CN107320699A - A kind of Chinese medicine compound prescription micro emulsion gels and its production and use - Google Patents
A kind of Chinese medicine compound prescription micro emulsion gels and its production and use Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/236—Ligusticum (licorice-root)
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/26—Aristolochiaceae (Birthwort family), e.g. heartleaf
- A61K36/268—Asarum (wild ginger)
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- A61K36/88—Liliopsida (monocotyledons)
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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Abstract
The present invention relates to a kind of Chinese medicine compound prescription micro emulsion gels and its production and use.Especially, the present invention relates to a kind of micro emulsion gel composition, its contain gaultherolin, menthol, camphor, borneol and containing Paeonol, eugenol, pipering isoreactivity composition Chinese medical extract, and micro emulsion gel matrix, wherein the active component is contained in micro emulsion.The invention further relates to the preparation method of the micro emulsion gel composition, and its purposes in promoting blood circulation and stopping pain.Invention formulation not only ensure that medicine is merged with the height of matrix, while having drugloading rate high, small to skin irritation, Transdermal absorption performance is good, the features such as preparation technology is simple.
Description
Technical field
The present invention provides a kind of new microemulsion gel preparation and preparation method thereof and the purposes in medicine.
Background technology
Blood-activating analgesic plaster prescription derives from " precious analgesic plaster " of the clear Kangxu between 7 years, the good limited public affairs of minister in ancient times's medicine company more than the peace section of Anhui
Independent development and production are taken charge of, nineteen sixty-five is changed to rubber paste formulation, so far the existing sales histories of more than 50 years.Blood-activating analgesic plaster in
Record within 2010 into《Chinese Pharmacopoeia》One, the effect of it has promoting blood circulation and stopping pain, channels sootheing and network vessel quickening is recorded, for arthralgia and myalgia, flesh
Nauseating numbness, subcutaneous nodule, joint pain.Due to determined curative effect, be widely recognized as since listing by patient, year single variety surpass hundred million
Member.
The prescription medicinal material of blood-activating analgesic plaster mainly include rhizoma zingiberis, kaempferia galamga, the root of Dahurain angelica, rhizoma nardostachyos, rheum officinale, unprocessed Arisaema erubescens, dried pinellia,
Myrrh, frankincense, borneol, menthol, camphor, dried orange peel, Radix Angelicae Sinensis, cloves, pepper, cortex periplocae, asarum, schizonepeta, cassia twig, the flower bud of lily magnolia, river
Rhizome of chuanxiong, levisticum, moutan bark, capsicum, rhizoma atractylodis, belladonna liquid extract, gaultherolin.In the prior art, the preparation step of blood-activating analgesic plaster
It is rapid as follows：The taste medicine of the above 28, in addition to menthol, borneol, gaultherolin, belladonna liquid extract, camphor, remaining root of Dahurain angelica etc. two
13 tastes are ground into coarse powder, and with 90% ethanol as solvent, dipping, diacolation collects percolate, reclaims ethanol and is condensed into relative
Density is about the clear cream of 1.05 (80 DEG C), adds the five tastes such as above-mentioned menthol, stirs evenly, separately Jia 4.5~5 times of weight are by rubber, pine
The matrix that perfume (or spice) etc. is made, is made coating, carries out painting cream, and cut-out, lid lining, section is produced.
Promoting blood circulation and stopping pain medicinal extract bulk drug is made up of two parts, and a part is rhizoma zingiberis, cloves, moutan bark, pepper, rhizoma nardostachyos etc. 23
Chinese medical extract medicinal extract obtained by taste Chinese medicinal material extract and belladonna liquid extract mixing, another part is camphor, menthol, ice
Piece, 4 kinds of volatile bulk drugs of gaultherolin.Active ingredient Paeonol and eugenol conduct are selected in Chinese medical extract medicinal extract
Gaultherolin is selected to be used as representative composition in representative composition, 4 kinds of bulk drugs.Investigation is used as using the content of these three compositions
Index.
Although blood-activating analgesic plaster is evident in efficacy, also there is weak point：
1st, in terms of adverse reaction
At present, there is sensitizing agent in rubber ointment, its abnormal, stimulation, stripping reaction reduce its medication comfortableness, peace
Full property and validity.Rubber ointment is made up of material of mounting, creme, the part of cream face covering three, and analysis finds Chinese medicine rubber paste
The allergy sex chromosome mosaicism and these materials of agent are closely related.Wherein, material of mounting often uses cotton, chemical fabric, elastical cloth, gas permeability
Difference, when skin surface attaches air-locked paste, the substantial amounts of excreta of skin is deposited in skin surface, and thorn is produced to skin
Swash, so as to form the allergic symptoms such as local redness, erythema, erythema, itch.Rubber mass in creme include rubber, tackifier,
Rosin acid in protein in many kinds of substance such as softening agent, filler, natural rubber, tackifier rosin easily causes skin
Allergic reaction, filler zinc oxide quality good or not directly affects the peel strength of rubber ointment, and skin is easily pulled in stripping process
Skin, causes flush, even heating, allergy.
2nd, in terms of preparation technology
Containing largely with volatile active ingredient, such as gaultherolin, borneol, camphor, peppermint in blood-activating analgesic plaster
Brain etc., accounts for preparation is eventually adding medicine (dry weight) 50%.However, the traditional preparation methods of rubber ointment mainly have solvent method
With two kinds of pressure sintering, it is required to complete at a higher temperature, inherently causes the loss of active ingredient, influences drug effect.And it is molten
Agent method largely consumes energy resources, and production process potential safety hazard is big, and gasoline easily burns, and drying course gasoline largely volatilizees to ring
Border is polluted, and is also unfavorable for the labour protection of direct labor；Rubber ointment prepared by pressure sintering has cream face brightless, holds viscous
Property is weak, and skin has the shortcomings that residue after patch.
In order to overcome the deficiencies in the prior art, promoting blood circulation and stopping pain rubber ointment dosage changing form is that promoting blood circulation and stopping pain micro emulsion coagulates by the present invention
Jelly.On the one hand, the partial liquefaction phenomenon that ingenious utilization menthol, camphor, borneol three mixing are produced, then use oily salicylic acid
Methyl esters dissolving is prepared into oil phase, adds other auxiliary materials and is prepared into micro emulsion, by the compound nanosizing containing 28 taste Chinese medicines, promotes medicine saturating
Skin absorbent properties, on the other hand, small with excitant, drugloading rate is high, the features such as medicine and matrix amalgamation are good.At present, micro emulsion
Viscosity is low, and mobility is strong, poor as carrier for transdermal delivery adhesiveness, and gel has good adhesiveness, hydrophilic gel
Good hand touch, homogeneous exquisiteness is easy to apply, washable to remove, not pollution clothes, small to skin and irritation on mucous membrane, and micro emulsion is made and coagulates
Glue, to play a part of mutual supplement with each other's advantages.
The content of the invention
The present invention is intended to provide a kind of micro emulsion gel composition, it contains 24 kinds of Chinese medicinal material extracts and four kinds of bulk drugs are made
For active principle and micro emulsion gel matrix, 24 kinds of Chinese medicinal material extracts are rhizoma zingiberis, kaempferia galamga, the root of Dahurain angelica, rhizoma nardostachyos, rheum officinale, raw day
Southern Star, dried pinellia, myrrh, frankincense, dried orange peel, Radix Angelicae Sinensis, cloves, pepper, cortex periplocae, asarum, schizonepeta, cassia twig, the flower bud of lily magnolia, Ligusticum wallichii, solely
Work, moutan bark, the extract of capsicum and rhizoma atractylodis, and belladonna liquid extract；Four kinds of bulk drugs are gaultherolin, peppermint
Brain, camphor, borneol；Wherein described active principle is contained in micro emulsion.
Corneocyte is made up of lipid bilayer, is the rate-limiting factor of Drug Percutaneous Absorption, and medicine passes through cutin
Layer mainly has without cell and through two kinds of approach of cell.And micro emulsion has hydrophilic area and lipophilic area, the micro emulsion of percutaneous dosing simultaneously
Once into cuticula, can change polarity and lipid approach simultaneously, its hydrophilic area can be such that cuticula is significantly hydrated
Effect, when the aqueous phase of micro emulsion flows into doping region, it will increase the film inner volume of Stratum corneum lipids bilayer, the same angle of some fat chains
Matter layer albumen evacuates covalent bond, causes the destruction of interfacial structure, the aquation of these protein will cause the destruction of double-layer of lipoid,
The absorption of medicine can be promoted；Lipophilic area can interact with cuticula in a number of ways, be dissolved in the medicine in micro emulsion lipid area
Can directly it distribute into the lipid of cuticula, or lipid carrier can insert the lipid area of cuticula in itself, thus destroy the double of it
Molecule Rotating fields, these interactions can cause to increase the infiltration of medicine.Lower alcohols used can improve skin in microemulsion system
The permeability of skin, promotes the overall percutaneous operating of drug-loading system, and micro emulsion storage is intracutaneous, plays reservoir effect, medicine is slowly released
Put, play long-acting.Micro emulsion particle diameter is generally 10~100nm, and particle size can also influence Medicated Permeation to act on.When particle compared with
Hour, the chance of carrier and cuticula interaction is increased by, therefore Drug Percutaneous Absorption increase.In addition, when particle is larger, no
The chance only interacted is reduced, and carrier is relatively difficult through skin.
Micro emulsion is that oil phase, aqueous phase, surfactant and cosurfactant are mixed by a certain percentage, the one kind spontaneously formed
Transparent or semitransparent, low viscosity, Thermodynamically stable and isotropic oil-water mixing system.
Micro emulsion gels are to add microemulsion to gel-type vehicle (such as natural polymerses, cellulose derivative, embedding
Section polymer Polymer material) in, the transparent of formation, homogeneous, stable gel networks contain micro emulsion in network structure
Drop.
In one embodiment of the invention, according to micro emulsion gel composition of the present invention, wherein described
The micro emulsion for containing active composition is O/W type micro emulsions.
According to the composition of oil phase, water, surfactant and cosurfactant, ratio it is different by micro emulsion be divided into three kinds it is basic
Structure type, i.e. O/W, W/O and B.C type.
In another embodiment of the present invention, according to micro emulsion gel composition of the present invention, wherein described
Micro-emulsion stroma be made up of surfactant, cosurfactant and oil phase.
In yet other embodiments, according to micro emulsion gel composition of the present invention, wherein described
Oil phase is the component gaultherolin dissolving borneol in medicine, the mixing oil phase obtained by Camphorae and menthue.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein institute
State surfactant be selected from tween, sapn, Crodaret, octanoic acid capric acid LABRAFIL M 1944CS one kind or
It is two or more mixtures, preferably Tween 80, polysorbas20, sorbester p17, sorbester p18, Crodaret (RH40), pungent
It is sour capric acid LABRAFIL M 1944CS, more preferably Tween 80, polysorbas20, Crodaret (RH40).
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein institute
State cosurfactant be selected from absolute ethyl alcohol, glycerine, propane diols, PEG-4000 (PEG400) one or two and more than
Mixture.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein institute
Gel-type vehicle is stated for hydrophilic gel matrix, preferably carbomer (CP), sodium carboxymethylcellulose (CMC-Na), hydroxypropyl methylcellulose
(HPMC), one or more kinds of mixing of Sodium Polyacrylate, sodium alginate, Arabic gum, tragacanth, polyvinyl alcohol
Thing.
In yet other embodiments, according to micro emulsion gel composition of the present invention, wherein, with group
The gross weight meter of compound, the percentage by weight of the oil phase is between 0.1%~10% preferably 0.5% to 5%, and with oil
The gross weight meter of phase, the percentage by weight of gaultherolin is 33.1%, borneol, the percentage by weight difference of Camphorae and menthue
For 22.3%.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, with
The gross weight meter of composition, the percentage by weight of the surfactant is between 1%~30%, between preferably 9% to 30%.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, with
The gross weight meter of composition, the percentage by weight of the cosurfactant between 0%~20%, preferably 3% to 15% it
Between.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, with
The gross weight meter of composition, the percentage by weight of the gel-type vehicle is between 0.3%~10%, between preferably 1%~3%.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, with
The gross weight meter of composition, the percentage by weight of the Chinese medical extract is between 0.5%~20%, and preferably 0.8%~12%
Between.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, it enters one
Step contain NMF, preservative, antioxidant, the NMF preferably glycerine, sorbierite, propane diols, one kind of polyethylene glycol or
Two or more mixtures, the preferred ethyl hydroxy benzoate of preservative, potassium sorbate, propylparaben, the one of phenmethylol
Kind or two kinds and the above mixture.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, bag
The average grain diameter of the micro emulsion of carrying active composition is between 20~50nm, and polydispersity coefficient PDI is below 0.3.
In presently preferred embodiment, according to micro emulsion gel composition of the present invention, wherein, it is micro-
The average grain diameter of curdling glue is between 20~50nm, and polydispersity coefficient PDI is below 0.4.
The present invention further provides a kind of preparation method according to micro emulsion gel composition of the present invention, it include with
Lower step：
1) weighing menthol in prescription, camphor, borneol and grinding makes its partial liquefaction, add gaultherolin mixing make it is molten
Solution, it is standby as oil phase；
2) Chinese medical concrete is made in the Chinese medicine for weighing recipe quantity；
3) by obtained oil phase and medicinal extract, surfactant, cosurfactant and optional preservative in step 1 in 20
~35 DEG C of stirrings, to medicine dissolving completely, are slowly added to water, stir, produce promoting blood circulation and stopping pain micro emulsion；Or
Oil phase, surfactant, cosurfactant and optional preservative are weighed in 20~35 DEG C of stirrings, is slowly added to
Water, stirs, and produces blank micro emulsion；Then by step 2) in obtained medicinal extract add into blank micro emulsion, stir, i.e.,
Obtain promoting blood circulation and stopping pain micro emulsion；
4) gel-type vehicle and optional antioxidant, plus suitable quantity of water are weighed, is fully swelled in 20~35 DEG C, step 3 is added) in
Obtained promoting blood circulation and stopping pain micro emulsion stirs, and pH is to 6~7 for regulation, produces promoting blood circulation and stopping pain micro emulsion gels of the present invention.
Another aspect of the present invention is provided to be prepared for promoting blood circulation and stopping pain according to micro emulsion gel composition of the present invention
Purposes in medicine.
The present invention further provides prepared according to micro emulsion gel composition of the present invention for arthralgia and myalgia, muscle
Purposes in paralysis, subcutaneous nodule, the medicine of joint pain.
In further preferred embodiment of the present invention, the present invention provides a kind of micro emulsion gel composition, and it contains work
Property component extract, the micro emulsion being made up of oil phase, surfactant and cosurfactant, hydrophilic gel matrix, NMF,
Preservative, antioxidant and appropriate water.With the gross weight meter of composition, the percentage by weight of each component is as shown in table 1 below.
Table 1
Wherein, surfactant includes but is not limited to Tween 80, polysorbas20, sorbester p17, sorbester p18, polyethylene glycol hydrogenated castor
Sesame oil (RH40), octanoic acid capric acid LABRAFIL M 1944CS (Labrasol) one or two and the above mixture.Help surface
Activating agent include but is not limited to absolute ethyl alcohol, glycerine, propane diols, PEG-4000 (PEG400) one or two and more than
Mixture.It is fine that hydrophilic gel matrix includes but is not limited to carbomer (CP), sodium carboxymethylcellulose (CMC-Na), hydroxypropyl first
Tie up plain (HPMC), Sodium Polyacrylate, sodium alginate, Arabic gum, tragacanth, the one or two of polyvinyl alcohol and the above
Mixture.NMF includes but is not limited to glycerine, sorbierite, propane diols, the one or two of polyethylene glycol and the mixing of the above
Thing.Preservative include but is not limited to ethyl hydroxy benzoate, potassium sorbate, propylparaben, phenmethylol one or two and
Mixture above.
The specific preparation method of micro emulsion gel composition of the present invention is as follows：
(1) preparation of oil phase is mixed
By prescription gaultherolin: camphor：Menthol: the ratio of borneol (1.5: 1: 1: 1) weighs medicine, first take camphor,
Menthol and borneol mixing are ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
(2) preparation of promoting blood circulation and stopping pain micro emulsion
Method one：Weigh the mixing oil phase of recipe quantity, it is Chinese medical extract medicinal extract, surfactant, cosurfactant, anti-
Rotten agent is stirred 40 minutes under the conditions of 20~35 DEG C, 300-500 revs/min of mixing speed, slow to add to medicine dissolving completely
Enter water, stirring balance 20 minutes produces promoting blood circulation and stopping pain micro emulsion.
Method two：The mixing oil phase of recipe quantity, surfactant, cosurfactant, preservative are weighed in 20~35 DEG C
Under the conditions of stir 10 minutes, 300-500 revs/min of mixing speed is slowly added to water, stirring balance 10 minutes, adds prescription
The Chinese medical extract medicinal extract of amount, well mixed, stirring balance 30 minutes, produce promoting blood circulation and stopping pain micro emulsion.
(3) preparation of promoting blood circulation and stopping pain micro emulsion gels
Method one：Recipe quantity hydrophilic gel matrix, antioxidant, plus suitable quantity of water are weighed, it is fully molten overnight in 20~35 DEG C
It is swollen, plus promoting blood circulation and stopping pain micro emulsion stirs, 150~350 revs/min of mixing speed, pH is to 6~7 for regulation, produces promoting blood circulation and stopping pain micro-
Curdling jelly.
Method two：Recipe quantity hydrophilic gel matrix, antioxidant, plus promoting blood circulation and stopping pain micro emulsion are weighed, in 20~35 DEG C of conditions
It is lower to be fully swelled overnight, stir, 150~350 revs/min of mixing speed adjusts pH to 6~7, produces promoting blood circulation and stopping pain micro emulsion
Gel.
Advantages of the present invention：
1) auxiliary material used in promoting blood circulation and stopping pain micro emulsion gels of the invention is the customary adjuvant in pharmaceutical preparation, in medication
Had a clear superiority in security, allergic reaction of the blood-activating analgesic plaster matrix to skin can be reduced, and moistening effect is good, can improve
The compliance of patient；
2) promoting blood circulation and stopping pain micro emulsion gels of the invention can be by promoting blood circulation and stopping pain medicinal extract nanosizing, and drugloading rate cream is conducive to
The release of medicine and Transdermal absorption, strengthen the therapeutic effect of medicine；
3) promoting blood circulation and stopping pain medicinal extract uses 90% alcohol extracting, thus can be by its turn containing a large amount of fat-soluble strong active ingredients
O/W type micro emulsions are turned to, are combined with hydrophilic gel, compatibility is good, the stability of preparation can be increased；
4) promoting blood circulation and stopping pain micro emulsion gels preparation technology of the invention is simple to operation, without the condition control such as heating and thermal insulation
System, can increase the stability of volatile effective component in medicine.
Brief description of the drawings
Fig. 1 is the grain size distribution of the promoting blood circulation and stopping pain micro emulsion obtained in embodiment 6.
Fig. 2 is the electron-microscope scanning figure of the promoting blood circulation and stopping pain micro emulsion obtained in embodiment 6.
Fig. 3 is the grain size distribution of obtained promoting blood circulation and stopping pain micro emulsion gels in embodiment 6.
Fig. 4 and Fig. 5 is the electron-microscope scanning figure of obtained promoting blood circulation and stopping pain micro emulsion gels in embodiment 6.
Fig. 6 is the rheology type curve of obtained promoting blood circulation and stopping pain micro emulsion gels in embodiment 6.
Fig. 7 is the accumulation H103 resin figure of obtained promoting blood circulation and stopping pain micro emulsion gels in embodiment 6.
Embodiment
The present invention is further described below by way of specific embodiment, it should be understood that these embodiments are merely to illustrate this hair
It is bright, the scope of the present invention is not limited in any form.
Experiment material
Camphor (lot number HY-029-1510004), menthol (lot number ZY-124-1511005), borneol (lot number ZY-040-
1510002), gaultherolin (lot number HY-004-1511009), belladonna liquid extract (lot number ZY-122-1511004), is purchased from
Anhui Anke Yuliang Medicine Co., Ltd.
Median chain triglyceride oil (MCT, 101091109, Thousand Islands fine chemistry industry Industrial Co., Ltd. of Jiande City)；Polyoxyethylene
Rilanit special (RH40,01932368EO, German BASF)；Polyoxyethylene sorbitan monoleate (Tween80,20120501, the day pharmacy of Hunan China
Co., Ltd)；Polysorbate 20 (Tween20,20121010, Chemical Reagent Co., Ltd., Sinopharm Group)；PEG-4000
(PEG400,13/34, German Sasol)；Glycerine (20140739, Suichang of Zhejiang Province Hui Kang pharmaceutcal corporation, Ltd)；Acritamer 940 is (beautiful
Guo Nuoyu companies)；Potassium sorbate (Shaanxi Western Mountain pharmaceutical Co. Ltd)；(Hua Yi pharmaceutic adjuvants manufacture in Chengdu has natrium adetate
Limit company)；Sodium carboxymethylcellulose (Anhui Shanhe Medicinal Subsidiary Material Co., Ltd.)；Ethyl hydroxy benzoate (103620140101, lake
Nan Erkang Pharmacy stock Co., Ltd)；Sodium Polyacrylate (Showa Denko K. K)；(Shijiazhuang timely snow pharmacy has sorbierite
Limit company)；Propylparaben (Guangzhou Pharmaceuticals Ltd of Han Consulting)；PVA (Lubrizol Advanced Materials Corporation) propane diols
(20140705, Nanjing Weir)；Absolute ethyl alcohol (150901, Sichuan Kingsoft pharmaceutical Co. Ltd)；Votalin Ointment (Beijing Novartis
Pharmaceutical Co. Ltd, lot number：X4407)；Methanol (chromatographically pure, 20140315001, Tianjin Sai Furui Science and Technology Ltd.s)；Wa Ha
Breathe out pure water (20150703, Tianjin Wahaha Food Co., Ltd).
Animal：Kunming mouse 90, male, body weight 19-21g, 6-7 week old.Cured purchased from Chinese People's Liberation Army's military affairs
Subject institute Experimental Animal Center, credit number：SCXK (army) 2012-0004.
Laboratory apparatus
Anton MCR102 types rheometer (Austrian Anton Paar company)；BSA223S-CW types electronic analytical balance (Germany
Sai Duolisi companies)；Magnetic stirring apparatus (Germany, IKA companies)；Zetasizer Nano ZS nano particle sizes instrument (Britain's Malverns
Company)；Franz diffusion cells (Shanghai Kai Kai Co., Ltds)；Dialysis membrane (Bioisystech Co., Ltd of HTC of system in Beijing Jing section)；T6 is new
Century ultraviolet-uisible spectrophotometer (Beijing Puxi General Instrument Co., Ltd)；PH meter (the METTLER of DELTA 320
TOLEDO)；SB25-12D types Ultrasound Instrument (NingBo XinZhi Biology Science Co., Ltd)；HC-2518 types supercentrifuge (peace
Hui Zhong Ke Zhongjia scientific instrument Co., Ltd)；C-MAG HS4 types magnetic stirring apparatus (German IKA companies)；H-7650 types transmission electricity
Sub- microscope (FDAC)；JEM-2200FS type 3-D transmission Electronic Speculum (Jeol Ltd.).
The preparation of the promoting blood circulation and stopping pain medicinal extract of embodiment 1
Blood-activating analgesic plaster (rubber paste) has included pharmacopeia (2010 editions one page 957,2015 editions one page 1294), its prescription
It is as follows with medicinal extract preparation method：
In addition to menthol, borneol, camphor, gaultherolin, belladonna liquid extract in above-mentioned prescription, remaining root of Dahurain angelica etc. 23
Taste pulverizing medicinal materials are into coarse powder, and with 90% ethanol as solvent, dipping, diacolation collects percolate, reclaims ethanol and is condensed into relative
Density is the clear cream of 1.2634 (25 DEG C), adds belladonna liquid extract, stirs evenly, produce Chinese medical extract medicinal extract.Above-mentioned menthol, ice
Piece, camphor, gaultherolin, menthol are standby.
The preparation example one of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 2
Prescription 1 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Mixing oil phase 1.15g, RH40 9.30g, PEG400 4.63g, potassium sorbate 0.075g are weighed in 20~35 DEG C of bars
Stirred 10 minutes under part, 300-500 revs/min of mixing speed, be slowly added to water, stirring balance 10 minutes is added in embodiment 1
Obtained Chinese medical extract medicinal extract 1.75g, stirring balance 30 minutes, produces promoting blood circulation and stopping pain micro emulsion.
Carbomer 1.00g, natrium adetate 0.05g, plus suitable quantity of water are weighed again, are fully swelled overnight in 20~35 DEG C, plus
Enter promoting blood circulation and stopping pain micro emulsion prepared above, propane diols 2.50g, stir, 150~350 revs/min of mixing speed uses three second
Hydramine adjusts pH to 6~7, produces promoting blood circulation and stopping pain micro emulsion gels of the present invention.
The preparation example two of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 3
Prescription 2 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh obtained Chinese medical extract medicinal extract 3.50g, mixing oil phase 2.30g, Tween 80 13.88g, nothing in embodiment 1
Water-ethanol 4.62g, is stirred 40 minutes, 300-500 revs/min of mixing speed in 20~35 DEG C, to medicine dissolving completely, slowly
Suitable quantity of water is added, stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
Weigh CMC-Na 2.50g, natrium adetate 0.10g again, add promoting blood circulation and stopping pain micro emulsion prepared above, in 20~
35 DEG C are fully swelled overnight, add propane diols 5.00g, stir, 150~350 revs/min of mixing speed uses triethanolamine
PH is adjusted to 6~7, promoting blood circulation and stopping pain micro emulsion gels of the present invention are produced.
The preparation example three of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 4
Prescription 3 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh Chinese medical extract medicinal extract 5.57g made from embodiment 1, mixing oil phase 3.68g, RH40 18.5g, propane diols
9.25g, potassium sorbate 0.10g, are stirred 40 minutes, 300-500 revs/min of mixing speed has dissolved to medicine in 20~35 DEG C
Quan Hou, is slowly added to suitable quantity of water, and stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
Sodium Polyacrylate 2.00g, plus suitable quantity of water are weighed again, is fully swelled overnight in 20~35 DEG C, are added prepared above
Promoting blood circulation and stopping pain micro emulsion stirs, 150~350 revs/min of mixing speed, adjusts pH to 6~7 with triethanolamine, produces this hair
Bright promoting blood circulation and stopping pain micro emulsion gels.
The preparation example four of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 5
Prescription 4 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh Chinese medical extract medicinal extract 5.57g made from embodiment 1, mixing oil phase 3.68g, polysorbas20 13.88g, the third two
Alcohol 6.94g, propylparaben 0.5g, are stirred 40 minutes, 300-500 revs/min of mixing speed, to medicine in 20~35 DEG C
After thing dissolving completely, suitable quantity of water is slowly added to, stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
Weigh Sodium Polyacrylate 0.5g, natrium adetate 0.2g again, add promoting blood circulation and stopping pain micro emulsion prepared above, in 20~
35 DEG C are fully swelled overnight, add sorbierite 2.50g, stir, 150~350 revs/min of mixing speed uses triethanolamine
PH is adjusted to 6~7, promoting blood circulation and stopping pain micro emulsion gels of the present invention are produced.
The preparation example five of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 6
Prescription 5 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh Chinese medical extract medicinal extract 3.50g made from embodiment 1, mixing oil phase 2.30g, RH40 9.30g, propane diols
4.63g, propylparaben 0.075g, are stirred 40 minutes, 300-500 revs/min of mixing speed, to medicine in 20~35 DEG C
After thing dissolving completely, suitable quantity of water is slowly added to, stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
CMC-Na 2.50g, natrium adetate 0.05g, plus suitable quantity of water are weighed, is fully swelled overnight in 20~35 DEG C, is added
Promoting blood circulation and stopping pain micro emulsion prepared above, glycerine 5.00g, stir, 150~350 revs/min of mixing speed uses triethanolamine
PH is adjusted to 6~7, promoting blood circulation and stopping pain micro emulsion gels of the present invention are produced.
The preparation example six of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 7
Prescription 6 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Mixing oil phase 0.58g, Tween 80 6.48g, absolute ethyl alcohol 3.24g, ethyl hydroxy benzoate 0.4g are weighed, in 20~35 DEG C
Stirring 10 minutes, 300-500 revs/min of mixing speed is slowly added to water, stirring balance 10 minutes.Add made from embodiment 1
Chinese medical extract medicinal extract 0.87g, stirring balance 30 minutes, produces promoting blood circulation and stopping pain micro emulsion.
Carbomer 1.00g, natrium adetate 0.5g are weighed again, promoting blood circulation and stopping pain micro emulsion prepared above are added, in 20~35
DEG C overnight be fully swelled, add sorbierite 7.00g, stir, 150~350 revs/min of mixing speed is adjusted with triethanolamine
PH is saved to 6~7, promoting blood circulation and stopping pain micro emulsion gels of the present invention are produced.
The preparation example seven of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 8
Prescription 7 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh Chinese medical extract medicinal extract 2.79g made from embodiment 1, mixing oil phase 1.84g, RH40 18.5g, PEG400
9.25g, potassium sorbate 0.05g, are stirred 40 minutes, 300-500 revs/min of mixing speed has dissolved to medicine in 20~35 DEG C
Quan Hou, is slowly added to suitable quantity of water, and stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
Weigh CMC-Na 3.00g, natrium adetate 0.05g again, add promoting blood circulation and stopping pain micro emulsion prepared above, in 20~
35 DEG C are fully swelled overnight.Separately take PVA5.00g to heat in suitable quantity of water to be swelled, after cooling, with CMC-Na gels prepared above
Mixing, adds glycerine 1.00g, stirs, and 150~350 revs/min of mixing speed adjusts pH to 6~7, i.e., with triethanolamine
Obtain promoting blood circulation and stopping pain micro emulsion gels of the present invention.
The preparation example eight of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 9
Prescription 8 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Weigh Chinese medical extract medicinal extract 11.13g, MCT 7.37g, RH40 27.75g, PEG400 made from embodiment 1
13.88g, propylparaben 0.15g, are stirred 40 minutes, 300-500 revs/min of mixing speed, to medicine in 20~35 DEG C
After thing dissolving completely, suitable quantity of water is slowly added to, stirring balance 20 minutes obtains promoting blood circulation and stopping pain micro emulsion.
Carbomer 1.20g, natrium adetate 0.10g are weighed again, promoting blood circulation and stopping pain micro emulsion prepared above are added, in 20~35
DEG C overnight be fully swelled, add sorbierite 1.00g, stir, 150~350 revs/min of mixing speed is adjusted with triethanolamine
PH is saved to 6~7, promoting blood circulation and stopping pain micro emulsion gels of the present invention are produced.
The preparation example nine of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 10
Prescription 9 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Mixing oil phase 1.15g, RH40 11.10g, propane diols 2.78g, ethyl hydroxy benzoate 0.075g are weighed, is stirred in 20~35 DEG C
Mix 10 minutes, 300-500 revs/min of mixing speed, be slowly added to water, stirring balance 10 minutes, in adding made from embodiment 1
Medicament extract medicinal extract 1.75g, stirring balance 30 minutes, produces promoting blood circulation and stopping pain micro emulsion.
Carbomer 0.80g, natrium adetate 0.05g are weighed again, promoting blood circulation and stopping pain micro emulsion prepared above are added, in 20~35
DEG C overnight be fully swelled, add glycerine 5.00g, stir, 150~350 revs/min of mixing speed is adjusted with triethanolamine
PH produces promoting blood circulation and stopping pain micro emulsion gels of the present invention to 6~7.
The preparation example ten of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of embodiment 11
Prescription 10 (based on 100 grams)
Prescription according to embodiment 1 weighs menthol, borneol, camphor, gaultherolin, first takes camphor, menthol and ice
Piece mixing is ground to partial liquefaction, and adding gaultherolin stirring makes to be completely dissolved, and is used as mixing oil phase.
Mixing oil phase 0.58g, Tween 80 10.0g, propane diols 5.00g, ethyl hydroxy benzoate 0.075g are weighed, in 20~35 DEG C
Stirring 10 minutes, 300-500 revs/min of mixing speed is slowly added to water, and stirring balance 10 minutes is added made from embodiment 1
Chinese medical extract medicinal extract 0.87g stirrings balance 30 minutes, produces promoting blood circulation and stopping pain micro emulsion.
Carbomer 0.60g, natrium adetate 0.05g are weighed again, promoting blood circulation and stopping pain micro emulsion prepared above are added, in 20~35
DEG C overnight be fully swelled, add glycerine 2.00g, stir, 150~350 revs/min of mixing speed is adjusted with triethanolamine
PH produces promoting blood circulation and stopping pain micro emulsion gels of the present invention to 6~7.
The sign of the promoting blood circulation and stopping pain micro emulsion produced by the present invention of test example 1 and micro emulsion gels
(1) sign of promoting blood circulation and stopping pain micro emulsion produced by the present invention
A, average grain diameter and PDI are determined
Obtained promoting blood circulation and stopping pain micro emulsion in each embodiments of 1ml is taken, is added in DTS0012 sample cells, respectively by sample cell
It is positioned in Zetasizer Nano ZS nano particle sizes instrument and determines average grain diameter and PDI.
As a result：The average grain diameter and PDI of the promoting blood circulation and stopping pain micro emulsion of the prescription 5 obtained in embodiment 6 be respectively：29.16±
0.2627nm and 0.163 ± 0.010 (see Fig. 1), while determining the average grain diameter of the promoting blood circulation and stopping pain micro emulsion of prescription 1~4 and 6~10
Between 20~50nm, PDI is below 0.3.
B, electron-microscope scanning
The promoting blood circulation and stopping pain micro emulsion of prescription 5 in embodiment 6 is diluted 5 times, the microemulsion for taking a drop to dilute is dropped on copper mesh, from
So dry 10 minutes, 2% phosphotungstic acid one is added dropwise and drips, dries naturally, is placed under H-7650 type transmission electron microscopes and observes micro emulsion
Form, as shown in Figure 2.
As a result：The drop of promoting blood circulation and stopping pain micro emulsion is spherical in shape or spherical.
(2) sign of promoting blood circulation and stopping pain micro emulsion gel produced by the present invention
A, average grain diameter and PDI are determined
Take in each embodiment obtained promoting blood circulation and stopping pain micro emulsion gel appropriate, be diluted with water 100 times, magnetic agitation is to completely molten
Solution, takes 1ml promoting blood circulation and stopping pain micro emulsion gels dilutions to be added to DTS0012 sample cells, is respectively positioned over sample cell
Average grain diameter and PDI are determined in Zetasizer Nano ZS nano particle sizes instrument.
As a result：The average grain diameter and PDI of the promoting blood circulation and stopping pain micro emulsion gels of obtained prescription 5 are respectively in embodiment 6：
29.91 ± 0.0100nm and 0.251 ± 0.006 (see Fig. 3), while the promoting blood circulation and stopping pain micro emulsion for determining prescription 1~4 and 6~10 coagulates
The average grain diameter of jelly is between 20~50nm, and PDI is below 0.4.
B, electron-microscope scanning
The promoting blood circulation and stopping pain micro emulsion gels of prescription 5 made from embodiment 6 are diluted with water 50 times, the micro emulsion for taking a drop to dilute
Coagulant liquid is dropped on copper mesh, is dried naturally 10 minutes, and 2% phosphotungstic acid one is added dropwise and drips, dries naturally 30 minutes, is placed in JEM-
The form of micro emulsion gel is observed under 2200FS type transmission electron microscopes.
As a result：Observe that micro emulsion drop is spherical in shape or spherical (as schemed in the micro emulsion gels of dilution under transmission electron microscope
4), the layer structure of gel is broken up in strip structure (such as Fig. 5).
C, rheology type judgement
Using measuring system model PP50 takes promoting blood circulation and stopping pain micro emulsion gels made from appropriate embodiment 6 in flat board
On, shear rate is set as 0.01~100 1/S, and measurement temperature is 25 DEG C, draws shear rate and viscograph, judges fluid
Type, such as Fig. 6.
As a result：Promoting blood circulation and stopping pain micro emulsion gels produced by the present invention in measurement range viscosity with the increase of shear rate
And reduce, the shear shinning characteristic of non-newtonian fluid is embodied, belongs to pseudoplastic fluid type, illustrates that promoting blood circulation and stopping pain of the present invention is micro-
Curdling jelly is tended to smear out, and is not in the phenomenon for the group of beating during smearing.
The Transdermal absorption characteristic research of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of test example 2
Using the Franz diffusion cells of improvement, diffusion pool volume is 18mL, and effective diffusion area is 3.14cm2, bath temperature
It is set to (32.5 ± 0.2) DEG C, reception liquid is PEG400-95% ethanol-physiological saline (1:3:6) it, will add and stir in receiving chamber
Son is mixed, and the dialysis membrane handled well is fixed between diffuser casing and receiving chamber.The promoting blood circulation for weighing the preparation of 0.35g embodiments 6 stops
Pain micro emulsion gel is spread evenly across on the dialysis membrane in diffuser casing, parallel 5 parts, and reception liquid is filled in receiving chamber, excludes bubble,
Magnetic stirring apparatus sets rotating speed to be 350rmin-1, it is that 0.5,1,2,4,6,8,12 and 24h is complete by reception liquid respectively at time point
Portion is poured out, while adding the fresh reception liquid of same volume.Each acceptable solution of collection is crossed into 0.22 μm of miillpore filter, subsequent filtrate is taken,
Produce need testing solution.
By need testing solution sample introduction in Ultra Performance Liquid Chromatography instrument：ACQUITYBEH C18Chromatographic column (2.1mm
× 50mm, 1.7 μm), mobile phase acetonitrile (A) -0.1% formic acid water (B) gradient elution (0~4min, 10%~90%A), detection
Wavelength 280nm, 30 DEG C of column temperature, flow velocity 0.6mLmin-1, the μ L of sample size 1.Determine need testing solution in Paeonol, eugenol and
The peak area of gaultherolin, calculates the cumulative release amount of 3 kinds of compositions to be measured, accumulative release rate Q is calculated, with preparation Q
Time t is mapped, accumulation H103 resin is drawn, sees Fig. 7.
Accumulative release rate Q is calculated by below equation：
Wherein, CnWhen being sampled for n-th in reception liquid each composition to be measured mass concentration, V be per sub-sampling volume, W
For the content of each composition to be measured in taken gel.
As a result：Paeonol in promoting blood circulation and stopping pain micro emulsion gels produced by the present invention, eugenol and gaultherolin 24h it is tired
Product release rate is respectively 76.64%, 78.44% and 62.94%, illustrates that promoting blood circulation and stopping pain micro emulsion gels of the present invention have well
Percutaneous abilities.
The pharmacodynamic study of the promoting blood circulation and stopping pain micro emulsion gels of the present invention of test example 3
Experiment packet and administration：By Kunming mouse, male, body weight 19-21g is randomly divided into 5 groups, every group 11.Control
Group：Smear equivalent blank matrix；Positive drug group, smears Votalin Ointment 0.1g/20g body weight；Promoting blood circulation and stopping pain micro emulsion of the present invention coagulates
The large, medium and small dosage group of jelly, the promoting blood circulation and stopping pain micro emulsion as made from 0.092,0.046,0.023g/20g body weight smear embodiment 6
Gel.One time a day, administration 4-6h removal ointment, cleaning skin, for three days on end.
Observation index：
A.20 there is the inhibiting rate of the number of times of writhing response and medicine to writhing response in each mouse in minute.
Inhibiting rate=(control group writhing mean-reagent group writhing mean)/control group writhing mean × 100%
B. peritoneal fluid absorbance (OD)
Experimental method：Each group administration 3 days is tested, 1 time a day.3rd day in 40 minutes after administration, animal intraperitoneal injection
0.6% acetic acid 0.1ml/10g body weight, observes each group in 20 minutes and the number of times of writhing response occurs, with abdominal cavity indent, after stretching, extension
Limb, buttocks is raised as positive indication.
In 1 hour after administration, each mouse was injected intravenously 0.5% Evans blue normal saline solution 0.1ml/10g body weight, 20 points
Take off cervical vertebra after clock to put to death, abdominal cut integumentary musculature, 5ml physiological saline fraction time washing abdominal cavity, suction pipe suctions out cleaning solution and merged,
3000rpm is centrifuged 15 minutes, takes supernatant in 590nm colorimetric estimation OD values.
Using SPSS19.0 statistical softwares, data withRepresent, multigroup is compared and use one-way analysis of variance,
Investigate anti-inflammatory, analgesic activity of the promoting blood circulation and stopping pain micro emulsion gels to mouse.Experimental result see the table below 2.
The promoting blood circulation and stopping pain micro emulsion gels analgesic and anti-inflammatory effects of table 2 investigate (x ± SD)
Note：Compared with control group, * * * P<0.001, * * P<0.01, * P<0.05
Conclusion：As seen from the above table, compared with control group, each dosage group absorbance of micro emulsion gels of the present invention and writhing number of times
Control group is significantly lower than, inhibitory rate is more than 50%.As can seen above, each dose of promoting blood circulation and stopping pain micro emulsion gels of the present invention
Amount can mitigate the abdominal pain of the animal pattern as caused by chemical stimulation, and the inflammatory for reducing intraperitoneal capillary oozes out, and drop
Low capillary vasopermeability.
Claims (19)
1. a kind of micro emulsion gel composition, it contains 24 kinds of Chinese medicinal material extracts and four kinds of bulk drugs as active principle and micro emulsion
Gel-type vehicle, 24 kinds of Chinese medicinal material extracts be rhizoma zingiberis, kaempferia galamga, the root of Dahurain angelica, rhizoma nardostachyos, rheum officinale, unprocessed Arisaema erubescens, dried pinellia, myrrh,
Frankincense, dried orange peel, Radix Angelicae Sinensis, cloves, pepper, cortex periplocae, asarum, schizonepeta, cassia twig, the flower bud of lily magnolia, Ligusticum wallichii, levisticum, moutan bark, capsicum and grey
The extract of art, and belladonna liquid extract；Four kinds of bulk drugs are gaultherolin, menthol, camphor, borneol；Wherein institute
Active principle is stated to contain in micro emulsion.
2. micro emulsion gel composition according to claim 1, wherein the micro emulsion for containing active principle is that O/W types are micro-
Breast.
3. micro emulsion gel composition according to claim 1 or 2, wherein the active principle contain Paeonol, eugenol,
Pipering is used as active component.
4. micro emulsion gel composition according to any one of claim 1 to 3, wherein described micro-emulsion stroma is lived by surface
Property agent, cosurfactant, oil phase and aqueous phase composition.
5. micro emulsion gel composition according to claim 4, wherein the oil phase is the gaultherolin dissolving in prescription
Mixture obtained by borneol, Camphorae and menthue is used as oil phase.
6. the micro emulsion gel composition according to claim 4 or 5, wherein the surfactant is selected from tween, sapn, gathered
Oxygen ethylene hydrogenation castor oil, octanoic acid capric acid LABRAFIL M 1944CS one or more kinds of mixtures, preferably Tween 80,
Polysorbas20, sorbester p17, sorbester p18, Crodaret RH40, octanoic acid capric acid LABRAFIL M 1944CS.
7. the micro emulsion gel composition according to any one of claim 4 to 6, wherein the cosurfactant is selected from nothing
Water-ethanol, glycerine, propane diols, one or more kinds of mixtures of PEG-4000.
8. micro emulsion gel composition according to any one of claim 1 to 7, wherein the gel-type vehicle is solidifying for hydrophily
Gel matrix, preferably carbomer, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, Sodium Polyacrylate, sodium alginate, Arabic gum, west
One or more kinds of mixtures of bassora gum, polyvinyl alcohol.
9. the micro emulsion gel composition according to any one of claim 4 to 8, wherein, with the gross weight meter of composition, institute
The percentage by weight for stating oil phase is between 0.1%~10% preferably 0.5% to 5%, and with the gross weight meter of oil phase, bigcatkin willow
The percentage by weight of sour methyl esters is 33.1%, and borneol, the percentage by weight of Camphorae and menthue are respectively 22.3%.
10. the micro emulsion gel composition according to any one of claim 4 to 9, wherein, with the gross weight meter of composition,
The percentage by weight of the surfactant is between 1%~30%, between preferably 9% to 30%.
11. the micro emulsion gel composition according to any one of claim 4 to 10, wherein, with the gross weight meter of composition,
The percentage by weight of the cosurfactant is between 0%~20%, between preferably 3% to 15%.
12. the micro emulsion gel composition according to any one of claim 4 to 11, wherein, with the gross weight meter of composition,
The percentage by weight of the gel-type vehicle is between 0.3%~10%, between preferably 1%~3%.
13. the micro emulsion gel composition according to any one of claim 1 to 12, wherein, with the gross weight meter of composition,
The percentage by weight of the Chinese medicinal material extract is between 0.5%~20%, between preferably 0.8%~12%.
14. the micro emulsion gel composition according to any one of claim 1 to 13, it further contains NMF, anti-corrosion
Agent, antioxidant, the NMF preferably glycerine, sorbierite, propane diols, one or more kinds of mixtures of polyethylene glycol,
The preferred ethyl hydroxy benzoate of preservative, potassium sorbate, propylparaben, one or more kinds of mixing of phenmethylol
Thing.
15. the micro emulsion gel composition according to any one of claim 1 to 14, wherein, contain the micro- of active composition
The average grain diameter of breast is between 20~50nm, and polydispersity coefficient PDI is below 0.3.
16. the micro emulsion gel composition according to any one of claim 1 to 15, wherein, the average grain diameter of micro emulsion gel
Between 20~50nm, polydispersity coefficient PDI is below 0.4.
17. the preparation method of the micro emulsion gel composition according to any one of claim 1 to 16, it includes following step
Suddenly：
1) weighing menthol in prescription, camphor, borneol and grinding makes its partial liquefaction, and adding gaultherolin mixing makes dissolving,
It is standby as oil phase；
2) Chinese medical concrete is made in the Chinese medicine for weighing recipe quantity；
3) by obtained oil phase and medicinal extract, surfactant, cosurfactant and optional preservative in step 1 in 20~35
DEG C stirring, to medicine dissolving completely after, be slowly added to water, stir, produce promoting blood circulation and stopping pain micro emulsion；Or
Oil phase, surfactant, cosurfactant and optional preservative are weighed in 20~35 DEG C of stirrings, water is slowly added to,
Stir, produce blank micro emulsion；Then by step 2) in obtained medicinal extract add into blank micro emulsion, stir, produce
Promoting blood circulation and stopping pain micro emulsion；
4) gel-type vehicle and optional antioxidant, plus suitable quantity of water are weighed, is fully swelled in 20~35 DEG C, add step 3) in be made
Promoting blood circulation and stopping pain micro emulsion stir, regulation pH to 6~7, produce promoting blood circulation and stopping pain micro emulsion gels of the present invention.
18. the micro emulsion gel composition according to any one of claim 1 to 16 is preparing the medicine for promoting blood circulation and stopping pain
In purposes.
19. the micro emulsion gel composition according to any one of claim 1 to 16 is being prepared for arthralgia and myalgia, muscle fiber crops
Purposes in numbness, subcutaneous nodule, the medicine of joint pain.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110693832A (en) * | 2019-10-12 | 2020-01-17 | 嘉应学院 | Cinnamomum camphora extract microemulsion gel and preparation method thereof |
| WO2020089682A1 (en) * | 2018-11-02 | 2020-05-07 | Shunmugaperumal Tamilvanan | An oil-less topical macroemulsion composition and process of preparation thereof |
| CN115554233A (en) * | 2022-09-30 | 2023-01-03 | 中国医学科学院肿瘤医院 | Preparation method and application of traditional Chinese medicine compound microemulsion gel |
| CN116850228A (en) * | 2023-08-21 | 2023-10-10 | 广州白云山医药集团股份有限公司白云山何济公制药厂 | Pseudo-ginseng ointment for treating traumatic injuries and rheumatism and preparation method thereof |
-
2017
- 2017-06-30 CN CN201710523887.6A patent/CN107320699A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020089682A1 (en) * | 2018-11-02 | 2020-05-07 | Shunmugaperumal Tamilvanan | An oil-less topical macroemulsion composition and process of preparation thereof |
| CN110693832A (en) * | 2019-10-12 | 2020-01-17 | 嘉应学院 | Cinnamomum camphora extract microemulsion gel and preparation method thereof |
| CN115554233A (en) * | 2022-09-30 | 2023-01-03 | 中国医学科学院肿瘤医院 | Preparation method and application of traditional Chinese medicine compound microemulsion gel |
| CN116850228A (en) * | 2023-08-21 | 2023-10-10 | 广州白云山医药集团股份有限公司白云山何济公制药厂 | Pseudo-ginseng ointment for treating traumatic injuries and rheumatism and preparation method thereof |
| CN116850228B (en) * | 2023-08-21 | 2024-02-06 | 广州白云山医药集团股份有限公司白云山何济公制药厂 | Pseudo-ginseng ointment for treating traumatic injuries and rheumatism and preparation method thereof |
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