Honeysuckle flower soft capsule preparation and preparation method thereof
Technical field
The present invention relates to a kind of honeysuckle preparation, relate in particular to a kind of honeysuckle flower soft capsule preparation, this soft capsule preparation has heat-clearing and toxic substances removing and antiinflammatory, antivirus action.
The invention still further relates to the preparation method of above-mentioned honeysuckle flower soft capsule preparation.
Background technology
Flos Lonicerae is Caprifoliaceae, woodbine Radix Ophiopogonis and the dry flower that belongs to various plants together.It is a kind of green natural product of " integration of edible and medicinal herbs ".Flos Lonicerae not only distributes extensively in China, and output is rich, and quality is also good, is an important medicine resource, and has recorded in " Chinese pharmacopoeia, have heat-clearing and toxic substances removing, the effect of wind-heat dissipating is used for the carbuncle furuncle, sore throat, erysipelas, toxic-heat and blood stasis, anemopyretic cold, epidemic febrile disease heating.
In recent years, the chemical constituent of Flos Lonicerae has been carried out a large amount of research both at home and abroad, the result shows that it is rich in volatile oil, also has flavonoid, organic acid, triterpenes isoreactivity composition in addition.Modern pharmacological research shows, Flos Lonicerae have drive away summer heat, heat clearing away, detoxifcation, antibacterial, antiviral, antiinflammatory, protect the liver, effect such as hemostasis, antioxidation, immunomodulating.
Yu Shenglan etc. report (Yu Shenglan, Zhang Long, Sun Ling, the progress of Flos Lonicerae, the time precious traditional Chinese medical science traditional Chinese medicines, 2002,13 (8): 498-499), contain compositions such as Palmic acid, Flos Lonicerae alcohol, linalool in the Flos Lonicerae volatile oil, based on Palmic acid.Report such as State of Zhao's tinkling of pieces of jade (State of Zhao's tinkling of pieces of jade, Liu Jiajia, Flos Lonicerae chemical analysis and pharmacological research progress, Chinese crude drug, 2002,25 (10): 762-763), also contain active ingredients such as chlorogenic acid in the Flos Lonicerae extract, have effects such as analgesic, antibiotic, antiinflammatory, antiviral.Thought in the past that the effective ingredient effect of Flos Lonicerae was volatile oil and chlorogenic acid chemical compound, in recent years discover that the saponin in the Flos Lonicerae and some other compositions also have very strong physiologically active.Therefore, utilize volatile oil and other class active ingredients in the preparation scientifically and rationally, can satisfy the needs of different clinical requirements.
The Flos Lonicerae preparation that has gone on the market at present mainly contains the Flos Lonicerae mixture and the Liquor Flos Lonicerae Distillata, is used for heat-clearing and toxic substances removing, and summer-heat is thirsty etc., and curative effect is sure.But there are following three aspect weak points in these two kinds of Flos Lonicerae preparations:
(1) though these two kinds of oral liquid formulations technologies are simple, and cost is low, because these two kinds of products are main component with volatile oil all, be solvent with water, profit does not dissolve each other, and causes the quality instability, is easy to generate precipitation.
(2) Flos Lonicerae mixture and Liquor Flos Lonicerae Distillata volume are all bigger, and use glass bottle packaging, not portable transportation, patient's medication inconvenience.
(3) both all be with Flos Lonicerae volatile oil for mainly containing effective constituent, can not make full use of Flos Lonicerae, effectively bring into play Flos Lonicerae extract antiinflammatory, antiviral effect.
As mentioned above, there are many deficiencies in existing Flos Lonicerae preparation, therefore needs the new Flos Lonicerae preparation of development, to address the above problem.
Summary of the invention
The object of the present invention is to provide a kind of honeysuckle flower soft capsule, this soft capsule is an effective ingredient with the Flos Lonicerae volatile oil, has heat-clearing and toxic substances removing and antiinflammatory, antivirus action, by existing preparation is carried out modified form, reach steady quality, effective aim easy to use.
Described honeysuckle flower soft capsule also can further comprise the effective ingredient Flos Lonicerae extract, to reach the purpose with better antiinflammatory, antivirus action.
Another object of the present invention is to provide the preparation method of above-mentioned honeysuckle flower soft capsule.
According to an aspect of the present invention, the Flos Lonicerae volatile oil that honeysuckle flower soft capsule of the present invention will be dissolved in the oil-based solvent is encapsulated in the soft capsule shell as medicinal liquid, can contain stabilizing agent in the medicinal liquid, make Flos Lonicerae volatile oil and solvent and stabilizing agent form the stable medicinal liquid of oil-oil coexistence.
In the present invention, oil-based solvent generally is meant natural oil and organic solvent, and preferred oil-based solvent is to be selected from one or more of liquid polyethylene glycol, isopropyl alcohol, tween 80, glycerol, propylene glycol and vegetable oil.
Preferred stabilizing agent is to be selected from one or more of glycerol, tween 80, ethyoxyl castor oil hydrogenated, soybean lecithin, Cera Flava, aluminum monostearate, ethyl cellulose and solid polyethylene glycol.
The proportioning of honeysuckle flower soft capsule herb liquid of the present invention is (weight portion):
Flos Lonicerae volatile oil 1
Solvent 0.25~10
Stabilizing agent 0.05~2
Honeysuckle flower soft capsule of the present invention also can further comprise Flos Lonicerae extract in medicinal liquid, this Flos Lonicerae extract will be for having extracted the water extract after the medicinal residues behind the Flos Lonicerae volatile oil extract again.
The weight proportion of the medicinal liquid of the above-mentioned honeysuckle flower soft capsule that contains Flos Lonicerae volatile oil and Flos Lonicerae extract is (weight portion):
Flos Lonicerae extract 1
The Flos Lonicerae volatile oil corresponding amount
Solvent 0.25~15
Stabilizing agent 0.05~3
Described corresponding amount is the extracted amount corresponding to volatile oil in the Flos Lonicerae of said extracted thing amount, be that described Flos Lonicerae extract and Flos Lonicerae volatile oil are all corresponding to the Chinese medicine honeysuckle raw material of same amount, behind the Flos Lonicerae feedstock production Flos Lonicerae volatile oil by same amount, the refabrication Flos Lonicerae extract.
Preferably, described honeysuckle flower soft capsule is characterized in that the weight proportion of medicinal liquid component is (weight portion):
Flos Lonicerae extract 1
Flos Lonicerae volatile oil 0.2~0.5
Solvent 0.25~15
Stabilizing agent 0.05~3
Further preferred, described honeysuckle flower soft capsule is characterized in that the weight proportion of medicinal liquid is (weight portion):
Flos Lonicerae extract 0.06
Flos Lonicerae volatile oil 0.03
Polyethylene Glycol 0.4
Glycerol 0.035
Above-mentioned liquid medicine filling is pressed into soft capsule, typing, drying can obtain honeysuckle flower soft capsule.The conventional material of soft capsule shell material dawn known to those skilled in the art that the present invention is used need not specify, and for example available gelatin, glycerol, water etc. are made plasticity rubber.
According to another aspect of the present invention, the preparation technology of honeysuckle flower soft capsule of the present invention may further comprise the steps:
1) with the stabilizing agent thermosol in partial solvent, obtain 35~45 ℃ thermosol thing;
2) the thermosol thing is joined in the residual solvent that is preheated to 35~45 ℃ lentamente, the limit edged stirs;
3) add Flos Lonicerae volatile oil, it is moistening fully fully to mix assurance;
4) cross colloid mill and pulverize the back pelleting, drying, promptly.
When further comprising Flos Lonicerae extract in the medicinal liquid of honeysuckle flower soft capsule of the present invention, preparation technology may further comprise the steps:
1) with the stabilizing agent thermosol in partial solvent, obtain 35~45 ℃ thermosol thing;
2) the thermosol thing is joined in the residual solvent that is preheated to 35~45 ℃ lentamente, the limit edged stirs;
3) add Flos Lonicerae extract and Flos Lonicerae volatile oil, fully mix guaranteeing moisteningly fully, described Flos Lonicerae extract is for after beating powder and crossing the 80-120 mesh sieve, and proportioning feeds intake by writing out a prescription;
4) cross colloid mill and pulverize the back pelleting, drying, promptly.
Flos Lonicerae volatile oil of the present invention can adopt the preparation of steam distillation or carbon dioxide supercritical extraction method, collects and extracts volatile oil and the medicinal residues that obtain, and is standby.
Flos Lonicerae extract of the present invention extracts water extract the medicinal residues that available conventional method is left after above-mentioned Flos Lonicerae is extracted volatile oil.
Honeysuckle flower soft capsule of the present invention is an oral Preparation, has effects such as heat-clearing and toxic substances removing, antiinflammatory, antiviral, is applicable to particularly all diseases of causing of viral infection of cat fever clinically.
Pharmacodynamic experiment of the present invention shows, only comprising the honeysuckle flower soft capsule of Flos Lonicerae volatile oil compares with the honeysuckle flower soft capsule that comprises Flos Lonicerae extract and Flos Lonicerae volatile oil simultaneously, both all have significant antipyretic and antidote functions, and the latter's antiinflammatory action is better than the former simultaneously.
The present invention has following significant technique effect:
1, honeysuckle flower soft capsule of the present invention is effective ingredient with the Flos Lonicerae volatile oil, can overcome the shortcoming of the existing dosage form of Flos Lonicerae, make it to carry taking convenience by making soft capsule, by in soft capsule, adding technological means such as stabilizing agent and employing oil-based solvent, make that the medicinal liquid that contains Flos Lonicerae volatile oil is stable oil-oil solution, thereby prevent sedimentation, raising stability of formulation.
2, contain Flos Lonicerae volatile oil and Flos Lonicerae extract when honeysuckle flower soft capsule provided by the invention, have more outstanding antiinflammatory, antivirus action, therefore can satisfy the needs of different clinical requirements, also can make full use of effective ingredient of honeysuckle, prevent the wasting of resources.
3, honeysuckle flower soft capsule provided by the invention satisfies the standard of such dosage form aspect outward appearance, hardness, disintegration etc. and physical and chemical stability, and soft capsule Chinese medicine composition granularity carefully and evenly, disintegrate is molten diffusing fast in vivo, absorbs soon the bioavailability height simultaneously.
Below by to the introduction of the specific embodiment of the invention, describe in detail but do not limit the present invention.
The specific embodiment of invention
The used Flos Lonicerae of the present invention is purchased in medical material company, through being accredited as the dry flower of caprifoliaceae plant Radix Ophiopogonis (Lonicerajaponica Thunb.).Other used adjuvants of the present invention are commercially available purchase commodity.
The preparation of Flos Lonicerae volatile oil
The used Flos Lonicerae volatile oil of the present invention can adopt steam distillation or supercritical extraction to extract preparation from Flos Lonicerae.
[embodiment 1] steam distillation
Method with reference to one one of version Chinese Pharmacopoeia in 2000 is extracted volatile oil with steam distillation, and extraction time is 6 hours.
[embodiment 2] supercritical extraction
Extracting honeysuckle is an amount of, and it is standby to pulverize 20 mesh sieves.Drop into extraction kettle, extraction-container, basin and heat respectively, when the extraction kettle temperature reaches 40 ℃, extraction-container I temperature reaches 50 ℃, when extraction-container II temperature is 35 ℃, opens CO
2Gas cylinder, when extraction kettle pressure reached 20Mpa, the pressure of extraction-container I was 10MPa, when the pressure of extraction-container II is 6MPa, beginning cycling extraction, CO
2Flow is about 18kg/h, extracts after 4 hours from extraction-container discharging volatile oil.
The preparation of Flos Lonicerae extract
Flos Lonicerae extract of the present invention, extract the remaining medicinal residues after Flos Lonicerae is extracted volatile oil with conventional method: medicinal residues decoct with water secondary, and 1 hour for the first time, gradation in 45 minutes for the second time filtered, filtrate merging is evaporated to every ml and is equivalent to Flos Lonicerae 2g, add 20% lime cream, regulate pH value to 12~13 and stir evenly, leave standstill, filter, discard filtrate, precipitation adds 2 times of amounts (in volume ratio), 95% ethanol and stirs evenly, and crosses sieve No. 4, regulate pH value to 3~4 with 50% sulfuric acid solution, stir evenly, filter, filtrate is neutralized to pH6.5~7.0 with 40% sodium hydroxide solution (in weight ratio), filter, filtrate decompression is condensed into the thick paste shape, the room temperature drying under reduced pressure, promptly.
The preparation of honeysuckle flower soft capsule
[embodiment 3]
The I prescription
Component amount (gram/grain)
Flos Lonicerae volatile oil 0.06
PEG400 0.4
Cera Flava 0.02
Glycerol 0.01
Capsule shells 0.22
II preparation technology
The Cera Flava thermosol in liquid polyethylene glycol 400, is obtained 35 ℃ thermosol thing, again this thermosol thing is joined in the glycerol that is preheated to 35-45 ℃ lentamente, the limit edged stirs, and adds Flos Lonicerae volatile oil then, fully mixes, cross colloid mill and pulverize the back pelleting, drying, promptly.
[embodiment 4]
The I prescription
Component amount (gram/grain)
Flos Lonicerae volatile oil 0.04
Oleum Arachidis hypogaeae semen 0.26
Tween 80 0.01
Ethyl cellulose 0.002
Capsule shells 0.19
II preparation technology
The ethyl cellulose thermosol in Oleum Arachidis hypogaeae semen, is obtained 45 ℃ thermosol thing, again this thermosol thing is joined in the tween 80 that is preheated to 35-45 ℃ lentamente, the limit edged stirs, and adds Flos Lonicerae volatile oil then, fully mixes, cross colloid mill and pulverize the back pelleting, drying, promptly.
[embodiment 5]
The I prescription
Component amount (gram/grain)
Flos Lonicerae volatile oil 0.08
Isopropyl alcohol 0.40
Propylene glycol 0.10
Soybean lecithin 0.05
Capsule shells 0.25
Propylene glycol and soybean lecithin thermosol in part isopropyl alcohol, are obtained 40 ℃ thermosol thing, again this thermosol thing is joined in the residue isopropyl alcohol that is preheated to 35-45 ℃ lentamente, the limit edged stirs, and adds Flos Lonicerae volatile oil then, fully mixes, cross colloid mill and pulverize the back pelleting, drying, promptly.
[embodiment 6]
The I prescription
Component amount (gram/grain)
Flos Lonicerae extract 0.06
Flos Lonicerae volatile oil 0.03
PEG400 0.4
Glycerol 0.035
Capsule shells 0.22
II preparation technology
After Flos Lonicerae extract beaten powder and cross 100 mesh sieves, feed intake by the prescription proportioning, elder generation in the part Polyethylene Glycol, obtains 45 ℃ thermosol thing with the glycerol thermosol, this thermosol thing is joined in the residue Polyethylene Glycol that is preheated to 45 ℃ lentamente again, the limit edged stirs, add Flos Lonicerae extract and Flos Lonicerae volatile oil then, it is moistening fully fully to mix assurance, crosses colloid mill and pulverizes the back pelleting, drying, promptly.
[embodiment 7]
The I prescription
Component amount (gram/grain)
Flos Lonicerae extract 0.04
Flos Lonicerae volatile oil 0.01
Oleum Arachidis hypogaeae semen 0.4
Tween 80 0.2
Ethyl cellulose 0.002
Capsule shells 0.19
II preparation technology
After Flos Lonicerae extract beaten powder and cross 100 mesh sieves, feed intake by the prescription proportioning, elder generation in Oleum Arachidis hypogaeae semen, obtains 35 ℃ thermosol thing with the ethyl cellulose thermosol, this thermosol thing is joined in the tween 80 that is preheated to 35 ℃ lentamente again, the limit edged stirs, add Flos Lonicerae extract and Flos Lonicerae volatile oil then, it is moistening fully fully to mix assurance, crosses colloid mill and pulverizes the back pelleting, drying, promptly.
[embodiment 8]
The I prescription
Component amount (gram/grain)
Flos Lonicerae extract 0.08
Flos Lonicerae volatile oil 0.04
Isopropyl alcohol 0.2
Propylene glycol 0.10
Soybean lecithin 0.12
Capsule shells 0.25
II preparation technology
After Flos Lonicerae extract beaten powder and cross 100 mesh sieves, feed intake by the prescription proportioning, earlier with propylene glycol and soybean lecithin thermosol in part isopropyl alcohol, obtain 40 ℃ thermosol thing, the thermosol thing is joined lentamente in the residue isopropyl alcohol that is preheated to 40 ℃ again, the limit edged stirs, add Flos Lonicerae extract and Flos Lonicerae volatile oil then, it is moistening fully fully to mix assurance, crosses colloid mill and pulverizes the back pelleting, drying, promptly.
Pharmacodynamics test
[embodiment 9] honeysuckle flower soft capsule causes the influence that rabbit body temperature raises to the fresh yeast suspension
Choose body temperature 36 of the healthy rabbits (medical animal experiment center, Guangdong Province provides) of 38 ℃~38.4 ℃ (every day, fluctuation was no more than 0.2 ℃), be divided into 3 groups at random, be respectively blank group, embodiment 5 honeysuckle flower soft capsule groups and embodiment 8 soft capsule groups.Give every rabbit intramuscular injection 4% fresh yeast suspension 1ml/kg after the grouping immediately, to irritate stomach respectively according to embodiment 5,8 made soft capsule preparations (30g/kg) simultaneously and give above-mentioned two honeysuckle flower soft capsule groups, and give above-mentioned blank group soft capsule adjuvant filling stomach.Below respectively organize the administration volume and be the 10ml/kg body weight, administration every day 3 times, delivery time is 3 hours.Regularly the surveying record rabbit body temperature changes after the administration first time, measures 1 time every 30 minutes, observes continuously 8 hours, and each administration group all compares with intensification value and the blank group of same time.
The results are shown in Table 1.The result shows that the rabbit body temperature that honeysuckle flower soft capsule causes the fresh yeast suspension raises the inhibitory action of highly significant is arranged, and heating is disappeared rapidly.The soft capsule of being made by Flos Lonicerae extract and volatile oil is separated thermal effect with the soft capsule made from volatile oil does not have significant difference.
Table 1 honeysuckle flower soft capsule causes the influence that rabbit body temperature raises to the fresh yeast suspension
Group | Rabbit body temperature changes |
1h | ?2h | 3h | 4h | 5h | 6h | 7h | 8h |
Blank | -0.21± 0.30 | ?0.02± ?0.23 | 0.38± 0.18 | 0.47± 0.18 | 0.90± 0.22 | 1.12± 0.23 | 0.96± 0.11 | 0.82± 0.35 |
Embodiment 3 honeysuckle flower soft capsules | -0.09± 0.12 | ?0.08± ?0.13 | 0.20± 0.16
* | 0.23± 0.35
* | 0.34± 0.35
** | 0.53± 0.38
** | 0.42± 0.19
** | 0.32± 0.22
** |
Embodiment 6 honeysuckle flower soft capsules | -0.11± 0.30 | ?0.10± ?0.43 | 0.24± 0.11
* | 0.27± 0.28
* | 0.40± 0.21
** | 0.42± 0.33
** | 0.46± 0.20
** | 0.29± 0.35
** |
Compare with the blank group:
*P<0.05,
*P<0.01
[embodiment 10] honeysuckle flower soft capsule is to the influence of rat carrageenan foot swelling
30 of male rats (medical animal experiment center, Guangdong Province provides), body weight 180 ± 20g divides equally 3 groups at random, is respectively blank group, embodiment 4 honeysuckle flower soft capsule groups and embodiment 7 soft capsule groups.To irritate stomach respectively according to the soft capsule preparation that embodiment 4,7 makes and give above-mentioned two honeysuckle flower soft capsule groups, and give above-mentioned blank group soft capsule adjuvant filling stomach.Continuous gastric infusion 5 days (20g/kg), after the last administration 1 hour, the carrageenin of 1% weight is only injected the subcutaneous 0.1ml/ of the sufficient sole of the foot, measured the foot swelling degree behind the Yu Zhiyan in 1,3,5,6,8 hour respectively.
The results are shown in Table 2.The result shows that honeysuckle flower soft capsule can obviously suppress foot swelling, and is better than the soft capsule made with volatile oil by the soft capsule antiphlogistic effects that Flos Lonicerae extract and volatile oil are made.
Table 2 honeysuckle flower soft capsule is to the influence of rat carrageenan foot swelling
Group | Foot swelling degree (mm) |
1 | 3 | 5 | ?6 | ?8 |
The blank group | 5.61± 1.69 | 10.89± 2.97 | 14.0±2.18 | ?15.0±2.52 | ?13.06±1.31 |
Embodiment 2 honeysuckle flower soft capsules | 5.21± 1.69 | 11.01± 2.03 | 13.56± 3.18 | ?14.1±1.52 | ?11.06± ?1.31
* |
Embodiment 4 honeysuckle flower soft capsules | 5.05± 2.36 | 11.56± 2.64 | 12.5± 1.39
* | ?11.44± ?1.91
* | ?10.28± ?1.62
* |
Compare with the blank group:
*P<0.05
Above detailed description of the present invention does not limit the present invention, and those skilled in the art can make various changes and distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the defined scope of claims of the present invention.