ vesicle complex having hair nourishing effect as claimed in claim 1, wherein the vesicle is formed by an amphiphilic molecule system, the concentration of amphiphilic molecules is in the range of 0.1-20 g/L, and the amphiphilic molecules are called vesicle precursor.
5. The Chinese herbal medicine active @ vesicle compound having the hair nourishing effect as claimed in claim 1, wherein the Chinese herbal medicine active @ is extracted from the following raw material medicines:
polygoni Multiflori radix, Concha Haliotidis, Ecliptae herba, radix Adenophorae, Atractylodis rhizoma, Alismatis rhizoma, radix Paeoniae Rubra, pericarpium Citri Reticulatae viride, cortex Phellodendri, rhizoma Polygonati, radix Polygoni Multiflori Preparata, herba Gynostemmatis, folium Platycladi, rhizoma Ligustici Chuanxiong, rhizoma Gastrodiae, mume fructus charcoal, Kochiae fructus, herba Trifolii Pratentis, and colla Corii Asini;
preferably, the Chinese herbal medicine extract comprises the following raw material medicaments in part by weight:
5-15 parts of polygonum multiflorum, 5-15 parts of groundsel, 5-15 parts of eclipta, 20-50 parts of adenophora stricta, 20-50 parts of bighead atractylodes rhizome, 5-15 parts of rhizoma alismatis, 20-50 parts of red paeony root, 5-15 parts of green tangerine peel, 5-15 parts of golden cypress, 20-50 parts of rhizoma polygonati, 20-50 parts of prepared polygonum multiflorum, 20-50 parts of gynostemma pentaphylla, 20-50 parts of cacumen biotae, 5-15 parts of ligusticum wallichii, 5-15 parts of gastrodia elata, 5-15 parts of dark plum charcoal, 5-15 parts of fructus kochiae, 20-50 parts of red clover and 20-50 parts of donkey-hide gelatin.
6. The Chinese herbal medicine active @ vesicle complex having hair nourishing effect as claimed in claim 4, wherein the vesicle precursor is selected from one or a combination of the following: fatty acid monoglyceride, monoalkyl phosphate ester and salt thereof, 2-hydroxy fatty acid and salt thereof, nicotinic acid and derivative thereof, and triblock copolymer.
7. The Chinese herbal medicine active @ vesicle complex having hair nourishing and hair restoring effects as claimed in claim 6, wherein the @ vesicle complex is prepared by mixing the above Chinese herbal medicine active @ vesicleThe fatty acid monoglyceride is a straight-chain fatty acid monoglyceride; preferably C8-C18A linear chain mono-fatty acid glyceride; more preferably: caprylin, caprin, lauric glyceride, myristic glyceride, pentadecanoic glyceride, palmitic glyceride;
preferably, the monoalkyl phosphate ester and the salt thereof are linear alkyl phosphate ester and the salt thereof; more preferably C8-C16A linear monoalkyl phosphate ester of chain length or a salt thereof; more preferably: octyl phosphate and its sodium, potassium, magnesium, zinc, decyl phosphate and its sodium, potassium, magnesium, zinc, lauryl phosphate and its sodium, potassium, magnesium, zinc, myristyl phosphate and its sodium, potassium, magnesium, zinc, palmityl phosphate and its sodium, potassium, magnesium, zinc;
preferably, the 2-hydroxy fatty acid and the salt thereof are 2-hydroxy straight chain fatty acid and the salt thereof; more preferably C8-C162-hydroxy straight chain fatty acids of chain length and salts thereof; more preferably: 2-hydroxyoctanoic acid and sodium salt, potassium salt, magnesium salt, zinc salt thereof, 2-hydroxydecanoic acid and sodium salt, potassium salt, magnesium salt, zinc salt thereof, 2-hydroxylauric acid and sodium salt, potassium salt, magnesium salt, zinc salt thereof, 2-hydroxymyristic acid and sodium salt, potassium salt, magnesium salt, zinc salt thereof, 2-hydroxypalmitic acid and sodium salt, potassium salt, magnesium salt, zinc salt thereof;
preferably, the nicotinic acid and the derivatives thereof are nicotinic acid, benzyl nicotinate and tocopherol nicotinate;
preferably, the chemical composition formula of the triblock copolymer is as follows: PEO (polyethylene oxide)x-PPOy-PEOxX is more than or equal to 13 and less than or equal to 133, and y is more than or equal to 29 and less than or equal to 65; more preferably: PEO (polyethylene oxide)77-PPO29-PEO77、PEO13-PPO30-PEO13、PEO24-PPO35-PEO24、PEO133-PPO50-PEO133、PEO19-PPO30-PEO19、PEO100-PPO65-PEO100、PEO26-PPO40-PEO26
8. The preparation method of the Chinese herbal medicine active substance @ vesicle compound with hair nourishing and hair growing effects as claimed in claim 1, comprises the following steps:
adding a mixed solvent into the raw material medicines for extraction, collecting the extract, adding the vesicle precursor, uniformly mixing, precipitating with ethanol, centrifuging, filtering, and concentrating to obtain the Chinese herbal medicine active substance @ vesicle compound.
9. The method for preparing the Chinese herbal medicine active substance @ vesicle compound having hair nourishing and hair growing effects as claimed in claim 8, wherein the mixed solvent is ethanol-water mixed solution;
preferably, the ethanol volume percentage concentration of the ethanol-water mixed solution is 40-80%;
preferably, the extraction times are 1-5 times, and the extraction time is 1-5 hours each time; the extraction temperature is 55-80 ℃.
10. The use of the Chinese herbal medicine active @ vesicle complex having hair nourishing effect of claim 1 in the field of cosmetics.
CN202210166059.2A 2022-02-23 2022-02-23 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof Pending CN114366707A (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN202210166059.2A CN114366707A (en) 2022-02-23 2022-02-23 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof
CN202211195633.3A CN115350136B (en) 2022-02-23 2022-09-28 Chinese herbal medicine active matter@vesicle compound with hair nourishing and developing effects and preparation method and application thereof
PCT/CN2023/076491 WO2023160458A1 (en) 2022-02-23 2023-02-16 Chinese herbal medicine active substance @ vesicle complex having hair care and growth effects, and preparation method therefor and use thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210166059.2A CN114366707A (en) 2022-02-23 2022-02-23 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof

Publications (1)

Publication Number Publication Date
CN114366707A true CN114366707A (en) 2022-04-19

Family

ID=81146638

Family Applications (2)

Application Number Title Priority Date Filing Date
CN202210166059.2A Pending CN114366707A (en) 2022-02-23 2022-02-23 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof
CN202211195633.3A Active CN115350136B (en) 2022-02-23 2022-09-28 Chinese herbal medicine active matter@vesicle compound with hair nourishing and developing effects and preparation method and application thereof

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202211195633.3A Active CN115350136B (en) 2022-02-23 2022-09-28 Chinese herbal medicine active matter@vesicle compound with hair nourishing and developing effects and preparation method and application thereof

Country Status (2)

Country Link
CN (2) CN114366707A (en)
WO (1) WO2023160458A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115350136A (en) * 2022-02-23 2022-11-18 山东大学 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105748437A (en) * 2014-12-17 2016-07-13 北京盈科瑞药物研究院有限公司 Vesicle and vesicle preparation, and preparation methods thereof
CN109939623A (en) * 2019-04-01 2019-06-28 山东大学 A kind of monoalkyl phosphoric acid esters (salt) vesica and its preparation and application
CN111388390A (en) * 2020-04-17 2020-07-10 广州章王化妆品有限公司 Chinese herbal medicine shampoo with alopecia preventing and hair nourishing effects and preparation method thereof
CN112190610A (en) * 2020-09-11 2021-01-08 湖州中科院应用技术研究与产业化中心 Plant-loaded active liposome for promoting hair regeneration and preparation method thereof

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5834014A (en) * 1995-10-06 1998-11-10 The Regents Of The University Of Michigan Stimulation of hair follicles
KR100757237B1 (en) * 2006-12-28 2007-09-10 김지활 Composite that have improvement effect vitality of hair
KR20090059445A (en) * 2007-12-06 2009-06-11 주식회사 솔레오 Composition for preventing alopecia or growing hair containing the cation/anion mixed surfactant comprising the extracts of medical herbs
KR100948204B1 (en) * 2009-06-23 2010-03-16 주식회사지피에이코리아 Composition for improving condition of hair and scalp containing a herb extracts mixture stabilized by liposome
CN102579340B (en) * 2011-01-07 2016-03-02 北京因科瑞斯医药科技有限公司 Sinomenine vesicle and preparation thereof and preparation method
JP7086354B2 (en) * 2017-05-29 2022-06-20 日光ケミカルズ株式会社 Vesicle composition and skin external preparations or cosmetics containing it
CN107260677B (en) * 2017-06-09 2020-12-18 山东大学 Non-fatty acid single-tail-chain single-surfactant vesicle and preparation method thereof
CN107349115B (en) * 2017-06-27 2020-12-11 张学记 Plant ethosome anti-hair loss pilatory as well as preparation method and using method thereof
CN111437299A (en) * 2020-06-01 2020-07-24 上海希尔维生物科技有限公司 Gynostemma pentaphylla plant extract solution and application thereof in preparing medicine for promoting hair growth
CN111643446A (en) * 2020-07-30 2020-09-11 济南磐升生物技术有限公司 Biological nutrition scalp hair follicle hair growth essence and preparation method thereof
CN112386507A (en) * 2020-12-09 2021-02-23 广州科缇生物科技有限公司 Preparation method of vesicle-type carrier and application of vesicle-type carrier in cosmetics
CN114366707A (en) * 2022-02-23 2022-04-19 山东大学 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105748437A (en) * 2014-12-17 2016-07-13 北京盈科瑞药物研究院有限公司 Vesicle and vesicle preparation, and preparation methods thereof
CN109939623A (en) * 2019-04-01 2019-06-28 山东大学 A kind of monoalkyl phosphoric acid esters (salt) vesica and its preparation and application
CN111388390A (en) * 2020-04-17 2020-07-10 广州章王化妆品有限公司 Chinese herbal medicine shampoo with alopecia preventing and hair nourishing effects and preparation method thereof
CN112190610A (en) * 2020-09-11 2021-01-08 湖州中科院应用技术研究与产业化中心 Plant-loaded active liposome for promoting hair regeneration and preparation method thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
杨继生: "《表面活性剂原理与应用》", 31 December 2012, 东南大学出版社 *
赵文: "《宗教与中医学发展》", 31 December 2008, 宗教文化出版社 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115350136A (en) * 2022-02-23 2022-11-18 山东大学 Chinese herbal medicine active matter @ vesicle compound with hair nourishing and hair growing effects and preparation method and application thereof
WO2023160458A1 (en) * 2022-02-23 2023-08-31 山东大学 Chinese herbal medicine active substance @ vesicle complex having hair care and growth effects, and preparation method therefor and use thereof
CN115350136B (en) * 2022-02-23 2024-01-19 山东大学 Chinese herbal medicine active matter@vesicle compound with hair nourishing and developing effects and preparation method and application thereof

Also Published As

Publication number Publication date
WO2023160458A1 (en) 2023-08-31
CN115350136B (en) 2024-01-19
CN115350136A (en) 2022-11-18

Similar Documents

Publication Publication Date Title
JP4563521B2 (en) Collagen production promoter and topical skin preparation
KR100761660B1 (en) A composition for promoting hair growth
JPH05503287A (en) Compositions based on hydrated lipid membrane layers or liposomes containing at least one derivative of labdan or a plant extract containing it; cosmetic or pharmacological, especially dermatological, compositions containing it
JP2010501551A (en) Use of rare earth elements for hair improvement
CN106265164A (en) There is compositions of hair growth promoting, scalp maintenance, moisture-keeping efficacy and preparation method thereof
JP6977233B2 (en) Head composition
CN115350136B (en) Chinese herbal medicine active matter@vesicle compound with hair nourishing and developing effects and preparation method and application thereof
WO2001074326A1 (en) Agents improving skin barrier function
KR20140067748A (en) Novel drug delivery system for percutaneous absorption, composition for external preparation preventing hair loss, and cosmetics using the same
CN112022767B (en) Anti-inflammatory antibacterial immunity-enhancing acne-removing composition and application thereof
CN108096174A (en) A kind of compound plant extract with hair care anti-off effect and preparation method and application
CN107349115B (en) Plant ethosome anti-hair loss pilatory as well as preparation method and using method thereof
JPH05255044A (en) Hair grower
CN111265642A (en) External medicine for removing nevus, wart and sweat duct tumor and preparation method thereof
KR20200060890A (en) The shampoo composition comprising extract of natural micro organism-fermented black ginseng
CN113230163B (en) Application of hydrolyzed yeast protein and chicory root extract in preparation of hair growth and hair nourishing products
CN108309896A (en) A kind of hair care anti-hair loss composition and its application
CN111281851A (en) PH-targeted flexible nanoliposome with acne removing effect and preparation method thereof
JP2001139436A (en) Hair tonic and grower
JP4577596B2 (en) Hair restorer or hair growth agent and method of use thereof
JPH09124500A (en) Therapeutic agent for atopic dermatitis
JP3159412B2 (en) Skin cosmetics
CN115869352B (en) Traditional Chinese medicine compound preparation for treating androgenetic alopecia and preparation method and application thereof
JP2002068931A (en) Composition for external use
CN112691187B (en) Sustained-release film for preventing forehead alopecia and preparation method thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20220419

WD01 Invention patent application deemed withdrawn after publication