CN106074587A - The preparation of gentiopicrin suppository and the application in antipyretic analgesics - Google Patents
The preparation of gentiopicrin suppository and the application in antipyretic analgesics Download PDFInfo
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- CN106074587A CN106074587A CN201610462221.XA CN201610462221A CN106074587A CN 106074587 A CN106074587 A CN 106074587A CN 201610462221 A CN201610462221 A CN 201610462221A CN 106074587 A CN106074587 A CN 106074587A
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- gentiopicrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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)
- A61K36/51—Gentianaceae (Gentian family)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
Abstract
The present invention uses the gentiopicrin extracted from gentianaceae plant Radix Gentianae Macrophyllae (Gentiana macrophylla Pall.), rectal suppository is made with Mixed Fatty Glyceride, using rabbit heat source check method in Chinese Pharmacopoeia is animal experimental model, with aspirin as positive control, it was demonstrated that gentiopicrin suppository has refrigeration function.
Description
Technical field
The present invention relates to gentiopicrin or the preparation method of the Radix Gentianae total glucosides suppository containing gentiopicrin more than 50% and solving
Application in medicine of a warm nature thing.
Technical background
Fever, is disease common in clinical medicine.Main performance is exactly that body temperature raises.The reason causing fever is a lot,
Mainly antibacterial, virus infection, tumor, autoimmune disease, hematopathy etc. and not clear fever.By contrast, children fever is outstanding
For common, children fever mainly food stagnation in addition to affection of exogenous wind-cold wind heat causes.
Gentiopicrin is the chemical composition extracted from Chinese medicine natural drug, and content, more than 98%, has antibacterial, disease-resistant
Poison, the effect of promotion digestive tract power, be suitable for the releasing of infantile fever symptom, produce refrigeration function.It addition, suppository is easy to use,
Painful few, medicine is directly absorbed by rectum, enters blood capillary, easy absorbed into serum, and effect is quick.
Summary of the invention
It is an object of the invention to provide gentiopicrin or the preparation side of the Radix Gentianae total glucosides suppository containing gentiopicrin more than 50%
Method and the application in ntipyretic analgesic medicine thereof.
The scheme solving above-mentioned technical problem is:
The preparation method of gentiopicrin suppository is: active ingredient is gentiopicrin or the Radix Gentianae total glucosides containing gentiopicrin more than 50%,
Fat-soluble substrate or water-soluble base, heating fusion method is used to make suppository.In the case of You Xuan, select sweet with fatty acid mixed
Oils and fats is substrate.
The gentiopicrin suppository that above-mentioned preparation method prepares application in antipyretic analgesics, described gentiopicrin suppository
Preferably rectal suppository.
The present invention uses the Radix Gentianae extracted from gentianaceae plant Radix Gentianae Macrophyllae (Gentiana macrophylla Pall.) bitter
Glycosides, makes rectal suppository with Mixed Fatty Glyceride, and using rabbit heat source check method in Chinese Pharmacopoeia is animal experimental model,
With aspirin as positive control, it was demonstrated that gentiopicrin suppository has refrigeration function.
Figure of description
Body temperature measured drawing after the administration of Fig. 1 rabbit；
Temperature change value after the administration of Fig. 2 rabbit；
Temperature variation after the administration of Fig. 3 rabbit.
Detailed description of the invention
Essence for a better understanding of the present invention, illustrates its new application in pharmaceutical field with experiment and result below.
The present invention extracts from Radix Gentianae Macrophyllae or other plant of Gentianaceae and isolates gentiopicrin or Radix Gentianae total glucosides (present patent application
Being the Radix Gentianae total glucosides provided with biological medicine key lab of Shaanxi Province of Northwest University, lot number is 20160503), with mixing-in fat
Acid glyceride is substrate, and heating fusion method makes suppository, uses the suppository mould of 1g to let cool molding.The heavy dose of group of preparation, middle dose
Amount group, small dose group, blank group, positive drug group (aspirin is positive control drug), with rabbit as laboratory animal, injection
Bacterial endotoxin produces rabbit fever pathological model, observes with the above-mentioned suppository in treatment made.Statistical analysis, result display sun
Property matched group, administration group have refrigeration function, make the hypothermia of fever rabbit, and wherein small dose group is right with the aspirin positive
According to group quite (P > 0.05).
Embodiment 1
1. test medicine gentiopicrin, bitter in the mouth, white crystalline solid, measuring content through HPLC method is 98.6%.
Positive control medicine Aspirin Enteric-coated Tablets, commercially available, content 240mg/ sheet, import drugs registration certificate number
H20130078, import subpackage enterprise, Bayer HealthCare Co.
The preparation of suppository
3.1 experiment materials and reagent
Water-bath, small beaker, Glass rod, pocket knife, bullet type suppository mould, balance, mixed fatty glycerides, Bai Asi
Woods enteric coatel tablets, glycerol.
The preparation of pure substrate bolt
Pure substrate: mixed fatty glycerides
Weigh 10g mixed fatty glycerides to be placed in small beaker, heat in 60 DEG C of water-baths, stop after 2/3 is ma trix melting
Heating, is stirred continuously and makes it all melt, when substrate becomes viscous pasty state, be poured into rapidly in the 1g suppository mould scribbling glycerol,
Prune spilling part on bolt mould with blade after cooled and solidified, the demoulding, obtain complete pure substrate bolt number piece.
The preparation of Asupirin (positive control)
Aspirin suppositories agent content: 240mg/ grain
By finely ground for Aspirin Enteric-coated Tablets for powder (medicated powder must cross No. six sieves).Weigh a certain amount of medicated powder and appropriate mixing
Fatty glyceride, stops heating after first being melted by the mixed fatty glycerides of 2/3 under 60 DEG C of waters bath with thermostatic control, stirring is to entirely
Add medicated powder after portion's fusing by several times, be stirred continuously and make medicine be dispersed in substrate, when it presents thick, rapidly by it
Inject in the bolt mould of the 1g scribbling glycerol, after it cools down, prune spilling part with blade, the demoulding, obtain complete containing stype.
The preparation of gentiopicrin suppository
Gentiopicrin suppository content: 1. heavy dose of 240mg/ grain 2. middle dosage 160mg/ grain 3. low dose of 80mg/ grain.
A certain amount of drug powder (medicine must cross No. six sieves) and mixed fatty glycerides is weighed according to above-mentioned content,
First under 50 DEG C of waters bath with thermostatic control by 2/3 ma trix melting after stop heating, stirring makes all to melt, the rear medicine that adds by several times, no
Disconnected stirring makes medicine be dispersed in substrate, when thing to be mixed is thick, is poured into rapidly in the 1g bolt mould scribbling glycerol, cold
But prune spilling part with blade after solidification, the demoulding, obtain complete containing stype number piece.
Antipyretic activity measures
4.1 laboratory animal
Laboratory animal: Male New Zealand rabbits 20, body weight, at 1.8kg～2.5kg, is had by Xi'an Di Lepu bio-resource exploitation
Limit company, credit number: SYXK(Shan) 2014-001, experimental unit uses licence to number: SYXK(Shan) 2010-004.
Rearing conditions: feedstuff is laboratory animal special feed (production of Xi'an Di Lepu bio-resource exploitation company limited)
White with fresh Flos Nelumbinis, feed at laboratory, adapt to one week；During experiment, animal sub-cage rearing is under the room temperature of 15～25 DEG C,
Air circulates, relative humidity about 42%～45%, drinking-water of arbitrarily ingesting.
Experiment material and reagent
Material: 5ml glass syringe, tweezers, tape, plank, electronic clinical thermometer (Omron's production), 100ml
Graduated cylinder, cotton ball soaked in alcohol, the little shears of operation, doctor's type scale (Jiangsu Su Hong Medical Devices Co., Ltd.).
Reagent: 0.9% normal saline, vaseline, bacterial endotoxin working standard (derives from Chinese food drug assay
Academy lot number 150601-201580 80EU/ props up)
4.3 experimental technique
4.3.1 the preparation of bacterial endotoxin
The bacterial endotoxin propped up by 80 EU/ first dissolves repeatedly with a small amount of 0.9% sodium chloride solution, pours into until completely dissolved
In 100ml graduated cylinder, then with 0.9% sodium chloride solution, bacterial endotoxin is diluted to 14.5 EU/ml.
Laboratory animal is grouped
5 groups it are randomly divided into, often group 2 after Male New Zealand rabbits is weighed.Respectively:
(1) blank group: pure substrate
(2) positive controls: aspirin suppositories agent content: 240mg/ grain
(3) small dose group: gentiopicrin suppository content: 80mg/ grain
Middle dosage group: gentiopicrin suppository content: 160mg/ grain
(5) heavy dose of group: gentiopicrin suppository content: 240mg/ grain
More than experiment is the most in triplicate, and ensures that between adjacent number of times, rabbit used is different；Measure 8 hours, each dosage group every time
Do 6 altogether.
Experimental procedure:
(i) before experiment, rabbit needs fasting 12h, during experiment in second day, rabbit is randomly divided into five groups, i.e. blank group, positive controls,
Heavy dose of group, middle dosage group, small dose group.After packet, weigh body weight the record of every rabbit.
(ii) the warm water of about 5ml is drawn with syringe to rabbit coloclysis so that it is in body cavity road, the feces of residual is discharged.Row
After going out feces, being fixed on plank by rabbit, upward, fixing about 1.5h, after its peace and quiet at back.
(iii) after rabbit peace and quiet, then (end of clinical thermometer is coated vaseline, so with its initial body temperature of thermometer measurement
The rear anus about 5cm inserting rabbit, reading after clinical thermometer is stable.Initial body temperature must measure twice or more than, treat adjacent two
The difference of secondary measurement body temperature is the most recordable less than 0.2 DEG C, asks twice meansigma methods to be initial body temperature.)
(iv) when its thermostasis, rabbit is placed in fixed bin its head is fixed, the hair of every family's rabbit ear edge is cut
So that auricular vein is high-visible, then from ear's intravenous injection bacterial endotoxin, injection volume is relevant with the body weight of rabbit, is 29
EU/kg。
(v) after having injected endotoxin, every the body temperature of a 0.5h rabbit of record, record 2 hours altogether.
(vi), after confirming that rabbit fever models has built up, the suppository prepared is filled in the anal of rabbit (during administration, first
Hold the tail of rabbit, after its buttocks is lifted slightly, be administered after having confirmed the position of anus), blank group is administered pure
Substrate suppository, positive controls is administered 240mg/ grain Asupirin, and heavy dose of group is administered the Radix Gentianae that content is 240mg/ grain
Bitter glycosides suppository, middle dosage group is administered the gentiopicrin suppository that content is 160mg/ grain, and it is 80mg/ grain that small dose group is administered content
The suppository of gentiopicrin.After being administered, start timing, record a body temperature every 30min, record 6h altogether.
Note: should block gently with toilet paper immediately at anus after being 1. administered 5 minutes, prevent suppository from melting in rabbit body
Flow out after change, thus affect experimental result；
It is required for when measuring temperature taking appropriate vaseline by being coated with on thermometer the most every time, so as not to viscous in destroying rabbit rectal tract
Film is hemorrhage；
3. indoor quiet and temperature constant is ensured during experiment as far as possible, in order to avoid having affected measuring temperature.
Data process
Calculate the temperature change value △ T of every rabbit adjacent time point, then obtain the meansigma methods often organizing six rabbit △ TWith
Standard deviation S, result of calculation is finally used± S represents；Data compare employing t inspection.Result after process is as follows:
Contrasting with blank group as shown in Table 1, the body temperature general trend of other groups all has substantially reduction；Fall is known through can be calculated
Temp effect is: and middle dosage group < heavy dose of group < small dose group < aspirin, and compared with blank group, middle dosage group body temperature is the brightest
Aobvious decline, but it is compared to low dose of more weak with heavy dose, it may be possible to dose-effect interval linear extent causes base rabbit individuality poor
Different cause.After being can be seen that fever model is set up by blank group in upper table, compared with the temperature of adstante febre, pure substrate temperature tends to
Rise, the body temperature of rabbit does not has a significant impact i.e. to pure based pharmaceutical；After to positive control medicine and gentiopicrin, its body
Wen Jun has downward trend, the most heavy dose of group, small dose group, positive controls and blank group suppository t inspection, all has significance poor
Different (P ＜ 0.01).
By Fig. 1, it is known that after rabbit fever models has built up, being administered it, in addition to blank group, other all have bright
Aobvious cooling, after being administered 4.5 hours, the body temperature of rabbit tends towards stability.When being administered 2-2.5h, temperature decline is the most obvious,
On the whole, it can be seen that gentiopicrin has cooling effect.
From Fig. 2, Fig. 3, compared with animal heating mean, upon administration, blank group is not lowered the temperature phenomenon, can say
Bright pure substrate is not result in that rabbit body temperature reduces；Positive controls cooling it is obvious that compared with positive controls, small dose group
Cooling-down effect is it is also obvious that next to that heavy dose of, the variations in temperature of middle dosage is less obvious.When 4.5h, body temperature tends towards stability.
In sum, illustrate that gentiopicrin has obvious cooling effect to the heating that rabbit endotoxin causes.
Embodiment 2
Medicinal gentiopicrin or gentiopicrin 8～24 grams
Mixed fatty glycerides about 100 grams
Preparation technology is fabricated to about 100 by suppository routine fashion.
Embodiment 3
Medicinal gentiopicrin or gentiopicrin 8～48 grams
Mixed fatty glycerides about 100 grams
Preparation technology is fabricated to about 100 by suppository routine fashion.
Embodiment 4
Medicinal gentiopicrin or gentiopicrin 8～48 grams
Water-soluble base (such as S-40) about 100 grams
Preparation technology is fabricated to about 100 by suppository routine fashion.
Claims (4)
1. the preparation method of gentiopicrin suppository, it is characterised in that: active ingredient is gentiopicrin or contains gentiopicrin more than 50%
Radix Gentianae total glucosides, use fat-soluble substrate or water-soluble base, heating fusion method makes suppository.
Preparation method the most according to claim 1, it is characterised in that: with Mixed Fatty Glyceride as substrate.
3. the gentiopicrin suppository that preparation method described in claim 1 prepares application in antipyretic analgesics.
Apply the most according to claim 3, it is characterised in that described gentiopicrin suppository is rectal suppository.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610462221.XA CN106074587A (en) | 2016-06-24 | 2016-06-24 | The preparation of gentiopicrin suppository and the application in antipyretic analgesics |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610462221.XA CN106074587A (en) | 2016-06-24 | 2016-06-24 | The preparation of gentiopicrin suppository and the application in antipyretic analgesics |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101396428A (en) * | 2007-09-30 | 2009-04-01 | 中国科学院西北高原生物研究所 | Tibetan capillary extract and preparation method, medicine composition and use thereof |
| CN102973585A (en) * | 2012-12-24 | 2013-03-20 | 西北大学 | Application of gentiopicroside in treatment of hyperuricemia |
-
2016
- 2016-06-24 CN CN201610462221.XA patent/CN106074587A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101396428A (en) * | 2007-09-30 | 2009-04-01 | 中国科学院西北高原生物研究所 | Tibetan capillary extract and preparation method, medicine composition and use thereof |
| CN102973585A (en) * | 2012-12-24 | 2013-03-20 | 西北大学 | Application of gentiopicroside in treatment of hyperuricemia |
Non-Patent Citations (2)
| Title |
|---|
| 刘学伟等: "龙胆碱的解热作用及机制研究", 《中国实验方剂学杂志》 * |
| 李丽等: "柴胡提取物栓包合前后对家兔解热作用的比较", 《现代畜牧兽医》 * |
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