CN105055528A - Traditional Chinese medicine composition self-emulsifying soft capsule used for treating cold, and preparation method thereof - Google Patents
Traditional Chinese medicine composition self-emulsifying soft capsule used for treating cold, and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine composition self-emulsifying soft capsule used for treating cold, and a preparation method thereof. According to the preparation method, fructus forsythia, Rhizoma et Radix Notopterygii, and mint are weighed according to a certain ratio, and volatile oil of the three ingredients is extracted, and is mixed with grease, an emulsifying agent, and a co-emulsifier so as to obtain a self-microemulsifying concentrated solution; and the traditional Chinese medicine composition self-emulsifying soft capsule is prepared via a conventional method. The preparation method is simple; oral absorption effect can be improved; curative effect is exact and safe; stability is high; and quality is controllable.
Description
Technical field
The invention belongs to the field of Chinese medicines, relate to a kind of Chinese medicine composition self-emulsifying soft capsule for the treatment of flu and preparation method thereof.
Background technology
Viral influenza is the respiratory tract disease caused by multiple influenza virus, is a kind of infectious disease of serious threat people ' s health, therefore is also called epidemic virus sexuality and emits (influenza).Influenza is a kind of common Acute respiratory infectious disease, and this disease transmission is strong, and onset is hurried, often causes endemicity even global prevalence, and the whole world about has 300-500 ten thousand population to infect influenza-like illness every year, and the number lethal because of influenza about has 25-50 ten thousand.The harm of influenza mainly contains: 1) because influenza virus very easily morphs, therefore all over the world, every year all can either large or small popular of occurrence scope, and infectiousness is strong.During influenza pandemic, a lot of people suffers from influenza simultaneously, not only hampers the work of people, study, even entail dangers to life time serious.2) influenza onset is hurried, and the serious symptoms such as hyperpyrexia (more than 38.5 DEG C), headache, muscular soreness of whole body can appear suddenly in patient, and the persistent period is more than one week.Patient has to interrupt study and work, lies up.3) influenza not only own severe symptoms, it also may cause increasing the weight of of the original disease of patient or cause the serious complication jeopardizing patient vitals, and complication causes flu victims's main causes of death.Therefore, the control for influenza is also one of field being badly in need of at present studying.
At present, the control of the respiratory infectious diseases such as popularity viral influenza, main by Western medicine and vaccination.Compare antiviral Western medicine, Chinese medicine has the feature of integrally-regulated Mutiple Targets, can not only antiviral, and also has the effect of heat clearing away, antiinflammatory and raising human immunologic function, has more advantage than single antiviral drugs alleviating in respiratory symptom.Chinese medicine not only has stronger antivirus action, and its effect is again often wide spectrum, can antiviral, anti-pathogenic bacterium, inflammation-inhibiting reaction and antipyretic, particularly influenza high fever, the more obvious and safety of Chinese medicine refrigeration function.
The prescription for the treatment of flu of the present invention is the Chinese medicine compound that novel antiviral sexuality is emitted, and has obtained Chinese invention patent (ZL200810122549.2).Fructus Forsythiae bitter in the mouth cold nature in side, heat-clearing and toxic substances removing expelling pathogenic factors from the exterior, the heat of the loose part of the body cavity above the diaphragm housing the heart and lungs, eliminating pathogenesis emphatically, is our monarch drug.Herba Menthae is clear light cool loose, and help principal agent heat-clearing and toxic substances removing, separate the heresy of wind heat, alleviating in wind heat and attack caused headache and laryngopharynx swelling and pain, is the ministerial drug of we.Rhizoma Et Radix Notopterygii acrid in the mouth, hardship, warm in nature, its a surname sends out lung qi, dispel the heat table, wind-expelling pain-stopping effect, use same with pungent and cold medicine for relieving the exterior syndrome, can strengthen the effect of diaphoretic medicine relieving the exterior syndrome by diaphoresis, with Herba Menthae compatibility, then be beneficial to heat radiation pain relieving sore-throat relieving, and in we pungent cool in be equipped with a little pungent using warming therapy product, be both beneficial to expelling pathogenic factors from the exterior, not carrying on the back again pungent cool purport, is the adjuvant of we.Full policy is to the pathogenesis of anemopyretic cold generation, and integrate heat-clearing and toxic substances removing, a surname sends out lung qi, sore-throat relieving promotes the production of body fluid medicine, expelling pathogenic factors from the exterior lets out lung, and enthusiasm poison is separated, and all diseases are from flat.
Fructus Forsythiae is the dry fruit of Oleaceae plants Fructus Forsythiae Forsythiasuspense (Thunb.) Vahl.Main containing phenethyl alcohol glycosides as the compound such as phillyrin, forsythol, volatile oil 1 ~ 2.5% etc., for broad spectrum antibiotic, inhibitory action is had to multiple Gram-positive and negative bacteria, its volatile oil has has obvious inhibitory action to staphylococcus aureus, Diplococcus pneumoniae, Candida albicans, and its decoct has refrigeration function.Rhizoma Et Radix Notopterygii is dry rhizome and the root of samphire Rhizoma Et Radix Notopterygii NotopterygiumincisumTingexH.T.Chang or Radix et Rhizoma Notopterygii NotoperygiumforbesiiBoiss..Main containing volatile oil about 2.3%, Coumarins, organic acid and the compound such as esters, amino acids, its volatile oil can make pyrogenicity rat temperature obviously reduce, and has significant refrigeration function, and its water extract has the effect of certain resisiting influenza virus.Herba Menthae is the dry aerial parts of labiate Herba Menthae MenthahaplocalyxBriq., main containing volatile oil about 0.8-1%, in oil, composition is mainly the composition such as menthone and Mentholum, flavonoid, organic acid, aminoacid etc., its volatile oil makes telangiectasis, increase heat radiation, sweating and heat resolving effect, its water decoction is external has stronger antibacterial action to staphylococcus aureus, Diplococcus pneumoniae, also has inhibitory action to herpes simplex.
Former patent (ZL200810122549.2) is to the volatile oil beta-cyclodextrin inclusion compound of above-mentioned three medicines, but inclusion essential oil rate is lower, and production cost is high, and volatile oil still can be deaden, and not only cause loss, and mouthfeel is poor, bioavailability is low.
For avoiding above-mentioned deficiency, special proposition the present invention.Self-emulsifying microemulsion medicine medicine-releasing system (SMEDDS), the solution of the transparent and homogeneous formed by medicine, grease, emulsifying agent and co-emulsifier, when ambient temperature (being often referred to about 37 DEG C) and gentle agitation, due to the existence of emulsifying agent, spontaneous emulsification becomes the Emulsion of 5 microns.Along with increasing of emulsifier, spontaneous formation microemulsion in gastrointestinal tract, medicine is present in these tiny oil droplets, be distributed in whole gastrointestinal tract fast, rely on the huge specific surface area of fine oil droplets to substantially increase the stripping of water-insoluble drug, make the hydrated sheath that medicine is more prone to by gastrointestinal wall, increase the epithelial permeability of medicine, promote the absorption of medicine, substantially increase drug bioavailability high.SMEDDS belongs to thermodynamic stable system, stable in properties, and not yet useful self-emulsifying microemulsion technological development at present goes out the report of prescription oral formulations of the present invention.
Summary of the invention
Be there is the deficiencies such as production cost is high, loss of effective components large (inclusion rate about about 80%), poor stability, dose are large, mouthfeel is not good, bioavailability is low in volatile oil cyclodextrin inclusion compound to make up traditional handicraft granule, the invention provides that a kind of technique is simple, dose is little, effective ingredient and bioavailability high, improve the utilization rate of volatile oil and the self-emulsifying soft capsule of stability and preparation method thereof.
Primary and foremost purpose of the present invention is to provide a kind of self-emulsifying soft capsule for the treatment of flu;
Another object of the present invention is to provide a kind of preparation method of this self-emulsifying soft capsule.
The present invention is achieved through the following technical solutions:
Treat a self-emulsifying soft capsule for flu, its content is made up of volatile oil and pharmaceutical carrier, and by weight percentage, described volatile oil is 10 ~ 30% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 15 ~ 35%, emulsifying agent 45 ~ 75% and co-emulsifier 5 ~ 25%;
Described volatile oil is for obtaining through supercritical extraction or extraction by steam distillation with Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae, and wherein, the weight ratio of Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 3 ~ 5:1 ~ 3:1 ~ 3.
Preferably: by weight percentage, described volatile oil is 15 ~ 25% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 20 ~ 30%, emulsifying agent 50 ~ 70% and co-emulsifier 10 ~ 20%;
The weight ratio of described Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 3.5 ~ 4.5:1.5 ~ 2.5:1.5 ~ 2.5.
More preferably: by weight percentage, described volatile oil is 20% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 25%, emulsifying agent 60% and co-emulsifier 15%;
The weight ratio of described Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 4:2:2.
Described grease be selected from MCT (MCT), ethyl oleate, olein, soybean oil, (Asia) oleic acid, Oleum Arachidis hypogaeae semen, olive oil one or more;
Described emulsifying agent be selected from polysorbas20, Tween 80, polysorbate85, pluronic, polyoxyethylene castor oil, phospholipid, liquid egg phospholipid, soybean lecithin and cholesterol one or more;
Described co-emulsifier be selected from ethanol, isopropyl alcohol, 1,2-PD, n-butyl alcohol, glycerol, Polyethylene Glycol, ethylene glycol monomethyl ether one or more.
The concrete preparation method of self-emulsifying soft capsule of the present invention comprises the steps:
A, by component composition and proportioning take Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, for subsequent use;
The extraction of b, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae Haplocalycis volatile oil
(1) CO
2supercritical extraction: by Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 ~ 60 object granules, CO
2supercritical extraction, at extracting pressure 20 ~ 35MPa, extraction temperature 45 ~ 65 DEG C, CO
20.5 ~ 3 hour is extracted, separated and collected volatile oil under flow velocity 20 ~ 40L/h condition;
Or (2) adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 ~ 8 times of medical material weight, and extraction time is 4 ~ 8 hours;
C, by step b extract volatile oil add grease mixing, obtain oil phase;
D, add emulsifying agent, co-emulsifier, ground and mixed, in 25 ~ 35 DEG C of waters bath with thermostatic control, stir 1 ~ 2h with the rotating speed of 30 ~ 40rpm, make it to dissolve completely, obtain Emulsion Phase;
E, oil phase to be mixed with Emulsion Phase, at 25 ~ 35 DEG C, to stir, to vibrate, ultrasonic or swirling manner mixing, form self emulsifying concentrated solution;
F, by above-mentioned self emulsifying concentrated solution, make self-emulsifying soft capsule in conventional manner.
F, take gelatin, glycerol, water preparation capsule shell, or add sorbitol plasticising, or add polyoxyethylene sorbitan monoleate froth breaking;
G, by above-mentioned self emulsifying concentrated solution and capsule shell, make soft capsule in conventional manner.
Preferably, the concrete preparation method of self-emulsifying soft capsule of the present invention comprises the steps:
A, by component composition and proportioning take Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, for subsequent use;
The extraction of b, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae Haplocalycis volatile oil
(1) CO
2supercritical extraction: by Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition;
Or (2) adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours;
C, by step b extract volatile oil add grease mixing, obtain oil phase;
D, add emulsifying agent, co-emulsifier, ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
E, oil phase to be mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
F, by weight 1:0.25 ~ 0.6:1 take gelatin, glycerol, water preparation capsule shell, or add the sorbitol plasticising with glycerol equivalent weight, or add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
G, by above-mentioned self emulsifying concentrated solution and capsule shell, make soft capsule in conventional manner.
In step f, capsule shell can select following prescription and proportioning preparation:
1) gelatin, glycerol, water, weight ratio is 1:0.25 ~ 0.6:1;
2) gelatin, glycerol, sorbitol, water, weight ratio is 1:0.25 ~ 0.6:0.25 ~ 0.6:1;
3) gelatin, glycerol, water, polyoxyethylene sorbitan monoleate, the weight ratio of gelatin, glycerol, water is 1:0.25 ~ 0.6:1, and polyoxyethylene sorbitan monoleate is 0.2% of capsule shell prescription weight;
4) gelatin, glycerol, sorbitol, water, polyoxyethylene sorbitan monoleate, the weight ratio of gelatin, glycerol, sorbitol, water is 1:0.25 ~ 0.6:0.25 ~ 0.6:1, and polyoxyethylene sorbitan monoleate is 0.2% of capsule shell prescription total amount.
Compared with prior art, tool has the following advantages self-emulsifying soft capsule of the present invention:
1, preparation of the present invention effectively can improve bioavailability: medicine of the present invention by oral enter gastrointestinal tract after, the little emulsion droplet of medicine carrying can be formed with contact with moisture wherein, add medical surfaces sum dissolubility, be able to evenly, rapidly distribute at gastrointestinal tract, be delivered to absorption site easily through hydrated sheath, improve dissolution and permeability, bioavailability improves greatly, efficiently solve the problem that volatile oil in prescription is difficult to absorb and bioavailability is low in human body, determined curative effect, safety.
2, invention formulation method is simple, and good stability is quality controllable.Through 24 months long-term stable experiments, every quality index without significant difference, showed that product quality was highly stable compared with 0 month.
3, invention formulation mouthfeel is good, enhance the compliance of patient, clinical observation result shows, the therapeutic effect of self-emulsifying soft capsule of the present invention to viral influenza is significantly better than granule, treating both the principal and secondary aspects of a disease, particularly remarkable to the curative effect of the symptoms such as viral influenza heating, pharyngalgia, nasal obstruction watery nasal discharge, headache, general malaise, thirsty and dry pharynx.Show that self-emulsifying soft capsule of the present invention treatment viral influenza has good therapeutic effect, clinic is promoted.
Specific embodiment:
By embodiment, technical scheme of the present invention is further described below; the advantage contributed to technical solution of the present invention, effect are had and further understands; embodiment does not limit protection scope of the present invention, and protection scope of the present invention is decided by claim.
Embodiment 1:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 4000g Rhizoma Et Radix Notopterygii 2000g Herba Menthae 2000g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 160g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add MCT mixing, obtain oil phase;
2, add polysorbate85, PEG400 ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, water preparation capsule shell by weight 1:0.5:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 2:
1, CO
2supercritical extraction volatile oil
Fructus Forsythiae 4000g Rhizoma Et Radix Notopterygii 2000g Herba Menthae 2000g
By Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition; Obtain volatile oil 240g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add ethyl oleate mixing, obtain oil phase;
2, add Tween 80,1,2-PD ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
4, gelatin, glycerol, water preparation capsule shell is taken by weight 1:0.5:1;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 3:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 3000g Rhizoma Et Radix Notopterygii 1000g Herba Menthae 3000g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 140g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add ethyl oleate mixing, obtain oil phase;
2, add polysorbate85, isopropyl alcohol ground and mixed, in 35 DEG C of waters bath with thermostatic control, stir 2h with the rotating speed of 40rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 35 DEG C, mixing, form self emulsifying concentrated solution;
4, gelatin, glycerol, sorbitol, water preparation capsule shell is taken by weight 1:0.25:0.25:1;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 4:
1, CO
2supercritical extraction volatile oil
Fructus Forsythiae 5000g Rhizoma Et Radix Notopterygii 3000g Herba Menthae 1000g
By Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition; Obtain volatile oil 270g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add the mixing of (Asia) oleic acid, obtain oil phase;
2, add pluronic, ethanol ground and mixed, in 25 DEG C of waters bath with thermostatic control, stir 2h with the rotating speed of 30rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 25 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, water preparation capsule shell by weight 1:0.6:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 5:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 3500g Rhizoma Et Radix Notopterygii 1500g Herba Menthae 2500g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 150g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Volatile oil 150g olein 200g polyoxyethylene castor oil 750g
Ethylene glycol monomethyl ether 50g
Make 2000
Preparation technology:
1, get volatile oil, add olein mixing, obtain oil phase;
2, add polyoxyethylene castor oil, ethylene glycol monomethyl ether ground and mixed, in 35 DEG C of waters bath with thermostatic control, stir 1h with the rotating speed of 40rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 35 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, sorbitol, water preparation capsule shell by weight 1:0.3:0.3:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 6:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 4500g Rhizoma Et Radix Notopterygii 2500g Herba Menthae 1500g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 175g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add soybean oil mixing, obtain oil phase;
2, add phospholipid, glycerol ground and mixed, in 25 DEG C of waters bath with thermostatic control, stir 2h with the rotating speed of 40rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 35 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, water preparation capsule shell by weight 1:0.4:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 7:
1, CO
2supercritical extraction volatile oil
Fructus Forsythiae 3500g Rhizoma Et Radix Notopterygii 2500g Herba Menthae 1500g
By Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition; Obtain volatile oil 220g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add ethyl oleate mixing, obtain oil phase;
2, add cholesterol, n-butyl alcohol ground and mixed, in 25 DEG C of waters bath with thermostatic control, stir 2h with the rotating speed of 30rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 35 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, water preparation capsule shell by weight 1:0.5:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 8:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 4500g Rhizoma Et Radix Notopterygii 1500g Herba Menthae 2500g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 175g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add Oleum Arachidis hypogaeae semen mixing, obtain oil phase;
2, add liquid egg phospholipid, 1,2-PD ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
4, gelatin, glycerol, sorbitol, water preparation capsule shell is taken by weight 1:0.3:0.3:1;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 9:
1, extraction by steam distillation volatile oil
Fructus Forsythiae 5000g Rhizoma Et Radix Notopterygii 1000g Herba Menthae 3000g
Adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours; Obtain volatile oil 180g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add olive oil mixing, obtain oil phase;
2, add polysorbas20, Polyethylene Glycol ground and mixed, in 35 DEG C of waters bath with thermostatic control, stir 2h with the rotating speed of 30rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 35 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, sorbitol, water preparation capsule shell by weight 1:0.25:0.25:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Embodiment 10:
1, CO
2supercritical extraction volatile oil
Fructus Forsythiae 3000g Rhizoma Et Radix Notopterygii 3000g Herba Menthae 1000g
By Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition; Obtain volatile oil 210g, for subsequent use.
2, self-emulsifying soft capsule preparation
Content prescription:
Preparation technology:
1, get volatile oil, add olive oil mixing, obtain oil phase;
2, add polysorbas20, Polyethylene Glycol ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
3, oil phase is mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
4, take gelatin, glycerol, water preparation capsule shell by weight 1:0.5:1, add the polyoxyethylene sorbitan monoleate froth breaking of capsule shell prescription total amount 0.2%;
5, by step 3 gained self emulsifying concentrated solution and step 4 gained capsule shell, soft capsule is made in conventional manner.
Comparative example's (preparation technology prepares cyclodextrin clathrate with reference to CN200810122549.2 embodiment):
Comparative example 1:
A, weighting raw materials material Fructus Forsythiae 4000g, Rhizoma Et Radix Notopterygii 2000g, Herba Menthae 2000g mix, and are ground into 20 object granules;
B, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae extraction by steam distillation volatile oil: add water 6 times amount, extract 6 hours;
The enclose of c, volatile oil: the ratio being 1:9 in the weight ratio of volatile oil and beta-schardinger dextrin-gets volatile oil and beta-schardinger dextrin-, add in beta-schardinger dextrin-weight be the water grinding of beta-schardinger dextrin-weight 3 times amount evenly, make beta-schardinger dextrin-aqueous solution.Volatile oil adds the ethanol that volume is volatile oil 30%, makes volatile oil alcoholic solution.Adopt polishing to carry out enclose, controlling the enclose time is 40 minutes, clathrate through sucking filtration, washing, in 40 DEG C of vacuum dryings and get final product.
Get above-mentioned clathrate, add suitable amount of sucrose, dextrin, granulate with 5%-8% starch slurry, dry, granulate, obtains granule 2000g, subpackage, every bag of 5g (being equivalent to crude drug 20g).
Comparative example 2:
A, weighting raw materials material Fructus Forsythiae 4000g, Rhizoma Et Radix Notopterygii 2000g, Herba Menthae 2000g mix, and are ground into 20 object granules;
B, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae supercritical extraction: at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition;
The enclose of c, volatile oil: the ratio being 1: 10 in the weight ratio of volatile oil and beta-schardinger dextrin-gets volatile oil and beta-schardinger dextrin-, add in beta-schardinger dextrin-weight be the water grinding of beta-schardinger dextrin-weight 2 times amount evenly, make beta-schardinger dextrin-aqueous solution.Volatile oil adds the ethanol that volume is volatile oil 20%, makes volatile oil alcoholic solution.Adopt polishing to carry out enclose, controlling the enclose time is 40 minutes, clathrate through sucking filtration, washing, in 40 DEG C of vacuum dryings and get final product.
Get above-mentioned clathrate, add suitable amount of sucrose, dextrin, granulate with 5%-8% starch slurry, dry, granulate, obtains granule 3200g, subpackage, every bag of 4g (being equivalent to crude drug 10g).
Experimental example:
Experimental example 1: self-emulsifying soft capsule treatment viral influenza of the present invention clinical observation
In order to observe the clinical efficacy of self-emulsifying soft capsule of the present invention to anemopyretic cold, we select the granule medicine (comparative example 1) in contrast prepared with reference to patent CN200810122549.2, carry out Ureteral Calculus to 66 routine anemopyretic cold patients, brief summary is as follows.
1 clinical data
1.1 the object of observation
This is organized 66 examples and is viral influenza patient, and at 18 ~ 65 years old age, Western medicine diagnose meets upper respiratory tract infection.Random selecting wherein 33 examples is self-emulsifying soft capsule treatment group of the present invention, and 33 examples are matched group.Male 20 example in treatment group, women 13 example, 43.3 years old mean age, maximum 62 years old, minimum 18 years old; Matched group male 19 example, women 14 example, 42.7 years old mean age, maximum 65 years old, minimum 22 years old.
2 groups of patients are in age, sex compared with in course of disease etc., and no significant difference (P > 0.05), has comparability.
1.2 diagnostic criteria
Flu main symptom: heating, aversion to wind, pharyngalgia, cough; Secondary card: nasal obstruction, watery nasal discharge, sneeze, feeling of fullness in the head and pain, general fatigue are uncomfortable, antiperspirant lets out smooth, thirsty and dry pharynx, tongue tip side of red, thin white fur of tongue, micro-Huang, floating and rapid pulse.Western medicine diagnose meets upper respiratory tract infection.Require that main symptom at least meets 1, accompanied symptoms meets 2.
1.3 administrated method
Treatment group: self-emulsifying soft capsule of the present invention (prepared by embodiment 1), each 5 (being equivalent to crude drug 20g), every day 3 times.
Matched group: granule prepared by comparative example 1, each 1 bag (5 grams, be equivalent to crude drug 20g), every day 3 times.
Be 3 days the course for the treatment of.
1.4 efficacy evaluation
With reference to " guideline of clinical investigations of new Chinese medicine treatment flu ", by main symptom, secondary card classification score computation therapeutic effect of syndrome index evaluation curative effect.Recovery from illness: normally, the symptom of flu all disappears, therapeutic index >95% to treat temperature recovery within 3 days.Effective: it is normal to treat within 3 days temperature recovery, most of transference cure of flu, therapeutic index >75%.Effective: to treat the comparatively front reduction of body temperature within 3 days, the cardinal symptom partial disappearance of flu, therapeutic index >30%.Invalid: to treat body temperature within 3 days and do not fall or raise, the cardinal symptom of flu without improvement, therapeutic index <30%.
2 results
2.1 comparitive study
Table 1 liang group patient treatment comparitive study
| Group | Recovery from illness | Effective | Effectively | Invalid | Total effective rate |
| Treatment group (n=33) | 18(54.54％) | 9(27.27％) | 5(15.15％) | 1(3.03％) | 96.97％ |
| Matched group (n=33) | 13(39.39％) | 8(24.24％) | 7(21.21％) | 5(15.15％) | 84.84％ |
Through Ridit inspection, flu self-emulsifying soft capsule of the present invention is evident in efficacy, is better than granule.
2.2 cardinal symptoms, sign curative effect
Table 2 cardinal symptom, sign comparitive study
Show that the therapeutic effect of self-emulsifying soft capsule of the present invention to heating, pharyngalgia, nasal obstruction watery nasal discharge, headache, general malaise, thirsty and dry pharynx is obviously better than granule.
Experimental example 2:SEDDS prescription, ratio are screened
Conventional emulsifying agent, co-emulsifier are recorded in a lot of document, and no longer test is chosen.
The selection of oil phase:
Measure MCT, ethyl oleate, olein, soybean oil, (Asia) oleic acid, Oleum Arachidis hypogaeae semen, olive oil, Oleum Ricini 30ml respectively in 50ml beaker, 50 DEG C of waters bath with thermostatic control.It is appropriate that precision takes 8 parts of volatile oil (prepared by embodiment 1), and gradation slowly adds in beaker, until volatile oil no longer dissolves in oil phase, calculates the dissolubility of volatile oil in three kinds of greases.Result show the saturation solubility of volatile oil in each grease be respectively 1.5,1.3,1.7,1.6,1.5,1.4,1.9mg/mL.In view of Oleum Ricini safety is lower, do not select; In view of MCT safety is higher, therefore first-selected MCT.
SEDDS prescription ratio is screened:
Result shows: SEDDS prescription ratio controlled in the scope of grease 15 ~ 35%, emulsifying agent 45 ~ 75% and co-emulsifier 5 ~ 25%, the granularity of self-microemulsion is all less than 50nm, and particle size distribution is narrow, uniform particle sizes.
Experimental example 3: granulometry is tested
1, the selection of self-emulsifying microemulsion medium
Self-emulsifying microemulsion concentrated solution prepared by Example 1, respectively with water, 0.1mol/L hydrochloric acid solution and phosphate buffer (pH=6.8) are self emulsifying medium, using 100ml as quantity of solvent, rotating speed 100 revs/min is tested, 15,30,45,60min time sample respectively, adopt laser particle analyzer to measure granularity, result is as following table:
Result shows, in three kinds of media, average self-emulsifying microemulsion particle diameter is basically identical, because 0.1mol/L hydrochloric acid solution more can simulate the sour environment of human gastric juice, therefore selects it as self-microemulsion medium.
2, self-emulsifying microemulsion concentrated solution shelf-stability test
Self-emulsifying microemulsion concentrated solution prepared by Example 1, with 0.1mol/L hydrochloric acid solution 100ml for self-emulsifying microemulsion medium, turns
Speed 100 revs/min, respectively at 0,2,4,6,8h measures particle diameter, investigation shelf-stability (seeing the following form).
| Time | 0h | 2h | 4h | 6h | 8h |
| Particle diameter (nm) | 42.16 | 42.45 | 42.76 | 43.18 | 43.51 |
Result shows, basicly stable in 8 hours under 0.1mol/L hydrochloric acid solution environment.
The self-microemulsion concentrated solution got prepared by other embodiments measures, and result is similar to.
Experimental example 4: self-emulsification soft capsules study on the stability of the present invention
According to the investigation project (character, discriminating, disintegration, microbial limit, content) in medicine stability test guideline listed by soft capsule study on the stability repertory, self-emulsifying soft capsule stability prepared by embodiment 1 is investigated.
The long-term stable experiment of table 1 embodiment of the present invention 1 self-emulsifying soft capsule
(experimental condition: temperature 25 DEG C ± 2 DEG C; Relative humidity: 60% ± 10%)
Result showed: through 24 months long-term stable experiments, and every quality index without significant difference, showed that product quality was highly stable compared with 0 month.
Claims (6)
1. treat a Chinese medicine composition self-emulsifying soft capsule for flu, it is characterized in that:
Its content comprises volatile oil and pharmaceutical carrier, and by weight percentage, described volatile oil is 10 ~ 30% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 15 ~ 35%, emulsifying agent 45 ~ 75% and co-emulsifier 5 ~ 25%;
Described volatile oil is for obtaining through supercritical extraction or extraction by steam distillation with Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae, and wherein, the weight ratio of Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 3 ~ 5:1 ~ 3:1 ~ 3.
2. self-emulsifying soft capsule as claimed in claim 1, it is characterized in that: by weight percentage, described volatile oil is 15 ~ 25% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 20 ~ 30%, emulsifying agent 50 ~ 70% and co-emulsifier 10 ~ 20%;
The weight ratio of described Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 3.5 ~ 4.5:1.5 ~ 2.5:1.5 ~ 2.5.
3. self-emulsifying soft capsule as claimed in claim 2, it is characterized in that: by weight percentage, described volatile oil is 20% of pharmaceutical carrier;
Described pharmaceutical carrier by weight percentage, is made up of grease 25%, emulsifying agent 60% and co-emulsifier 15%;
The weight ratio of described Chinese crude drug Fructus Forsythiae, Rhizoma Et Radix Notopterygii, Herba Menthae is 4:2:2.
4. the self-emulsifying soft capsule as described in as arbitrary in claims 1 to 3, it is characterized in that, described grease be selected from MCT (MCT), ethyl oleate, olein, soybean oil, (Asia) oleic acid, Oleum Arachidis hypogaeae semen, olive oil one or more; Described emulsifying agent be selected from polysorbas20, Tween 80, polysorbate85, pluronic, polyoxyethylene castor oil, phospholipid, liquid egg phospholipid, soybean lecithin and cholesterol one or more; Described co-emulsifier be selected from ethanol, isopropyl alcohol, 1,2-PD, n-butyl alcohol, glycerol, Polyethylene Glycol, ethylene glycol monomethyl ether one or more.
5. the preparation method of self-emulsifying soft capsule as claimed in claim 1, it is characterized in that, this self-emulsifying soft capsule prepares through the following steps:
A, by component composition and proportioning take Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, for subsequent use;
The extraction of b, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae Haplocalycis volatile oil
(1) CO
2supercritical extraction: by Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 ~ 60 object granules, CO
2supercritical extraction, at extracting pressure 20 ~ 35MPa, extraction temperature 45 ~ 65 DEG C, CO
20.5 ~ 3 hour is extracted, separated and collected volatile oil under flow velocity 20 ~ 40L/h condition;
Or (2) adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 ~ 8 times of medical material weight, and extraction time is 4 ~ 8 hours;
C, by step b extract volatile oil add grease mixing, obtain oil phase;
D, add emulsifying agent, co-emulsifier, ground and mixed, in 25 ~ 35 DEG C of waters bath with thermostatic control, stir 1 ~ 2h with the rotating speed of 30 ~ 40rpm, make it to dissolve completely, obtain Emulsion Phase;
E, oil phase to be mixed with Emulsion Phase, at 25 ~ 35 DEG C, to stir, to vibrate, ultrasonic or swirling manner mixing, form self emulsifying concentrated solution;
F, take gelatin, glycerol, water preparation capsule shell, or add sorbitol plasticising, or add polyoxyethylene sorbitan monoleate froth breaking;
G, by above-mentioned self emulsifying concentrated solution and capsule shell, make soft capsule in conventional manner.
6. the preparation method of self-emulsifying soft capsule as claimed in claim 5, it is characterized in that, the method comprises the following steps:
A, by component composition and proportioning take Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, for subsequent use;
The extraction of b, Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae Haplocalycis volatile oil
(1) CO
2supercritical extraction: by Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae three taste medical material, be ground into 20 object granules, CO
2supercritical extraction, at extracting pressure 25MPa, extraction temperature 60 DEG C, CO
21.5 hours are extracted, separated and collected volatile oil under flow velocity 30L/h condition;
Or (2) adopt the volatile oil of extraction by steam distillation Fructus Forsythiae, Rhizoma Et Radix Notopterygii and Herba Menthae, amount of water is 6 times of medical material weight, and extraction time is 6 hours;
C, by step b extract volatile oil add grease mixing, obtain oil phase;
D, add emulsifying agent, co-emulsifier, ground and mixed, in 30 DEG C of waters bath with thermostatic control, stir 1.5h with the rotating speed of 35rpm, make it to dissolve completely, obtain Emulsion Phase;
E, oil phase to be mixed with Emulsion Phase, sonic oscillation at 30 DEG C, mixing, form self emulsifying concentrated solution;
F, by weight 1:0.25 ~ 0.6:1 take gelatin, glycerol, water preparation capsule shell, or add the sorbitol plasticising with glycerol equivalent weight, or add the polyoxyethylene sorbitan monoleate froth breaking of blastocysts injection total amount 0.2%;
G, by above-mentioned self emulsifying concentrated solution and capsule shell, make soft capsule in conventional manner.
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| CN107028911A (en) * | 2017-05-15 | 2017-08-11 | 江西九华药业有限公司 | It is a kind of to treat Chinese medicine composition self-emulsifying soft capsule of hemorrhoid and preparation method thereof |
| CN110101659A (en) * | 2019-05-20 | 2019-08-09 | 山西大学 | A kind of phillygenol is from micro emulsion and preparation method thereof |
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| CN1919192A (en) * | 2006-08-21 | 2007-02-28 | 高保安 | Curcumenol self-emulsifying capsule and preparation method thereof |
| CN101293015A (en) * | 2008-06-24 | 2008-10-29 | 中国药科大学 | Chinese medicinal composition, preparation method and application thereof |
| CN102349991A (en) * | 2011-05-29 | 2012-02-15 | 王红芳 | Composition for killing virus and preventing influenza and cold prevention plaster prepared by composition |
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| CN1813916A (en) * | 2005-11-25 | 2006-08-09 | 中国药科大学 | Compound chinese medicine formulation for treating common cold and its preparing process |
| CN1919192A (en) * | 2006-08-21 | 2007-02-28 | 高保安 | Curcumenol self-emulsifying capsule and preparation method thereof |
| CN101293015A (en) * | 2008-06-24 | 2008-10-29 | 中国药科大学 | Chinese medicinal composition, preparation method and application thereof |
| CN102349991A (en) * | 2011-05-29 | 2012-02-15 | 王红芳 | Composition for killing virus and preventing influenza and cold prevention plaster prepared by composition |
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| CN107028911A (en) * | 2017-05-15 | 2017-08-11 | 江西九华药业有限公司 | It is a kind of to treat Chinese medicine composition self-emulsifying soft capsule of hemorrhoid and preparation method thereof |
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