CN102886030A - Traditional Chinese medicine refreshment intravenous injection nasal delivery preparation used for resuscitation and refreshment and preparation method of nasal delivery preparation - Google Patents

Traditional Chinese medicine refreshment intravenous injection nasal delivery preparation used for resuscitation and refreshment and preparation method of nasal delivery preparation Download PDF

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CN102886030A
CN102886030A CN2012104353408A CN201210435340A CN102886030A CN 102886030 A CN102886030 A CN 102886030A CN 2012104353408 A CN2012104353408 A CN 2012104353408A CN 201210435340 A CN201210435340 A CN 201210435340A CN 102886030 A CN102886030 A CN 102886030A
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preparation
radix curcumae
nasal
xingnaojing
nasal delivery
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CN102886030B (en
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夏敏
王一飞
廖小丹
汪怡
韩小翠
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Guangdong Tongde Pharmaceutical Co ltd
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Guangdong Tongde Pharmaceutical Co ltd
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Abstract

The invention relates to a traditional Chinese medicine refreshment intravenous injection nasal delivery preparation used for resuscitation and refreshment and a preparation method of the nasal delivery preparation, and belongs to the technical field of production of nasal delivery preparation. The preparation consists of a muscone extracting solution, natural borneol, geniposide extracts, radix curcumae curcumin extracts, radix curcumae essential oil, a cosolvent (namely, tween-80 or 1.2 propylene glycol), a promoting penetrating agent (namely, cyclodextrins), a preservative (namely, ethylparaben or potassium sorbate), and a solvent (namely, distilled water or water for injection). The preparation method comprises the following steps of: weighing the natural borneol, dissolving the natural borneol by using the cosolvent, adding the potassium sorbate or the ethylparaben to dissolve, filtering, adding the secondary distillate of musk into a filtrate, sequentially adding the radix curcumae essential oil and the promoting penetrating agent, stirring, adding the gardenia extracts and the radix curcumae curcumin extracts, stirring for 2 hours, filtering, adjusting PH to be 6.0-7.0 by using a phosphate buffer, and finally preparing the distillate or water for injection into 100ML of the preparation. According to the nasal delivery preparation, the potency of the active ingredients is improved greatly, and the volume is reduced, so that the nasal delivery preparation is suitable for nasal delivery.

Description

A kind of for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation and preparation method thereof
Technical field
The present invention relates to a kind of nasal cavity administrated preparation, be particularly related to and a kind of the Chinese medicine injection XINGNAOJING changed over nasal-cavity administration innovation preparation, it specifically is a kind of heat clearing away solution, removing heat from blood and promoting blood circulation, inducing resuscitation Chinese medicine XINGNAOJING nasal-cavity administration system, this system can prepare nasal spray and nasal drop, belongs to medical production technical field.
Background technology
The safety issue of Chinese medicine injection is perplexing the Chinese medicine industry always, the theoretical system of tcm clinical practice treatment is different from the doctor trained in Western medicine theoretical system, administrated method is different with the clinical treatment guidance, causes Chinese medicine is difficult to clear and definite effective substance, Chinese medicine medication the monarch and his subjects assistant, it is many that flavour of a drug appear in formation Chinese medicine, complicated component, some composition dissolubility is little, perhaps through placing a period of time after the sterilization, variable color appears in medicinal liquid, muddy and precipitation.In order to increase the dissolubility of medicine, added tween 80 in the XINGNAOJING ZHUSHEYE, tween 80 is a kind of non-ionic surface active agent, obvious haemolysis occurs when being used for vascular drug delivery, occurs the obvious distending pain in injection site during intramuscular injection.So the clinical practice risk also just increases naturally.
Address these problems, research and standard formulation except the material composition of strengthening Chinese medicine injection itself, and outside the restriction inspection of related substance, what also have worth encouragement is exactly the drug-delivery preparation technology of development of new, some Chinese medicine can be by changing route of administration, reach same therapeutic effect, and avoid injection anaphylaxis risk.Xing Nao Jing ' injection mainly is inducing resuscitation, can consider to substitute XINGNAOJING ZHUSHEYE by the administering mode of nose approach brain targeting, reaches equally therapeutic effect.
Nasal drug delivery system, refer to bring into play general action by Nasal Mucosa Absorption, it is long-pending that nasal cavity has abundant mucomembranous surface, the blood capillary clump of enriching under the mucosa, nasal cavity contains a large amount of hole and nervi olfactory smelt, all be the important channel that enters the brain targeting, therefore, nasal-cavity administration is brain target therapeutic agent optimum selection and approach.Nasal-cavity administration to the requirement of medicine and drug-supplying system must arrive 1, medicine is to the nasal mucosa nonirritant, 2, drug delivery system has bioadhesive to nasal mucosa, prevent that the nasal mucosa cilium from draining outward, 3, the single administration volume is unsuitable excessive, 4, the rapidity of onset, 5, in system, must consider short penetrating agent and osmotic pressure regulator.
The medicine that the present invention selects is the XINGNAOJING ZHUSHEYE of having gone on the market, raw medicinal material component and consumption are according to " Drug Standard of Ministry of Public Health of the Peoples Republic of China ", but the present invention has carried out extracting separation with this component according to the nasal-cavity administration specification requirement to be concentrated, effective ingredient is improved greatly, volume-diminished, and the research invention according to the prescription ratio of having carried out effective ingredient and preparation system makes its suitable nasal-cavity administration, reaches the therapeutic effect of same XINGNAOJING ZHUSHEYE.The Patents of relevant XINGNAOJING preparation is many, patent CN102526619A has related to the XINGNAOJING nasal cavity administrated preparation, this patent has stated that the injection manufacture process according to published listing obtains 4 flavor Chinese medicine extraction liquid, add short penetrating agent and antiseptic and osmotic pressure regulator and form the nasal cavity spray, Borneolum Syntheticum in the said preparation and muscone composition have zest as producing without suitable enclose processing to nasal mucosa, cause stream nose younger brother and sneeze, said preparation does not have bioadhesive, and the nose cilium can be discharged medicine outward.Simultaneously, the effective dose of the single-dose of preparation is considerably less, is difficult to guarantee effective dose concentration.Patent CN1785415A has invented three kinds of novel forms when relating to the preparation injection, nanometer microemulsion, and inferior nanometer microemulsion, Lipidosome, prepared Emulsion is not suitable for nasal-cavity administration microemulsion system in this patent, is not suitable for the nasal-cavity administration volume requirement.Patent CN102526602A relates to a kind of preparation of Xingnaojing self-emulsifying soft capsule, and this emulsification system is to be fit to oral administration rather than the strong administration of suitable nasal cavity equally.Chinese herbal medicine Chinese Traditional and Herbal DrugsThe 43Volume the 3In March, 2012 phase " iridoid glycoside effective constituents nasal absorption study in the XINGNAOJING ", this article is mainly studied in the XINGNAOJING prescription release behavior of the nasal mucosa of two separation and purification material jasminoidins in the Fructus Gardeniae and genipin gentiobioside with cape jasmine composition.Still rarely has report for some technical research by nasal-cavity administration.
Summary of the invention
The purpose of this invention is to provide that a kind of this nasal cavity administrated preparation can improve the effectiveness of effective ingredient greatly for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, volume-diminished is fit to nasal-cavity administration.
This XINGNAOJING nasal-cavity administration composing system is: the ⑴ pharmaceutical composition is by muscone extracting solution 80-90mL, natural Broneolum Syntheticum 0.33g, jasminoidin extract 0.6-0.8g, Radix Curcumae curcumin extraction 0.24-0.26g, Radix Curcumae volatile oil 0.01-0.02mL; ⑵ cosolvent: tween 80 or 1.2 propylene glycol, content are 1.6-2.0%(L/L); ⑶ urge penetrating agent: and alpha-cyclodextrin (α-CD), gamma-cyclodextrin (γ-CD) and derivant hydroxypropyl α cyclodextrin (HP-a-CD) thereof, hydroxypropyl beta cyclodextrin (HP-β-CD), hydroxypropyl γ cyclodextrin (HP-γ-CD), its consumption is 3.5-5%(W/L); ⑷ antiseptic: ethyl hydroxybenzoate or potassium sorbate, consumption 0.01(W/L); ⑸ solvent: distilled water or water for injection, content are surplus; Phosphate buffer: its addition is to 6.0-7.0 with the liquid pH regulator;
The muscone extracting solution adopts the second distillation method, the 1st distillation: 7.5g adding distil water 1000mL stops distillation behind the collection distillate 300mL; The 2nd distillation: among the 1st the distillate 300mL, adding distil water 100mL, distillate 250mL is collected in the steam distillation of intaking again;
The jasminoidin extract: the 30g Fructus Gardeniae is ground into 40 orders, the ethanol that adds 8 times of medical material weight, 70% alcohol reflux secondary each 2 hours, is collected extracting solution, Recycled ethanol, the relative density of fluid extract is 1.05, adds 5 times of water and carries out water precipitating, and supernatant concentrates, drying gets Fructus Gardeniae ethanol extract 2-3g at last;
Radix Curcumae volatile oil extracts preparation: the 30g turmeric powder is broken into 40 orders, adds 8 times of distilled water according to hydrodistillation distillation 10 hours, collects at last distillate 1-2mL, for subsequent use, Radix Curcumae curcumin extraction preparation: after the oven dry of the Radix Curcumae medicinal residues after the distillation, add 70% ethanol of 10 times of amounts of medicinal residues dry weight, reflux, extract, 6 hours, Recycled ethanol, fluid extract is dry, and dry thing adds 10 times of 90% ethanol again, reflux, extract, 2 hours, dry behind the Recycled ethanol, get the Radix Curcumae curcumin and carry thing 0.5-1g.
This system can be made nasal spray and nasal drop.
Described short penetrating agent is hydroxypropyl beta cyclodextrin HP-β-CD.
Another object of the present invention provides a kind of method for the preparation of inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, comprises the steps:
Take by weighing natural Broneolum Syntheticum 0.33g, with 1,2-propylene glycol or tween 80 1.6mL dissolving, adding potassium sorbate or ethyl hydroxybenzoate 0.01g dissolves, filter, filtrate adds 2 distillate 80mL of Moschus, adds successively Radix Curcumae volatile oil 1mL, short penetrating agent 3.5g, stirring, mixing speed 1000 turns/hour, stir after 0.5 hour, add Fructus Gardeniae extract 0.6g, Radix Curcumae curcumin extraction 0.20g stirred 2 hours, filtered, regulate pH to 6.0-7.0 with phosphate buffer, last distilled water or water for injection are prepared into the 100mL preparation.
Among the related drug level 100mL of XINGNAOJING nasal-cavity administration system of the present invention: muscone 0.080-0.1200mg.mL -1Natural d-borneol 0.80-1.00mg.mL -1Jasminoidin 0.80-1.50mg.mL -1Radix Curcumae curcumin 0.080-0.120mg.mL -1
The present invention's XINGNAOJING nasal cavity administrated preparation involved in the present invention includes nasal spray and nasal drop, specifically comprise: every spray 100-200uL, or every, containing medicine comprises: muscone 0.0080-0.0120mg, dextro Borneolum Syntheticum 0.080-0.100mg, jasminoidin 0.080-0.150mg, Radix Curcumae curcumin 0.008-0.012mg.
Beneficial effect of the present invention: observe by 20 examples due to drunk unconsciousness, matched group 10 people take conventional relieving alcoholic intoxication treatment (glucose+naloxone)+nose spray normal saline; Test group 10 people are in conventional relieving alcoholic intoxication treatment, increase the present invention's " XINGNAOJING nasal spray " every spray in 1 hour once, spray altogether 3 times, the relieving alcoholic intoxication time contrast group relieving alcoholic intoxication time average of test group shortens 3 ± 0.5 hours as a result, prove that refreshment nasal spray of the present invention can improve the effectiveness of effective ingredient greatly, volume-diminished reaches the effect of quick refreshment, is fit to nasal-cavity administration.
The specific embodiment
Below by example the present invention is described in further details, these examples only are used for illustrating the present invention, do not limit the scope of the invention.
Embodiment 1
XINGNAOJING nasal cavity administrated preparation Chinese medicine extract preparation method involved in the present invention
1, muscone two distillates preparation
The 1st distillation: 7.5g adding distil water 1000mL stops distillation behind the collection distillate 300mL; The 2nd distillation: among the 1st the distillate 300mL, adding distil water 100mL, the steam distillation of intaking is again collected distillate 250mL(and is wherein contained muscone concentration 0.080-0.1200mg.mL -1)
2, Radix Curcumae volatile oil extracts preparation
The 30g turmeric powder is broken into 40 orders, adds 8 times of distilled water immersions 24 hours, according to hydrodistillation distillation 10 hours, collects at last distillate 1-2mL, and is for subsequent use
3, Radix Curcumae curcumin extraction preparation
After the oven dry of the Radix Curcumae medicinal residues after the distillation, 70% ethanol that adds 10 times of amounts of medicinal residues dry weight, reflux, extract, 6 hours, Recycled ethanol, fluid extract is dry, and dry thing adds 10 times of 90% ethanol again, reflux, extract, 2 hours, dry behind the Recycled ethanol, get the about 0.5-1g(of Radix Curcumae ethanol extract and contain curcumin 0.800-0.120mg.mL -1).
4, the preparation of jasminoidin extract
The 30g Fructus Gardeniae is pulverized, 40 orders, add 8 times of medical material weight, 70% alcohol reflux secondary, each 2 hours, collect extracting solution, Recycled ethanol, the relative density 1.05 of fluid extract add 5 water and carry out water precipitating, and supernatant concentrates, drying, last Fructus Gardeniae ethanol extract 2-3g (contains jasminoidin 0.80-1.50mg.mL -1).
Embodiment 2
The 100mL preparation prescription forms 1
Form Dosage Active substance content
The Moschus distillate 80Ml Muscone 0.080-0.1200mg.mL-1
Natural Broneolum Syntheticum 0.33g Dextro Borneolum Syntheticum 0.80-1.00mg.mL-1
Fructus Gardeniae alcohol glucoside extract 0.60 Jasminoidin 0.80-1.50mg.mL-1
Radix Curcumae volatile oil 0.5mL ?
The Radix Curcumae curcumin extraction 0.15g Curcumin 0.080-0.120mg.mL-1
The 1-2 propylene glycol 1.6mL ?
HP-β-CD 3.5g  
Potassium sorbate 0.01g  
Distilled water Complement to 100mL ?
Preparation prescription forms 2
Form Dosage Active substance content
The Moschus distillate 90mL Muscone 0.080-0.1200mg.mL-1
Natural Broneolum Syntheticum 0.33g Dextro Borneolum Syntheticum 0.80-1.00mg.mL-1
Fructus Gardeniae alcohol glucoside extract 0.80g Jasminoidin 0.80-1.50mg.mL-1
Radix Curcumae volatile oil 1mL ?
The Radix Curcumae curcumin extraction 0.24g Curcumin 0.080-0.120mg.mL-1
The 1-2 propylene glycol 2mL ?
HP-β-CD 5g  
Ethyl hydroxybenzoate 0.01g  
Preparation prescription forms 3
Form Dosage Active substance content
The Moschus distillate 90mL Muscone 0.080-0.1200mg.mL-1
Natural Broneolum Syntheticum 0.33g Dextro Borneolum Syntheticum 0.80-1.00mg.mL-1
Fructus Gardeniae alcohol glucoside extract 0.80g Jasminoidin 0.80-1.50mg.mL-1
Radix Curcumae volatile oil 1mL ?
The Radix Curcumae curcumin extraction 0.24g Curcumin 0.080-0.120mg.mL-1
Tween 80 2mL ?
HP-β-CD 5g  
Ethyl hydroxybenzoate 0.01g  
Implement 3 nasal cavity administrated preparation preparation methoies
Take by weighing natural Broneolum Syntheticum 0.33g, with 1,2-PD 1.6mL dissolving, add methyl hydroxybenzoate 0.01g and dissolve, filter, filtrate adds 2 distillate 80mL of Moschus, add successively Radix Curcumae distillate 1mL, HP-β-CD 3.5g stirs, mixing speed 1000 turns/hour, stir after 2 hours, add Fructus Gardeniae ethanol extract 0.6g, Radix Curcumae ethanol extract 0.20g stirred 2 hours, filtered, regulate pH to 6.0-7.0 with phosphate buffer, last distilled water prepares the 100mL preparation.
Embodiment 4
The prescription of XINGNAOJING has clearing away heat-fire, removing pathogenic heat from blood and toxic substance from the body, and the inducing resuscitation function, XINGNAOJING nasal cavity administrated preparation of the present invention is tested the impact of the pentobarbital sodium in mice length of one's sleep:
Get 24 of the qualified mices of screening, male and female half and half are divided into negative control group (normal saline group), positive controls (caffeine and sodium benzoate normal saline group 2mg.mL at random -1), XINGNAOJING nasal cavity preparation (self-control), XINGNAOJING ZHUSHEYE group (commercial preparation 45mg.kg -1).
Except nasal cavity administrated preparation, other several groups amount of liquid medicine of pressing respectively conversion mice dosage, the special administrator of nasal cavity group sprays into nasal cavity (dosage reaches the administration effective dose of injection, sprays 3 times), injects simultaneously 3mg.mL -1The barbital sodium normal saline.The record areflexia the results are shown in Table to recovery time.As can be seen from the table, positive control combination XINGNAOJING ZHUSHEYE and nasal-cavity administration group and the apparent in view shortening wakeup time of normal saline group, XINGNAOJING nasal-cavity administration group is better than the XINGNAOJING ZHUSHEYE group.
  The length of one's sleep min X±S
Group 1 2 3 4 5 6  
The normal saline group 22.6? 29.0? 25.0? 24.7 30.1? 31.6 27.1±3.5
Positive controls 8.9 10.1? 12.5? 8.9 11.0? 13.7 10.85±4.0**
XINGNAOJING nasal-cavity administration group 10.2? 14.4? 9.8 10.9 11.9? 14.7 11.98±3.9**★
The XINGNAOJING ZHUSHEYE group 14.5? 15.9? 20.1? 12.0 14.7 18.5 15.95±5.7**
Compare with the normal saline group *<0.01, ★<0.05, and nasal-cavity administration group and injection group are relatively.
Embodiment 5
Impact on mouse writhing40 of 18-20 g ICR mices, male and female half and half are divided into blank group (normal saline), positive controls (the aspisol normal saline is molten), nasal-cavity administration group (of the present invention group), injection group (commercially available 45mg.kg at random -1), 10 every group.Dosage according to the conversion mice, administration injection liquid (1 time), positive drug (1 time), nasal-cavity administration (conversion administration every day 3 times), successive administration 2 days, 15 min after the last administration, every lumbar injection 0.6% glacial acetic acid solution 0.3ml respectively organizes the mouse writhing number of times in 15 min behind the record injection algogen, calculate and respectively organize mouse writhing number of times meansigma methods and standard deviation, proofread and correct the t check, with blank group comparing difference significance, the results are shown in Table.
Group Dosage mL.kg-1 Unit interval writhing number of times
The normal saline group 20 30.85±10.0
Positive controls 20 10.85±4.0**
XINGNAOJING nasal-cavity administration group 0.05 17.85±6.9**
The XINGNAOJING ZHUSHEYE group 20 18.05±5.9**
*?P?<0.01
Above result shows: the XINGNAOJING nasal spray has obvious alleviation mice pain.Although effect and injection comparison do not have significance, have the trend that is better than injection.
Implementation column 6
(1) jasminoidin HPLC content
Measure determining of wavelength :It is an amount of to take by weighing jasminoidin, and with the mobile phase dissolving, at 200-400nm wave-length coverage scanning samples, therefore its obtained the maximum absorption selects 237nm as detecting wavelength at 237nm.Determining of chromatographic condition: with reference to the method for Pharmacopoeia of People's Republic of China, take second eyeball-water (15:85) as mobile phase, flow velocity: 1.0mL. min -1, detect wavelength: 237nm; Chromatographic column: Kromasmil C18ODS post, 150 X 4.6mm, 5um; Column temperature: room temperature; Sample size: 20ul.Jasminoidin separates well under this condition, and it is fast to go out the peak, and once methanol-water (25:75) on probation was mobile phase, and jasminoidin separates also good, but appearance time is slow, and the peak shape symmetry is relatively poor, is mobile phase so adopt second eyeball one water (15:85).The preparation of solution: reference substance and test liquid dissolve the drafting of preparation standard curve with mobile phase: precision is drawn 1mg.mL respectively -1Jasminoidin standard solution 0.30,0.50,0.70,0.90,1.10,1.30,1.50mL, put in the l0mL measuring bottle, add mobile phase and be diluted to scale, mixing carries out HPLC and measures, with the standard substance peak area to concentration (ug.mL -1) the drawing standard curve.Jasminoidin is at 30ug. mL as a result -l-150ug. mL -1, scope internal linear relation is good.Regression equation is: Y=16470X+4980.3, r=0.9997.Algoscopy: precision is drawn reference substance solution and each 20 μ l of need testing solution respectively, and the injection liquid chromatography is measured, and measures above-mentioned drafting under the chromatographic condition, calculates content with external standard method.
This product contains Fructus Gardeniae in jasminoidin, content range: 0.80-1.50mg.mL -1
(2) curcumin HPLC assay
Measure wavelength: 421 nm are as detecting wavelength, the determining of chromatographic condition: chromatographic column: Kromasmil C 18The ODS post, 150 x 4.6mm, 5uL; Mobile phase: second eyeball-water (45:55); Flow velocity: 1.0mL. min -1, detect wavelength: 421 nm; Column temperature: room temperature; Sample size 20uL.The preparation of solution: it is an amount of that the preparation precision of standard solution takes by weighing the curcumin reference substance, adds dissolve with methanol and be diluted to 0.1 mg.mL -1Standard solution.The accurate nasal drop 1.00mL that draws of the preparation of need testing solution puts water bath method, and residue adds methanol jolting dissolving 5 times, each 2.00m1, need testing solution extracts four times with the methanol jolting, merges methanol solution, 0.45 the um filter membrane filters, and with methanol constant volume to 10.00mL.Algoscopy: precision is drawn reference substance solution and each 20 μ l of need testing solution respectively, and the injection liquid chromatography is measured, and be get final product.
This product contains Radix Curcumae in curcumin, content range 0.080-0.120mg.mL -1
(3) muscone and Borneolum Syntheticum dextro Borneolum Syntheticum GC assay
Reference substance solution: get muscone, the dextro Borneolum Syntheticum reference substance is an amount of, the accurately weighed dissolve with ethanol that adds is made every milliliter and is contained muscone 0.100mg, dextro Borneolum Syntheticum 1.000mg stock solution.Getting stock solution dilution makes every milliliter and contains muscone 50ug, dextro Borneolum Syntheticum 512ug solution.
Need testing solution: accurate sampling 5mL to the 50mL volumetric flask, adds ethanol dilution to scale.
Chromatographic condition: DB-FFAP (0.1umx0.53mmx30m) gas chromatographic column; Flame ionization ditector; Nitrogen flow 2.5mL min -1, hydrogen flowing quantity 30 mL min -1, air mass flow 300 mL min -1Split ratio 15:1; Heating schedule (85 ℃ of initial temperatures; With 5 ℃ of min -1Be warming up to 185 ℃, with 20 ℃ of min -1Appreciate 215 ℃, with 1 ℃ of min -1Rise to 230 ℃, keep 5min); Sample size 1 μ L, external standard method is quantitative.
This law records Moschus and calculates with muscone, muscone content range 0.080-0.1200mg.mL -1
This law records Borneolum Syntheticum and calculates with dextro Borneolum Syntheticum, natural d-borneol content range 0.80-1.00mg.mL -1
Embodiment 7
Every spray amount is according to the proportional valve regulation of selecting, the present invention is set as 100 or 200uL or every (200uL), adopt the method for embodiment 6, measuring 100uL and 200 uL contains respectively: muscone: 0.0080 and 0.0120mg, dextro Borneolum Syntheticum 0.080 and 0.100mg, jasminoidin 0.080 and 0.150mg, Radix Curcumae curcumin 0.008 and 0.012mg.

Claims (6)

1. one kind is used for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, it is characterized in that: this XINGNAOJING nasal-cavity administration composing system is: the ⑴ pharmaceutical composition is by muscone extracting solution 80-90mL, natural Broneolum Syntheticum 0.33g, jasminoidin extract 0.6-0.8g, Radix Curcumae curcumin extraction 0.24-0.26g, Radix Curcumae volatile oil 0.01-0.02mL; ⑵ cosolvent: tween 80 or 1.2 propylene glycol, content are 1.6-2.0%(L/L); ⑶ urge penetrating agent: and alpha-cyclodextrin (α-CD), gamma-cyclodextrin (γ-CD) and derivant hydroxypropyl α cyclodextrin (HP-a-CD) thereof, hydroxypropyl beta cyclodextrin (HP-β-CD), hydroxypropyl γ cyclodextrin (HP-γ-CD), its consumption is 3.5-5%(W/L); ⑷ antiseptic: ethyl hydroxybenzoate or potassium sorbate, consumption 0.01(W/L); ⑸ solvent: distilled water or water for injection, content are surplus; Phosphate buffer: its addition is to 6.0-7.0 with the liquid pH regulator;
The muscone extracting solution adopts the second distillation method, the 1st distillation: 7.5g adding distil water 1000mL stops distillation behind the collection distillate 300mL; The 2nd distillation: among the 1st the distillate 300mL, adding distil water 100mL, distillate 250mL is collected in the steam distillation of intaking again;
The jasminoidin extract: the 30g Fructus Gardeniae is ground into 40 orders, 70% ethanol that adds 8 times of medical material weight, 70% alcohol reflux secondary each 2 hours, is collected extracting solution, Recycled ethanol, the relative density that makes fluid extract is 1.05, adds 5 times of water again and carries out water precipitating, and supernatant concentrates, drying gets Fructus Gardeniae ethanol extract 2-3g at last;
Radix Curcumae volatile oil extracts preparation: the 30g turmeric powder is broken into 40 orders, adds the distilled water of 8 times of Radix Curcumae weight according to hydrodistillation distillation 10 hours, collects at last distillate 1-2mL, for subsequent use, Radix Curcumae curcumin extraction preparation: after the oven dry of the Radix Curcumae medicinal residues after the distillation, add 70% ethanol of 10 times of amounts of medicinal residues dry weight, reflux, extract, 6 hours, Recycled ethanol, fluid extract is dry, and dry thing adds 10 times of 90% ethanol again, reflux, extract, 2 hours, dry behind the Recycled ethanol, get the Radix Curcumae curcumin and carry thing 0.5-1g.
2. according to claim 1 a kind of for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, it is characterized in that: this system can be made nasal spray and nasal drop.
3. according to claim 1 a kind of for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, it is characterized in that: described short penetrating agent is HP-β-CD.
4. according to claim 1 a kind of for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, it is characterized in that: the related drug level of described XINGNAOJING nasal-cavity administration system: muscone 0.080-0.1200mg.mL -1, natural d-borneol 0.80-1.00mg.mL -1, jasminoidin 0.80-1.50mg.mL -1, Radix Curcumae curcumin 0.080-0.120mg.mL -1
5. according to claim 1 a kind of for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation, it is characterized in that: described XINGNAOJING nasal cavity administrated preparation specifically comprises: every spray 100-200uL, or every, contain medicine: muscone 0.0080-0.0120mg, dextro Borneolum Syntheticum 0.080-0.100mg, jasminoidin 0.080-0.150mg, Radix Curcumae curcumin 0.008-0.012mg.
6. one kind for the preparation of the method for inducing resuscitation Chinese medicine XINGNAOJING nasal cavity administrated preparation claimed in claim 1, it is characterized in that: comprise the steps:
Take by weighing natural Broneolum Syntheticum 0.33g, with 1,2-propylene glycol or tween 80 1.6mL dissolving, adding potassium sorbate or ethyl hydroxybenzoate 0.01g dissolves, filter, filtrate adds 2 distillate 80mL of Moschus, adds successively Radix Curcumae volatile oil 1mL, short penetrating agent 3.5g, stirring, mixing speed 1000 turns/hour, stir after 0.5 hour, add Fructus Gardeniae extract 0.6g, Radix Curcumae curcumin extraction 0.20g stirred 2 hours, filtered, regulate pH to 6.0-7.0 with phosphate buffer, last distilled water or water for injection are prepared into the 100mL preparation.
CN201210435340.8A 2012-11-05 2012-11-05 Traditional Chinese medicine refreshment intravenous injection nasal delivery preparation used for resuscitation and refreshment and preparation method of nasal delivery preparation Active CN102886030B (en)

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CN104940134A (en) * 2015-06-30 2015-09-30 深圳清华大学研究院 Method using traditional Chinese medicine injection for preparing mucosal drug delivery dosage form
CN108821956A (en) * 2018-05-25 2018-11-16 无锡济民可信山禾药业股份有限公司 A method of it distills to extract from XINGNAOJING ZHUSHEYE and recycles curcumin in waste residue
CN112611823A (en) * 2020-11-18 2021-04-06 上海和黄药业有限公司 Method for detecting main active ingredients of borneol and artificial musk in medicinal preparation

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