CN1184973C - Thrombolytic leech capsule and its preparing method - Google Patents
Thrombolytic leech capsule and its preparing method Download PDFInfo
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- CN1184973C CN1184973C CNB021498008A CN02149800A CN1184973C CN 1184973 C CN1184973 C CN 1184973C CN B021498008 A CNB021498008 A CN B021498008A CN 02149800 A CN02149800 A CN 02149800A CN 1184973 C CN1184973 C CN 1184973C
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- hirudo
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- thrombolytic
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Abstract
The present invention relates to a soft leech thrombolysis capsule which comprises a capsule shell and leech extract in the capsule shell. A method for preparing the soft leech thrombolysis capsule comprises: (1) water is added to gelatin, and thus, the gelatin is expanded; glycerol and residual distilled water are heated to 70 to 80 DEG C in a gelatin cooker; mixture is uniformly mixed, and the expanded gelatin is added to the mixture to be stirred and dissolved; then conserving agents are added to the mixture to be treated with heat preservation for 1 to 2 hours; the mixture stands still, and is treated with filtration and heat preservation for spare use; (2) after being heated and melted, beeswax is added to mixed suspension liquid prepared from vegetable oil and leech extract; mixture is uniformly stirred to present flowing semi-solid substances, or mixture is uniformly dispersed in a homogenizer; (3) a soft capsule is prepared with a pressing method or a dripping method. The present invention overcomes the defects of the existing preparations, and the active components of the medicine can be completely dispersed in base materials; under the special situation, the soft capsule can be swallowed without water. The soft capsule has the advantages of high bioavailability, beautiful appearance and no obviously-bad smell of the capsule, and standards in the aspects of appearance, disintegration and physical and chemical stability of capsules can be satisfied.
Description
Technical field
The present invention relates to a kind of is the oral drugs and preparation method thereof of feedstock production with the animal medicinal material, specifically is that the extract with the animal drug Hirudo is the soft capsule of feedstock production.
The invention still further relates to described preparation of soft capsule method.
Background technology
Hirudo is the dry body of Hirudinidae animal blood-eating hirudo, Hirudo Whitmania pigra Whitman, Hirudo Hirudo nipponica Whitman or Folium Salicis Babylonicae Hirudo Whitmania acranulata Whitman.Salty in the mouth, hardship, property is flat.Have removing blood stasis, removing blood stasis, the effect of stimulating the menstrual flow.Yong Yu mass in the abdomen mass in the abdomen, blood stasis amenorrhea, diseases such as traumatic injury.China's pharmacology monograph Shennong's Herbal the earliest carries Hirudo " by the stagnant blood blood stasis ".The merit of the removing blood stasis removing blood stasis of Hirudo has obtained the abundant affirmation of ancient Chinese medicine doctor.Key medicine for the logical stasis of blood of removing blood stasis.Clinical practice proof Hirudo treatment blood stasis symptom over nearly 2,000 years has remarkable effect.The clinical apoplexy that is usually used in, hemiplegia, facial hemiparalysis, stiff tongue speech is not smoothgoing, more is applicable to diseases such as cephalophyma behind the hypertensive cerebral hemorrhage, cerebral thrombosis; And the toxic and side effects of Hirudo is minimum.
" the Hirudo injection " that with Hirudo extract be main effective ingredient has better curative effect to the hemiplegia of the cephalophyma behind the hypertensive cerebral hemorrhage, cerebral thrombosis and apoplexy sequela performance, blood pressure, breathing, heart rate there is not influence, there is not irritated reaction, no obvious toxic and side effects.But the clinical use of injection is convenient not as oral formulations, and safety is not as oral formulations.Particularly the Chinese medicine of commute pollution also is difficult to guarantee the stability and the safety of its effective ingredient though process is sterilized.Moreover the frangible rapid wear of aqueous injection ampoule, and owing to the content of the special route of administration effective ingredient of injection is lower.With Hirudo extract is that the oral formulations of main effective ingredient has dosage forms such as oral liquid.Existing oral formulations such as oral liquid and injection all belong to liquid preparation, animal medicinal material Hirudo in the prescription, belong to biological medicine category, less stable in aqueous solution, its active component is leech polypeptide and small protein, and easily gathering forms precipitation and makes the oral liquid formulations muddiness in solution, and outward appearance and inherent quality are all destroyed, and Hirudo extract has the bad flavor of smelling, and can not make us very satisfied acceptance even add correctives.
Summary of the invention
The object of the present invention is to provide a kind of is the soft capsule of main effective ingredient with Hirudo extract, product is an oral administered dosage form, can overcome the shortcoming of existing dosage form, the effective ingredient high degree of dispersion of medicine in substrate, and in particular cases not water can swallow.The bioavailability height, good looking appearance can be covered the bad flavor of smelling of medicine, satisfies the standard of such dosage form aspect outward appearance, disintegrate and physical and chemical stability.
The present invention also aims to provide the preparation method of described Hirudo thrombolytic soft capsule.
Hirudo thrombolytic soft capsule of the present invention comprises the Hirudo extract in softgel shell and the softgel shell.
Described softgel shell can prepare with existing method, and its composition of raw materials is as follows: gelatin 40～60 weight portions, glycerol 16～24 weight portions, water 40～60 weight portions.
Can also contain following prescription in the softgel shell:
Dispersant 100～600 weight portions
Suspending agent 15～90 weight portions
Antioxidant 1～10 weight portion
Antiseptic 0.1～5 weight portion
Available prior art for preparing Hirudo extract correspondingly needs Hirudo 500～3000 weight portions.
Described dispersant can be vegetable oil such as Oleum Glycines, Oleum Arachidis hypogaeae semen, Oleum Camelliae, corn wet goods, one or more in mineral oil, polyethylene glycols, the propylene glycol.
Antiseptic can be sorbic acid, sorbic acid methyl ester, one or more in methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, the benzoic acid etc.
Antioxidant can be one or more in sodium sulfite, sodium pyrosulfite, sodium thiosulfate, pyrogallic acid ester, thiourea, alpha-tocopherol, the ascorbic acid etc.
Suspending agent can be a Cera Flava, methylcellulose, ethyl cellulose, one or more in the hydroxypropyl emthylcellulose etc.
The invention solves a following main difficult problem:
1. softgel shell prescription
Key component is a gelatin in the prescription of soft capsule shell, and the character of gelatin is to the formability of softgel shell, and it is very important that dissolubility all seems, ideal soft capsule shell gelatin, its viscosity should be at 25～45mPas, and bloom power should be between 150～250g, and pH value should be between 3.6～7.6.The amount of gelatin, glycerol and the ratio between the water are difficult for grasping in the prescription in addition.The amount of glycerol is too many, and softgel shell is softer, than being easier to extrusion: the amount of glycerol very little, softgel shell is harder, crisp, influences the quality stability and the disintegration time of soft capsule.We have carried out experimental study to the proportioning of the gelatin in the softgel shell, glycerol.
2. the extraction of medical material:
Get the Hirudo (scalding) of recipe quantity and adopt decoction and alcohol sedimentation technique refining, filter, the filtrate vacuum drying was pulverized 80～100 mesh sieves, got the pressed powder of Hirudo extract.
3. medicinal liquid is write out a prescription:
With the gelatin is the soft capsule of softgel shell, because the hydrophilic of gelatin, therefore the medicinal liquid to soft capsule has special requirement, has determined that the used dispersant of medicinal liquid can not be water, ethanol, and the bigger organic solvent of some toxicity.Be that moisture in the medicinal liquid prescription of soft capsule must could guarantee the quality of soft capsule less than 8%, cause capsule deformation and leakage because of organic solvent destruction softgel shells such as moisture in the absorption medicinal liquid or ethanol to prevent soft capsule.Ideal is that disperse medium is an oil substances.But because the Hirudo dry extract can not be dissolved in the vegetable oil, in order to increase the stability of medicinal liquid, we need add suspending agent, can be good at helping Hirudo extract to be suspended in the vegetable oil, and can keep stable for a long time.As Cera Flava, Polyethylene Glycol etc.
An amount of Cera Flava heating is dissolved the back add in the suspension of an amount of vegetable oil and Hirudo extract formation, stirring is mobile semi-solid; Or in homogenizer, be uniformly dispersed.Make it become stable suspension.
Preparation of soft capsule technology of the present invention may further comprise the steps:
(1) gelatin adds an amount of water earlier and makes its expansion, and glycerol and remaining distilled water are heated to 70～80 ℃ in glue pot, and mix homogeneously adds expansible gelatin and stirs and dissolve, and adds antiseptic, is incubated 1～2 hour, leaves standstill filtration, heat preservation for standby use;
(2) will add behind an amount of Cera Flava heating and melting in the suspension of an amount of vegetable oil and Hirudo extract formation, stirring is mobile semi-solid; Or in homogenizer, be uniformly dispersed.Make it become stable suspension;
(3) medicinal liquid for preparing is poured in the medicinal liquid bucket, adopted pressing or dropping preparation method to prepare soft capsule.
Soft capsule dosage form is compared with existing dosage forms such as " Hirudo injection ", " NIAOXUEKANG KOUFUYE ", and advantage is a steady quality, carries, convenient drug administration; The effective ingredient stripping is fast, onset in time; Can cover the bad smell of medicine.
Product of the present invention prepares as stated above, and its detailed component is provided by the following example, but protection scope of the present invention is not limited to this.
The specific embodiment
Embodiment 1
Prescription
Hirudo 1500g
Oleum Arachidis hypogaeae semen 300g
Cera Flava 20g
Gelatin 50g
Glycerol 20g
Water 45g
Sodium sulfite 5g
Ethylparaben 0.5g
Make 1000 altogether
Preparation method:
(1). the preparation of capsule material gelatin solution: the gelatin of getting recipe quantity adds suitable quantity of water makes its expansion.In addition glycerol and remaining water are heated to 70～80 ℃ in glue pot, mix homogeneously adds expansible gelatin and stirs, and dissolves, and is incubated 1～2 hour, leaves standstill, and makes the foam come-up, scrapes off the foam of come-up, filters heat preservation for standby use with clean calico.
(2) preparation of medicinal liquid: water intaking trematodiasis (scalding) 1500g, washing was soaked in water 4 hours, rub, add 10 times of water gagings and decoct three times, boiled 2 hours for the first time, second, three times each 1.5 hours, collecting decoction filtered, filtrate is concentrated into about 500ml (relative density 1.05-1.08), put coldly, add ethanol and make that to contain alcohol amount be to reach 70%, fully stir, left standstill 24 hours, filter, filtrate is concentrated into the thick paste shape, extremely does (moisture content＜8%) through vacuum drying again, pulverize, add heat sterilization, clarifying medicinal plant oil and antioxidant, even matter mixing makes and is the runny plaste shape, promptly.
(3) pill: the gelatin solution that will make is put and is controlled at about 60 ℃ in the gelatin solution storage tank, medicinal liquid is put into liquor tank, and the control temperature is at 50 ℃～60 ℃, and liquid coolant liquid paraffin temperature is controlled at 10～17 ℃, the pill room temperature is controlled at 10～20 ℃, 40～50 ℃ of water dropper temperature; Regulate the rubber weight and the thickness uniformity to the regulation requirement, begin to drip a glue ball.
(4) whole ball is with dry: the soft gelatin capsule that oozes is put on the gauze of soft gelatin capsule machine, dry more than 4 hours at low temperature below 10 ℃, place pill wiping machine to wipe the liquid paraffin on ball surface again, and then in the blowing of low temperature below 10 ℃ taking-up more than 20 hours, remove surperficial oil reservoir, dry up washing liquid, 40-50 ℃ following dry about 24 hours.Take out exsiccant soft gelatin capsule, lamp inspection, remove useless ball after, use 95% washing with alcohol, dry up at 40-50 ℃ again, quality inspection is packed, promptly.
Embodiment 2
Hirudo 750g
Oleum Camelliae 250g
Cera Flava 15g
Gelatin 50g
Glycerol 20g
Sodium sulfite 2.5g
Ethylparaben 0.5g
Make 1000 altogether
Preparation method is with embodiment 1.
Embodiment 3
Hirudo 1500g
Polyethylene Glycol (PEG400) 270g
Polyethylene Glycol (PEG2000) 30g
Gelatin 50g
Glycerol 20g
Water 50g
Alpha-tocopherol 5g
Ethylparaben 0.5g
Make 1000 altogether
Preparation method:
(1). the preparation of capsule material gelatin solution is with embodiment 1
(2) preparation of medicinal liquid: water intaking trematodiasis (scalding) 1500g, washing was soaked in water 4 hours, rub, add 10 times of water gagings and decoct three times, boiled 2 hours for the first time, second, three times each 1.5 hours, collecting decoction filtered, filtrate is concentrated into about 500ml (relative density 1.05-1.08), put coldly, add ethanol and make that to contain alcohol amount be to reach 70%, fully stir, left standstill 24 hours, filter, filtrate is concentrated into the thick paste shape, extremely does (moisture content＜8%) through vacuum drying again, pulverize, add in the mixed solution of Polyethylene Glycol (PEG400) and Polyethylene Glycol (PEG2000), even matter mixing makes and is the runny plaste shape, promptly.
(3) pill: the gelatin solution that will make is put in the gelatin solution storage tank and is controlled at about 60 ℃, and medicinal liquid is put into liquor tank, and the control temperature is selected the mould of predetermined weight at 50 ℃～60 ℃, regulates to drip speed and water dropper diameter extremely till the weight up to specification.The pill room temperature is controlled at 10～20 ℃, 40～50 ℃ of water dropper temperature; Regulate the rubber weight and the thickness uniformity to the regulation requirement, begin to suppress soft gelatin capsule.
(4) with embodiment 1
Soft capsule of the present invention proves its performance by following pharmacological experiment:
Pharmacodynamic experiment is the result show, the Hirudo thrombolytic soft capsule has blood circulation promoting and blood stasis dispelling, removing blood stasis eliminating stagnation function.
1, can significantly reduce stasis syndrome disease rat whole blood viscosity (low cutting with height cut), whole blood reduced viscosity (low cutting) and plasma viscosity, compare P＜0.05 with model group;
2, can significantly alleviate the weight in wet base and the dry weight of rat vein thrombosis, compare P＜0.05 with matched group;
3, can significantly improve the recovery rate of thrombosis hemiplegia mice, compare P＜0.01 with matched group;
4, ischemic tissue of brain there is protective effect
5, can significantly reduce the content of acute cerebral ischemia rat model cerebral tissue MDA, compare P＜0.01, also can improve the vigor of acute cerebral ischemia rat model cerebral tissue SOD, but compare P＞0.05 with model group with model group;
But the life span of 6 significant prolongation acute cerebral ischemia model mices compares P＜0.05 with model group;
But dehisce the time of breathing behind the 7 significant prolongation mices broken end, compare P＜0.01 with matched group;
8, can significantly reduce the seepage discharge of acute cerebral ischemia rat model brain blood capillary azovan blue, compare P＜0.01 with model group.
The generation of cerebral thrombosis disease and development and vascular lesion and hemorheology obstacle; be that blood stasis is relevant; clinical often with symptoms such as hemiplegia, cerebral edema and disturbance of consciousnesss; the function of promoting blood circulation to disperse blood clots of Hirudo thrombolytic soft capsule reaches the protective effect to cerebral ischemia, may be pharmacological basis of its treatment cerebrovascular disease.
The toxicological study result:
1. acute toxicity test
It is 30g crude drug/kg body weight that mice once gavages maximum dosage-feeding, is 200 times of clinical maximum consumption per day.Illustrate that it is safe and reliable that said preparation is intended consumption clinically.
2. long term toxicity test
Respectively to nine weeks of rat oral gavage, the result shows with Hirudo thrombolytic soft capsule 0.5, two dosage of 5.0g/kg and normal saline: the experiment of Hirudo thrombolytic soft capsule increases rat body weight in early days obvious facilitation; Except obvious reduction platelet count is arranged, conventional other index of rat serum there is not obvious effect; Serum biochemistry T-BIL, BUN, CRE value, the administration group is starkly lower than matched group, and the administration treated animal heart, liver weight coefficient are lower than matched group, but can recover after two weeks of drug withdrawal, all the other internal organs spleens, lung, kidney device weight coefficient and the equal no significant difference of matched group; The pathological examination animal heart, liver, spleen, lung, kidney are not found obviously unusual.
Claims (5)
1, a kind of Hirudo thrombolytic soft capsule is characterized in that comprising the Hirudo extract in softgel shell and the softgel shell.
2, Hirudo thrombolytic soft capsule according to claim 1 is characterized in that the feedstock production of the following prescription of described softgel shell needs: gelatin 40～60 weight portions, glycerol 16～24 weight portions, water 40～60 weight portions.
3, Hirudo thrombolytic soft capsule according to claim 1 and 2 is characterized in that also comprising in the softgel shell following prescription:
Dispersant 100～600 weight portions
Suspending agent 15～90 weight portions
Antioxidant 1～10 weight portion
Antiseptic 0.1～5 weight portion
Described dispersant is one or more in Oleum Glycines, Oleum Arachidis hypogaeae semen, Oleum Camelliae, Semen Maydis oil, mineral oil, polyethylene glycols, the propylene glycol; Antiseptic is one or more in sorbic acid, sorbic acid methyl ester, methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, the benzoic acid; Antioxidant is one or more in sodium sulfite, sodium pyrosulfite, sodium thiosulfate, pyrogallic acid ester, thiourea, alpha-tocopherol, the ascorbic acid; Suspending agent is one or more in Cera Flava, methylcellulose, ethyl cellulose, the hydroxypropyl emthylcellulose.
4, Hirudo thrombolytic soft capsule according to claim 3 is characterized in that described Hirudo extract needs Hirudo 500～3000 weight portions to prepare.
5, the preparation method of the described Hirudo thrombolytic soft capsule of claim 1 is characterized in that comprising:
(1) gelatin adds water earlier and makes its expansion, and glycerol and remaining distilled water are heated to 70～80 ℃ in glue pot, and mix homogeneously adds expansible gelatin and stirs and dissolve, and adds antiseptic, is incubated 1～2 hour, leaves standstill filtration, heat preservation for standby use;
(2) will add behind the Cera Flava heating and melting in the suspension of vegetable oil and Hirudo extract formation, stirring is mobile semi-solid; Or in homogenizer, be uniformly dispersed;
(3) pressing or dropping preparation method prepare soft capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021498008A CN1184973C (en) | 2002-12-31 | 2002-12-31 | Thrombolytic leech capsule and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021498008A CN1184973C (en) | 2002-12-31 | 2002-12-31 | Thrombolytic leech capsule and its preparing method |
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| Publication Number | Publication Date |
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| CN1425391A CN1425391A (en) | 2003-06-25 |
| CN1184973C true CN1184973C (en) | 2005-01-19 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB021498008A Expired - Fee Related CN1184973C (en) | 2002-12-31 | 2002-12-31 | Thrombolytic leech capsule and its preparing method |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100432604C (en) * | 2007-01-10 | 2008-11-12 | 苏式兵 | Vacuum freeze-drying method for hirudo |
| CN102379859B (en) * | 2011-11-07 | 2014-06-18 | 无锡福尔顺科技有限公司 | Method for preparing alginate soft capsule wrapping function substrate suspension |
| CN108354174A (en) * | 2018-05-25 | 2018-08-03 | 云南众爱生物科技有限公司 | A kind of Sialic acid soft capsule and preparation method thereof |
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Granted publication date: 20050119 Termination date: 20111231 |